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Rates of posttraumatic stress disorder (PTSD) among military personnel have surged in recent years. In response, the Department of Veterans Affairs (VA) has launched nationwide training initiatives to disseminate two PTSD treatments with strong empirical support: prolonged exposure (PE) therapy and cognitive processing therapy (CPT). Despite the well-documented effectiveness of PE and CPT, only a minority of Veterans with PTSD initiate these trauma-focused treatments. One approach to addressing PTSD in a non-trauma-focused fashion is to utilize empirically supported treatments focused on safety aid reduction. Safety aids are maladaptive cognitive and/or behavioral strategies designed to prevent, avoid, or alleviate anxiety. Initially introduced as a way to explain how pathological anxiety can persist despite repeated exposure to feared stimuli, safety aids have been found to play a critical role in the etiology and maintenance of various anxiety and related conditions including PTSD. Importantly, a separate line of research suggests that safety aids are amenable to change through cognitive behavioral interventions. Although promising, these trials did not include patients with PTSD. In this context, the purpose of this project is to examine the efficacy of a safety aid reduction treatment (START), compared to a wait-list control. Participants will include veterans with a diagnosis of PTSD who decline to participate in evidence-based psychotherapies (EBPs) for PTSD, namely PE or CPT. It is hypothesized that participation in START, compared to a wait-list control, will be associated with decreased PTSD symptom severity immediately and over time. | The purpose of this project is to examine the efficacy of a safety aid reduction treatment (START), compared to a wait-list control, among Veterans with posttraumatic stress disorder (PTSD). It is hypothesized that participation in START, compared to a wait-list control, will be associated with decreased PTSD symptom severity immediately and over time. |
A Phase 2b randomised, double-blind, placebo-controlled and open-label active comparator study to evaluate the effect of Cotadutide at 100, 300 or 600 micrograms in participants who have Chronic Kidney Disease with Type 2 Diabetes Mellitus.~The study plans to randomise approximately 225 subjects. Subjects will be randomised to receive double-blind Cotadutide or placebo at 100, 300 or 600 micrograms once daily for 26 weeks, or open-label semaglutide at 1.0 miligrams once a week for 26 weeks. Japanese participants will not be randomised to the semaglutide arm. | A Phase 2b, study to measure the effect of Cotadutide at different doses versus placebo or comparator (semaglutide) in participants who have Chronic Kidney Disease with Type 2 Diabetes Mellitus. |
Approximately 20% of Americans over 65 have mild cognitive impairment (MCI), defined as experiencing more memory problems than normally expected with aging, but no other symptoms of dementia such as impaired judgment or reasoning. Persons with MCI (patients) are at great risk for developing dementia (10-33% per year). Memory problem (poor executive function) diminish the patient's confidence and ability to perform meaningful and/or important activities (e.g. socialization, medication management).~Deteriorating life satisfaction in patients and care partners (caregivers) is a prevalent problem due to diminished meaningful activity engagement which occurs as a result of patient frustration and embarrassment, lack of self-efficacy (confidence), and diminishing activity performance. As a result, patients experience additional negative health outcomes: 38% report depressive symptoms and anxiety. Caregivers often lack confidence to manage their own and the patient's daily challenges and meaningful activity engagement, leading to high caregiver burden, depressive symptoms, and anxiety. As a dyad, both patients and caregivers report diminished satisfaction within their communication and relationship due to disagreement about the patient's functional ability to effectively and safely perform meaningful activities.~Emerging evidence indicates regular engagement in social, physical or cognitive activities can improve life satisfaction, activity performance, depressive symptoms, anxiety, and dyad communication; health outcomes are even better when the activities are self-selected and meaningful. To promote patients' and caregivers' life satisfaction and health outcomes, interventions to maximize patients' capacity for full engagement in meaningful activities are essential; yet, there is a marked absence of such empirically validated interventions.~The investigators developed and tested the Daily Engagement in Meaningful Activities (DEMA) intervention to improve life satisfaction and health outcomes for patients and caregivers. DEMA is a positive health focused, theoretically grounded, tailored, family-centered, multi-faceted intervention. Over 7 session, dyads work with a nurse to 1) identify meaningful activities, assess capacity, problem-solve barriers, and establish routines for engagement and 2) learn more about MCI by working through six Self-Management Toolkit topics (e.g., benefits of meaningful activity; planning the future).~The investigators' purpose is to evaluate the efficacy of DEMA in a two-group randomized controlled trial with 200 patient/caregiver dyads (DEMA intervention vs. the information support (IS) attention control group).~Aim 1 (Primary Objective): Test DEMA's efficacy for improving life satisfaction in patients and their caregivers over time.~Aim 2 (Secondary Objective): Over time, evaluate DEMA's efficacy for patient and caregiver to:~increase patient activity performance and diminish depressive symptoms and anxiety.~Hypothesis 2.1: Compared to the IS group, patients receiving DEMA will have improved activity performance and decreased depressive symptoms and anxiety.~decrease caregivers burden, depressive symptoms, and anxiety . Hypothesis 2.2: Compared to the IS group, caregivers receiving DEMA will have decreased burden, depressive symptoms, and anxiety.~Aim 3: Explore improvement in health outcomes over time in the sub-sample of patients with depressive symptoms using the (PHQ)-9 ≥ 5 at baseline) and explore the burden on caregivers when patients have PHQ-9 is >5. Compared to the non-depressed participants:~Hypothesis 3.1. Patients with depressive symptoms (scores > 5 on PHQ-9 measured at baseline) will have improved activity performance.~Hypothesis 3.2 Caregivers of patients with depressed symptoms (scores > 5 on PHQ-9 measured at baseline) will report reduced burden.~Hypotheses 3.3. Patients with depressive symptoms (scores > 5 on PHQ-9 measured at baseline) and their caregivers randomized to DEMA will report improved: confidence to manage daily challenges, communication satisfaction, life satisfaction, relationship satisfaction, decreased depressive symptoms and anxiety. | The investigators developed and tested the Daily Engagement in Meaningful Activities (DEMA) intervention to improve life satisfaction and health outcomes for patients and caregivers. DEMA is a positive health focused, theoretically grounded, tailored, family-centered, multi-faceted intervention. Over 7 session, dyads work with a nurse to 1) identify meaningful activities, assess capacity, problem-solve barriers, and establish routines for engagement and 2) learn more about MCI by working through six Self-Management Toolkit topics (e.g., benefits of meaningful activity; planning the future). The investigators' purpose is to evaluate the efficacy of DEMA in a two-group randomized controlled trial with 200 patient/caregiver dyads (DEMA intervention vs. the information support (IS) attention control group). |
Breast cancer is the most common cancer in women. Its incidence increases with 58,459 new cases in France in 2018, however its mortality decreases with a survival rate of 87% at 5 years.~Therapeutic options are surgery, radiotherapy, chemotherapy and hormone therapy. Hormone therapy is one of the major treatments for hormone-sensitive tumors with a prescription made in around 70% of breast cancer cases. These different hormone therapies cause a hormonal imbalance with in particular an important anti-estrogenic action. Hormonal deprivation and menopause can be responsible for the occurrence of pelvic statics disorder.[5-9] Pelvic static disorder (PTS) is a common problem for women, which can occur at any age.~These disorders include urinary incontinence, stress or urgency, anal incontinence, genital prolapse.~Hypothesis's investigator is that hormone therapy may be responsible for PTS. In this study, investigator propose to assess the prevalence of pelvic static disorders in women undergoing adjuvant hormone therapy for localized breast cancer and to assess the overall quality of life in these patients. | In this study, investigator propose to assess the prevalence of pelvic static disorders in women undergoing adjuvant hormone therapy for localized breast cancer and to assess the overall quality of life in these patients |
This study will include the patients who signed the subject informed consent form among the patients with MDS who were chosen to be treated with Decitabine (Part I), plus additional 140 MDS patients as a historical control (Part II). Approximately, 68 patients will be included who satisfy the following inclusion and exclusion criteria in the Part I study.~Prospective collection of DNA from peripheral blood will be performed in the patients with MDS before commencement of decitabine therapy. We will evaluate the efficacy decitabine therapy according to the DNMT or HDAC gene SNPs in terms of following parameters: 1) hematolotic response (HR) or improvement (HI), or requirement of decitabine dose to achieve HR or HI, 2) complete (CR) or partial response (PR), or requirement of decitabine dose to achieve CR or PR, and 3) time to relapse or progression of MDS.~Genotyping will be undertaken using the Sequenom® iPLEX platform™, according to the manufacturer's instructions (www.sequenom.com; Sequenom Inc, San Diego, CA, USA). Whole blood samples will be obtained according to the declaration of Helsinki. DNA will be extracted using the Puregene DNA purification Kit (Gentra Systems Inc, Minneapolis, MN, USA). The detection of SNPs will be performed by the analysis of primer extension products generated from previously amplified genomic DNA using a Sequenom chip-based matrix-assisted laser desorption / ionization time-of-flight (MALDI-TOF) mass spectrometry platform. Multiplex SNP assays will be designed using SpectroDesigner software (Sequenom). Ninety-six well plates containing 2.5 ng DNA in each well will be amplified by PCR following the specifications of Sequenom. Unincorporated nucleotides in the PCR product will be deactivated using shrimp alkaline phosphatase. Allele discrimination reactions will be conducted by adding the extension primer(s), DNA polymerase, and a cocktail mixture of deoxynucleotide triphosphates and di-deoxynucleotide triphosphates to each well. MassExtend clean resin (Sequenom) will be added to the mixture to remove extraneous salts that could interfere with MALDI-TOF analysis. The primer extension products will be then cleaned and spotted onto a SpectroChip. Genotypes will be determined by spotting an aliquot of each sample onto a 384 SpectroChip (Sequenom), which is subsequently read by the MALDI-TOF mass spectrometer.~All statistical tests will be two-sided with the significance level set as 0.05 unless otherwise stated. The statistical data will be obtained using an SAS version 9.1 (SAS Institute, Cary NC, USA). Followings are the endpoints for the study.~Primary endpoint evaluation data~• Response rate: A response rate will be obtained and its confidence interval estimated to be evaluated through chi-square test. If the main endpoints which may influence the final evaluation must be controlled, stratified analysis (Cochran-Mantel-Haenzel, etc.) will be conducted. If all the subjects' characteristic endpoints must be controlled, the logistic regression model will be used for analysis.~Secondary endpoint evaluation data~Overall survival: survival will be evaluated from the registration day to death through Kaplan-Meier method.~Progression free survival: : The time of progression from MDS to AML and death from any cause. Progression free survival will be analyzed through Kaplan-Meier method. | Recent investigations have demonstrated that DNMT gene polymorphisms can contribute to the inter-individual variants in DNMT expression. Accordingly, we hypothesized that the DNMT and HDAC genes SNPs could predict the outcomes of decitabine therapy for myelodysplastic syndrome. Prospective collection of DNA from peripheral blood will be performed in the patients with MDS before commencement of decitabine therapy. We will evaluate the efficacy decitabine therapy according to the DNMT or HDAC gene SNPs in terms of following parameters: 1) hematolotic response (HR) or improvement (HI), or requirement of decitabine dose to achieve HR or HI, 2) complete (CR) or partial response (PR), or requirement of decitabine dose to achieve CR or PR, and 3) time to relapse or progression of MDS.~The objective of this study is 1) to determine genotypes from DNA samples from MDS patients receiving Decitabine therapy, 2) to determine the association of clinical outcomes (HR, HI, CR, PR or time to progression to leukemia) following decitabine therapy with DNMT or HDAC genotypes, and 3) to analyze the impact of cytogenetic risk on the response or leukemic evolution following decitabine therapy for MDS. |
Background Hypertension (HT) has been known for its prominent risk of cardiovascular events. Although there are various pharmacological choices, many patients fail to adhere to them. Therefore, adjunctive non-pharmacological treatment is a promising approach. Foot Reflexology is one of the complementary therapies that has been proved for its ability to decrease blood pressure (BP), however, there is limited data in patients with stage-2 HT.~Objective To examine the effectiveness of foot reflexology as adjunctive therapy for BP lowering.~Methods This was a single-center randomized clinical trial. Hypertensive patients who were regularly followed up at the hypertension clinic were enrolled and randomized into the intervention group (n=47) and control group (n=47). Foot reflexology was performed in the intervention group during a clinical visit. Office BP and pulse rate (PR) were measured before and immediately at 15 minutes (min) and 30 min after the procedure in the intervention group and after resting in the control group. | Hypertension (HT) has been known for its prominent risk of cardiovascular events. Although there are various pharmacological choices, many patients fail to adhere with them. Therefore, adjunctive non-pharmacological treatment is a promising approach. Foot Reflexology is one of a complementary therapies that has been proved for its ability to decrease blood pressure (BP), however, there is limited data in patients with stage-2 HT. We aimed to examine the effectiveness of foot reflexology as adjunctive therapy for BP lowering. This was a single-center randomized clinical trial. Hypertensive patients who were regularly followed up at the hypertension clinic were enrolled and randomized into the intervention group (n=47) and control group (n=47). Foot reflexology was performed in the intervention group during a clinical visit. Office BP and pulse rate (PR) were measured before and immediately at 15 minutes (min) and 30 min after the procedure in the intervention group and after resting in the control group. |
In this open-label, compassionate extended use study, patients who have completed their participation in an Amylyx sponsored protocol for ALS may be offered compassionate use extension of treatment with AMX0035 under this protocol. Patient currently treated with AMX0035 will continue to receive treatment at their current dose/regimen. Patients who have interrupted AMX0035 for more than 28 days will resume AMX0035 treatment with 1 sachet (oral [or feeding tube]) once a day in the morning to be escalated to twice a day (morning and evening) after approximately 2 weeks on the basis of GI tolerance. Enrolled patients will complete regular outpatient visit approximately every 16 weeks (± 2 weeks). Completion of the ALS functional rating scale (ALSFRS-R) will be optional. | The protocol is intended to provide extended treatment with AMX0035 to patients who previously participated in an Amylyx sponsored study of AMX0035 for ALS. |
PURPOSE:~To determine the effect of Transcranial direct current stimulation on sensory integration and risk of falling in diabetic polyneuropathy.~BACKGROUND:~Diabetic polyneuropathy is the most prevalent chronic complication affecting 30% - 50% of diabetic patients. Diabetic polyneuropathy usually affect the peripheral, autonomic, and central nervous systems with several clinical symptoms .About 80% of the cases of DN manifest as distal symmetrical sensorimotor polyneuropathy which is responsible for cases of chronic pain; impaired sleep quality; increase of the falling risk associated with weakness and increase of the risk of extremities amputation. Transcranial direct current stimulation is neurophysiologic intervention that alters cortical excitability to enhance lower extremity somato-sensation and thus improve functional outcomes.~HYPOTHESES:~There will be no effect of Transcranial direct current stimulation on sensory integration and risk of falling in diabetic polyneuropathy | To determine the effect of Transcranial direct current stimulation on sensory integration and risk of falling in diabetic polyneuropathy. |
The aim of our study is to compare the effects of NGT-based trunk training, video-based trunk training and video-based trunk training applied with Theratogs in children with hemiparetic type Cerebral Palsy. It is planned to include 45 patients with hemiparetic cerebral palsy between the ages of 5-15 and with Gross Motor Function Classification System (GMFCS) level I-III. Patients with cerebral palsy will be divided into 3 groups in a randomized controlled manner. Each group will continue and follow routine physiotherapy and rehabilitation treatments for 8 weeks. Then, structured trunk training will begin. NGT-based trunk training (45 minutes) to the first group, video-based trunk training (45 minutes) to the second group, and Video-based trunk training (45 minutes) will apply with Theratogs to the third group. Treatments will be applied two days a week for 8 weeks. | The aim of our study is to compare the effects of NGT-based trunk training, video-based trunk training and video-based trunk training applied with Theratogs in children with hemiparetic type Cerebral Palsy. |
This is an open-label, single-arm study to evaluate the safety and efficacy of bilateral subretinal administration of voretigene neparvovec in Japanese patients with biallelic RPE65 mutation-associated retinal dystrophy. Assessments will include full-field light sensitivity threshold testing, visual fields, visual acuity, vector shedding, immunogenicity and adverse events. Participants will be monitored for 5 years after treatment. | The purpose of this study is to provide safety and efficacy data for voretigene neparvovec, administered as subretinal injection, in Japanese patients with biallelic RPE65 mutation-associated retinal dystrophy. |
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that requires long-term corticosteroid and/or immunosuppressive agents. Thus lupus patients are immunocompromised patients, and the incidence of herpes zoster is higher than general population (asian population 32.5-91.4/1000 person-years vs general population 2.58-4.89/1000 person-years). Patients with active SLE are more susceptible because they require stronger immunosuppressive therapy. However, even mild or even stable lupus patients are highly susceptible, and they account for about two-thirds of the events. In addition, herpes zoster may trigger lupus flare. A case-control study showed a close correlation between herpes zoster reactivation and the diagnosis of lupus, and our previous studies indicated that recent VZV infection was associated with increased risk of disease flares. The risk of virus reactivation limited the use of live-attenuated shingles vaccine in SLE patients, especially in whom with high dose of prednisone or immunosuppressants. Whether the introduction of recombinant herpes zoster could reduce the risk of zoster reactivation in lupus patients is to be explored in this study. | The risk of herpers zoster reactivation is higher in SLE patients than general population. It has shown that mild or even inactive patients could also have varicella zoster virus (VZV) infections, and they account for about two-thirds of the events. And our previous study indicated that recent various VZV infection was associated with increased risk of disease flares. The risk of virus reactivation limited the use of live-attenuated shingles vaccine in SLE patients, especially in whom with high dose of prednisone or immunosuppressants. Whether the introduction of recombinant zoster vaccine could reduce the risk of zoster reactivation in lupus patients is to be explored in this study. |
Background: Sarcopenia is defined as an abnormal loss of muscle mass and strength. Declines in muscle mass and strength are expected with aging, but physical inactivity and low protein intake have been suggested as risk factors of sarcopenia. Recently, Taiwan is known as the fastest-aging nation in the world, and the prevalence of sarcopenia has been reported as 3.9-7.3%; even more 9-64% in Dr. Chen's study. So far, lifestyle interventions, especially exercise and nutritional supplementation, prevail as mainstays of treatment for sarcopenia.~Objective: To explore the effect and benefits of protein supplementation on the improvement of muscle mass and physical performance in older people with sarcopenia.~Study design: A randomized, double-blind, placebo-controlled clinical trial which will be conducted between September and November, 2020.~Participants: The study will be conducted in Keelung, Taiwan. A total of 9 day-care centers, including 180 over 65 years of residents, will be invited to participate the study via telephone calls.~Eligible participants will be invited to attend this randomized, double-blind, placebo-controlled, 2-parallel-groups trial, and will be randomly assigned to the experimental and control groups with 1:1 ratio.~Intervention: The intervention period will be 12 weeks. The control group will receive 150c.c placebo oat drink (1.5g protein, 0.5g fat, 0.1g carbohydrate each pack, Zhan Xuan Co. Ltd., Taiwan) per day, five days per week, while the experimental group will receive 150c.c protein supplementation drink (14g protein, 0.6g fat, 7g carbohydrate, 4.4 g BCAA , 2.4g glutamate, 0.5g arginine and 0.4g taurine each pack, Affix Health, Taiwan Branch) per day, five days per week.~Supplementation in the experimental group contains 90 kcal/d and the placebo oat drink contains 8.3kcal/d. Participants in the control group will be asked to maintain participants' usual diet and physical activity. There are 3 time-points to measure outcomes and observe other required information, at week 0(baseline), 6 and 12.~Sample size calculation: Referring to the setting in a published paper that gave a sample size of 30 participants/group, a sample size of 40 participants in each group is considered in the study, by considering potential dropouts.~Random assignment and blinding: An independent external researcher prepared a computer generated cluster random sampling. After random assignment, the external researcher newly assigned a subject ID to each participant. All other study personnel and participants remained blinded to the identity codes throughout the course of the study. When participants withdrew from or completed the study, researchers were provided with the participants' identities, and the participants were told what supplement participants had received.~Ethical approval: The study was approved by Taipei Hospital Human Trial Committee of the Ministry of Health and Welfare. All participants were assured that data collected from participants would be strictly confidential, and the physical condition and safety were given priority. Investigators conducted intervention only after obtaining participants ethical approval (registration number: TH-IRB-00190046). Anyone who feel uncomfortable during the study will be allowed to quit immediately with no any restriction.~Study measurement: Kihon Checklist, MNA, GDS-SF, SPPB, IADL, MMSE, handgrip, 6m gait speed, (SMI), SF-12 questionnaire and Tw-FROP-Com.~Statistical methods: Statistical analysis was conducted using the IBM SPSS software (version 22, IBM Corporation, New York, NY). An intention-to-treat analysis was performed. (1) Descriptive statistics: describe the distribution of category variables by number and percentage, and the mean and standard deviations describe the distribution of continuous variables. (2) Inference statistics: chi-square: to verify whether the pre-measured category variants between the experimental group and the control group are homogeneous. ANOVA: Check whether the continuous variables measured between the experimental group and the control group are homogeneous. Generalized estimating equations (GEE) with interactions of time and group in the models will be conducted to evaluate the intervention effect. A two-sided p-value < 0.05 is considered statistically significant. | Background: Declines in muscle mass and strength are expected with aging, but physical inactivity and low protein intake have been suggested as risk factors of sarcopenia. So far, lifestyle interventions, especially exercise and nutritional supplementation, prevail as mainstays of treatment for sarcopenia.~Objective: To explore the effect and benefits of protein supplementation on the improvement of muscle mass and physical performance in older people with sarcopenia.~Design: A randomized, double-blind, placebo-controlled clinical trial. Methods: Participants aged 65-95y who meet the following criteria will be invited: (1) muscle mass: bioimpedance, <7.0 kg/m² (male) and <5.7 kg/m² (female), (2) handgrip strength: <28 kg (male) and <18 kg (female), and (3) low physical performance: 6-m gait Speed <1.0 m/s. Study participants will be randomly assigned to two groups. The experimental group will receive a 12-week intervention with【protein (14g)+ BCAA(4.4g)】 drink per day, while the parallel control group will receive a placebo oat drink per day.~Participants in the control group will be asked to maintain participants' usual diet and physical activity. There are 3 time-points to measure outcomes and observe other required information, at week 0(baseline), 6 and 12. |
This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of ZN-c3. This study consists of 4 cohorts in participants with platinum-resistant ovarian, peritoneal, or fallopian tube cancer. Each cohort will test a combination of ZN-c3 with either pegylated liposomal doxorubicin (PLD), carboplatin, paclitaxel, or gemcitabine. | This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of ZN-c3 in combination with other drugs. |
The stunning response rate of anti-CD19(cluster of differentiation antigen 19) auto-CAR(chimeric antigen receptor)-T cell therapy brings hope to patients with relapsed or refractory B-cell hematologic malignancies. However, for B-ALL patients suffered from relapse after allo-HSCT (hematopoietic stem cell transplant), the T cells derived from healthy donor seems like a better origin for CAR-T cells producing because T cells derived from healthy matched sibling or unrelated donors have not been restrained by tumor micro-environment and retain anti-leukemia ability. So after we designed a clinical trial to manifest the safety and efficacy of anti-CD19 CAR-T cells for patients with relapsed B cell ALL. | The patients with relapsed B cell acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplant (HSCT) have a poor prognosis, especially for these relapsed in a short time after transplantation. Nowadays there is no effective way to salvage patients in such conditions. T cells derived from healthy matched sibling or unrelated donors have not been restrained by tumor micro-environment and retain anti-leukemia ability, which makes it serve well for patients with relapsed B-ALL. So we launched a multi-center clinical trial to proved the safety and efficacy of anti-CD19 CAR-T cells for relapsed B cell ALL. |
The pandemic of COVID-19 (coronavirus desease 19) led to a strict quarantine from 15 March 2020 to 11 May 2020. Maternal depression is a current pathology , especially in the post-partum (more than 15%). The quarantine could lead to anxious and/or depressive symptoms and difficulties in parents-children bonding.~Women who have experenced post-partum period have more chance to developp subsequent depression.~Among women who have experienced post-partum depression, those who were able to benefit from psychiatric follow-up during the quarantine by tele-consultation have a lower risk of anxious and depressive symptoms than those who did not receive follow-up. | Women who were able to benefit from psychiatric follow-up during the quarantine by tele-consultation have a lower risk of anxious and depressive symptoms than those who did not receive follow-up. |
Since 13 November 2013, XOFIGO has been authorised on the European zone for the treatment of patients with prostate cancer, in the phase of resistance to castration, with symptomatic bone metastases. Prostate cancer is the most common non-cutaneous cancer in men internationally, and more than 90% of patients with hormone-resistant prostate cancer will have bone metastases.~They frequently give rise to bone events that include spinal cord compressions and pathological fractures requiring surgery or external radiotherapy.~Bone metastases are an important cause of death, disability, quality of life degradation and increase the cost of treatment.~There is therefore a need for bone-targeting therapeutic agents that provide a benefit in terms of survival.~Xofigo is indicated in patients with bone metastases symptomatic of hormone-resistant prostate cancer and without known visceral metastases.~This treatment appears to have fewer side effects than chemotherapy (and does not call into question subsequent chemotherapy) or that the currently available metabolic bone radiotherapy as well as better pain control and survival gain than the latter do not | Since 13 November 2013, XOFIGO has been authorised on the European zone for the treatment of patients with prostate cancer, in the phase of resistance to castration, with symptomatic bone metastases.~bone metastases frequently give rise to bone events that include spinal cord compressions and pathological fractures requiring surgery or external radiotherapy.~Bone metastases are an important cause of death, disability, quality of life degradation and increase the cost of treatment.~Xofigo is indicated in patients with bone metastases symptomatic of hormone-resistant prostate cancer and without known visceral metastases. |
Primary central nervous system tumors (PCNST) correspond to all primitive tumors involving central nervous system structures, meninges and the origin of the cranial and paraspinal nerves. They have a malignant, benign, or borderline evolution. TPSNC represent a heterogeneous group of tumors, with more than 140 subtypes described in the WHO classification. The causes, prognostic factors, and therapeutic management differ according to the histological subtype.~The incidence of all of TPSNCs ranges from 17.6 to 22.0/105 in North American and European studies. However, because of the high number of different histological subtypes, most of them must be considered as rare tumors. Moreover, they represent a major public health problem due to high morbidity [8] and mortality.~In this context, the creation of a clinical database including data for all PCNST patients is of high interest. This database will allow us to develop clinical studies on:~The clinical, radiological and biological presentation of tumors, the impact of oncological treatments and the evaluation of survival for the different subtypes of PCNST. This is particularly important for rare histological subtypes of PCNST for which the current knowledge is scarce;~Clinical, radiological and biological factors predictive of tumor response to treatments;~Prognostic factors.~The database will also allow us to develop or participate in multicentric clinical studies, at the national or international level, as well as to facilitate the identification of patients for inclusion in translational studies | the creation of a clinical database including data for all PCNST patients is of high interest. This database will allow us to develop clinical studies on:~The clinical, radiological and biological presentation of tumors, the impact of oncological treatments and the evaluation of survival for the different subtypes of Primary central nervous system tumors (PCNST). This is particularly important for rare histological subtypes of PCNST for which the current knowledge is scarce;~Clinical, radiological and biological factors predictive of tumor response to treatments;~Prognostic factors. |
glioblastomas are the most common primary malignant tumours of the central nervous system.They represent about 2000 new cases per year in France.~Despite active treatments including surgery, radiotherapy and chemotherapy, patient survival is limited without possible cure.~Most patients with glioblastoma have impaired cognitive function, autonomy, and quality of life. Exploration of verbal memory in these patients shows that its deterioration is correlated with a more unfavourable prognosis, after adjustment with other usual prognostic factors.~This clinical situation, combined with a limited life expectancy, makes the preservation of quality of life a major objective, in a supportive environment that respects family integration. This is especially true since there is an established relationship between health-related quality of life, as measured by questionnaires.~The feasibility of introducing early accompaniment in GBM should be assessed in the diagnostic and therapeutic announcement environment. In order to measure the expected impact as favorable in the patient and his family, a broad survey of the classic domains of quality of life and more specifically dedicated to neurological symptomatology. | Most patients with glioblastoma have impaired cognitive function, autonomy, and quality of life.~This clinical situation, combined with a limited life expectancy, makes the preservation of quality of life a major objective, in a supportive environment that respects family integration. This is especially true since there is an established relationship between health-related quality of life, as measured by questionnaires.~In this context, and despite the lack of impact on overall survival, improving quality of life becomes a priority objective in recent Phase III trials.~The feasibility of introducing early accompaniment in GBM should be assessed in the diagnostic and therapeutic announcement environment. In order to measure the expected impact as favorable in the patient and his family, a broad survey of the classic domains of quality of life and more specifically dedicated to neurological symptomatology. |
The ARCADIA Trial will assess the safety and efficacy of AZD1656 in 150 patients with either Type 1 or Type 2 diabetes who have been hospitalised with COVID-19.~AZD1656 is a glucokinase (GK; hexokinase 4) activator which has been shown to reduce blood glucose for up to 4 months in humans. Diabetic patients admitted to hospital with COVID-19 often present with hyperglycaemia and are particularly vulnerable to progression to severe COVID-19. Treatment with AZD1656 (in addition to their usual care) may provide additional glucose control which could help improve clinical outcomes in both Type 1 and Type 2 diabetic populations.~In addition to its glucose lowering effect, AZD1656 may have additional benefits to COVID-19 patients via its effects on immune function. In many patients with severe COVID-19, an overreaction of the body's own immune system can cause severe problems including damage to the lungs and heart, which can lead to breathing problems necessitating intubation and ventilation. AZD1656 has been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments. This migration of Treg cells to inflamed tissue is crucial for their immune-modulatory function (Kishore et al (2017)). AZD1656 could enhance Treg migratory capacity and may prevent the development of cardiorespiratory complications observed in hospitalised patients with COVID-19, leading to lower requirements for oxygen therapy and assisted ventilation, and reduced incidences of pneumonia and acute respiratory distress syndrome (ARDS).~Diabetic patients hospitalised with COVID-19 will be randomised to receive either AZD1656 tablets or placebo tablets on a 1:1 basis until they are discharged from hospital or until they require intubation/mechanical ventilation. The aim of the study is to determine whether AZD1656 improves clinical outcomes in diabetic patients hospitalised with COVID-19. The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement will be used as the standard methodology for measuring patient outcomes. | The ARCADIA Trial is a randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with either Type 1 or Type 2 diabetes, hospitalised with COVID-19. |
Full Title: A prospective, randomized, placebo-controlled, double-blinded, phase III clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID-19.~Short Title: PROTECT-Patient study~Aim: Assess the safety and efficacy of COVID-19 convalescent plasma (CCP) as a therapeutic treatment for hospitalised patients with moderate to severe COVID-19~Study Design: Randomised, double-blinded, placebo-controlled, phase III clinical trial~Intervention: Randomised 1:1 to either CCP plus standard of care (SOC) or to SOC plus placebo (200 mL normal saline)~Active Agent: A single unit of approximately 200-250 mL of CCP that contains anti-SARS-CoV-2 collected by plasmapheresis from a volunteer who recovered from COVID19 with SOC as determined by local practice and guidelines.~Placebo: A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines~Sample Size: 600~Study Population: Consenting adult inpatients with moderate to severe COVID-19, not requiring invasive ventilation, who are admitted to a participating public or private sector hospital and who are not enrolled in another COVID-19 treatment trial.~Settings: Participating public and private sector hospitals in South Africa | A prospective, randomized, placebo-controlled, double-blinded, phase III clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID-19 |
After the frightful outbreak in the city of Wuhan, China and its evidence of being contagious, governments around the world particularly United States in an effort to stop the transmission- imposed travel restrictions to and from China. Though it's a novel virus and little is known about it, the spread was drastic across the world. In fact the spread was so rapid that by end of February 2020, the number of new cases outside China had levelled up to 13 fold as compared to the number of cases in China. Moreover, the number of infected countries with COVID-19 tripled. The first two reported cases in Pakistan were from Karachi and Islamabad on 27 February 2020. These two cases presented with a recent travel history from Iran. The current statistics showed the confirmed cases in Pakistan reached upto 284,121 till 9 August 2020.~Regarding the Pakistan's government response to COVID-19, quick steps were taken to curtail the transmission of virus as China is in northeast of Pakistan and also shares its borders with Iran where the number of cases are increasing exceptionally. As an initial response Pakistan closed its borders with China and implies strict methods at the Pakistan-Iran border. Still, in the initial days of pandemic Pakistan lacked the diagnosis kits and relied on China and Japan for testing purpose. However, later Pakistan was able to receive kits and started testing samples.~Pakistan's federal government along with the Ministry of Health (Moh) initiated a plan known as National Action Plan for Corona Virus Disease Pakistan. The basic motive behind developing this plan was to generate policies and methods to combat with the deadly virus across Pakistan. MoH managed to deliver crucial supplies like masks, gloves and suits to the doctors and paramedical staffs working at frontlines. A state of confusion existed at different levels in health care system in Pakistan, particularly in Orthopaedic departments of hospital where elective and emergency services were severely affected during the lockdown period that started from 19 March 2020.~Orthopaedic and Spine Center Ghurki Trust Teaching Hospital Lahore:~During the lockdown period most of the public hospitals and trust closed their Outpatient departments and started to deal with emergency cases only. Even the private hospitals were reluctant to perform elective and emergency orthopaedic procedures. This attitude was may be due to the information published from other countries on the post operative complications and reduction of orthopaedic procedures during the period. The closure of orthopaedic health services brings a great shock to poor people for whom trusts and foundations is the last hope as they cannot afford the private setups for their health care facilities. However even in such situation there are some trust hospitals worth mentioning who never closed their services and worked day and night to entertain their patients by observing all the precautions and safety measures. Ghurki trust teaching hospital is one of them. This hospital adopted a SMART STRATEGY or SMART hospital lockdown. The orthopaedic department divided the members into five teams performing a 1:5 rotations. Each team comprised of one professor, one assistant professor, one senior registrar and ten trainee residents. Similarly the other departments like anesthesia, paramedics, nurses and physiotherapists were also subdivided. Out of two hundred staff, thirty were tested positive for COVID-19 but they all were managed and returned to normal after home quarantine.~Orthopaedic Surgeries during COVID-19:~Since 19th March 2020 till 13th July 2020, the period of lockdown, two thousand one hundred and sixty surgeries were performed by the orthopaedic team of Ghurki hospital. The breakup of surgeries during lockdown was as follows: 1514 cases of trauma, 173 procedures of spine, 51 for arthroplasty, 51 for arthroscopy, 21 for tumors and 350 miscellaneous. The team was available 24 hours, 7 days a week under the supervisor of Professor Amer Aziz, to play their part in these terrible circumstances. The team started their day with recitation of Quranic prayer which is translated as In the name of Allah by whose name harm cannot be done by anything in the earth or in heavens. He is All-Hearing, All-Seeing (Tirmidhi, Hadith: 3388). The smart approach utilized was that the patients were operated as soon as possible preferably within first twenty four hours and discharged them early also one to two days post op in most cases with complete education. All the patients were screened for COVID but Polymerase Chain Reaction test (PCR) and Pulmonary High-Resolution Computed Tomography (HRCT) was not done in all the patients unless if they presented with suspicious history. Fortunately, none of the patient tested positive pre operatively. Strict asepsis was observed during the period. | After the frightful outbreak in the city of Wuhan, China and its evidence of being contagious, governments around the world particularly United States in an effort to stop the transmission- imposed travel restrictions to and from China. Though it's a novel virus and little is known about it, the spread was drastic across the world. In fact the spread was so rapid that by end of February 2020, the number of new cases outside China had leveled up to 13 fold as compared to the number of cases in China. Moreover, the number of infected countries with COVID-19 tripled. The first two reported cases in Pakistan were from Karachi and Islamabad on 27 February 2020. These two cases presented with a recent travel history from Iran. The current statistics showed the confirmed cases in Pakistan reached upto 284,121 till 9 August 2020.~During the lockdown period most of the public hospitals and trust closed their Outpatient departments and started to deal with emergency cases only. However even in such situation there are some trust hospitals worth mentioning who never closed their services and worked day and night to entertain their patients by observing all the precautions and safety measures. Ghurki trust teaching hospital is one of them. This hospital adopted a SMART STRATEGY or SMART hospital lockdown.~Since 19th March 2020 till 13th July 2020, the period of lockdown, two thousand one hundred and sixty surgeries were performed by the orthopaedic team of Ghurki hospital. The breakup of surgeries during lockdown was as follows: 1514 cases of trauma, 173 procedures of spine, 51 for arthroplasty, 51 for arthroscopy, 21 for tumors and 350 miscellaneous. The team was available 24 hours, 7 days a week under the supervisor of Professor Amer Aziz, to play their part in these terrible circumstances. |
During the COVID-19 pandemic, the classical subsequent treatment regimen for ITP of immunosuppressants and/or steroids might increase patients' susceptibility of virus infections. To minimize ITP patients' risk during the COVID-19 global crisis and to improve treatment efficacy, this treatment regimen of eltrombopag plus recombinant human thrombopoietin (rhTPO) should be investigated.~Recombinant human thrombopoietin (rhTPO) is a full-length glycosylated-TPO produced by Chinese hamster ovary cells, which showed its effectiveness in ITP in a variety of studies.~Eltrombopag, a small molecule agonist of thrombopoietin receptor (TPO-RA), was recommended as the subsequent treatment for ITP patients, which also already showed robust efficacy.~Both eltrombopag and rhTPO demonstrated good safety in ITP patients. Since they increase the number of platelets through different mechanisms, and previous studies demonstrated that they might exert synergic effect. The investigators hypothesized that the combination of these two agents could be a promising option for ITP treatment.~This study aimed to evaluate the sustained responses and safety of eltrombopag plus rhTPO as treatment for corticosteroid-resistant or relapsed ITP patients during the COVID-19 pandemic. | This is a prospective, multicenter, randomized, open-label study to investigate the efficacy and safety of eltrombopag plus recombinant human thrombopoietin (rhTPO) versus eltrombopag as treatment for corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) during the COVID-19 pandemic. |
Coronaviruses are among the most common causes of the common cold in humans.1,2 In recent decades, coronavirus has caused several epidemic worldwide with a vast number of deaths such as severe acute respiratory syndrome-SARS (2003) with 8098 people infected and 774 people died over 29 countries. The disease caused by SARS CoV-2 (COVID19) is manifest by fever, fatigue, dry cough, pharyngitis, and headache. In addition to the common clinical presentation of respiratory distress, and increasing frequency of cardiovascular manifestations has become evident.~In this context, the investigators propose to evaluate the safety of intravenous administration of convalescent plasma (CP) obtained from COVID19 survivors in patients requiring hospitalization for symptomatic high risk COVID19 disease. The study team wants to test the hypothesis that treatment with COVID19 CP will demonstrate salutary effects on COVID19 disease severity/duration, with the primary objective to reduce mortality. In addition, a major secondary objective to reduce the requirement for and/or duration of mechanical ventilation This is a single-arm, non-randomized, open-label treatment of eligible subjects defined as those who satisfy all inclusion criteria.~Written informed consent will be obtained all eligible subjects prior to participation.~Convalescent plasma will be obtained from male donors, nulliparous females, or female donors negative for HLA antibodies at least 14 days following recovery from COVID-19 infection. | The investigators propose to evaluate intravenous administration of convalescent plasma (CP) obtained from COVID19 survivors in COVID19 patients who are in the medium stage. Supportive data exist for use of convalescent plasma in the treatment of COVID19 and other overwhelming viral illnesses. The study team wants to test the hypothesis that treatment with COVID19 CP will demonstrate salutary effects on COVID19 disease severity/duration, with the primary objective to reduce mortality. In addition, a major secondary objective to reduce the requirement for and/or duration of mechanical ventilation. The first phase is to test the safety of CP therapy. |
This monocentric, three-arm, randomized, controlled clinical trial evaluates the effect of an activity tracker based exercise program in cancer patients on the Quality of life after oncological therapy. Quality of Life and the intensity of fatigue will be documented with the FACT-G total score of the FACIT Questionnaire six months after completion of radiotherapy. | Evaluation of the impact of an activity tracker based fitness programme on the Qualitiy of Life after oncological therapy. |
Epilepsy is a chronic brain disease with recurrent seizures and the comorbidity of psychiatric diseases are very common. The prevalence of depression in patients with refractory epilepsy is about 60%. However, the early diagnosis is usually difficult due to the unclear mechanism and untypical clinical symptoms, and there are no extremely effective treatments for depression in patients with epilepsy until now. In this prospective, multi-center, cohort study, we aim to investigate and screen two different types of depression (cognitive and somatic) in patients with epilepsy by using the combination of regular moods evaluating scales and heart rate variability instrument. The intervening methods of combining transcranial direct current stimulation (tDCS) and serotonin re-uptake inhibitors (SSRIs) are used to treat the patients with comorbidity of epilepsy and depression. And resting-state functional MRI will be conducted in patients with the comorbidity of epilepsy and depression before and after the combing treatment of tDCS and SSRIs. | Epilepsy is a chronic brain disease with recurrent seizures and the comorbidity of psychiatric diseases are very common. The prevalence of depression in patients with refractory epilepsy is about 60%. However, the early diagnosis is usually difficult due to the unclear mechanism and untypical clinical symptoms, and there are no extremely effective treatments for depression in patients with epilepsy until now. In this prospective, multi-center, cohort study, we aim to investigate and screen two different types of depression (cognitive and somatic) in patients with epilepsy by using the combination of regular moods evaluating scales and heart rate variability instrument. The intervening methods of combining transcranial direct current stimulation (tDCS) and serotonin re-uptake inhibitors (SSRIs) are used to treat the patients with comorbidity of epilepsy and depression. |
This Phase 1/2 study will gather data in an observational phase Natural History Cohort to further characterize and evaluate natural disease progression in male patients with genetically-confirmed X-linked retinitis pigmentosa (XLRP) caused by mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR). The study will also evaluate the safety and tolerability, as assessed by frequency and severity of ocular and systemic adverse events, as well as preliminary clinical efficacy of a single intravitreal (IVT) injection of 4D-125 at two dose levels in this patient population in one or both eyes (the contralateral eye dose provided the subject is eligible and provides consent).~4D-125 has been developed as a gene replacement therapy for XLRP. After receiving 4D-125, patients will be followed for 24 months with continued safety follow-up and 36 additional months of long-term follow-up. Secondary endpoints will assess preliminary efficacy measures over time after 4D-125 administration. | This is a Phase 1/2 multicenter study with two parallel parts: an observational natural history cohort and an open-label, prospective interventional trial in males with non-syndromic X-linked retinitis pigmentosa (XLRP) due to mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR). |
About 4-10% of patients with nasopharyngeal carcinoma (NPC) have metastatic disease at diagnosis. The treatment recommendation of primary metastatic NPC is systemic chemotherapy. However, the optimal regimen is yet to determine due to lack of prospective randomized trial for this unique group of patients. Generally, GP regimen is used as the first-line treatment of primary metastatic NPC. The aim of this study is to compare the efficacy of Toripalimab Combined with GP Regimen Chemotherapy Versus GP Regimen Chemotherapy for Primary Metastatic NPC. | The aim of this study is to compare the efficacy of Toripalimab Combined with GP Regimen Chemotherapy Versus GP Regimen Chemotherapy for Primary Metastatic NPC. |
The pilot study examines the feasibility of a cluster randomized controlled trial to measure the effectiveness of Invest in My Recovery Bank (IMRB) compared to usual care (UC). IMRB is a peer-led, manualized intervention to support youth and young adults receiving treatment for early psychosis with reducing or stopping problematic substance use. Peer providers, who represent clusters of service participants, will participate in a multi-day IMRB training. Training will include exploring the theoretical basis for the intervention approach and logic model, impact of service participant and peer provider on intervention design, the intervention strategies, and opportunities to build skill in each intervention component (e.g., role play with feedback). Peer providers will also receive twice monthly supervision to support intervention fidelity and resolve questions.~The proposed pilot study aims to: (a) determine if peer providers can implement IMRB with adequate fidelity; (b) determine if youth and young adults engage in the intervention with peer providers and find it acceptable; (c) estimate the rates of drop-out for each of the two study arms; (d) estimate both between-participant (within-provider team) and between-team variability (e.g., standard deviation, interquartile range) on key outcome measures for a future comparative cluster randomized trial of the intervention; and (e) identify any changes needed to the intervention approach, manual, or training materials.~Nineteen teams across 16 sites will be randomly assigned to IMRB or UC, ensuring that the three sites with more than one team have at least one team randomized to each arm. All youth meeting eligibility criteria will be enrolled in the study and will receive either IMRB or UC, based on the assignment status of their provider team. Intervention integrity will be measured through a peer-completed fidelity checklist. Participant outcomes will be measured through existing data collection at each participating organization. All participant outcome and service data is reported through the EPINET-TX platform, which allows for measurement-based care at participating sites and research using de-identified data. | The aim of the study is to pilot a peer-provided, manualized intervention to increase the proportion of young people with first episode psychosis who reduce or stop substance use and improve psychiatric and functional outcomes. Coordinated specialty care teams will be randomly assigned to implement the intervention, Invest in My Recovery Bank (IMRB), or usual care. The pilot study aims to: (a) determine if peer providers can implement IMRB with adequate fidelity; (b) determine if youth and young adults engage in the intervention with peer providers and find it acceptable; (c) estimate the rates of drop-out for each of the two study arms; (d) estimate both between-participant (within-provider team) and between-team variability on key outcome measures; and (e) identify any changes needed to the intervention approach, manual, or training materials. The pilot study will set the stage for a future comparative cluster randomized trial of the intervention; |
A Phase II, Single-center, Randomized Study of Eribulin Plus Cisplatin (EP) Versus Gemcitabine Plus Cisplatin (GP) as First-Line Treatment in Patients With Advanced Triple-Negative Breast Cancer. | Eribulin Plus Cisplatin Versus Gemcitabine Plus Cisplatin in Triple Negative Breast Cancer (TNBC) |
This prospective randomized controlled study compares the analgesic effects and dermatomal blockade distributions of single and double injection bilateral thoracic paravertebral block (TPVB) techniques in patients undergoing reduction mammaplasty.~After obtaining ethics committee approval; 60 patients scheduled for elective bilateral reduction mammoplasty and gave written informed consent, were included in the study. The inclusion criteria were female gender, aging between 18 and 70 years, American Society of Anesthesiologists (ASA) physical status of 1-3, capable of consenting, understanding the instructions for using the NRS pain scores and replying the study-based questions, lack of contraindications to regional anesthesia (allergy to a LA, local infection, and coagulopathy) and especially TPVB, absence of mental/psychiatric disorders, chronic analgesic/opioid use and alcohol/illicit drug use. The patients were randomized in one of single (Group S: T3-T4-bupivacaine 0.375% 20 mL/injection) or double injections (Group D: T2-T3&T4-T5-bupivacaine 0.375% 10 mL/injection) bilateral TPVB groups using the sealed envelopes technique. All patients' dermatomal (sensorial) blockade distributions (T2-T6) were tested bilaterally between T2 and T6 dermatomal levels on the midclavicular line in every 5 minutes through the first 30 minutes after TPVB performances, by using the pin-prick test, and then they were given standard general anesthesia. Before extubation, 1 g IV paracetamol was applied to all. The NRS pain scores (0: no pain and 10: worst pain imaginable), and the dermatomal blockade distribution/numbers of blocked dermatomes of all patients on both sides were asked and documented on postoperative 0th min, 1st, 2nd, 6th, 12th, 24th and 48th hours. Postoperatively, patients in both groups received IV paracetamol 1 g when NRS pain score ≥4, and also tramadol 1 mg/kg if they defined NRS≥4 again after 1 h. The primary endpoint was NRS pain score at 12th hour. The secondary endpoints included the NRS pain scores and the dermatomal blockade distribution/numbers of blocked dermatomes through the postoperative first 48 hours, block application times, number of patients experienced hypotension or required fentanyl intraoperatively, length of stay in postoperative care unit (PACU), postoperative time until first pain (NRS≥4), the total numbers of paracetamol and tramadol requirements, incidence of postoperative nausea and vomiting (PONV) and duration of sleep on postoperative days 1 and 2, patient and surgeon satisfaction scores. | This study compares the analgesic effects and dermatomal blockade distributions of single and double injection bilateral thoracic paravertebral block (TPVB) techniques in patients undergoing reduction mammaplasty.~After obtaining ethics committee approval; 60 patients scheduled for elective bilateral reduction mammoplasty and gave written informed consent, were included in the study. The patients were randomized in one of single (Group S: T3-T4) or double injections (Group D: T2-T3&T4-T5) bilateral TPVB groups (bupivacaine 0.375% 20 mL per side). All patients' dermatomal blockade distributions (T2-T6) were followed for 30 minutes, and then they were given general anesthesia. Before extubation, 1 g IV paracetamol was applied to all. Postoperatively, patients in both groups received IV paracetamol 1 g when numeric rating scale (NRS) pain score ≥4, and also tramadol 1 mg/kg if they defined NRS≥4 again after 1 h. The primary endpoint was NRS pain scores at postoperative 12th hour. The secondary endpoints were NRS scores and dermatomal blockade distributions through the postoperative first 48 hours, postoperative time until first pain, the total numbers of analgesic requirements on days 1 and 2. |
Over 340,000 people have incurred a mild traumatic brain injury (mTBI) as a result of the military conflicts in Iraq and Afghanistan. mTBI leads to a host of poor rehabilitation outcomes including impairments in cognition, physical health, and psychological health. These impairments among people with TBI lead to poor quality of life (QOL). Worsening this clinical picture, the prevalence of chronic pain is estimated to be 51.5% among civilians with TBI and 43.1-70% among Veterans with TBI. Opioids are used for treating chronic pain including among people with TBI. Thus, given the ongoing opioid epidemic in the United States, it is very timely to develop alter-native, non-pharmacologic treatments for chronic pain among Veterans with mTBI. Yoga is a promising activity-based intervention for TBI and chronic pain. Yoga is an activity generally comprised of breathing exercises, gentle stretching, and meditation. Neuromodulation through transcranial magnetic stimulation (TMS) is a prom-ising non-invasive, non-pharmacological treatment for TBI and chronic pain. Intermittent theta burst stimulation (iTBS) is a type of patterned, excitatory TMS. iTBS can induce a window of neuroplasticity, making it ideally suited to boost the effects of treatments provided after it. Thus, iTBS shows promise to prime the brain for combined interventions and may magnify the impacts that these interventions would have when used alone, in order to boost outcomes. The purpose of this SPiRE project is to develop a novel, combined neuromodulation and yoga neurorehabilitation intervention for Veterans with mTBI and chronic pain, and to examine the intervention's feasibility and acceptability. Using an existing, evidence-based, yoga program created specifically for people with TBI (LoveYourBrain Yoga), the investigators will first develop a neurorehabilitation intervention that combines iTBS with yoga (iTBS+yoga), and then collect pilot data about its feasibility and acceptability. Aim 1 will develop a novel, combined iTBS+yoga neurorehabilitation intervention for Veterans with mTBI and chronic pain. Aim 2 will examine the feasibility and acceptability of the iTBS+yoga intervention for Veterans with mTBI and chronic pain. Aim 3 will gather preliminary data to provide the foundation for sample size and power considerations for a future clinical trial to examine the effectiveness of iTBS+yoga on Veterans' quality of life, function and pain out-comes. The combined intervention will be provided in small group settings once a week for 6 weeks. iTBS will be administered immediately prior to the LoveYourBrain Yoga session. Emphasizing National Institute of Neuro-logical Disorders and Stroke (NINDS) Traumatic Brain Injury Common Data Elements (TBI CDEs), the investigators will collect preliminary outcome data related to quality of life, function and pain to inform a future Merit application, should the intervention prove feasible. This SPiRE project will directly benefit Veterans and VA Services by developing a new, non-pharmacological neurorehabilitation treatment for Veterans with mTBI and chronic pain in need of non-opioid treatment options. TMS is now offered at 30 VA hospitals nationwide for treatment-resistant depression, and yoga is among the complementary and integrative health programs being rolled out as a part of VAs nation-wide Whole Health implementation efforts, with classes offered through VA service lines such as recreational therapy. Therefore, should iTBS+yoga ultimately prove to be efficacious and effective, VA facilities will be well-poised to offer this treatment. A novel, activity-based, non-pharmacological treatment for Veterans with mTBI and chronic pain is of great need given the high prevalence of chronic pain, increased risk of opioid therapy, and increased risk of developing opioid use disorders. | The objectives of this VA SPiRE application are to develop a combined neuromodulation and yoga (iTBS+yoga) intervention for Veterans with mild traumatic brain injury (mTBI) and chronic pain, assess the intervention's feasibility and acceptability, and to gather preliminary clinical outcome data on quality of life, function and pain that will guide future studies. This SPiRE project will directly benefit Veterans and VA Services by developing a new, non-pharmacological neurorehabilitation treatment for Veterans with mTBI and chronic pain in need of non-opioid treatment options. Neuromodulation is now offered at 30 VA hospitals and yoga is among the complementary and integrative health programs being rolled out as a part of VAs Whole Health implementation efforts. Thus, should iTBS+yoga ultimately prove to be efficacious, VA facilities will be well-poised to offer this treatment. A novel, activity-based, non-pharmacological treatment for Veterans with mTBI and chronic pain is of great need given the high prevalence of chronic pain. |
In France, the notion of autonomy concerning the patient's place in the healthcare system has been written into legal texts for several years (Loi Kouchner, 2002; Loi Leonetti, 2005; Loi Leonetti-Claeys, 2016, etc.) . In addition,government policies are trying to adapt a strategy for transforming the health system. One of the priorities is to place the patient at the heart of the system . This orientation of positioning the patient at the center of the healthcare system taken by the Government, proves the importance of a contemporary reflection on the subject of the patient's autonomy. This notion is also fully recognized in our society and in the medical field by caregivers. Indeed, it constitutes a fundamental right of respect for the patient to decide for himself - in particular at the level of his health - what seems to be suitable, his therapeutic plan, his care, etc. However, the notion of autonomy is polysemous and complex. There is no unambiguous definition given the existence of plural conceptions of autonomy, especially in the field of psychology. Thus, through the literature, it can be understood as a psychological state, a personality variable, an attitude, a value, even a standard (Auzoult, 2008).~Given its omnipresence in public health, legislative, ethical, institutional as well as among caregivers, the investigators assume in our study that autonomy could be the object of social valuation and thus be understood as a shared norm. and conveyed. (Dubois & Beauvois, 2002). Norms are defined in particular as cultural rules which guide behavior in a society (Ross, 1973). In this perspective, the investigators can rely on the results of the work of Sonia Hadj Cherif's thesis on the representation of the autonomous patient in decision-making in the context of recurrence. In this questionnaire survey of physicians practicing in oncology, the participants were asked to perform a verbal association task inviting them to evoke the 5 words or expressions that came to their mind following the inductive word autonomous patient. The most salient elements associated with autonomy were: a good general state, management of daily life, valid, capacity for comprehension, hygiene, cognitive capacities preserved, movement, etc., thus representing the autonomous patient as a patient with all of his physical, motor and intellectual capacities. It is thus a functional autonomy in which the recognition of the patient depends first of all on his capacity to act and to do, which seems to prevail in medical discourse. Based on these findings, it would be interesting to study the autonomy perceived by the patient himself.~To do this, in our research, we will build a questionnaire intended for patients, the first part of which will be composed of a series of questions relating to the most significant associated words and their associated values for each patient to define his own representation of the autonomous patient. The second part of the questionnaire will consist of three sub-questionnaires including items relating to patient autonomy. The items of these three questionnaires will be identical in all respects. Only the instruction requested from the patient will differ. In fact, patients will first of all be asked to respond as authentically as possible in order to situate their own perceived autonomy . Secondly, they will have to respond with a fictitious perspective of giving their doctor a favorable image of themselves. Finally, as a last step, they will have to give an unfavorable image of themselves to their doctor. These questionnaires will allow us to know whether cancer patients use different self-presentation strategies depending on whether they present to themselves, or to their doctor. | In France, the notion of autonomy concerning the patient's place in the healthcare system has been written into legal texts for several years. This notion is also fully recognized in our society and in the medical field by caregivers. However, the notion of autonomy is polysemous and complex. There is no unambiguous definition given the existence of plural conceptions of autonomy, especially in the field of psychology. A precedent thesis on the representation of the autonomous patient in decision-making in the context of recurrence. Physicians practicing in oncology have been asked to perform a verbal association task inviting them to evoke the 5 words or expressions that came to their mind following the inductive word autonomous patient. The results shows that for doctors, the autonomous patient is a patient with all of his physical, motor and intellectual capacities. Based on these findings, it would be interesting to study the autonomy perceived by the patient himself. |
Background and objectives:~This study is driven by the hypothesis that provision of task-orientated training via a non-immersive virtual reality platform enhances upper limb motor and neural function more than current routine physical therapy for people with stroke. Before this hypothesis can be tested in a randomised controlled clinical trial. If evidence of concept is found, then the next step is identification of the optimum therapeutic dose of exercised-based therapy delivered via the Virtualrehab Platform as a precursor to a clinical efficacy trial. The specific objectives of the study reported here were:~to assess the acceptability and usability of the VirtualRehab platform for delivery of stroke rehabilitation at home:~to find if stroke survivors adhere to 'prescribed' use of the VirtualRehab platform over a 12-week period;~to assess the viability of using randomised length of baselines and repeated measures during the intervention period to inform subsequent study to find the optimum therapeutic dose~to estimate how a 12-week period of~Design:~A series of replicated single case studies with an AB design (2.1). During the A, control, phase participants will not receive the experimental intervention. Participants will receive the experimental intervention during the B phase. At the beginning of the control phase, participants will complete the measurement battery. These will be the baseline-one measures. The measurement battery will be repeated at the end of the baseline phase (baseline-two) and at the end of the intervention phase (outcome). Progress measures will be made at the end of every week of the intervention (B) phase.~Both sets of baselines and the outcome measures will be taken in the Movement and Exercise Laboratory (MovExLab) at the University of East Anglia (UEA). Progress measures will be made in participants' homes. The control phase will last for a randomised period of between one and four weeks. The time period for the control phase will be decided for each participant by a randomised sequence generated before the study begins, by a researcher independent of the research team for this study. The intervention phase will last for 12 weeks. During the intervention phase, each participant will undertake weekly progress measures in their home. These will be administered by the researchers prescribing and monitoring training. At the end of the control and the intervention phase, all participants will participate in a 1:1 semi-structured interview with the researcher.~A group of adults without any reported neurological damage undertook the measurement battery to provide reference values. The measurement battery and progress measures are described below. | This study will deliver a 12-week exercise-based upper limb virtual reality, non-immersive, rehabilitation programme for stroke survivors. The aims are to:1. to assess the acceptability and usability of the VirtualRehab platform for delivery of stroke rehabilitation at home:~2. to find if stroke survivors adhere to 'prescribed' use of the VirtualRehab platform over a 12-week period; 3. to assess the viability of using randomised length of baselines and repeated measures during the intervention period to inform subsequent study to find the optimum therapeutic dose 4. to estimate how a 12-week period of using the VirtualRehab platform could change motor impairment and functional capacity. |
PRIMARY OBJECTIVES I. To determine the correlation between HER2 specific T-cell response in HER2-positive breast cancer patients with stage I-IV who receive anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib and clinical responses.~II. To determine the correlation between antibody response in HER2-positive breast cancer patients with stage I-IV who receive anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib and clinical responses.~EXPLORATORY OBJECTIVES:~I. To estimate the proportion of patients who develop HER2-specific T cell and endogenous antibody responses.~II. To examine within individual patients trends in levels of HER2 CD4 T-cells, HER2 CD8 T-cells, and HER2-specific antibodies over the course of treatment.~III. To determine if combination therapy induces immunity to common breast cancer associated antigens (i.e. CEA, IGFBP2, and P53).~IV. To determine if induction of HER2-specific T cell or antibody immunity is associated with improved progression-free and overall survival in patients.~V. To determine if there are Fc gamma receptor (R) or HLA genotypes associated with the ability to generate immunity in response to anti-HER2 therapy.~VI. To determine whether anti-HER2 therapy induces HER2 loss and modulation of HER2-specific adaptive immune responses.~VII. To determine if loss-of-function mutations in antigen presenting genes are associated with recurrence in patients with HER2+ breast cancer.~VIII. To determine gene expression levels in tumors from patients who did not achieve pathologic complete response (pCR) that are associated with recurrence.~OUTLINE:~Patients undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence for patients with stage I-III, or progressive disease for patients with stage IV. Patients with stage IV HER2 positive breast cancer with no disease progression >= 2 years on the same line of therapy, undergo blood sample collection at baseline anytime during their treatment with anti-HER2 therapies, 8 and 16 weeks after the first blood draw, and at the time of invasive disease recurrence. Patients also undergo tumor tissue collection for the evaluation of gene expression and deoxyribonucleic acid (DNA) variants. | This study gathers information from the blood cells and tumor tissue during treatment with anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib, in patients with HER2 positive stage I-IV breast cancer who are scheduled to start anti-HER2 therapy. The information gained from this study may help researchers better understand the relation between cell response and anti-HER2 therapies. |
Research objectives~Research and follow-up of the course and outcome of high-risk pregnant women with perinatal depression in the third trimester;~Factors affecting the outcome of the disease;~Recurrence of PND in pregnancy again;~The influence of different intervention methods on the course of the disease. Research process: 1. The pregnant women who were filed at Xinhua Hospital and Tongji Hospital and were receiving perinatal care from July 2019 to December 2019 were evaluated in the third trimester of pregnancy using the General Situation Questionnaire, SSRS, PHQ-9, and GAD-7. Those with PHQ-9 score ≥ 5 or GAD ≥ 5 were classified as having symptoms of depression and anxiety, and those who were screened positive were included in the study cohort; 42 days postpartum, 3 months postpartum, 6 months postpartum, 12 months postpartum, 18 months postpartum , 24 months postpartum, use PHQ-9, GAD-7 scale, 6 quality of life questionnaires, and SSRS to evaluate the cohort. If the PHQ-9 score is greater than or equal to 5 or the GAD is greater than or equal to 5, the psychiatrist will perform a clinical examination based on DSM-IV to make a clinical diagnosis; the outcome of the cohort and the incidence and influencing factors; 2 . During the follow-up process, the cohort developed high-risk pregnant women with depression, anxiety symptoms and other perinatal depressive disorders during the follow-up process. Based on the WeChat platform, integrated general hospitals, psychological counseling centers, social families and other service resources were carried out throughout the prenatal and first delivery period. Intervention methods such as community intervention for perinatal depression that focus on the comprehensive physiology, psychology, and society of the whole process after the first childbirth. Pregnant women diagnosed with PND will be evaluated by a psychiatrist to determine the treatment plan, and follow-up will continue. | Research and follow-up of the course and outcome of high-risk pregnant women with perinatal depression in the third trimester;~Factors affecting the outcome of the disease;~Recurrence of PND in pregnancy again;~The influence of different intervention methods on the course of the disease. |
Post-traumatic stress disorder (PTSD) is the brain's long-term imprint of a traumatic event. PTSD is characterized by intrusive thoughts, nightmares and flashbacks of past traumatic events, avoidance of trauma reminders, hypervigilance, and sleep disturbance, all of which lead to considerable social, occupational, and interpersonal dysfunction. The current available treatments for PTSD include medications and psychotherapy. However, a substantial proportion of patients have treatment resistant PTSD.~In recent years there is growing evidence that traumatic events can induce changes in the brain's structure and function that may persist months or even years after the acute event. The non-healing brain wound can be visualized using functional imaging. The new insight regarding the biological nature of PTSD obligates biological intervention that can induce neuroplasticity and recovery of the damage brain tissue.~Hyperbaric Oxygen Therapy (HBOT) includes the inhalation of 100% oxygen in a pressurized chamber with pressures exceeding 1 atmosphere absolute (ATA), thus enhancing the amount of oxygen dissolved in the body's tissues. It is now understood that the combined action of both hyperoxia and hyperbaric pressure together with, oxygen fluctuations generated by a pre-defined protocol may target both oxygen and pressure sensitive genes, resulting in improved mitochondrial metabolism with anti-apoptotic and anti-inflammatory effects. Moreover, these genes induce the proliferation of stem cells, augmented circulating levels of endothelial progenitor cells (EPCs) and angiogenesis factors, which induce angiogenesis and improved blood flow in the ischemic area. In recent years there is growing evidence that HBOT induced brain neuroplasticity leads to repair of chronically impaired brain functions in post-stroke and in traumatic brain injury (TBI) patients with prolonged post-concussion syndrome, even years after the brain insult, as well as in healthy aging adults. HBOT can also induce neuroplasticity and significantly improve the clinical symptoms of the most common prototype of central sensitization syndrome - fibromyalgia syndrome.~The effects of HBOT on patients suffering from chronic unremitting PTSD due to combat trauma were evaluated in a pilot study done in the investigator's institute. The recently done study included veterans with combat associated PTSD according to the Ministry of Defense (MOD) criteria, who failed to improve using the current available treatments. The results of the study demonstrated the beneficial effect of HBOT in this unfortunate severely injured unremitting PTSD population. Clinically significant improvement was demonstrated in a major fraction of study participants. In correlation with the clinical improvement, a significant improvement in brain activity was demonstrated in the functional MRI imaging.~The aim of the current study is to evaluate the effect of HBOT on chronic unremitting combat associated PTSD in an double blind sham control study | The study evaluates the effect of hyperbaric oxygen therapy on veterans with combat-associated PTSD in an double blind sham control study. |
The purpose of this study is to compare the outcomes of medial UKA and HTO in the treatment of AMOA by investigating the performance of these 2 procedures in terms of functional outcome, radiographic assessment, range of motion, postoperative complications, revision rate and relevant health economics outcome, then identify factors associated with better clinical performance. It is aimed to provide evidence-based guidelines for selecting the appropriate procedure in managing AMOA in Chinese population based on the findings of this study.~The secondary endpoints will include:~Pain Numerical Rating Scale (NRS)~SF-12 Health Survey~Radiographic assessment includes pre-op and post-op mechanical femorotibial angle (mFTA), patella height, patellofemoral medial and lateral articular surfaces, and displacement angle of patella~Range of motion~Adverse event rate and classification (including complication)~Operating time~Total blood loss (BRECHER formula)~Revision rate~Health economic outcomes based on hospital discharge days, recovery time, physiotherapy and complications/ reoperations will also be analyzed. | The purpose of this study is to compare the performance and safety of medial UKA and HTO in the treatment of AMOA in term of functional outcome, radiographic assessment, range of motion, postoperative complications, revision rate and relevant health economics outcome. |
This study will evaluate the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered during pregnancy and postpartum.~IMPAACT 2026 is a Phase IV observational clinical study. Participants are not assigned to the drugs under study, but are already receiving the drugs for clinical care by prescription of their clinical care providers. They are enrolled into study arms according to the drugs they are receiving through clinical care, and if on multiple drugs of interest, are able to enroll into multiple arms simultaneously. No ARVs or TB treatment drugs are supplied as part of this study. All drugs under study are provided by non-study sources. The study sponsor added this observational study to an existing investigational new drug (IND) number for off-label use in case the participant's clinical care provider decides to prescribe a higher dose than the approved dose if the PK results for the approved dose indicate that drug exposure may be inadequate.~This study is comprised of five components which in turn are comprised of arms specific to each drug or drug combination being evaluated:~Component 1 (Arms 1.1, 1.2. 1.3. 1.4. and 1.5): Pregnant women living with HIV (WLHIV) receiving oral ARVs and no TB drugs, and their infants.~Component 2 (Arm 2.1): Pregnant WLHIV and HIV-uninfected women who received long-acting/extended release ARVs during pregnancy, and their infants.~Component 3 (Arms 3.1, 3.2, and 3.3): Pregnant WLHIV receiving ARVs and first-line TB treatment, and their infants.~Component 4 (Arm 4.1): Pregnant WLHIV and HIV-uninfected women receiving second-line TB treatment, and their infants.~Component 5 (Arms 5.1, 5.2. and 5.3): Postpartum WLHIV breastfeeding while receiving oral ARVs, and their infants.~Each arm will open to accrual independently and will accrue independently over approximately 36 months from the first enrollment in each arm.~Participants in Component 1 will be followed up to 12 weeks after delivery for mothers and up to 24 weeks after birth for infants. Participants in Component 2 will be followed up to 5 weeks after delivery for mothers and infants. Participants in Components 3, 4, and 5 will be followed up to 24 weeks after delivery for mothers and infants.~Study visits may include:~Component 1: Maternal clinical and laboratory evaluations and PK sampling at second trimester (2T), third trimester (3T), delivery, and 6-12 weeks post-partum (PP). Infant clinical evaluations and washout PK sampling at birth and 5-9 days after birth.~Component 2: Maternal clinical and laboratory evaluations and PK sampling at delivery. Infant clinical evaluations and washout PK sampling at birth, 5-9 days, and 12-16 days after birth. Maternal and infant breast milk transfer PK sampling at 5-9 days, 12-16 days, and 3-5 weeks after delivery.~Component 3: Maternal clinical and laboratory evaluations and PK sampling at second trimester (2T), third trimester (3T), delivery, and 2-8 weeks post-partum (PP). Infant clinical evaluations and washout PK sampling at birth and 5-9 days after birth. Maternal and infant breast milk transfer PK sampling at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.~Component 4: Maternal clinical and laboratory evaluations and PK sampling at second trimester (2T), third trimester (3T), delivery, and 2-8 weeks post-partum (PP). Infant clinical evaluations and washout PK sampling at birth and 5-9 days after birth. Maternal and infant breast milk transfer PK sampling at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.~Component 5: Maternal and infant clinical evaluations and breast milk transfer PK sampling at 5-9 days, 2-12 weeks, and 16-24 weeks after delivery. | The purpose of this study is to evaluate the pharmacokinetic (PK) properties of antiretroviral (ARV) and anti-tuberculosis (TB) drugs administered during pregnancy and postpartum. |
The present study focuses on adult persons living with HIV who are not highly adherent to HIV medication and who do not evidence undetectable HIV viral load (the ultimate goal of HIV treatment). The study uses technology, is grounded in principles of behavioral economics, and uses the multiphase optimization strategy (MOST) to examine the acceptability, feasibility, and evidence of efficacy of three intervention components. The components are intended to increase rates of HIV viral suppression in the sample. All participants receive a core intervention comprised of referrals to care and case management. The three components are: compensation for viral suppression (fixed compensation or lottery-type prizes), weekly text messages and quiz questions (TMQQ) for 21 weeks that generate points to earn compensation (to foster engagement), and three counseling sessions grounded in the motivational interviewing (MI) approach to help participants articulate goals with respect to health and viral suppression, identify and resolve barriers to HIV medication use, and build motivation for viral suppression. We have previously tested variations of these components together as a packaged intervention and found high acceptability, feasibility, and evidence of efficacy. We now seek to understand this approach with more precision by testing the effects of individual components using MOST. The components will be tested in a factorial design with 8 intervention conditions. Consistent with the factorial design, each condition will comprise a unique combination of components. Each condition includes at least one component. Participants will be recruited by a proven hybrid strategy that includes peer recruitment, ads placed in a free newspaper, and direct recruitment from an NYU Recruitment Registry managed by Dr. Gwadz. Participants will be screened for eligibility and a total of 80 adult persons living with HIV and with detectable HIV viral load will be enrolled in the study and randomly assigned to an intervention condition. Participants will be assessed at baseline and 5- and 8-months post-baseline with a structured assessment battery. A subset will receive in-depth interviews. The primary outcome is viral suppression. This is a pilot study. It is not powered for efficacy but we will examine evidence of efficacy. All study activities can be carried out in a virtual format, and we can switch to in-person contact for screening, assessment, and some components when appropriate. In-person activities would be conducted at the New York University Silver field site in Manhattan. The study is funded through the Constance and Martin Silver Artificial Intelligence and Social Impact Fund at the New York University Silver School of Social Work. | The present study focuses on adult persons living with HIV in the New York City and Newark, New Jersey metropolitan areas who are not highly adherent to HIV medication and who do not evidence undetectable HIV viral load (the ultimate goal of HIV treatment). Those who have not decided whether they wish to take HIV medications are invited to enroll. The study uses technology, is grounded in principles of behavioral economics, and uses the multiphase optimization strategy (MOST) to examine the acceptability, feasibility, and evidence of efficacy of three intervention components. The components are intended to increase rates of HIV viral suppression in the sample. The three components are: prizes for viral suppression (fixed compensation [$275] or lottery prizes [up to $500]), text messages and quiz questions that generate points to earn prizes (to foster engagement), and counseling sessions grounded in the motivational interviewing approach to help participants articulate goals with respect to health and viral suppression, identify and resolve barriers to HIV medication use, and build motivation for viral suppression. Participants are assessed at baseline and then 5- and 8-months later. |
There is high incidence of developmental and socioemotional delay and postoperative complications in pediatric living donor liver transplantation patients. In this prospective observational clinical study, the investigators aim to investigate the correlation between the intraoperative cerebral and renal tissue oxygen saturation and the incidence of developmental and socioemotional delay and postoperative complications. This study will enroll patients aged from 6 to 36 months old who are scheduled for elective standard living-donor liver transplantation and have signed informed consent before the surgery. | This rSO2 study is a prospective clinical study. The purpose of the rSO2 study is to investigate whether there is a correlation between the intraoperative cerebral and renal tissue oxygen saturation and the incidence of developmental and socioemotional delay after living donor liver transplantation for children. This study will also investigate whether intraoperative cerebral and renal tissue oxygen saturation are related to postoperative complications. |
Applied Behavior Analysis (ABA) remains the most effective and scientifically-validated approach to remediate the deficits caused by Autism Spectrum Disorders (ASD) and intellectual disabilities (ID). Clinical trials will evaluate the efficacy of expert guiding technology to support instructors to better help individuals with developmental challenges due to ASD and ID learn life and vocational skills. Single Case Research Designs (SCRD) will be used to evaluate expert guiding technology interventions to support Task Analysis. SCRDs are a viable alternative to large group studies such as randomized clinical trials. Single case studies involve repeated measures, and manipulation of an independent variable. SCRD studies allow for rigorous experimental evaluation of intervention effects and provide a strong basis for establishing causal inferences.~Research design: A multiple baseline across tasks or participants will be used to evaluate the impact of the expert guiding technology on staff and consumers' performance.~Dependent Variables. DV1: Staff performance: The percentage of teaching steps correctly implemented will be calculated and monitored. The teaching steps are predetermined including what types of prompts will be used for each step of the task analysis of the identified consumer's adaptive living skills, record data on consumer's performance, and the timing of delivery of reinforcers and prompts. DV2: Consumers' performance: The percentage of Independent completion of the steps of task analyses for identified daily living skills will be calculated and monitored. The completed step is considered independent when the consumer completed the step without prompts from the staff within five seconds of the initial instruction (discriminative stimulus) given or the completion of the previous step. DV3: Consumers' performance: the amount of time taken to independent completion.~Independent Variable: Versions of expert guiding technology to support instructors in providing Task Analyses instruction while collecting data on consumer performance.~GAINS: During the GAINS sessions, the staff will follow the pre-programmed teaching protocol in the expert guiding technology. The system will provide step-by-step verbal prompts to the staff throughout the sessions. This includes which prompt to use for each step, when to provide reinforcers, and which target task to work on. The system will also monitor the consumer's progress and notify the staff if the target task is mastered or not.~Procedural fidelity: procedural fidelity checklist will be implemented to ensure the accuracy of implementation of baseline and intervention procedures. The percentage of accurate implementation will be calculated by dividing the number of steps implemented accurately by the total steps of procedures multiplying by 100.~Develop and conduct survey of staff and consumers to evaluate social validity of expert guiding technology. | Clinical trials will evaluate the efficacy of expert guiding technology to support instructors to better help individuals with developmental challenges due to ASD and ID learn life and vocational skills. Single Case Research Designs (SCRD) will be used to evaluate expert guiding technology interventions to support Task Analysis. SCRDs are a viable alternative to large group studies such as randomized clinical trials. Single case studies involve repeated measures, and manipulation of an independent variable. SCRD studies allow for rigorous experimental evaluation of intervention effects and provide a strong basis for establishing causal inferences.~Research design: A multiple baseline across tasks or participants will be used to evaluate the impact of the expert guiding technology on staff and consumers' performance.~Dependent Variables. DV1: Staff performance: The percentage of teaching steps correctly implemented will be calculated and monitored. The teaching steps are predetermined including what types of prompts will be used for each step of the task analysis of the identified consumer's adaptive living skills, record data on consumer's performance, and the timing of delivery of reinforcers and prompts. DV2: Consumers' performance: The percentage of Independent completion of the steps of task analyses for identified daily living skills will be calculated and monitored. The completed step is considered independent when the consumer completed the step without prompts from the staff within five seconds of the initial instruction (discriminative stimulus) given or the completion of the previous step. DV3: Consumers' performance: the amount of time taken to independent completion.~Independent Variable: Versions of expert guiding technology to support instructors in providing Task Analyses instruction while collecting data on consumer performance.~GAINS: During the GAINS sessions, the staff will follow the pre-programmed teaching protocol in the expert guiding technology. The system will provide step-by-step verbal prompts to the staff throughout the sessions. This includes which prompt to use for each step, when to provide reinforcers, and which target task to work on. The system will also monitor the consumer's progress and notify the staff if the target task is mastered or not. |
The study will be conducted in Conservative Dentistry Department, Faculty of Dentistry, Cairo University; The operator in charge will be Esraa Esmeail Hussien.~Null-hypothesis: There are no differences in the clinical performance of indirect CAD/CAM milled composite when compared to direct bulk-fil composite endocrowns when in the posterior area.~Aim: This clinical trial will be conducted to assess the clinical performance of using indirect Milled composite or direct bulk-fill resin composite Endo-crowns for restoring the endo-treated teeth, as well to measure the amount of wear on the occlusal tables of both restorations using Digital Scanner.~Patients will be selected from the outpatient clinic of the department Conservative Dentistry Department, Faculty of Dentistry, Cairo University~Clinical Steps:~A tapered stone with rounded end in a high-speed handpiece with air /water coolant will be used to properly prepare the cavity walls to receive the indirect restoration and any remaining carious dentin will be excavated and removed.~Cuspal tipping will be done by a wheel stone about 1.5-2mm.~The entrance to the pulpal canal will be opened. Gutta percha will be removed to a depth not exceeding 2 mm to take advantage of the saddle-like anatomy of the cavity floor. This should be done with a nonabrasive instrument to maintain the integrity of the canal's entrance. No drilling into the dentin will be carried out.~Any remaining undercuts will be blocked with conventional resin composite.~The impression will be taken, and the final restoration will be fabricated either direct or indirect.~The final restoration should be checked intraorally for proximal contacts, occlusion and marginal fit before cementation.~Isolation of operatory field using rubber dam.~Selective enamel etching technique will be applied for bonding of tooth structure, 35-40% phosphoric acid gel will be applied to the enamel margins only for 15 seconds, rinsed for 15 seconds and gently dried by cotton pellet.~Adhesive will be used according to the manufacturers' instructions.~Adhesive resin cement will be applied into the preparation. The restoration will be placed in the cavity and checked for complete seating. The cement will be light cured for only 2 seconds to facilitate removal of the excess. Then light curing will be done from all directions each for 40 seconds for achieving the final set.~The proximal contacts will be checked with dental floss.~The occlusion will be adjusted using articulating paper.~Finishing and Polishing using finishing stones and polishing rubber points.~Primary Objective: To evaluate clinical performance of different Techniques of Composite Restorations (Indirect restorations using a CAD/CAM grinding process, BRILLIANT Crios, Coltène/Whaledent AG, Switzerland or Direct a light-cured, bulk-fill nanocomposite restorative material, Filtek™ One Bulk Fill Restorative, 3M ESPE Dental Products, USA) in Endodontically treated posterior teeth. | In patients with endodontically treated teeth, will the Indirect Milled composite Endo-crown restorations have a better clinical performance and more wear resistance than the Direct Bulk-Fill resin composite restorations over one year?~Primary Objective: To evaluate clinical performance of different Techniques of Composite Restorations (Indirect restorations using a CAD/CAM grinding process, BRILLIANT Crios, Coltène/Whaledent AG, Switzerland or Direct a light-cured, bulk-fill nanocomposite restorative material, Filtek™ One Bulk Fill Restorative, 3M ESPE Dental Products, USA) in Endodontically treated posterior teeth. |
This is a retrospective cohort study of all consecutive patients who underwent colon or rectal resection, between the years 2012-2017 at Rabin Medical Center, a tertiary referral center in Israel. Data were obtained from patients' electronic medical files. The study was approved by the Institutional Review Board (IRB) of Rabin Medical Center (RMC). The study met the guidelines outlined in the Declaration of Helsinki. Due to the minimal risk nature of this study, the need for informed consent was waived by the IRB.~Patient population:~All patients aged 70 years and above who underwent large bowel resection were included in the analysis. Inclusion criteria were: age ≥70; all patients undergoing any colonic or rectal resection for benign or malignant etiologies in an open or minimally-invasive approach Exclusion criteria were: age<70; colon resection without anastomoses; re-operations during the same admission .~Data retrieved included demographic data (age, gender, Charlson comorbidity score, place of residency, functional capacity, BMI), surgical data (indication for surgery, elective vs urgent surgery, surgical approach, length of surgery, peri-operative morbidity and mortality.All surgeries were performed by at least one senior surgeon. The surgical approach (laparoscopic or laparotomy) was at the senior surgeon's discretion and deemed most appropriate for the patient's problem, physiological status and underlying illnesses. The extent of the resection was according to oncological guidelines when relevant.~Endpoints:~Primary endpoint was the occurrence of postoperative anastomotic leak. Secondary end-point was postoperative mortality Statistical Analysis The statistical analysis for this paper was generated using SAS Software. Continuous variables were presented by Mean±Std, Categorical variables were presented by (N, %). T-Test was used to compare the value of continuous variables between study groups and Fisher's exact test (for two groups) or Chi-square (for more than two groups) were used to compare the value of categorical variables between study groups. Two-sided p values less than .05 were considered statistically significant | This is a retrospective cohort study of all consecutive patients who underwent colon or rectal resection, between the years 2012-2017 at Rabin Medical Center, a tertiary referral center in Israel. Data were obtained from patients' electronic medical files. The study was approved by the Institutional Review Board (IRB) of Rabin Medical Center (RMC). The study met the guidelines outlined in the Declaration of Helsinki. Due to the minimal risk nature of this study, the need for informed consent was waived by the IRB.~Patient population:~All patients aged 70 years and above who underwent large bowel resection were included in the analysis. Inclusion criteria were: age ≥70; all patients undergoing any colonic or rectal resection for benign or malignant etiologies in an open or minimally-invasive approach Exclusion criteria were: age<70; colon resection without anastomoses; re-operations during the same admission .~Data retrieved included demographic data (age, gender, Charlson comorbidity score, place of residency, functional capacity, BMI), surgical data (indication for surgery, elective vs urgent surgery, surgical approach, length of surgery, peri-operative morbidity and mortality.All surgeries were performed by at least one senior surgeon. The surgical approach (laparoscopic or laparotomy) was at the senior surgeon's discretion and deemed most appropriate for the patient's problem, physiological status and underlying illnesses. The extent of the resection was according to oncological guidelines when relevant~Endpoints:~Primary endpoint was the occurrence of postoperative anastomotic leak. Secondary end-point was postoperative mortality Statistical Analysis The statistical analysis for this paper was generated using SAS Software. Continuous variables were presented by Mean±Std, Categorical variables were presented by (N, %). T-Test was used to compare the value of continuous variables between study groups and Fisher's exact test (for two groups) or Chi-square (for more than two groups) were used to compare the value of categorical variables between study groups. Two-sided p values less than .05 were considered statistically significant |
Frailty is a geriatric syndrome which relies on the reduction of multisystem reserve capacity, whereas pre-frailty is a condition predisposing and preceding the frailty state. Frail people have a lower potential to respond to external stressors and various life incidents as well as they present a weak prognosis particularly in cardiovascular diseases. However, frailty is not only a set of physical deficits, but it also concerns psychological and social dimensions of human functioning. Hence, an approach to frailty should be multidimensional because such a concept more adequately reflects a functional degradation in the elderly. Frailty is usually associated with the impaired condition of circulatory system, and therefore, an identification of subclinical cardiovascular abnormalities which are associated with frailty is paramount in a context of frailty prevention and treatment. In this study, a comprehensive echocardiography will investigate cardiac function with a particular attention to features which typically change with age, like flow and diastolic parameters, as well as chambers sizes. Specifically, the impact of the impaired diastolic filling pattern on the frailty development will be thoroughly investigated. Another potential mechanism which may predispose to frailty is a dysfunction of the autonomic nervous system (ANS) - especially, its cardiac branch. ANS plays a crucial role in the response to internal or external stressors such as diseases and activities of daily living, and it plays a pivotal role in the homeostasis. Since frail people present a progressive homeostatic dysregulation, it is possible that the impairment in the cardiac ANS may maintain or accelerate the frailty process. In the present study, both tonic and reflex activities of the cardiac ANS will be explored with Finapres device (Finapres Medical Systems B.V., Amsterdam, the Netherlands) which is a gold standard for non-invasive continuous blood pressure monitoring and also allows ECG and respiratory signals recording. The study participants will also undergo routine medical examination, standard 12-lead electrocardiography, and measurements of body mass index and ankle-brachial index - the latter will reflect the degree of lower extremity arterial disease. A cognitive function and a psychological condition will be evaluated with the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale, respectively. A nutrition status will be checked with the Mini Nutritional Assessment (MNA). The Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) will be assessed with dedicated scales. A risk of fall will be judged with the questionnaire concerning the falls history and by examining a postural stability on a force plate (AccuSway, AMTI, Watertown, MA, USA). The study group will comprise community dwelling elderly individuals over the age of 65 years who get around by themselves. The exclusion criteria include: institutionalization, inability to move around, and terminal diseases with an anticipated survival of less than 1 year. After 2 and 5 years, the participants will be re-examined for their frailty and independence status, and in addition, their life status will be checked with national identification numbers by using the National Health Found registration system. Sample size calculation indicates that the minimum sample size to investigate frailty development should equal 994 subjects (1% margin of error and 95% confidence interval), however, assuming 10% loss in follow-up, the final sample size is 1093 subjects.~The primary endpoints of this study are: (i) to identify risk factors associated with multidimensional and physical frailty and pre-frailty in community dwelling elderly people over the age of 65 years; (ii) to find determinants for the development of different types of frailty in a prospective observation. The secondary endpoints are: (i) to explore the impact of various modes of frailty and other clinical factors on the elderly people mortality; (ii) to identify predictors for frailty development, disability or mortality as a composite endpoint; (iii) to explore the rate and determinants of a frailty status transition to a more robust status; (iv) to establish the prevalence of multidimensional frailty, and physical frailty and pre-frailty in elderly people in Polish community; (v) to determine a concordance/discordance between physical and multidimensional frailty. | Frailty syndrome (i.e. frailty) is a geriatric syndrome which relies on the reduction of multisystem reserve capacity. Frail people have a lower potential to respond to external stressors and various life incidents as well as they present a weak prognosis particularly in cardiovascular diseases. Yet, frailty is not only a set of physical deficits, but it also concerns psychological and social dimensions of human functioning. Hence, an approach to frailty should be multidimensional because such a concept more adequately reflects a functional degradation in the elderly. Frailty is usually associated with the impaired condition of circulatory system, and therefore, an identification of subclinical cardiovascular abnormalities is paramount in the frailty prevention and treatment. Another potential mechanism which may predispose to frailty is a dysfunction of the autonomic nervous system. This system plays a crucial role in the response to internal or external stressors such as diseases and activities of daily living. An impairment of the autonomic nervous system function may maintain or accelerate the frailty process.~In this scientific project, a comprehensive echocardiography will investigate cardiac function with a particular attention to features which typically change with age, like flow parameters and chambers sizes. The activity of the autonomic nervous system will be explored with the analysis of heart rate, blood pressure and respiratory signals. The study participants will also undergo routine medical examination and a number of additional tests, including: assessment of cognitive function, psychological condition, nutrition status, activities of daily living, and risk of falls. The study group will comprise community dwelling elderly individuals over the age of 65 years who get around by themselves. After 2 years, the participants will be re-examined for their frailty and independence status, as well as their survival will be checked with the National Health Found electronic system. The aim of this project is to seek for factors determining frailty and to explore the frailty impact on the elderly people survival. Particular attention will be paid to the multidimensional frailty which is a new concept of the functional decline in the elderly. In addition, the prevalence of different modes of frailty in Polish community will be investigated. The results of this research should help to establish preventative and therapeutic strategies against frailty. |
This study is about preparing people with cancerous tumours, soft-tissue sarcoma (STS), in the leg to recover more quickly from surgery. Prehabilitation or surgery school is done before surgery while undergoing other cancer-related treatments. The tumour can be anywhere in the leg so exercises must be specially designed for each person. This process is novel and therefore has to be tested to see if it is practical and if it helps people recovery more quickly. To test this idea, two groups will be formed. One group will have the prehabilitation program and the other group will have the same amount of attention from the research team who will visit them at the time of the radiotherapy sessions to provide support and any information they may need. Assessments of how well participants can do basic activities of daily living will be assessed at study entry, just prior to surgery and then at 2, 6 and 12 weeks after surgery. Other measures of recovery will be distance covered while walking for six minutes, quality of the walking, and how quickly participants can walk outdoors for 1000 steps, and then 3000, 5000 and 9000. The investigators will ask participants which of these outcome measures they think best reflected their recovery and why. The investigators will also assess whether people were willing to enter the study and complete all the processes required. The results of the study will indicate whether it is a good idea to conduct a bigger study that would involve many centres in Canada. | This study is about preparing people with cancerous tumours, soft-tissue sarcoma (STS), in the leg to recover more quickly from surgery. Prehabilitation or surgery school is done before surgery while undergoing other cancer-related treatments. To test this idea, two groups will be formed. One group will have the prehabilitation program and the other group will have the same amount of attention from the research team who will visit them at the time of the radiotherapy sessions to provide support and any information they may need.The results of the study will indicate whether it is a good idea to conduct a bigger study that would involve many centres in Canada. |
Ovarian cancer is the leading cause of death from gynecologic tumors in the western world. Most patients have relapses, and responses to subsequent therapies are generally short-lived. Currently, the population that can benefit from PARPi is mainly focusing on BRCAm, then homologous-recombination deficiency patients. Limited data revealed the ORR was only 3-4% in homologous recombination proficiency patients with PARPi therapy. New treatments are urgently needed to improve patient outcomes.~The investigators' studies have shown that combination therapy with Fuzuloparib and Arsenic trioxide demonstrated a synergistic anti-tumor effect in BRCAness/HR-proficiency ovarian cancer cells:~Firstly, CCK8 and clone formation assays showed that the combination of Fuzuloparib and Arsenic trioxide produced notable tumor cell growth inhibition than either single agent in SKOV3 and CAOV3 cells.~Further, the combination therapy resulted in significantly increased level of γ-H2AX and decreased level of RAD51 by IF.The investigators also found that combination therapy could remarkably induced cell apoptosis, which is associated with induction of cleave-PARP and reduction of p-AKT, when compared with either single drug. (Data not published) Therefore, the investigators hypothesis is that for those platinum-resistance relapsed patients who have received at least twice platinum-based chemotherapy, patients with combinate therapy will get 25% of ORR. And platinum-resistance in combination with Arsenic trioxide therapy is well tolerated. | Ovarian cancer is the leading cause of death from gynecologic tumors in the western world. Most patients have relapses, and responses to subsequent therapies are generally short-lived. Currently, the population that can benefit from PARPi is mainly focusing on BRCAm, then homologous-recombination deficiency patients. Limited data revealed the ORR was only 3-4% in homologous recombination proficiency patients with PARPi therapy. New treatments are urgently needed to improve patient outcomes.~To explore the efficacy and safety of Fuzuloparib in combination with Arsenic trioxide therapy in platinum-resistance relapsed Ovarian cancer patients. |
In this proposed study, the investigators will evaluate the safety and efficacy of Lipoic acid in treatment of ALS. The study will recruit 150 ALS patients, then these patients will be randomized to lipoic acid group or control group (75 patients per arm) for 6 courses for about 5 months. Clinical efficacy and safety assessment will be done at screen/baseline, 3th course and 6th course. The specific aims are to compare lipoic acid versus placebo on: (1) Lipoic acid could improve the motor function, delay the disease progression and extend survival time in patients with ALS, measured by the ALSFRS-R Scale, ROADS Scale, upper motor neuron Scale, Muscle strength Scale and Electromyography; (2) Lung function will be collected to prove the hypothesis lipoic acid may help respiratory function. (3) Safety index including blood and urine routine, liver and kidney function, coagulation index will be recorded. | In this proposed study, the investigators will evaluate the safety and efficacy of lipoic acid in treatment of Amyotrophic lateral sclerosis (ALS). The study will recruit 150 AD patients, and then these patients will be randomized to lipoic acid group or control group (75 patients per arm) for 6 courses for about 5 months. Clinical assessment will be done at screen/baseline, 3th course and 6th course. The specific aims are to compare lipoic acid versus control on: motor function and disease progression. During the study period, clinical effect index will be recorded, including bulbar function, motor function, respiratory function, and safety index including blood and urine routine, liver and kidney function, coagulation function. |
This prospective randomized double-blind study will be carried out on 80 female patients who will be presented for elective C.S in the Obstetric department in Tanta university hospitals.~Full-term pregnant female aged 21- 30 years presented for elective cesarean section under spinal anesthesia will be included in the study.~The patients will be randomly allocated into two groups by the aid of computer-generated software of randomization. All the local anesthetic mixtures will be prepared under complete aseptic precautions by an anesthesia resident who will not participate in the study and will be blinded to its groups in to: - Group F (40 Patients): Patients in this group will receive spinal anesthesia with 10 mg hyperbaric bupivacaine (2 ml) plus 25 ug of fentanyl (0.5 ml).~Group FN (40 patients): Patients in this group will receive spinal anesthesia with 10 mg hyperbaric bupivacaine (2 ml) plus 25 ug of fentanyl (0.5 ml) plus 20 ugs naloxone.~Once the patient will be admitted to the operating theatre, all monitors will be applied with introduction of 18-gauge peripheral venous cannula and starting fluid preload in the form of lactated ringer solution 7 ml/kg over 30 minutes. While the patient in a sitting position and under complete aseptic precautions, patients will receive spinal block at lumbar 3-4 or 4-5 intervertebral space with an injection of the pre-prepared local anesthetic mixture according to the group of patient. After giving anesthesia and positioning for surgery with a left lateral tilt of 15 degrees, supplemental oxygen at a rate of 4 liters/minute will be applied. | This randomized prospective double-blind trial will be conducted on 80 Full-term pregnant females aged 21- 30 years presented for elective cesarean section under spinal anesthesia where they will be randomly allocated into two equal groups:-~Group F (40 Patients): Patients in this group will receive spinal anesthesia with 10 mg hyperbaric bupivacaine (2 ml) plus 25 ug of fentanyl (0.5 ml).~Group FN (40 patients): Patients in this group will receive spinal anesthesia with 10 mg hyperbaric bupivacaine (2 ml) plus 25 ug of fentanyl (0.5 ml) plus 20 ug naloxone.~The study aim is to evaluate the effect of adding an ultra-low dose of naloxone (20 ug) to hyperbaric bupivacaine (10 mg0 and fentanyl (25 ug) in spinal anesthesia for C.S.~Primary outcome: The incidence of pruritis Secondary outcome: The onset, the duration, the site, and the severity of pruritis. |
The main problem in mitral valve repair surgery in children is the high number of postoperative residual lesions (49% of the total cases). Residual lesions after mitral valve repair are associated with morbidity and complications in the form of hemolysis and could affect the postoperative reverse remodeling process. Surgery techniques for mitral valve repair in children have fewer choices than adult patients because of the smaller and thinner valve structure. Besides, the weakness of the mitral valve repair technique that often occurs in large left ventricles with severe mitral regurgitation, after repairing with ring annuloplasty, there is usually a mild residual regurgitation due to posterior mitral leaflet that tends to become restrictive due to being attracted by the left ventricular wall that remains big. No technique has been found to overcome the problem of mitral regurgitation residuals that occur postoperatively.~Therefore, by analyzing postoperative mitral valve structural abnormalities with conventional techniques, an additional posterior mitral valve elevation technique was designed. The posterior annulus elevation technique is a technique that is carried by lifting the posterior mitral annulus towards the cranial so that the posterior mitral leaflet can meet perfectly with the anterior mitral leaflet indicated by a larger coaptation area. This technique can be applied after repair with conventional techniques done optimally to reduce the possibility of postoperative residual lesions.~The hypothesis in this study is that pediatric patients with mitral regurgitation who undergo mitral valve repair surgery with posterior annulus elevation techniques can reduce residual mitral regurgitation, improve clinical and metabolic outcomes of postoperative heart failure, and reduce the risk of postoperative hemolysis. | The main problem in mitral valve repair surgery in children is the high number of postoperative residual lesions (49% of the total cases). Residual lesions after mitral valve repair are associated with morbidity and complications in the form of hemolysis and could affect the postoperative reverse remodeling process. Surgery techniques for mitral valve repair in children have fewer choices than adult patients because of the smaller and thinner valve structure. Besides, the weakness of the mitral valve repair technique that often occurs in large left ventricles with severe mitral regurgitation, after repairing with ring annuloplasty, there is usually a mild residual regurgitation due to posterior mitral leaflet that tends to become restrictive due to being attracted by the left ventricular wall that remains big. No technique has been found to overcome the problem of mitral regurgitation residuals that occur postoperatively. Therefore, by analyzing postoperative mitral valve structural abnormalities with conventional techniques, an additional posterior mitral valve elevation technique was designed to increase the area of coaptation between two leaves of the mitral valve so that the incidence of postoperative regurgitation lesions can be reduced. |
This study aims to prove that emerging CT-based tools are suitable to measure changes in central and peripheral bone density, geometry, micro-structure, and marrow adipose tissue (MAT) among patients treated with oral steroids. To do this, investigators will recruit 10 non-smokers (defined as < 10 pack-year smoking history) age 25-45 years with a diagnosis of severe, persistent asthma who either chronically use oral steroids or do not use any oral steroids. Participants will undergo dual-energy X-ray absorptiometry (DXA), dual-energy mid-tibia CT, high-resolution single-energy ankle CT, and low-radiation hip CT scans at baseline and 6-month follow-up visits. The images obtained will be used to analyze cross-sectional differences in central and peripheral bone density, geometry, micro-structure, and MAT between patients using oral steroids versus those who do not use any oral steroids. Differences in imaging at baseline and six-month follow visits will be used to analyze longitudinal bone changes among patients with oral steroid treatment. | The goal of this study is to assess the feasibility of emerging CT-based tools to measure changes in central and peripheral bone density, micro-structure, and marrow adipose tissue (MAT) among patients treated with oral steroids. |
This study is a single-center, non-randomized, open label, no control, prospective clinical trial to evaluate the safety, tolerability and efficacy of ex-vivo expanded allogeneic γδT cells from of a blood-related donor of Hepatocellular Carcinoma (HCC) Patients. This study will include the following sequential phases: sign informed consent, γδT cell pre-culture, screening and registration to the trial, apheresis, γδT cell preparation, treatments and follow-ups. | This study aims to evaluate the safety, tolerability and efficacy of ex-vivo expanded allogeneic γδT cells obtained from a blood-related donor of hepatocellular carcinoma patients. |
Eltrombopag, a small molecule agonist of thrombopoietin receptor (TPO-RA), was recommended as the subsequent treatment for ITP patients, which also already showed robust efficacy.Recombinant human thrombopoietin (rhTPO) is a full-length glycosylated-TPO produced by Chinese hamster ovary cells, which showed its effectiveness in ITP in a variety of studies.~Both eltrombopag and rhTPO demonstrated good safety in ITP patients. Because of their non-immunosuppressive nature, both of them serve as a reasonable choice during the global COVID-19 pandemic.~Since they increase the number of platelets through different mechanisms, and previous studies demonstrated that they might exert synergic effect. The investigators hypothesized that the combination of these two agents could be a promising option for treatment of corticosteroid-resistant or relapsed ITP patients. | This is a prospective, single-arm study to investigate the efficacy and safety of the combination of fixed low-dose eltrombopag plus recombinant human thrombopoietin (rhTPO) as treatment for corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients during the COVID-19 pandemic. |
The mandible is the commonest facial bone to fracture. Mandibular fractures represent more than 74% of all maxillofacial fractures.~To compare between the effect of shockwave therapy and low-intensity pulsed ultrasound on healing process of fresh mandibular fractures.~A total of 21 patients; aged between 20-40 years, who have mandibular fracture were selected for this study from the outpatient clinic of the Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Alexandria University. In this study all patients were subjected to closed reduction and intermaxillary fixation. This will be followed by shockwave therapy in seven patients as a study group and by low-intensity pulsed ultrasound in seven patients as study group. Seven patients will receive neither and will constitute the control group. | compare between the effect of shockwave therapy and low-intensity pulsed ultrasound on healing process of fresh mandibular fractures |
This single-center, randomized, double-blind, feasibility study to evaluate the safety and potential for effectiveness of an intraarticular Injection of Rejoint Gel after platelet-rich plasma administration in patient with single knee OA, parallel-design study will enroll approximately eligible 30 subjects with single knee OA.~The subjects will be randomized (1:1) to receive 1 of 2 treatments below:~Treatment Group: Rejoint Gel, intra-articular injection, with platelet-rich plasma (PRP) in 2:1 volume ratio or~Control Group: Normal saline, intra-articular injection with PRP in 2:1 volume ratio Beginning on treatment period, subjects will receive a single treatment cycle of either 150 mg/ml Rejoint Gel or normal saline with PRP intra-articular injection twice for one month (Visit 3 and 4). Subjects will be followed to Visit 5, 6 and 7 for safety and potential for effectiveness assessments. | To assess the safety and tolerability of intra-articular Injection doses of Rejoint Gel after platelet-rich plasma administration in unilateral knee OA subjects. |
Neonatal eye examinations are the standard of best practice in pediatrics. In the acute clinical setting, infants' eyes are inspected for eye development, defect, and disease. There is anecdotal and clinical evidence that infants experience stress after eye dilation. Investigators will evaluate whether eye shields for infants after dilated eye exam lessen stress and discomfort. | The eyes of hospitalized infants are often assessed by dilated exam, and there is evidence that infants experience post-exam stress. Investigators will evaluate whether eye shields for infants after dilated eye exam lessen stress and discomfort. |
Virometix designed and developed a candidate vaccine coded V-306 based on synthetic virus like particles (SVLP) that present the neutralizing Palivizumab epitope of the antigenic site II region of the F-protein (FsII). V-306 has been evaluated in cotton rats, mice and rabbits for safety and immunogenicity. Strong immunogenicity was demonstrated in mice and rabbits by ELISA and RSV A and B neutralization. Full protection with no vaccine-associated enhanced respiratory disease (VAERD) was demonstrated in a validated mouse challenge model. Reduction of the viral load with no VAERD was also shown in the cotton rat challenge model.~The primary objective of the first-in-human Phase 1 study is to assess the safety of two administrations of the RSV vaccine candidate at three different dosages of V-306.~The secondary objective is to assess the immunogenicity of two administrations of the RSV vaccine candidate at three different dosages of V-306.~The study has a randomized, placebo-controlled, double-blind, sequential, parallel cohorts, dose-escalation (three dosages) design. It will be conducted in one centre. Each of the three cohorts (N=20 subjects per cohort, total of 60 subjects) will receive placebo (n=5), or a low (15 µg/administration, n=15), intermediate (50 µg/administration, n=15) or high dosage (150 µg/administration, n=15) of candidate vaccine, on two occasions (Day 0 and Day 56). Subjects will be healthy adult women aged between 18 and 45 years. The enrolment schedule with sentinel dosing will be the same in each cohort. After each administration, the subject will be observed in the clinical trial centre for 120 minutes, before being discharged.~The study will be in two phases: (1) an active treatment phase from Day 0 to Month 3, i.e. one month post 2nd administration, with unblinding and primary analysis of data collected up to Month 3, and (2) a follow-up phase from Month 3 + 1 day to Month 12 post-1st administration for safety and immunogenicity. The sponsor will be unblinded at Month 3, while the clinical site and laboratory will remain blinded during the whole study.~During the active phase, subjects will complete diary cards to record oral temperature (daily), solicited local and general adverse events (AEs) and unsolicited AEs for 7 days after each administration. Unsolicited AEs will be recorded up to Day 28 post-each administration. Serious adverse events (SAEs) and adverse events of specific interest (AESI) will be recorded throughout the duration of the active phase. Subjects will visit the clinical site for safety monitoring on Days 1, 7 and 28 following each administration. A time window will be defined for each visit.~Blood will be drawn at a screening visit (up to 14 days before Day 0 for lab safety analyses and up to 2 months before Day 0 for serology analyses) and the safety test data will be available just before 1st administration. The screening set includes markers of infection with hepatitis B virus, hepatitis C virus and human immunodeficiency virus. These data will be part of the baseline health status of each subject. A serum sample will be taken for detection of pregnancy. At the next scheduled time points, pregnancy will be screened in a urine sample and if positive will be confirmed by blood analysis. Laboratory safety parameters will be examined further at Days 0, 1, 7, 28, 56, 57, 63 and 84.~During the follow-up phase, visits for safety monitoring are scheduled at Months 6, 9 and 12 post-1st administration. SAEs and AESI will be recorded at each visit.~Humoral immunity will be measured on Days 0, 28, 56, Month 3, Month 6, Month 9 and Month 12. Months 6, 9 and 12 aim to evaluate the persistence of the humoral response.~Cellular immunity will be measured on Days 0, 7, 28, 56, 63 and 84. Data collection will use an electronic Case Report Form (eCRF). The duration of the study for each subject will be approximately 13 months. The total duration of the study will be approximately 18 months. | The primary and secondary objectives of this Phase 1 study are respectively to assess the safety and the immunogenicity of two administrations of the RSV vaccine candidate at three different doses.~The study has a randomized, placebo-controlled, double-blind, sequential, parallel cohorts, dose-escalation (three dosages) design. Each of the three cohorts (N=20 subjects per cohort, total of 60 subjects) will receive placebo (n=5), or a low (15 µg, n=15), intermediate (50 µg, n=15) or high dosage (150 µg, n=15) of candidate vaccine, on two occasions (Day 0 and Day 56). Subjects will be healthy adult women aged between 18 and 45 years.~There will be two phases: an active treatment phase from Day 0 to Month 3, and a follow-up phase from Month 3 + 1 day to Month 12.~During the active phase, subjects will complete diary cards to record oral temperature (daily), solicited local and general adverse events (AEs) and unsolicited AEs for 7 days after each administration. Unsolicited AEs will be recorded up to Day 28 post-each administration. Serious adverse events (SAEs) and adverse events of specific interest (AESI) will be recorded throughout the duration of the active phase. Subjects will visit the clinical site for safety monitoring on Days 1, 7 and 28 following each administration.~Blood will be drawn at a screening visit and the safety test data will be available just before 1st administration. The screening set includes markers of infection with hepatitis B virus, hepatitis C virus and human immunodeficiency virus. A serum sample will be taken for detection of pregnancy. At the next scheduled time points, pregnancy will be screened in a urine sample. Laboratory safety parameters will be examined further at Days 0, 1, 7, 28, 56, 57, 63 and 84.~During the follow-up phase, visits for safety monitoring are scheduled at Months 6, 9 and 12 post-1st administration. SAEs and AESI will be recorded at each visit.~Humoral immunity will be measured on Days 0, 28, 56, Month 3, Month 6, Month 9 and Month 12. Cellular immunity will be measured on Days 0, 7, 28, 56, 63 and 84.~The duration of the study for each subject will be approximately 13 months. The total duration of the study will be approximately 18 months. |
Acute appendicitis is one of the most common causes of abdominal pain in emergency departments as well as one of the most common indications for emergency abdominal surgery. The clinical diagnosis has been based on patient history, physical examination and laboratory findings as well as the clinical eye of the surgeon. Still the diagnosis remains challenging. One of the main problems is that many other disorders can mimic the clinical presentation of appendicitis, thus increasing the role of imaging techniques to aid in diagnostic accuracy. Now preoperative imaging in patients with suspected acute appendicitis is currently widely accepted as the gold standard and CT has been shown to clearly outperform US in terms of diagnostic performance. Currently CT imaging is considered the primary imaging modality in the diagnosis for acute appendicitis as it is appraised for its high sensitivity and specificity. The main disadvantage of CT imaging is exposure to radiation. Thus the favorable diagnostic performance of CT imaging has encouraged optimization of protocols to minimize exposure to radiation through the development of low-dose CT protocols. Initial studies have indicated that contrast enhanced low-dose CT was not inferior to standard-dose contrast enhanced CT with no statistical significance in negative appendectomy rates, appendiceal perforation rates or patients requiring additional imaging.~This study focuses on the use of contrast enhanced low-dose CT imaging as a modality to differentiate between uncomplicated and complicated acute appendicitis in patients with BMI over 30 kg/m2. Accurate differential diagnosis allows the assessment of all available treatment options. Complicated acute appendicitis requires emergency appendectomy, while uncomplicated acute appendicitis can be safely and efficiently treated with antibiotics in the majority of patients. Our study group already published the results of the initial OPTICAP trial enrolling patients with BMI under 30 showing similar accuracy between the low-dose and the stadard dose CT, but a significant dose reduction associated with the low-dose CT. All patients will undergo both imaging protocols as the standard CT is also optimized for a low as possible radiation dosage and imaging sequence per patient is randomized due to the optimization of contrast media injection timing. All patients participating in this study will be treated operatively with a laparoscopic appendectomy to obtain histological confirmation for the diagnosis to evaluate the accuracy of the CT imaging. The aim of this study is to optimize a well-performing low-dose CT imaging protocol to use in the diagnosis of uncomplicated acute appendicitis in patients with body mass index over 30 kg/m2. | This study focuses on the use of contrast enhanced low-dose CT imaging as a modality to differentiate between uncomplicated and complicated acute appendicitis. Accurate differential diagnosis allows the assessment of all available treatment options. Complicated acute appendicitis requires emergency appendectomy, while uncomplicated acute appendicitis can be safely and efficiently treated with antibiotics in the majority of patients. Our study group already published the results of the initial OPTICAP trial enrolling patients with BMI under 30 showing similar accuracy between the low-dose and the stadard dose CT, but a significant dose reduction associated with the low-dose CT. All patients will undergo both imaging protocols as the standard CT is also optimized for a low as possible radiation dosage and imaging sequence per patient is randomized due to the optimization of contrast media injection timing. All patients participating in this study will be treated operatively with a laparoscopic appendectomy to obtain histological confirmation for the diagnosis to evaluate the accuracy of the CT imaging. The aim of this study is to optimize a well-performing low-dose CT imaging protocol to use in the diagnosis of uncomplicated acute appendicitis in patients with body mass index over 30 kg/m2. |
Obesity is a dominant risk factor for the development of cardiovascular disease (CVD). The public health relevance of this relationship is underscored by the fact that 40% (93 million) of adult Americans are obese.~Activation of the mineralocorticoid receptor (MR) is a major mechanism implicated in the pathogenesis of obesity-associated CVD. MR activation causes vascular stiffness, inflammation, and fibrosis, and MR antagonists improve clinical outcomes in heart failure with reduced ejection fraction, especially in obesity. However, even in the absence of heart failure, multiple mechanisms of CVD in obesity are mediated by excessive activation of the MR. These mechanisms include: autonomous aldosterone production, increased cortisol action, high sympathetic nervous system activity, increased leptin, inflammation, and oxidative stress.~Autonomous aldosterone production is a highly prevalent and poorly recognized disorder that causes CVD independent of blood pressure (BP). Autonomous aldosterone production manifests across a wide severity spectrum, ranging from mild/subclinical (rarely recognized) to overt (primary aldosteronism). The investigators' work has characterized autonomous aldosterone production as a phenotype of non-physiologic, non-suppressible, and renin-independent aldosterone production that is highly prevalent in the general population of the U.S.A..~Autonomous aldosterone production and MR activation are especially enriched in obesity, particularly among obese/overweight individuals with hypertension and/or metabolic syndrome. Current treatment guidelines do not recommend the early use of MR antagonists in obesity or hypertension, thereby delaying or omitting a targeted therapy that may specifically mitigate the mechanism of CVD in this high-risk population.~The investigators have validated cardiac MRI methods to measure coronary microvascular function and myocardial fibrosis, both strong surrogates for CVD that correlate with aldosterone production and that improve with MR antagonist therapy.~Prospective studies to investigate the early mechanistic contribution of aldosterone-MR activation in the pathogenesis of CVD in obesity, and whether MR antagonists can prevent this, are lacking. Mechanistic studies, using innovative and robust intermediate phenotypes of clinical CVD outcomes in a cost-effective manner, could have a major public health impact by implicating a targeted medical therapy (MR antagonists) to prevent CVD in high-risk obesity (overweight/obese individuals with hypertension and/or metabolic syndrome).~HYPOTHESIS: MR antagonists in high-risk obesity improve cardiac MRI-derived myocardial perfusion reserve and fibrosis, independent of BP, and proportionately to the severity of autonomous aldosterone production.~STUDY DESIGN: This mechanistic study will investigate whether MR antagonist therapy in high-risk overweight or obese participants can be a targeted strategy to prevent CVD.~80 participants with overweight/obesity, untreated hypertension, and/or at least one other feature of the metabolic syndrome, will be enrolled. Participants will undergo a deep-phenotyping protocol to characterize aldosterone and cortisol physiology before randomization to eplerenone (25-100 mg/d) or chlorthalidone (6.25-25 mg/d + KCl 20 mEq/d) for one year. BP will be maintained in a target range to ensure outcomes are independent of BP control. Cardiac MRI-derived outcomes will be measured at baseline and after one year.~AIM 1: To investigate whether eplerenone therapy in high-risk obese/overweight participants, when compared to chlorthalidone + KCl, can improve coronary microvascular function independent of BP, as measured via stress cardiac MRI-derived myocardial perfusion reserve (a strong predictor for incident cardiovascular events and death that has been shown to improve with MR antagonist therapy).~AIM 2: To investigate whether eplerenone therapy in high-risk obese/overweight participants, when compared to chlorthalidone + KCl, can decrease myocardial fibrosis independent of BP, as measured via extracellular volume fraction on T1 mapping cardiac MRI (an established surrogate for myocardial fibrosis and inflammation that is also strongly associated with autonomous aldosterone production and mortality).~Exploratory Aims: To investigate whether the severity of autonomous aldosterone production is associated with cardiac MRI-derived outcomes and predicts the response to eplerenone therapy; and, to investigate whether eplerenone therapy can improve measures of cardiac fat content, arterial stiffness (via pulse-wave velocity), and inflammation (via inflammatory markers and adipocytokines), when compared to chlorthalidone + KCl.~IMPACT: Obesity/overweight status is enriched with autonomous aldosterone production and MR activation, mechanisms known to cause CVD. This study will investigate targeted mechanisms for the prevention of MR-mediated CVD in high-risk obesity using innovative physiologic phenotyping and surrogate imaging outcomes. This study will establish a mechanistic foundation for future outcome studies in obesity with incident CVD events. | This study will evaluate whether the mineralocorticoid receptor antagonist eplerenone, when compared to chlorthalidone plus potassium chloride, can improve cardiac MRI-derived myocardial perfusion reserve and fibrosis, independent of blood pressure, and proportionately to the severity of autonomous aldosterone production. |
Background and Rationale:~Cardiac vasoplegia is a known phenomenon after cardiopulmonary bypass (CPB) occurring in up to 44% of patients. Severe forms of such condition refractory to vasopressors are associated with poor outcomes. New agents e.g. ascorbic acid that can alter the systemic vascular resistance in cardiac vasoplegia have been suggested as an attempt to avoid or at least reduce the use of IV vasopressors and their induced systemic hypo-perfusion.~Objectives :~Primary objective: to study the effect of vitamin C administration on the amount of noradrenaline given post-operatively to patients after CPB~Secondary objectives: to study the effect of vitamin C administration on the time to weaning from noradrenaline~Study population & Sample size :~Patients undergoing cardiac surgeries with CPB having risk factors for cardiac vasoplegia like diabetes mellitus and chronic renal failure.~50 patients will be needed in each group (treatment and control)~Study Design :~A parallel group double-blind, randomized-controlled trial, with 1:1 randomization ratio 2 groups will be included;~-Group (A) patients undergoing open heart surgeries who will receive IV ascorbic acid. -Group (B) patients undergoing open heart surgeries who will not receive ascorbic acid or will receive a placebo (Control Group).~Methods :~Each patient will be subjected to the following assessments:~-Pre-operative patient characteristics: demographic data, co-morbidities, pre-operative echo findings,… -Intra-operative details: procedures, time parameters,… the doses of noradrenaline given from the end of surgery until weaning or death and hemodynamics in the first 2 hours and then at intervals of 6 hours up to 3 days following surgery. -Postoperative data: echo parameters, patient outcome, time of discharge,…~Outcome parameter (s):~-Primary outcome: the area under the dose-time curve of noradrenaline -Secondary outcome measures: the duration of vasopressor (noradrenaline) infusion till weaning up to 3 days following surgery. | This is a parallel group double-blind, randomized-controlled trial with 1:1 randomization ratio which will be conducted over a period of 6 months to study the effect of vitamin C administration on the amount of noradrenaline given post-operatively to patients after CPB. Two groups will be included; Group (A) patients undergoing open heart surgeries who will receive IV ascorbic acid (treatment group) and Group (B) patients undergoing open heart surgeries who will not receive ascorbic acid or will receive a placebo (control group). Each patient will be subjected to assessments of the doses of noradrenaline given from the end of surgery until weaning as well as hemodynamics in the first 2 hours and then at intervals of 6 hours up to 3 days following surgery. |
Nasal packing has many uses, such as prevention of postoperative bleeding following endoscopic sinus surgery, stabilization of the nasal septum, prevention of adhesions following septoplasty, and treatment of active epistaxis1,2.~The utilization of tampons for nasal packing during nasal and sinus surgeries is widely used and safe. Nasal tampons assist in creating a moist supportive environment for tissue healing without causing local irritation or foreign body reaction3. The removal is performed after 24-48 hours. On the other hand, there are some disadvantages to the uses of nasal tampons: trauma to the nasal mucosa, infection of the nose and sinuses, aspiration of part of the tampon, and even toxic shock syndrome3. One of the most troublesome aspects to the patient and the clinician is the pain and discomfort during insertion and removal of the tampons3,4. In our experience, these symptoms are of considerable significance to the patient experience and satisfaction.~There is a wide range of commercially available nasal packings such as Merocel and Nasopore.~In our practice, Merocel nasal tampons are used, which contain polyvinyl acetate. This type of material expands upon contact with fluids, and it is not soluble. This product is used at the end of endoscopic nasal surgeries and in the treatment of active epistaxis, not amenable to local pressure and without a recognizable source of bleeding. In case of unstoppable bleeding despite the use of nasal tampons, a nasal balloon is inflated in the nasal cavity. Its insertion and inflation are associated with patient pain and discomfort.~Lidocaine is a drug commonly used for local anesthesia. It is used for local nasal anesthesia by a variety of commercially available sprays, atomizers, nebulizers, gels, and ointments. Lidocaine causes local anesthesia by affecting sodium channels, causing decreased initiation and conduction of neural impulses. In turn, fewer afferent impulses reach the central nervous system6. In healthy individuals, side effects are negligible, but it could influence patients with cardiac infarction. The main side effects of lidocaine are neurological, which could be of significance in the case of inflamed or damaged tissue because of rapid absorption. The use of Lidocaine spray (Xylocaine 10%) is commonly available worldwide and is routinely used in our institution before fiberoptic laryngoscopy.~Previous publications have mentioned the positive effect of local anesthesia during the removal of nasal tampons5,7. In a recent meta-analysis, local anesthetics were associated with less pain during the removal of nasal tampons and shortened time of the procedure. Yet, the authors recognized the need for additional randomized controlled trials7. There are no previous publications on the effect of local anesthetics on the insertions of nasal tampons during active nasal bleeding. In the experience of the senior author, for many years, the application of lidocaine spray 10% before the insertions of nasal tampons for epistaxis was associated with a significant reduction of pain and discomfort.~This study aims to investigate the effect of local nasal anesthesia with lidocaine spray on the insertion of nasal tampons during active nasal bleeding. Secondary objectives include the impact on nasal tampons removal after the cessation of nasal bleeding and after endoscopic sinus surgery.~Research hypothesis: local anesthesia with lidocaine before the insertion of nasal tampons or inflatable balloon reduces patients' pain, discomfort, and stress during insertion for the treatment of active nasal bleeding, and during removal of nasal tampons either postoperatively or after cessation of epistaxis.~The study population involves 30 patients with spontaneous epistaxis and another 30 patients who went tampon removal postoperatively in our institution. Recruitment includes patients who came to the emergency department with active epistaxis and still had active bleeding after the application of local pressure without an identified source of bleeding, requiring treatment with tampons or an inflatable balloon. The second group included patients who require postoperative removal of nasal tampons. | This study aims to investigate the effect of local nasal anesthesia with lidocaine spray on the insertion of nasal tampons during active nasal bleeding. |
This is a pilot, multi-center, open-label study evaluating selinexor's ability to overcome resistance for multiple myeloma patients who are refractory to lenalidomide-containing therapies.~Enrollment:~The study will enroll up to a total of 22 Multiple Myeloma (MM) patients with progressive disease.~Study Assessments:~The study will consist of:~screening period;~study treatment until disease progression or intolerable toxicity;~a final assessment to occur up to 28 days after the end of the last treatment cycle; and~follow-up period.~The screening period will be conducted within 14 days before baseline (baseline being day 1 of cycle 1, before study drug administration). During this period, a medical history will be obtained along with complete physical examination including vital signs measurements, height, weight, Eastern Cooperative Oncology Group (ECOG) performance status, and 12-lead electrocardiogram (EKG). MM assessments will be performed, including β2 microglobulin (β2M), serum free light chain (SFLC) serum and urine protein electrophoresis, quantification of serum immunoglobulins, urine and serum immunofixation, and 24-hour total protein. An additional serum sample will be obtained for evaluation of biomarkers. In addition, a postero-anterior and lateral chest radiographs, skeletal survey, and a bone marrow aspirate (BM) and biopsy will be performed within 28 days of baseline. Clinical laboratory tests including hematology, clinical chemistry (blood urea nitrogen [BUN], serum creatinine, uric acid, lactate dehydrogenase [LDH], total bilirubin, alkaline phosphatase, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), electrolytes (potassium, sodium, chloride and calcium), random glucose, total protein, amylase, albumin, and urinalysis as well as serum pregnancy tests for females of child-bearing potential (FCBPs). Subjects will also be asked to fill out quality of life assessments at several time points during this study.~Subjects eligible for this study will receive treatment with study drug until disease progression or intolerable toxicity does not allow ongoing treatment.~Assessments:~Schedule of assessments: Subjects that meet the inclusion/exclusion criteria during the screening period will continue to Day 1 of Cycle 1, when baseline evaluations will be conducted. Subjects who continue to meet the inclusion/exclusion criteria will be enrolled in the trial and study drug will be administered. During Cycle 1, subjects will also have study visits during which assessments will be performed on Days 8, 15 and 22. MM assessments will be performed on Day 22 during all subsequent cycles. Starting with Cycle 2, study visits will take place on Days 1 and 22. See Table 1~Assessment overview: During the treatment period, each subject will have clinical laboratory tests performed to monitor for potential toxicity. Additional procedures performed at these visits will include monitoring for adverse events (AEs), review of concomitant medications and other support therapies (e.g. growth factors and transfusion), MM disease assessments, ECOG performance status, vital signs measurements, and physical examination. Subjects will remain on study until documentation of progressive disease (PD) as defined by the International Myeloma Working Group (IMWG) criteria. Subjects with stable disease will remain in the study. For subjects who show disappearance of urine and serum M-protein by protein electrophoresis and immunofixation on 2 consecutive assessments and the subject shows no other signs of disease activity, a bone marrow (BM) aspirate and biopsy will be required to confirm their CR. A BM aspirate and biopsy will not be required for subjects in any other response group categories.~Up to twenty-eight days after the last dose of study drug, subjects are to complete a final assessment (herein referred to as the End-of-Study treatment visit). Procedures to be conducted at this visit include a MM disease assessment, measurement of vital signs and weight, a complete physical examination, assessment of adverse events, a review of concomitant medications, assessment of ECOG performance status, hematology and clinical chemistry laboratory tests including electrolytes, total protein, amylase and albumin, and an assessment of response to treatment with the use of SFLC assay and ratio, serum and urine protein electrophoresis, quantification of serum immunoglobulins, urine and serum immunofixation, 24-hour total urine protein, and serum β2M. Subjects who withdraw from the study before the completion of the eight 28-day cycle evaluation periods will have all End- of-Study treatment assessments performed at their final visit.~Following the End-of-Study treatment visit, subjects will be monitored for PD and survival by clinic visits every 3 months and every 6 months, respectively, until alternate therapy needs to be started or death intervenes.~Dosing Regimens:~All subjects enrolled will receive (Dose Level 0) 1) selinexor, PO, at 60 mg once weekly on days 1, 8, 15, and 22 of a 28-days cycle, 2) lenalidomide, PO, 10 mg daily on days 1-21 of a 28-day cycle and 3) steroids at the same dose and schedule as the last lenalidomide-containing regimen if it contained steroids that they had failed to meet eligibility for this study.~Recommended Concomitant Therapy:~Subjects may receive full supportive care, including hydration prophylaxis, treatment with a 5-HT3 antagonist and/or other anti-nausea agents, antibiotics, antivirals, vitamins, and supplements as appropriate. Patients should receive anti-platelet therapy with baby aspirin or other agents if they have additional risk factors for developing thrombotic events.~Number of Patients (planned): 22~Study Population: Multiple myeloma patients who are refractory to a lenalidomide-containing therapy | This is a pilot study evaluating the safety and efficacy of selinexor among multiple myeloma (MM) patients that are refractory to lenalidomide-containing regimens with or without steroids. |
This study aims to test the effectiveness of positive airway pressure therapy on reducing clinical failure after rhythm control treatment and restoring with regular heart beat in atrial fibrillation patients with obstructive sleep apnea. The study is designed as a multi-center randomized control trial, which plans to recruit 129 atrial fibrillation patients with obstructive sleep apnea (86 in the intervention group with atrial fibrillation standard care and positive airway pressure therapy, 43 in the control group with atrial fibrillation standard care but no positive airway pressure therapy). The subjects will in total visit the hospital 4 times during their 6 months follow-up period, at baseline, 1st, 3rd, and 6th month. Subjects will undergo questionnaire surveys and medical examinations at each visit. The primary objective is to compare after 6months, the clinical failure rate between the group with positive airway pressure therapy and the group with no positive airway pressure therapy. | This study aims to test the effectiveness of positive airway pressure therapy on reducing clinical failure after rhythm control treatment and restoring with regular heart beat in atrial fibrillation patients with obstructive sleep apnea. |
Subjects with grades ranging from 4-55 on the Quantitative Global Scarring Grading System (QGSGS)1 will be randomized to receive up to 1cc of Juvéderm Vollure on one side of their face and up to 1cc of Saline on the other. On Day 30, this treatment with the same left-right assignment can be repeated if optimal correction on the active intervention side has not been achieved according to the treating investigator. Subjects will return 24-48 hours after their first treatment to fill out questionnaires, take pictures, and to be assessed by blinded evaluators regarding short term adverse events. Subjects will fill out a 30 day subject diary and also return 30 and 90 days after their last treatment to fill out questionnaires, take pictures, complete the Global Aesthetic Improvement Scale (GAIS), and to be assessed on the QGSGS and for long-term adverse events by blinded evaluators. The subjects will be eligible to receive treatment with Juvéderm Vollure 90 days after their last treatment on the placebo-controlled side if they choose. In addition, at 12 months, 18 months, and 24 months, the subjects will return to fill out questionnaires, take pictures, and to be assessed by blinded evaluators for long-term efficacy. | Subjects will be randomized to receive up to 1cc of Juvéderm Vollure on one side of their face and up to 1cc of Saline on the other. On Day 30, this treatment with the same left-right assignment can be repeated. Subjects will return 24-48 hours after their first treatment to fill out questionnaires, take pictures, and to be assessed by blinded evaluators regarding short term adverse events. Subjects will fill out a 30 day subject diary and also return 30 and 90 days after their last treatment to fill out questionnaires, take pictures, complete the Global Aesthetic Improvement Scale (GAIS), and to be assessed on the QGSGS and for long-term adverse events by blinded evaluators. At 12 months, 18 months, and 24 months, the subjects will return to fill out questionnaires, take pictures, and to be assessed by blinded evaluators for long-term efficacy. |
Multiple Ascending Dose (MAD), Double-Blind, Placebo Controlled Study.~To evaluate the safety and tolerability of multiple ascending doses of CTI-1601 in subjects with Friedreich's ataxia.~Secondary Objectives:~To evaluate the pharmacokinetics (PK) of CTI-1601 following, multiple, increasing, doses of subcutaneously (SC) administered CTI-1601.~To evaluate the pharmacodynamics (PD) of CTI-1601 following, multiple, increasing, doses of SC administered CTI-1601. | To evaluate the safety and tolerability of multiple ascending doses of CTI-1601 in participants with Friedreich's ataxia |
Crohn's disease (CD), a chronic transmural inflammatory disease of the gastrointestinal tract, continues to increase in incidence for unknown reasons. According to population based studies, at least 26% of patients with CD will develop perianal fistulas in the first two decades following diagnosis, particularly those with colonic and rectal involvement. These patients experience significant morbidity due to pain, persistent drainage, recurrent perianal sepsis, and ongoing need to access medical care resulting in increased costs and impaired quality of life.~Unfortunately, perianal fistulizing Crohn's disease is notoriously difficult to cure with 37% of patients experiencing refractory disease. As a result, patients cycle through numerous immunosuppressive medications that can have significant side effects, and >90% undergo multiple surgical interventions putting them at risk of incontinence.~The specific rationale for MSCs in perianal Crohn's fistulas is based upon 1) their anti-inflammatory and immunomodulatory properties; 2) several studies reporting the safety and efficacy of MSCs for the treatment of perianal Crohn's fistula; 3) existence of safe manufacturing methods for isolation and expansion of MSCs.~This study will enroll 20 participants that have Crohn's disease with medically and surgically refractory perianal fistulizing disease. Participants enrolled will be those that meet particular criteria for participation in the clinical trial.~Enrolled participants will be randomized to treatment group with adult allogeneic bone marrow derived mesenchymal stem cells, versus placebo in a 3:1 fashion. Participants in the treatment group will have a direct injection of MSCs at a dose of 75 million cells. This will be given as a direct injection in and around the fistula tract. Participants will be evaluated for complete healing at three months. If complete healing has been achieved, participants will continue to be followed for one year. If complete healing has not been achieved at three months, participants will be eligible for a second injection of MSCs at the same dose of 75 million cells. Control participants without complete healing from placebo will cross over at the 6 month visit to receive an injection of MSCs and again three months after this as above, and will be followed for one year after treatment to a total duration of 18 months. | The purpose of this study is to determine the safety and efficacy of using adult allogeneic bone marrow derived mesenchymal stem cells (MSCs), to treat people for medically refractory perianal fistulizing Crohn's disease. |
This is a prospective multicenter, open-label, dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of 4D-310 following a single IV administration. The study population is comprised of adult males and females with Fabry Disease. | This is a prospective multicenter, open-label, dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of 4D-310 following a single IV administration. The study population is comprised of adult males and females with Fabry Disease. |
Depression is a highly prevalent and disabling mental health problem. It is associated with significant morbidity and mortality and it has a significant economic impact. Effective and feasible strategies aimed at the population-level to reduce the risk of onset are urgently needed to manage this ubiquitous condition. Developed from research in the fields of epidemiology, mental health, and implementation science, the proposed intervention provides individualized information designed to trigger actions that can reduce the risk of MDE. Specifically, and as the first step, the investigators developed the first sex-specific multivariable risk predictive algorithms (MVRPs) for MDE using data from over 10,000 Canadians. This innovative early work shows that the risk of onset of MDE can be quantified in the same way as can other physical disorders such as cardiovascular diseases and cancer. Knowing the individualized risk estimated by the MVRPs may serve as a trigger to empower people to actively engage in effective self-help actions. Self-help strategies are commonly used to deal with depression and promoting effective self-help strategies to the public as an early intervention strategy has been recommended as one way to reduce the large disease burden of depression. Subsequently, the investigators conducted a randomized controlled trial (RCT) and found that providing individualized depression risk causes no psychological harm in participants. Using the MVRPs as the foundation and working with future users, the investigators developed a personalized depression risk communication tool (PDRC) for sharing information about individualized depression risk, risk profile (risk factors present), potential risk reduction, and self-help strategies.~Risk communication is the open two way exchange of information and opinions about harms and benefits, with the aim of improving the understanding of risk and of promoting better decisions about clinical management. Risk communication goes beyond simply sharing information about the probability of developing a problem (i.e., individualized risk); it also shares possible actions to be taken. The notable clinical guidelines for coronary heart disease (CHD) and the Institute of Medicine report recommend that baseline risk should be estimated; individuals should know their personal risk; and high-quality risk communication tools should be developed.~The existing literature reveals that effective risk communication often includes multiple components: (1) Individualized risk information presented as an absolute risk, as opposed to a relative risk. The risk information may also list the individual's risk factors. (2) Appropriate format of presentation (e.g., graphic, visual). The format of presentation can influence the degree to which individuals perceive their risk and will affect behavioural change. (3) Presentation of risk reduction. A review of evidence recommends that information on risk reduction should be presented using absolute risk reduction. Presenting the risk reduction of behavioural change to the individual is the most commonly used behavioural change technique in the literature. (4) Framing. Describing the consequences of performing or not performing an action, presented as a gain versus a loss,18 and (5) Decision aids to help consumers participate in decisions by providing clear evidence based information on available choices. Personalized risk communication tools with these components are instrumental for making informed decisions regarding the uptake of preventive measures, adhering to risk-reducing therapy, and improving risk perception and health-related behaviours. In mental health, self-help and help-seeking are particularly important for reducing the disease burden of mental disorders. However, changing health-related behaviours to improve mental health and encouraging help-seeking have been very challenging. Based on the theoretical model and the experience of other medical disciplines (to be described below), risk communication may offer a unique opportunity for promoting behaviour change, and if successful, will make a significant contribution to depression prevention.~The principle research question of the proposed study is: Are individuals who are at high risk of having a MDE and who receive the coach-guided PDRC more likely to take self-help actions than those who receive the PDRC without coach guidance? It was hypothesized that high risk people who receive the coach-guided PDRC are more likely to take self-help actions than those receive the PDRC without coach guidance.~The secondary research questions include:~What are the impacts of receiving the coach-guided PDRC on psychological distress, depressive symptoms and mental health service use?~What are the demographic and clinical factors associated with the behavioural changes?~This is a randomized controlled trial with two arms. After screening and baseline assessment, participants will be randomized into: (1) Control group: Receiving PDRC only, and (2) Intervention group: Receiving PDRC + coach guidance. The trial was designed to compare the costs and effectiveness between the groups to inform future implementation. The randomization will be conducted in males and females separately because the MVRPs are sex-specific and the thresholds of high-risk differ by sex. Participants will be assessed at baseline and 3-month. After each assessment, the following materials will be mailed to participants: (1) a thank-you letter, including the date of the next interview. (2) Self-help strategies34 and a summary of research evidence supporting the effectiveness of the self-help strategies, and (3) a $20 incentive as appreciation for their participation. Participants in the PDRC+coach arm will have access to coach to guide them. Participants in the control group will receive their PDRC only if they are interested.~The recruitment, baseline assessment and randomization will be contracted to a telephone interview firm. The target population of the study are individuals who are at high risk of having a MDE in Canada. Telephone recruitment using the random digit dialing method, screening and data collection are a feasible and economic way for the proposed study. A random sample of landline and cell phone numbers will be selected. When a household is reached, the person who is 18+ years will be assessed for eligibility. If a household has 2+ persons aged 18+ years, one will be randomly selected. The interviewers will explain the study objectives and procedures and answer questions. Oral consent will be obtained before assessment of eligibility.~Screening: Once a potentially eligible participant is identified, the interviewer will confirm the participant's age and administer the Composite International Diagnostic Interview - Major Depression (CIDI) MDE module and the sex-specific MVRPs via telephone. The CIDI is a fully structured diagnostic interview for mental disorders, that is commonly used in community-based mental health surveys, and can be administered by trained lay interviewers. Interviewees who have a MDE at the time of the interview or are below the risk thresholds based on the MVRPs, will be excluded. Individuals with an ongoing MDE will be encouraged to contact their family doctors and information about local mental health resources will be provided. For those who are at low risk, the web site of the MVRPs will be provided so they may monitor their risk in the future.~Baseline assessment: In eligible participants, the interviewer will administer the questionnaire about self-help behaviours, mental health service use, depressive symptoms and quality of life.~Randomization will be carried out in male and in female participants separately. Most survey firms use a survey software built by VOXCO. The tool contains a random number generator which randomly creates a digit when the telephone script reads the function. This randomization approached was used in the IMPACT trial, and the intervention and control groups of the trial were similar in baseline characteristics.~The survey firm will securely transfer encrypted baseline data to the project coordinator on a daily basis. The group assignment data will be transferred in a separate file. The follow-up assessments will be conducted at the PI's telephone interview laboratory at the Institute of Mental Health Research (IMHR). One month before the scheduled follow-up interviews, letters will be sent to participants to remind them of the upcoming interview. After the 3-month interview, group status will be linked with interview data by study ID numbers.~Over the study period, investigators will be blinded to participants' group status. The survey firm interviewers who conduct randomization, will not be involved in follow-up interviews. The interviewers who conduct the follow-up interviews in Ottawa will not have access to participants' group status. The coaches will not be involved in follow-up assessments. Given our description of study objectives, some participants may know their group status. Therefore, it is possible that some participants in the control group may try to find more information about the PDRC. At the follow-up assessments, the investigators will ask if they have used any risk prediction tools over the study period. At the follow-up assessments, if participants develop a MDE, they will be encouraged to contact their family doctors and information about local mental health resources will be provided.~Duration of intervention. The intervention includes delivering the PDRC report via email and coach guidance in its interpretation and planning self-help actions. The PDRC will be sent to the participants within one week after randomization and the coach will initiate contact the following week. | Depression is a highly prevalent and disabling mental health problem. It is associated with significant morbidity and mortality and it has a significant economic impact. Effective and feasible strategies aimed at the population-level to reduce the risk of onset are urgently needed to manage this ubiquitous condition. Developed from research in the fields of epidemiology, mental health, and implementation science, the proposed intervention provides individualized information designed to trigger actions that can reduce the risk of MDE. Specifically, and as the first step, the investigators developed the first sex-specific multivariable risk predictive algorithms (MVRPs) for MDE using data from over 10,000 Canadians. This innovative early work shows that the risk of onset of MDE can be quantified in the same way as can other physical disorders such as cardiovascular diseases and cancer. Knowing the individualized risk estimated by the MVRPs may serve as a trigger to empower people to actively engage in effective self-help actions. Self-help strategies are commonly used to deal with depression and promoting effective self-help strategies to the public as an early intervention strategy has been recommended as one way to reduce the large disease burden of depression. Subsequently, the investigators conducted a randomized controlled trial (RCT) and found that providing individualized depression risk causes no psychological harm in participants. These studies have laid the required foundation for communicating individualized risk information to a broad population as a first step towards effecting changes in self-help and help-seeking behaviours and reducing the risk of MDE onset.~Using the MVRPs as the foundation and working with future users, the investigators developed a personalized depression risk communication tool (PDRC) for sharing information about individualized depression risk, risk profile (risk factors present), potential risk reduction, and self-help strategies. At this stage of our research program, the investigators need to answer the question: Does the PDRC lead to positive changes in self-help and help-seeking behaviours? Prior to a large scale RCT, the investigators proposed to conduct a pilot study to gain preliminary understanding about the effect of PDRC on self-help and help-seeking behaviors. The results will inform the design of a large RCT. |
Severe asthma is observed in 3 to 5% of the asthmatic population and is characterized by a higher rate of exacerbations, poorly controlled asthma and/or a poor lung function. During the last ten years, anti-IgE and anti-IL5 (and anti-IL5R) have considerably improved severe asthma status. Treatment with chronic or oral course of corticosteroids is indeed responsible for a lot of side effects. There is however a lack of biomarkers for the prediction of responders to anti-IL5 and anti-IgE.~The investigators have previously found that sputum eosinophil counts are good predictors for improvement in lung function of severe asthmatics using anti-IL5. Sputum cells might not be the only relevant sputum marker for responders to biologics.~The objective is to evaluate the ability of sputum cytokines (protein levels and genes) (IL-3, IL-4, IL-5, IL-13, IL-33 and GM-CSF) to predict the response of severe asthmatics after 6 months and 1 year of treatment with biologics in terms of reduction in exacerbations and corticosteroid use, improvement in FEV1, in asthma control, in asthma quality of life and the effect on sputum and blood inflammation.~Severe asthmatics seen in the Asthma Clinic of CHU of Liege are very well characterized using baseline measure of blood samples, induced sputum, lung function, FeNO, asthma control questionnaires (ACT - ACQ) and asthma quality of life questionnaires (AQLQ).~Data on exacerbations during the previous year and current inhaled and oral treatment is also recorded. If FEV1 value is upper than 70% of the predicted value, severe asthmatics also perform a methacholine challenge to evaluate bronchial hyperresponsiveness.~All these measures are repeated after 6 months and 1 year of treatment with anti-IgE and anti-IL5 or anti-IL5R. All the sputum supernatants are stored at -80°C and RNA from sputum cells is also available.~Target sample size: 50 patients~The investigators plan to measure different cytokines in the sputum (IL3, GM-CSF, IL5, IL-13, IL-33, IL-4…) and to evaluate their ability to predict the response after 6 months and 1 year of treatment with different biologics in terms of reduction in exacerbations and corticosteroid use, improvement in FEV1 (+200ml), in asthma control (ACQ decrease >0.5, ACT increase >3), in asthma quality of life (increase in AQLQ score > 0.5) and the effect on sputum and blood inflammation.~Asthmatic patients are recruited through the outpatient clinic and pulmonary rehabilitation centre (CHU, Sart-Tilman, Liege). Asthma is diagnosed as described in the GINA guidelines.~Sputum induction and processing. The sputum is induced and processed as follow: The whole sputum is collected in a plastic container, weighed, and homogenized with three volumes of phosphate-buffered saline (PBS), vortexed for 30 s, and centrifuged at 800g for 10 min at 4° C. The supernatant is separated from the cell pellet by filtration through 2 layers of sterile gauze. A mucolysis is performed by adding an equal volume of 6.5 mM dithiothreitol and the suspension is rocked during 20 min. After a centrifugation of 10 min at 550g, the squamous cells and total cell counts as well as the cell viability are checked by trypan blue exclusion with a manual hemocytometer. The differential leukocyte count is performed on cytospins stained with May-Grünwald-Giemsa on 500 cells.~If the quality criteria (< 30% of squamous cells and viability > 50%) are respected, the cell pellet is mixed with 5 volumes of RNAprotect cell reagent (Qiagen, Hilden, Germany) and kept at -80 °C until RNA extraction.~In total, 50 patient with successful induced sputum supernatant samples before anti-IL-5, anti-IL5R or anti-IgE therapy as well as 6 months and 1 year after will be analyzed. Regarding the sputum cells, patients with good quality samples before and after therapy will allow gene expression analysis.~Immunoassays: The concentrations of the mediators contained in the sputum supernatant are assessed by ELISA Luminex performance assay (R and D systems, Minneapolis, USA) according to the manufacturer's instructions. Spiking experiments of cytokines in sputum supernatants are performed to check that the recovery is between 80% and 120% for all the analytes.~The mediator protein levels will be obtained using Luminex performance XL discovery kit (R and D systems, Minneapolis, USA) for IL-3 and IL-4 (detection limit : 0.09 pg/ml for both). A Luminex high sensitivity performance kit will be used for IL-5, IL-13, IL-33 and GM-CSF. Detection limits are 0.4, 5.1, 1.8 and 1.6 pg/ml respectively.~RNA extraction and RT-qPCR methods Regarding the mediator gene expression levels, primers and probes will all be obtained from IDT (Integrated DNA Technologies, Skokie, IL, USA). PCR efficiencies will be calculated using qbase+ qPCR analysis software (Biogazelle, Zwijnaarde, Belgium). The same program will be used to obtain relative quantitation in gene expression using the 2-∆∆Ct method. HPRT1 and GNB2L1 will be used as reference genes. The patients will be compared with a cohort of 7 healthy subjects.~The Taqman PCR step is performed in 96-well plates and for each sample, 2 µl of cDNA (diluted 1:4) is used in a total reaction volume of 12.5 µl including 500 nM forward primer, 500 nM reverse primer and 250 nM probe for all the tested genes. Every qPCR are realized in duplicate and included non-template controls for each gene. Amplification is performed on the LightCycler 480 Real-Time PCR (Roche, Pleasanton, CA, USA) during 45 cycles as follows: initial activation step: 95 °C for 15 min; denaturation stage: 94 °C for 15 s; annealing and elongation stage: 60 °C for 1 min. All the procedure is done according to the MIQE guidelines for the minimum information required for a qPCR experiment.~Cytokines will also be measured in the blood of a subset of patients.~Study Endpoints~Primary endpoint:~To identify predictors of reduction in exacerbations and in oral corticosteroids dose.~Secondary endpoint:~To identify predictors of improvement in ACQ (-0.5), ACT (+3pts), AQLQ (+ 0.5), sputum eosinophils (<3%), FEV1 (+ 200ml).~Statistical Plan or Data analysis The results will be expressed as mean¡SD or mean¡SEM for continuous variables; median (range) for skewed distributions. For categorical variables, the number of observations and percentages will be given in each category. Comparisons between different subgroups will be performed with a Kruskal-Wallis test or paired t-test / Wilcoxon signed rank test. The Spearman correlation coefficient will be used to measure the association between clinical parameters.~Power calculations indicated a required total sample size of 50 subjects to confirm a change in outcomes. | The investigators will measure different cytokines in the sputum (IL3, GM-CSF, IL5, IL-13, IL-33, IL-4…) and in the blood to evaluate their ability to predict the response after 6 months and 1 year of treatment with a biologic treatment (anti-IgE, anti-IL5, anti-IL5R) in terms of reduction in exacerbations and corticosteroid use, improvement in FEV1 (+200ml), in asthma control (ACQ decrease >0.5, ACT increase >3), in asthma quality of life (increase in AQLQ score > 0.5) and the effect on sputum and blood inflammation. |
Decades of research have demonstrated that behavioral obesity treatments can produce clinically significant weight losses that improve health and disease risk/severity. However, these treatments have not been disseminated widely due to high costs and lack of qualified providers. The investigators therefore aim to develop and test a fully automated online obesity treatment that would produce clinically significant weight losses (i.e., ≥ 5 % of initial body weight) when delivered online. In order to maximize the public health impact of online obesity treatment, and advance the science of online behavioral intervention in general, it is imperative to evaluate innovative behavioral intervention components with the potential to optimize weight loss outcomes. Because digital health technology evolves rapidly, this research will use the Multiphase Optimization Strategy (MOST) framework to most quickly and efficiently determine which, if any, of 5 innovative intervention components, alone or in combination, increases the proportion of patients achieving a ≥5% weight loss, and mean weight loss, of the online Rx Weight loss (RxWL) program at 12- months. The 5 intervention components to be tested are: (a) Web-based virtual reality intervention for training in basic behavioral weight loss skills; tailored interactive intervention targeting (b) structured physical activity and (c) dysregulated eating; (d) a platform for social interaction including opportunities for friendly competition, and (e) interactive video feedback with content tailored to the unique needs of each participant and a focus on dietary skills. A sample of 384 individuals with BMI ≥ 25 will be randomized to receive RxWL and 0-5 of the experimental intervention components in a full factorial experiment. This design will allow the investigators to determine which intervention components maximize weight loss and whether there are favorable combinations of components. In addition, by evaluating the effects of each component on proximal outcomes (i.e., mediators) it will be possible learn not only which components are (or are not) effective but also why or how they exert their effects. This project advances the science of behavioral obesity treatment, and will directly impact the care of patients receiving RxWL. | When delivered online, behavioral obesity treatments have the potential to reach large numbers of individuals with overweight/obesity and produce significant improvements in health and wellbeing. In order to maximize the public health benefit of disseminating these treatments online, this study will use the Multiphase Optimization Strategy (MOST) framework to most quickly and efficiently determine which, if any, of 5 innovative intervention components, alone or in combination, increases the proportion of patients achieving a ≥5% weight loss, and mean weight loss, after a 12-month online behavioral obesity treatment. |
Zhineng Qigong is a self-training method which enables the participant to take an active part in a possible recovery process.~The aims of this study are: 1) evaluate a Zhineng Qigong intervention regarding health aspects (both subjective and objective outcomes) in patients with chronic low back pain and/or leg pain; 2) test different aspects of feasibility including recruiting from different patient populations and testing outcome measurements; and, 3) get a basis for power calculation for a future Randomised Controlled Trial.~Based on previous experiences after Zhineng Qigong training with European Zhineng Qigong, this study is based on the following hypotheses:~Zhineng Qigong training gives pain reduction and reduced consumption of analgesics.~Zhineng Qigong training reduces lumbar spine-related symptoms (other than pain).~Zhineng Qigong training reduces healthcare utilisation, including lumbar spine surgery.~Zhineng Qigong training improves walking ability, mobility, and functional capacity.~Zhineng Qigong training improves Health-Related Quality of Life, including perceived concentration ability, distress, sleeping quality, vitality, depression, mood, and anxiety.~The investigators´ idea was to give patients with chronic low back pain and/or leg pain the opportunity to practise Zhineng Qigong in an intervention arranged by European Zhineng Qigong. To this prospective interventional study without control group, patients were recruited from the Swedish spine surgery register (SweSpine), Orthopaedic clinic, and Primary Healthcare. The intervention period was 12 weeks, with measurements once before and once after intervention. However, because of difficulties in recruiting, 15 of the respondents were enrolled to 3 weeks shorter intervention, joining respondents who already started the 12 weeks intervention. Totally, 55 respondents were enrolled.~Background data:~Age~Gender~Marital status~Children at home (number and age)~Duration of symptoms in the lumbar spine and/or leg (year-month when the symptoms started)~Lumbar spine diagnosis (name and year-month of the diagnosis)~History of lumbar spine surgery (number of times and which years)~Type of surgery and surgery level(s) (for postoperative patients)~Sick- or disability pension (since which year-month and main reason)~Treatments and/or training methods already tried (also for how long time)~Educational level~Occupation or living situation~Smoking habits~Financial difficulties~The same physiotherapist examined the respondents once before and once after the intervention period. Two weeks before and two weeks after the intervention period, a pain diary was filled in by the respondents. Also, they filled in questionnaires once before and once after the intervention.~During the intervention period participation in the group activities was registered on an attendance list. Every day during the intervention period and two weeks after, the respondents filled in a training diary with information about how much Zhineng Qigong was practised besides the group activities.~The respondents that were on waiting list for lumbar spine surgery were asked by telephone if lumbar spine surgery was performed or not. This was done six months after the intervention was completed.~Descriptive and analytical statistics are used to present the results. | The purpose of this study is to evaluate a Zhineng Qigong intervention for patients with chronic low back pain and/or leg pain, and to test feasibility aspects. |
Materials and Methods Study design and Patient Selection A split-mouth, randomized controlled clinical trial enrolling 13 patients (8 males and 5 females, mean age 52.3 ± 9.4 years) was set-up. The patients were informed about the benefits and risks of the study and each participant signed informed consent.~Non-surgical periodontal treatment A single periodontist (L.C.) performed all periodontal treatments. NSPT consisted of two sessions of scaling and root planing (SRP) within 48 hours under local anesthesia using ultrasonic and hand instrumentation. Additionally, the sites associated with PPD ≥ 6 mm in the quadrant assigned to the test group were irrigated with L-PRF exudate and filled with longitudinal pieces of L-PRF membrane. The patients received instructions about soft diet, a carefully and soft mouth rinse with chlorhexidine 0.12%, and no toothbrushing during 7 days in order to avoid the L-PRF removal. After this period, the following instructions were given: modified Bass brushing technique, dental floss, and interdental brushes, and chlorhexidine 0.12% mouth rinse for an extra 7 days. Strict hygiene control by the clinician was also performed in each appointment.~L-PRF membrane preparation Two samples of venous blood were collected in 2 vacutainer tubes (red cup) of 10 ml without anticoagulant. They were centrifuged at 408 g for 12 minutes using a table centrifuge (IntraSpinTM, Intralock®, Florida, USA) according to the protocol described by Temmerman et al.18 The L-PRF clots were removed from the tube, separated from the red cells and placed in the Xpression box (IntraSpinTM, Intralock®, Florida, USA) to gently compress them in membranes. The membranes were chopped in longitudinal pieces to fill the periodontal pockets ≥ 6mm. The exudate, released during the compression, called L-PRF exudate was aspirated to rinse the treated pockets. (Figure 1)~Clinical Measurements All clinical measurements were performed by a single trained and calibrated examiner (N.J.) who was masked for the treatment assigned, using a basic examination instrument kit and a University of North Carolina no. 15 color-coded periodontal probe. The following clinical parameters were measured at baseline and 6 weeks, 3 months and 6 months after treatment: probing pocket depth (PPD), clinical attachment level (CAL), gingival recession (GR), bleeding on probing (BOP), and O´Leary plaque index (PI).19 Additionally, the root sensitivity (RS) was evaluated using a 100-mm visual analogue scale (VAS) (0 indicating no pain, 50 indicating average, and 100 indicating an unbearable pain) at 24 hrs., 6 weeks, 3 months, and 6 months after treatment. The change in PPD, CAL, GR, BOP, PI, and RS (difference between baseline measures and at 1, 3, and 6 months) were calculated.~GCF collection GCF samples were collected from the deepest pocket from each quadrant before recording the clinical measurement (baseline, and 6 weeks and, 3 months after treatment) in order to evaluate the concentration of Porphyromona gingivalis (P.g), Aggregatibacter actinomycetemcomitans (A.a), Prevotella intermedia (P.i) and Fusobacterium nucleatum (F.n). The sample area was isolated with cotton rolls, and contamination with saliva was avoided using an appropriate suction and air spray. Then, an endodontic #35 paper-point was inserted until a slight resistance was felt and it was held for 30 seconds. The paper-points were immediately inserted in an Eppendorf tube and stored at -80ºC for future analysis.~Microbiological processing After defrosting the samples, 1ml of phosphate-buffered saline (PBS) was added and homogenized. Then, 400 μl of each sample was centrifuged at 13200 rpm for 3 minutes. The obtained pellet was dispersed in 200 μl InstaGene. DNA was extracted with InstaGene matrix (Bio-Rad Life Science Research, Hercules, CA, USA) according to the instructions of the manufacturer. Five microliters of the purified DNA were used for the quantification of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Prevotella intermedia. A quantitative polymerase chain reaction (qPCR) assay was performed with a CFX96 Real-Time System (Biorad, Hercules, CA, USA) using the Taqman 5' nuclease assay PCR method for detection and quantification of bacterial DNA. Taqman reaction contained 12.5 μl Mastermix (Eurogentec, Seraing, Belgium), 4.5 μl sterile distilled water, 1 μl of both species-specific primers and probe (Table 1) and 5 μl template DNA. Assay conditions for all primer/probe set consisted of an initial 2 min at 50°C, followed by a denaturation step for 10 min at 95°C, followed by 45 cycles of 95°C for 15 sec and 60°C for 60 sec. Quantification was based on a plasmid standard curve. The delta for bacterial concentration at 6 weeks, 3 and 6 months (difference between baseline measures and at 6 weeks, 3 and 6 months) were calculated.~Randomization, allocation concealment and calibration A coin toss method was used to assign the patients' quadrants into two treatment groups: (SRP + L-PRF) or control (SRP alone).~Before beginning the study, two recordings of the following parameters were done: PPD, GR, and CAL in five patients, with a 24-hour interval between first and second records in order to validate the intra-examiner accuracy. All teeth, excluding third molars, were measured by periodontal probing at 6 sites (mesiobuccal, mediobuccal, distobuccal, mesiolingual/palatal, mediolingual/palatal, and distolingual/palatal). Calibration was accepted if the measurements at baseline and after 24 hours were within 1 mm at the 95% level (correlation coefficients between duplicate measurements; r = 0.95).~Statistical analysis To detect a mean difference in PPD of 1.2 mm with a standard deviation of 1.0 at an α level of 0.05 and a β level of 0.10 (power = 0.9), a sample size of 10 patients was required. Despite the results but to anticipate potential drop outs during the study, a sample size of n = 16 patients was considered.~Bacterial counts were log-transformed. A linear mixed model was applied with the variable patient, as a random factor and time and treatment as two crossed fixed factors. Smoking and PI were considered as covariables. Contrasts were set up to calculated the change from baseline for the different time points between the treatments and for each treatment apart. A correction for simultaneous hypothesis testing according to Sidak was applied. A normal quantile plot and residual dot plot of the residual values were created showing that the assumptions underlying the statistical model could be made. | Abstract:~Background: Leucocyte and Platelet-Rich Fibrin (L-PRF) has shown to promote regenerative processes, even reporting antibacterial effect. The aim of this split-mouth clinical trial was to evaluate the effect of L-PRF as an adjuvant to scaling and root planing (SRP).~Methods: 13 patients with chronic periodontitis and at least 1 bilateral periodontal pocket ≥ 6 mm were recruited. The sites were randomly treated with SRP + L-PRF (test group) or SRP alone (control group). The following parameters were evaluated at baseline and 6 weeks, 3 and 6 months after treatment: Probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP); gingival recession (GR), and root sensitivity (RS). Additionally, the concentrations of Porphyromona gingivalis (P.g), Aggregatibacter actinomycetemcomitans (A.a), Prevotella intermedia (P.i) and Fusobacterium nucleatum (F.n) in the gingival crevicular fluid (GCF) were evaluated at baseline, 6 weeks and 3 months after treatment. |
Symptomatic hand osteoarthritis (HOA) affects 8-16% of the general population above 50 years and involves interphalangeal (IP) joints. HOA symptoms include pain, stiffness and are responsible for disability and substantial burden. Erosive HOA (EHOA) (10% prevalence among symptomatic HOA from the general population and 40-50% prevalence in tertiary centers) is the most severe HOA phenotype characterized by inflammatory flares, more IP joint destruction, pain, soft swelling joints (ie, synovitis), and more disability (similar to rheumatoid arthritis (RA)) than its non-erosive counterpart.~Current symptomatic pharmacological treatments of HOA or EHOA have a poor efficacy on pain (ie, paracetamol) or safety issues (ie, non-steroidal anti-inflammatory drugs (NSAIDs)) in this aging population with frequent comorbidities. Systemic and joint inflammation contribute to EHOA but 4 studies using TNF inhibitors, 2 using hydroxychloroquine, 1 using methotrexate and 1 using a new anti-IL1α/β failed to show any efficacy on pain in HOA or in EHOA. Therefore, innovative therapeutic approaches are awaited.~Stimulation of the vagus nerve (VNS), belonging to parasympathetic system, dampens pro-inflammatory cytokines production by splenic macrophages, through to the binding of acetylcholine neurotransmitter to α7nicotinic receptor on macrophages: this is the cholinergic anti-inflammatory pathway (CAP). VN stimulation (VNS) by cervical implantable device activating CAP has given promising results in refractory RA patients. Beyond its anti-inflammatory effects, VNS is analgesic in chronic pain disorders (headache, fibromyalgia). However, the use of such implantable device is limited by the need of cervical surgery and subsequent potential side effects.~Besides implantable devices, VNS may be also performed using transcutaneous VNS (tVNS) of the ascendant auricular branch of the VN that selectively innervates the cutaneous zone of cymba conchae at the left ear. Auricular tVNS avoids invasive neurosurgery and its potential side effects and is less expensive than implantable VNS, making it an attractive candidate for neurostimulation. Auricular tVNS has given positive results in chronic migraine and is currently tested in RA, Crohn's disease, widespread pain, irritable bowel syndrome and musculoskeletal pain related to systemic lupus.~We hypothesize that auricular tVNS using a transcutaneous electrical nerve stimulation (TENS) device could be a novel, simple and well-tolerated analgesic and anti-inflammatory treatment of symptomatic (i.e., painful) and inflammatory EHOA.~ESTIVAL is a 12 weeks randomized sham-controlled trial investigating the symptomatic efficacy and the safety of tVNS in patients with symptomatic and inflammatory EHOA.~tVNS will be performed using an active or sham transcutaneous electrical nerve stimulation (TENS) device connected to an auricular electrode stimulating the cutaneous area of the left ear innervated by the auricular ascendant branch of the vagus nerve.~Exploratory and ancillary studies will include i) changes of serum biomarkers of inflammation and of cartilage degradation that will be assess at inclusion and at week 12 ii) hand MRI at W0 and W12 of the most symptomatic joint at inclusion for HOAMRIS socring at W0 and W12 for the center of Saint Antoine.~A phone call at D7± 3 days by the clinical research technician or the clinical nurse or the doctor who has performed the education during the D0 visit to check the proper use of the device. | Erosive hand osteoarthritis (EHOA) is a difficult-to-treat subtype of HOA characterized by local and systemic low-grade inflammation as well as by high level of pain and of disability.~Auricular transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic strategy that may reduce inflammation and pain level.~ESTIVAL is a 12 weeks randomized sham-controlled trial investigating the symptomatic efficacy and safety of tVNS in patients with symptomatic and inflammatory EHOA.~tVNS will be performed using a transcutaneous electrical nerve stimulation (TENS) device connected to an auricular electrode stimulating the cutaneous area of the left ear innervated by the auricular ascendant branch of the vagus nerve.~The active and sham device's will display similar appearance but the sham one will not give electric signal. |
This study will evaluate the infectivity, safety, and immunogenicity of a single dose of a recombinant, live-attenuated respiratory syncytial virus (RSV) vaccine, LID/ΔM2-2/1030s, in RSV-seronegative infants and children 6 to 24 months of age.~Participants will be randomly assigned to one of two groups to receive a single dose of intranasal RSV LID/ΔM2-2/1030s vaccine or placebo at study entry (Day 0). Group 1 (intensive) and Group 2 (less intensive) will differ only in the frequency of study visits and nasal swab collections.~Participants will receive study product between April 1 and October 15, outside of the RSV season, and will remain on the study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. Participants' total study duration is between 6 and 13 months, depending upon time of enrollment.~Participants will attend several study visits throughout the study, which may include blood collection, nasal swabs, and physical examinations. Some of these visits may be remote if a stay at home order is put in place after enrollment. | The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of a recombinant, live-attenuated respiratory syncytial virus (RSV) vaccine, LID/ΔM2-2/1030s, in RSV-seronegative infants and children 6 to 24 months of age. |
The impact of dysarthria goes beyond communication. However, there have been no clear directives guiding clinical practice to date, and despite increasing evidence directing treatment, research remains limited and predominantly consists of case studies or case series. Despite the importance of postural control in voice production, the effects of postural alignment on speech production efficiency are either little investigated or not at all explored in the dysarthric population. This study determined the effectiveness of a single 10-min postural repositioning session on the maximum phonation duration (MPD) in individuals with acquired dysarthria. | To determine the effectiveness of a single 10-min postural repositioning session on the maximum phonation duration in individuals with acquired dysarthria. |
The safety and effectiveness of the microwave ablation treatment system produced by Suzhou Hengrui Hongyuan Medical Technology Co., Ltd. for the ablation treatment of primary liver cancer is verified through the implementation of prospective, multi-center, single-group target value research. According to the requirements of the trial, 139 patients who were diagnosed with primary liver cancer before surgery and met the inclusion criteria without any exclusion criteria were selected for treatment of their liver cancer with a microwave ablation treatment system, 1 month, 3 months and 6 months after surgery Carry out clinical and imaging follow-up to evaluate the safety of the operation and the effect of tumor ablation. | Through the implementation of prospective, multi-center, single-group target value research to verify the safety and effectiveness of the microwave ablation treatment system for the ablation treatment of primary liver cancer. |
Coronaviruses are among the most common causes of the common cold in humans. In recent decades, coronavirus has caused several epidemics worldwide with a vast number of deaths such as severe acute respiratory syndrome-SARS (2003) with 8098 people infected, and 774 people died over 29 countries. The disease caused by SARS CoV-2 (COVID19) is manifest by fever, fatigue, dry cough, pharyngitis, and headache. In addition to the common clinical presentation of respiratory distress, and increasing frequency of cardiovascular manifestations has become evident.~In this context, the investigators propose to evaluate the safety and efficacy of intravenous administration of convalescent plasma (CP) obtained from COVID19 survivors in patients requiring hospitalization for symptomatic high risk COVID19 disease. The study team wants to test the hypothesis that treatment with COVID19 CP will demonstrate salutary effects on COVID19 disease severity/duration, with the primary objective to reduce mortality. In addition, a major secondary objective to reduce the requirement for and/or duration of mechanical ventilation. This is a randomized clinical trial comparing convalescent plasma with the standard of care therapy in patients hospitalized for COVID-19 in Vietnam. Patients were randomized 1:1 and received 500 ml of plasma with anti-SARSCoV-2 neutralizing antibody titers of at least 1:80.~Written informed consent will be obtained all eligible subjects prior to participation.~Convalescent plasma will be obtained from male donors, nulliparous females, or female donors negative for HLA antibodies at least 14 days following recovery from COVID-19 infection. | Prior findings in various viral respiratory diseases including SARS-CoV-related pneumonia suggest that convalescent plasma can reduce mortality, although formal proof of efficacy is still lacking. The investigators propose to evaluate intravenous administration of convalescent plasma (CP) obtained from COVID19 survivors in COVID19 patients who are in the medium stage. Supportive data exist for use of convalescent plasma in the treatment of COVID19 and other overwhelming viral illnesses. The study team wants to test the hypothesis that treatment with COVID19 CP will demonstrate salutary effects on COVID19 disease severity/duration, with the primary objective to reduce mortality. In addition, a major secondary objective to reduce the requirement for and/or duration of mechanical ventilation. This phase is to test the safety and efficacy of CP therapy. |
Myofascial pain syndrome (MPS) is a common problem with manifesting itself such as trigger points, taut bands, range of motion limitations and pain. One of the most common place for MPS is neck region and trapezius muscle is the common cause of these symptoms and 9 different trigger point location has been identified on trapezius muscle. Myofascial trigger points, characterized by hypersensitive nodules, can be palpated in stretched bands in the affected muscles. In order to eliminate trigger points fascial releasing, dry needling, kinesio taping and other physical therapy applications can be used.~Although there are several studies investigating the effectiveness of Kinesio taping (KT) and Dry needling(DN) methods in MPS, it is controversial which one is superior to others.~The aim of this study is to compare the effects of exercise, KT, and DN methods on pain and disability in the treatment of upper trapezoidal muscle MPS. | The aim of this study is to compare the effectiveness of kinesio tape and dry needling in the treatment of myofascial pain syndrome of the trapezius muscle. |
Assessing the efficacy and safety of DEXTENZA, sustained release dexamethasone 0.4 mg insert, when placed within the lower or upper eye lid canaliculus in conjunction with topical prednisolone acetate 1% for the treatment of pain, and inflammation following corneal transplant surgery (PKP, DSEK, DMEK) as compared to topical prednisolone acetate 1%. | Assessing the efficacy and safety of DEXTENZA, sustained release dexamethasone 0.4 mg insert following corneal transplant surgery (PKP, DSEK, DMEK) as compared to topical prednisolone acetate 1%. |
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy is a curable and effective method. However, the recurrence rate is as high as 50%~70% in 5 years after surgery. Perioperative treatment with immunotherapy combined with target therapy is expected to improve the patient's prognosis. This study aims to evaluate the efficacy, safety and tolerability of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. This trial includes subjects with CNLC Ib/IIa/IIb/IIIa HCC. All eligible subjects will be randomized (1:1) to experimental group or control group. In the experimental group, patients will be treated with following: neoadjuvant therapy (camrelizumab and apatinib, 2 cycles), radical surgery, postoperative TACE treatment, adjuvant therapy (camrelizumab and apatinib, 6 cycles); in the control group, patients will be treated with following: radical surgery, postoperative TACE treatment. The primary purpose of this study is to evaluate the rate of subjects with major pathological response and 3-year event-free survival (EFS) of camrelizumab combined with apatinib mesylate in the perioperative period of HCC. The secondary research purpose is to evaluate the R0 resection rate, the rate of subjects with pathological complete response, EFS, overall survival and disease-free survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable HCC. The safety and tolerability is also evaluated. | Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Hepatectomy is a curable and effective method. However, the recurrence rate is as high as 50%~70% in 5 years after surgery. Perioperative treatment with immunotherapy combined with target therapy is expected to improve the patient's prognosis. This study aims to evaluate the efficacy, safety and tolerability of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The primary purpose of this study is to evaluate the rate of subjects with major pathological response and 3-year event-free survival (EFS) of camrelizumab combined with apatinib mesylate in the perioperative period of hepatocellular carcinoma (CNLC Ib-IIIa). The secondary research purpose is to evaluate the R0 resection rate, the rate of subjects with pathological complete response, EFS, overall survival and disease-free survival of camrelizumab combined with apatinib mesylate in the perioperative period of resectable hepatocellular carcinoma. The safety and tolerability is also evaluated. |
According to previous studies, IFN-β has strong antiviral activity and also has an acceptable safety profile. Based on possible therapeutic effects, we decided to lead an Investigation into Beneficial Effects of high-dose Interferon Beta 1a, Compared to low-dose Interferon Beta 1a (the base therapeutic regimen) in Moderate to Severe COVID-19.~Previous studies demonstrate that IFN-β 1a could be used against some coronaviruses including avium infectious, bronchitis virus, murine hepatitis virus, and SARS- CoV because they are susceptible in vitro or in vivo. In a current study, the efficacy of IFN-β 1a in COVID-19 patients were evaluated, and they found than IFN-β 1a reduced the disease symptoms.~The present study is a randomized clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran. | The present study is a randomized clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Loghman Hakim Medical Education Center in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal. |
Rationale:~Chronic Obstructive Pulmonary Disease (COPD) is a progressive inflammatory disease characterised by airway and lung parenchyma damage. At end-stage disease patients may develop chronic hypercapnic respiratory failure, a disease characteristic that is however not uniformly seen in other end-stage lung diseases, such as in patients with pulmonary fibrosis. The underlying process for the development of chronic hypercapnic respiratory failure is incompletely understood and the role of respiratory muscle alterations is unclear.~Home noninvasive ventilation with high-intensity ventilatory settings (HI-NIV) has been shown to be effective in these severe COPD patients. However, in patients being mechanically ventilated on the intensive care unit for diverse reasons, high-intensity ventilation, especially high tidal volumes, has been shown to result in ventilator associated lung and diaphragm injury. Whether this occurs in home high-intensity NIV, is however completely unknown.~Objective: The aims of the study are to get insight in:~A. changes respiratory muscles in end-stage respiratory disease, comparing COPD with restrictive lung disease (RLD) due to pulmonary fibrosis B. the effects of long-term HI-NIV in severe COPD patients on the respiratory muscles; i.e. the contractile strength and the structure of single diaphragm and intercostal muscle fibres and the lungs; i.e. alveolar structure and damage and inflammation, by comparing COPD patients that had been treated with long-term NIV to COPD patients that were not treated with long-term NIV.~Study design: In order to investigate this, the investigators will include in a small pilot cohort study patients being lung transplanted. In these patients there is lung tissue available and respiratory muscle biopsies will be performed during lung-transplant surgery.~Study population: Patients that are listed for lung transplantation for an underlying diagnosis of COPD or RLD will be asked to participate. Three groups will be included: patients with a RLD due to pulmonary fibrosis, COPD patients that had been treated with long-term NIV prior to being lung transplanted and COPD patients that were not treated with long-term NIV. Patients will be included definitely once being lung transplanted.~Main study parameters/endpoints: The study is an exploratory pilot study. The study aims to get data on respiratory muscle and lung and airway pathology in order to, if important results are observed, set up a larger prospective trial investigating both clinical outcomes and pathology of the respiratory muscles/lungs. Both contractile strength and the structure of single diaphragm and intercostal muscle fibres as well as lung injury; i.e. alveolar structure and damage and inflammation in the alveoli, will be investigated. | Rationale:~The pathophysiological changes in respiratory muscle morphology and functioning in patients with end-stage pulmonary disease are not very well known. Furthermore, in COPD, long-term high-intensity NIV is applied without knowing the exact consequences on the lungs and respiratory muscles.~Objective: The aims of the study are to get insight in:~A. changes respiratory muscles in end-stage respiratory disease, comparing COPD with restrictive lung disease (RLD) due to pulmonary fibrosis B. the effects of long-term HI-NIV in severe COPD patients on the respiratory muscles and the lungs; by comparing COPD patients that had been treated with long-term NIV to COPD patients that were not treated with long-term NIV.~Study design: In order to investigate this, the investigators will include in a small pilot cohort study patients being lung transplanted. In these patients there is lung tissue available and respiratory muscle biopsies will be performed during lung-transplant surgery.~Study population: Patients that are listed for lung transplantation for an underlying diagnosis of COPD or RLD will be asked to participate. Three groups will be included: patients with a RLD due to pulmonary fibrosis, COPD patients that had been treated with long-term NIV prior to being lung transplanted and COPD patients that were not treated with long-term NIV. Patients will be included definitely once being lung transplanted.~Main study parameters/endpoints: The study is an exploratory pilot study. Both contractile strength and the structure of single diaphragm and intercostal muscle fibres as well as lung injury; i.e. alveolar structure and damage and inflammation in the alveoli, will be investigated. |
. Trial of the group program (nutrition, exercise) delivered via telehealth through fruit street to families of overweight and obese children between 7-17 years of age referred from selected pediatric practices on the Eastern Shore of Maryland and Western Maryland with use of noninvasive lifestyle tracking options (drink water aquarium app for water consumption and fitbit charge 3- steps, sleep monitoring) provides novel options for expansion of family- based lifestyle intervention to underserved areas. Investigators plan as a pilot study to assess the sensitivity of noninvasive measures for the detection of sleep apnea (pediatric sleep questionnaire (PSQ) and fitbit charge 3 sleep data) in comparison to clinically indicated polysomnography among children with clinical suspicion for sleep apnea. | There has been a steep rise in the prevalence of obesity among children and adults in the United States. The Weigh Smart program, a family based weight management program was developed in 2005 with significant improvement in the severity of obesity among children in the Baltimore are participating in the group program with limited impact outside the region due to transportation. Trial of the group program (nutrition, exercise) delivered via telehealth through fruit street on the Eastern Shore and Western Maryland with use of noninvasive lifestyle tracking options (drink water aquarium app for water consumption and fitbit- steps, sleep monitoring) provides novel options for expansion of family- based lifestyle intervention to underserved areas. Investigators plan as a pilot study to assess the sensitivity of noninvasive measures for the detection of sleep apnea (pediatric sleep questionnaire (PSQ) and fitbit re: sleep data) in comparison to clinically indicated polysomnography among children with clinical suspicion for sleep apnea. |
Infectious uveitis is a very important blinding disease. Some people who have been diagnosed with idiopathic uveitis may also have the activity of pathogens in the eye. However, due to the limitation of the amount of ocular samples, it is difficult to make a rapid and effective diagnosis of infection.~The study is to explore the infective cause of uveitis in China by using a broad diagnostic approach of detection, including multiple molecular bio-techniques. We also plan to explore the distribution of pathogens in infectious uveitis. | Infectious uveitis is a very important blinding disease. Some people who have been diagnosed with idiopathic uveitis may also have the activity of pathogens in the eye. However, due to the limitation of the amount of ocular samples, it is difficult to make a rapid and effective diagnosis of infection.Current study is to explore the infective cause of uveitis in China by using a broad diagnostic approach of detection. |
This is an open-label, multicenter Phase 1 study to evaluate safety, tolerability and preliminary efficacy of oral LY3410738 in patients with IDH1 R132-mutant advanced solid tumors, including but not limited to cholangiocarcinoma, chondrosarcoma, and glioma or IDH2 R140 or R172 mutant cholangiocarcinoma.~This study includes 2 parts: Phase 1 dose escalation and Phase 1 dose expansion. The Phase 1 dose escalation monotherapy cohort will enroll any eligible patient with IDH1 R132-mutant advanced solid tumor or IDH1 or IDH2 mutant cholangiocarcinoma. The Phase 1 dose expansion will include 5 cohorts to further evaluate safety and clinical activity. Three cohorts will be administered LY3410738 monotherapy. The fourth cohort will administer LY3410738 at or below the monotherapy RP2D in combination with gemcitabine and cisplatin. The fifth cohort (US only) will administer LY3410738 at or below the monotherapy RP2D in combination with durvalumab.~IDH1 R132, IDH2 R140, or IDH2 R172 mutations will be identified through genomic testing utilizing material collected prior to patient consent. Molecular assays utilized for enrollment are required to be performed in CLIA, ISO/IEC, CAP, or other similarly certified laboratory. Enrollment of patients with cholangiocarcinoma, chondrosarcoma or glioma may be made based on molecular tests performed in either tumor or blood. Enrollment of patients with other tumor types is limited to testing performed in tumor tissue. | This is an open-label, multicenter Phase 1 study to evaluate safety, tolerability and preliminary efficacy of oral LY3410738 in patients with isocitrate dehydrogenase 1 (IDH1) arginine 132 (R132)-mutant advanced solid tumors, including but not limited to cholangiocarcinoma, chondrosarcoma, and glioma or isocitrate dehydrogenase 2 (IDH2) arginine 140 (R140) or arginine 172 (R172) mutant cholangiocarcinoma. |
This study is a proof of concept study to demonstrate that EMP16-02, a fixed dose combination (FDC) of orlistat and acarbose in an oral multiple-unit modified release (MR) formulation leads to a clinically relevant decrease in body weight. The study aims to evaluate the efficacy, safety and tolerability of treatment with two different doses of EMP16 02 (120 mg orlistat/40 mg acarbose and 150 mg orlistat/50 mg acarbose) for 26 weeks on reducing body weight in obese patients.~EMP16-02 will be given to obese patients with an initial BMI ≥ 30 kg/m² or ≥ 28 kg/m² in the presence of other risk factors (e.g., hypertension, glucose dysregulation such as impaired glucose tolerance and type 2 diabetes mellitus (T2DM) and/or dyslipidaemia.~The study consists of 6 visits to the research clinic, including screening and follow-up. There will be no overnight stays at the clinic.~Visit 1: Screening (Visit 1) will take place from Day -28 to Day -1. Visit 2: Eligible and consenting patients will arrive at the research clinic in the morning of the first dosing day (Day 1, Visit 2) after at least 8 hours overnight fasting.~A re-check of eligibility including a brief physical examination, vital signs and assessment of body weight will be conducted. The patients will be randomised to either of two doses of EMP16-02 or placebo:~EMP16-02 120 mg O/40 mg A~EMP16-02 150 mg O/50 mg A~Placebo (identical capsules) Blood sampling (fasting), and anthropometric measurements will be performed. Patients will receive electronic diary instructions and will be asked to fill in a satiety and craving questionnaire before breakfast (at the clinic), and then once every hour for 4 hours until before lunch (at home). A standardised breakfast will be served at the clinic. Halfway through breakfast at Visit 2, all patients will receive a placebo capsule independent of the treatment arm to which the patients have been randomised, to provide patients with the opportunity to train on self administering the Investigational Medicinal Product (IMP) under supervision of clinic staff. The patients will also receive instructions for filling in more questionnaires regarding health and quality of life, meal pattern, activity and sleep, and gastrointestinal symptoms (gastrointestinal rating scale [GSRS]). The patients will be instructed to take EMP16-02 or placebo halfway through each meal, together with approximately 100-200 mL water (or other drink) on all subsequent treatment days. Once IMP has been handed out, the patients are free to leave the clinic. The first randomised IMP dose will be taken during lunch (or the next meal) at home.~Between visit 2 and 3: Patients randomised to EMP16-02 will start with a run-in period of 6 weeks during which the dose is sequentially increased. From week 7, all patients will have reached their final intended dose and a 20 week treatment and observation period will start. The run-in phase will start at a dose of 60 mg O and 20 mg A TID, which will sequentially be increased with 30 mg O/10 mg A every two weeks until the target doses of 120 mg O/40 mg A TID (for the lower dose group) and 150 mg O/50 mg A TID (for the higher dose group) are reached. Placebo treatment consists of matching oral capsules. Placebo and EMP16-02 capsules need to be taken TID together with three daily meals.~Visit 3-5: Patients will come to the clinic at Visit 3 (week 7), Visit 4 (week 14) and Visit 5 (week 26) for safety assessments and assessments of weight and anthropometric measurements. Patients will arrive in the morning after at least 8 hours overnight fasting. All visits will start with a brief physical examination followed by blood sampling (fasting) and assessment of body weight and body composition. A standardised breakfast will be served during which the patient will take the IMP. All or a selection of the questionnaires, including the satiety and craving questionnaire, will be filled in in a similar way as during Visit 2.~New IMP will be handed out to the patients at Visit 2, 3 and 4. At Visit 5 (week 26), the patients will take the last dose during breakfast at the clinic.~After 18 and 22 weeks of treatment (Day 123 ± 3 days and Day 151 ± 3 days, respectively), patients will be asked to answer questions about IMP compliance, occurrence of adverse events (AEs) and use of concomitant medication using an electronic diary.~Visit 6: A follow up safety visit. | This study is a proof of concept study to demonstrate that EMP16-02, a fixed dose combination (FDC) of orlistat and acarbose in an oral multiple-unit modified release (MR) formulation leads to a clinically relevant decrease in body weight. The study aims to evaluate the efficacy, safety and tolerability of treatment with two different doses of EMP16 02 (120 mg orlistat/40 mg acarbose and 150 mg orlistat/50 mg acarbose) for 26 weeks on reducing body weight in obese patients. |
Total hip replacement (THR) is being considered as one of the most effective medical procedures. Since its introduction, there was a worldwide debate over proper implant selection in terms of size, bearing type and shape. The diameter of used femoral heads components grew throughout the years - from 22 mm in the 1960s to 32 mm in the 2000s, which is the most commonly used size nowadays. In recent years there was a visible use of large femoral heads (>=36mm) in several registers. In the USA there was a significant grow in use of this heads rising from 1% in early 200s to even 58% in 2009. There is a strong evidence data and many researchers concerning range of movement, risk of dislocation, functional results, pain and prosthesis wear depending of femoral head size.~In terms of gait characteristics there are several deviations reported concerning both patients with hip osteoarthritis (OA) and following THR. It is well-proven that those with hip OA have reduced stride length and reduced cadence, reduced gait velocity, and reduced joint excursion. Patients after THR walk with lower hip-abduction moments, sagittal-plane range of motion. It is believed that it might be a consequence of pain-avoidance mechanism developed as an adaptation for joint disease, which is still present after the surgery. What is more, there are publications, which underline that lower limb biomechanics during gait do not return to normal following THR.~However there is a lack of literature concerning influence of used implants on gait parameters and whether this goal of the surgery can be achieved.~According to authors best knowledge this study is the first to ever describe potential differences in gait parameters between THR performed with standard femoral heads (28-32mm) and large ones (>=36mm).~Aim of the study The aim of this study was to assess potential differences of lower limb biomechanics during gait in patients following total hip replacement surgery depending on femoral head diameter and compare them to the normal gait of healthy volunteers. As a secondary outcome authors wanted to inspect correlation between gait parameters and patient-reported outcome. | Total hip replacement (THR) is being considered as one of the most effective medical procedures. Since its introduction, there was a worldwide debate over proper implant selection in terms of size, bearing type and shape. The diameter of used femoral heads components grew throughout the years - from 22 mm in the 1960s to 32 mm in the 2000s, which is the most commonly used size nowadays. In recent years there was a visible use of large femoral heads (>=36mm) in several registers. In the USA there was a significant grow in use of this heads rising from 1% in early 200s to even 58% in 2009. There is a strong evidence data and many researchers concerning range of movement, risk of dislocation, functional results, pain and prosthesis wear depending of femoral head size.~In terms of gait characteristics there are several deviations reported concerning both patients with hip osteoarthritis (OA) and following THR. There is a lack of literature concerning influence of used implants on gait parameters and whether this goal of the surgery can be achieved.~The aim of this study was to assess potential differences of lower limb biomechanics during gait in patients following total hip replacement surgery depending on femoral head diameter and compare them to the normal gait of healthy volunteers. As a secondary outcome authors wanted to inspect correlation between gait parameters and patient-reported outcome. |
TXA reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. Results from randomised trials (CRASH-3 and NCT01990768) show that early treatment with TXA (given intravenously) reduces head injury deaths (pooled RR 0.89, 95% CI 0.80-0.99). In the CRASH-3 trial, the reduction in head injury deaths with TXA was largest in patients with mild and moderate head injuries, particularly if patients were treated soon after injury. However, the CRASH-3 trial included mild TBI patients only if they had intracranial bleeding on CT scan. It is uncertain whether the results apply to mild TBI patients more generally. CRASH-4 is a randomised, double blind, placebo-controlled trial in symptomatic mild TBI in about 10,000 older adults. The pilot phase will include about 500 patients. The trial aims to provide reliable evidence about the effects of early intramuscular TXA on intracranial haemorrhage, disability, death, and dementia in older adults with symptomatic mild head injury. | Tranexamic acid (TXA) reduces head injury deaths. The CRASH-4 trial aims to assess the effects of early intramuscular TXA on intracranial haemorrhage, disability, death, and dementia in older adults with symptomatic mild head injury |
The purpose of this study is to provide medication for opioid use disorder (MOUD) with buprenorphine and naloxone, or bup/nx, and pre-exposure prophylaxis (PrEP) for HIV prevention for persons who inject opioids accessing syringe services programs (SSPs), as part of a comprehensive harm reduction program, and assess the acceptability and feasibility of using telemedicine to implement the program.~The study objectives are the following:~To assess uptake and persistence to bup/nx and PrEP as part of a comprehensive harm reduction program among people who inject drugs using SSPs.~To assess feasibility and acceptability of implementing a telemedicine-based MOUD and PrEP program~The study population is people who inject drugs, specifically opioids, and who access services at SSPs in Charlotte and Wilmington, NC. The study team will enroll 20 PWID accessing the participating SSPs in Charlotte and Wilmington, NC (10 from each site). Participants will be enrolled in the study for 6 months. At the end of the study, they will be referred to MOUD and PrEP providers identified in the community.~Data collection~Enrollment visit:~The study coordinator will administer the SOCRATES 8D and a baseline survey to collect demographics, HIV risk behaviors, and substance use history. Participants will undergo laboratory testing at the SSP to determine eligibility and enrolled participants will be prescribed bup/nx and PrEP free of charge.~Follow up visits:~Follow-up visits will be conducted via telemedicine at the SSPs. For the first month (Month 1), telemedicine visits will be weekly with each study participant to ensure that they are stable on the appropriate bup/nx dose. Starting at Month 2, the telemedicine visits will take place monthly. Participants will be asked to complete a questionnaire at Month 3 and Month 6 which include questions on HIV risk and drug use, as well as adherence evaluation for both bup/nx and PrEP.~By the end of the study, we hope to determine the following:~The proportion of persons who demonstrate no or minimal opioid use~The proportion of persons who remain HIV negative.~Retention or persistence in care~We will also examine whether participants are more apt to remain on paired/combined therapy compared to individual treatment.~Under the secondary ID, IRB Pro00104148, we will conduct an ancillary study to contribute to the overall feasibility purpose of the primary study (Pro00104147) by collecting qualitative data from program users. The ancillary study will include conducting in-depth interviews (IDIs) with 10 to 20 participants in the primary study at the end of their month 1 telemedicine visit and at the end of their month 6 telemedicine visit (completion of the primary study). We will use applied thematic analysis to analyze participants' narratives. We chose to position this assessment within an ancillary protocol rather that embed it within the primary study in order to reduce the potential for socially desirable responses. | The purpose of this study is to provide medication for opioid use disorder (MOUD) with buprenorphine and naloxone, or bup/nx, and pre-exposure prophylaxis (PrEP) for HIV prevention for persons who inject opioids accessing syringe services programs (SSPs), as part of a comprehensive harm reduction program, and assess the acceptability and feasibility of using telemedicine to implement the program.~The initial visit will be conducted in person or remotely via telemedicine given COVID-19 protocols at the SSP sites in Charlotte and Wilmington, North Carolina (NC); follow-up visits will be conducted via telemedicine. |
Background: the investigator aimed to investigate the gastroesophageal reflux disease (GERD) along with esophageal motility in thoracolumbar kyphotic patients who meet surgical spinal correction criteria. Because some patients refused to receive spinal correction surgery, our patients divided into surgical and non-surgical treatment (for example: brace) groups. The investigator intended to use (1) multichannel intraluminal impedance-pH (MII-pH) monitoring to assess the height, non-acidic and acidic regurgitation of gastroesophageal reflux disease (GERD) (2) high resolution impedance manometry (HRIM) to esophageal motility between pretreatment and posttreatment period. (3) the questionnaire to evaluate the reflux-related symptoms: the frequency scale for the symptoms of GERD (FSSG), gastrointestinal symptom rating scale (GSRS) and Carlsson-Dent self-administered questionnaire (QUEST)~Objectives:~To determine whether acid or weakly acidic reflux in to the esophagus decreases after patients receiving treatment.~To investigate the change of esophageal motility after patients receiving treatment.~To determine whether the GERD symptoms would get improved after surgical or nonsurgical treatment.~Patients and methods: After the surgeon explained the spinal correction surgery, patients decided to recieve the correction surgery or wear brace treatment. Three types of evaluation were conducted in (1) patients receiving surgical correction [preoeprative and postoeprative surgical spinal correction (within 6 months)] (2) patients receiving brace treatment for 3 month [pretreament and wearing brace after 3 month within 6 months]; namely, HRIM, 24h MII-pH monitoring and three different questionniare surveys: the freqeuncy scale for the symptoms of GERD (FSSG), gastrointestinal symptom rating scale (GSRS) and Carlsson-Dent self administered questionniare (QUEST).The primary outcome was to evaluate the efficacy of surgical spinal correction for GERD by questionniare in patients with severe kyphotic deformity.~Expected result: 1.To precisely estimate efficacy of kyphosis surgical correction and brace treatment 2. To determine whether spinal correction for kyphosis patients with GERD is a surgical indication for the treatment of GERD along with for the treatment of kyphotic deformity. | The investigator aimed to investigate the gastroesophageal reflux disease (GERD) along with esophageal motility in thoracolumbar kyphotic patients who meet surgical spinal correction criteria. Because some patients refused to receive spinal correction surgery, our patients divided into surgical and non-surgical treatment (for example: brace) groups. The investigator intended to use (1) multichannel intraluminal impedance-pH (MII-pH) monitoring to assess the height, non-acidic and acidic regurgitation of gastroesophageal reflux disease (GERD) (2) high resolution impedance manometry (HRIM) to esophageal motility between pretreatment and posttreatment period. (3) the questionnaire to evaluate the reflux-related symptoms: the frequency scale for the symptoms of GERD (FSSG), gastrointestinal symptom rating scale (GSRS) and Carlsson-Dent self-administered questionnaire (QUEST) |
A total of 80 volunteers of patients with rheumatoid arthritis will be recruited from the Chinese medicine or Western medicine clinics in China Medical University Hospital and Dalin Tzu-Chi Hospital. These patients will be randomized to receive electroacupuncture (40 participants) or transcutaneous electrical nerve stimulation (40 participants) treatment two sessions per week and for 10 treatments in total.~The investigators expect that electroacupuncture or transcutaneous electrical nerve stimulation can reduce the severity of pain in the patients with rheumatoid arthritis. The effectiveness of electroacupuncture or transcutaneous electrical nerve stimulation can be detected by visual analogue scale, simplified disease activity index, and disease activity score and be used to improve the clinical symptoms and quality of life. | The aim of this pilot study is to compare the effectiveness of electroacupuncture or transcutaneous electrical nerve stimulation in reducing the tenderness in the patients with rheumatoid arthritis. The study adopted a pragmatic, randomized, patient-centered approach to investigate the effectiveness of clinical symptoms and quality of life. |
The objectives of this phase I study are:~to evaluate the safety profile of the AdimrSC-2f vaccine, and~to assess the immunogenicity of the AdimrSC-2f vaccine. | This study aims to evaluate the safety and immunogenicity of the preventative vaccine, AdimrSC-2f, in healthy volunteers aged from 20 to 60 years old. |
The response to COVID-19 means social isolation/distancing for the majority of the UK. This has the potential to negatively affect all domains of quality of life (QoL). QoL can be improved by giving feedback on gaps between someone's perceived QoL in a domain and how important it is to them (plus prompting reflective questions). However, interventions that are designed to improve QoL may increase the effectiveness of this as optimised behaviour change techniques can be used. This study aims to develop and test a quality of life intervention during social isolation/distancing. | The response to COVID-19 means social isolation/distancing for the majority of the UK. This has the potential to negatively affect all domains of quality of life (QoL). QoL can be improved by giving feedback on gaps between someone's perceived QoL in a domain and how important it is to them (plus prompting reflective questions). However, interventions that are designed to improve QoL may increase the effectiveness of this as optimised behaviour change techniques can be used. This study aims to develop and test a quality of life intervention during social isolation/distancing. |
This is a multi-center, open-label, randomized, Phase 2 study of IONIS-GHR-LRx in up to 40 participants with acromegaly. Participants will be randomized to 1 of 3 treatment groups to receive a single dose of IONIS GHR-LRx monthly for 73 weeks. At the end of 73 weeks, participants will enter a 14-week post-treatment (PT) evaluation period. | The purpose of this study is to determine the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy in patients with acromegaly. |
The purpose of this Phase 1b study is to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of MEDI5752 in combination with Lenvatinib (or Axitinib) in subjects with advanced renal cell carcinoma. | The purpose of this study is to evaluate MEDI5752 in combination with Lenvatinib (or Axitinib), in subjects with advanced renal cell carcinoma. |
Phase IV clinical trial, single-center, double-blind, randomized, two-period crossover, placebo-controlled, to determine the effect of treatment with umeclidinium/vilanterol 55/22 μg compared with placebo on the increase in left systolic chamber function during exercise in patients with COPD, lung hyperinflation and mild to moderate left ventricular dysfunction.~The participants will be patients from the outpatient offices of the Cardiology, Pulmonology and Internal Medicine departments of the Gregorio Marañon University Hospital in Madrid, over 40 years of age with a diagnosis of COPD, lung hyperinflation with a residual volume more than 135 % and stable heart failure with a left ventricular ejection fraction between 35-55%.~Patients will be randomly assigned (1:1) to either umeclidinium/vilanterol 55/22 μg Ellipta for 14 days followed by a washout period of 14 days and then placebo for 14 days, or the same treatments in reverse order.~The randomization numbers will be generated by blocks of 4 elements selected with a computer-generated random list.~Patients, investigators, individuals in charge of the assessments, sponsor, CRO staff, and data analysts will be blinded to the identity and assignment of the treatments from the time of randomization until database lock, using the following methods:~Randomization data will be kept confidential until the time of unmasking (unlocking the database) and will not be accessible to anyone else involved in the study and~The identities of the treatments will be concealed by the use of active drugs and placebo identical in packaging, labeling, schedule of administration, appearance, and taste.~Two crossover treatment periods (treatments 1 and 2) of 14 days each separated by 14 days washout, and follow-up. The active treatment will be a combination of umeclidinium/vilanterol 55/22 μg Ellipta given by inhalation once per day over 14 days. Matching placebo will be used as a control. Any ongoing hypertensive and cardiovascular medications (including beta-blockers if prescribed) will be kept stable throughout the study. All previous COPD medications except inhaled corticosteroids (if dose stable for at least 30 days) will be withdrawn. Patients will be given salbutamol as rescue medication throughout the study and the respective study drugs in the treatment phases.~All adverse effects (AEs) spontaneously referred to either by the patients or during the visits will be registered and notified. All AEs will be collected, including those that are not considered associated with the study treatment.~All clinical information will be anonymously recorded in an e-CRF system programmed using in-house resources.~Any abnormal result of the study variables that the investigator considers clinically significant and require adjustments or transient or permanent interruption of treatment or any type of intervention or diagnostic evaluation to assess the associated risk for the patient will be collected as an adverse event and should be investigated and monitored adequately.~During the study, cardiac parameters will be determined by exercise echocardiography and MRI and assessed by experienced cardiologists (with cardiac MRI experience) blinded to all clinical and trial-related data.~Lung function will be assessed using constant-volume body plethysmography and spirometry in accordance with the American Thoracic Society and European Respiratory Society standards.~Patients will undergo a symptom-limited bicycle-exercise test at 30⁰ lateral decubitus in a dedicated ergometer (Easystress, Ecogito Medical SPRL, Liege, Belgium). Workrate will be initiated at 25 W and increased by 15 W every 3 min. The gas exchange will be simultaneously analyzed breath-by-breath (Ergostik, Geratherm, Germany). Doppler-derived stroke volume, systolic ejection period, and left ventricular outflow tract, at a specific point from the aortic valve, will be measured as recommended. The LV outflow tract cross-sectional area will be assumed constant so that the change in SV will be determined by the change in the outflow tract time-velocity integral as measured by pulsed-wave Doppler. We have recently validated the Doppler-derived method for measuring SV during exercise.~Baseline LV volumes and ejection fraction will be measured using the biplane Simpson's method. In addition, color-Doppler M-mode images will be acquired at baseline and during all exercise phases both for the ejection and diastolic phases at the outflow and inflow tract locations, respectively. These recordings have been validated both in clinical and preclinical studies as robust and load-independent indices of global LV systolic chamber function and diastolic suction, respectively. Furthermore, the ejection intraventricular pressure difference (EIVPD) is a simple but very sensitive method to detect subtle changes in LV systolic function, undetectable by other conventional methods.~Because frequently patients do not reach the anaerobic threshold during exercise echocardiography (decubitus…), a separate maximal ergospirometry on a cycle ergometer will be performed to measure peak exercise capacity. The cycle ergometer (ER-900, Vyasis, Hochberg, Germany) exercise test will start with a period of quiet breathing for at least 3 min followed by unloaded pedaling for 3 min, thereafter an immediate increase in work rate to 10 W and then by further increments of 10 W every minute until symptom limitation during which breath by breath gas exchange ( i.e. VO2 and VCO2) (Oxycon-pro Vyasis, Hoechberg Germany) lactate threshold (if attained by the patient) maximum ventilation and heart-rate dyspnea, inspiratory capacity and exercise flow-volume loops (every 2 min) and HR recovery rate will be measured. Peak oxygen uptake will be defined as the greatest work rate that was maintained for ≥30 s at 50-70 rpm.~Patients will undergo a conventional cardiac MRI study (Philips Achieva 1.5 T) without gadolinium to assess the size of the left and right ventricles. In addition, phase-contrast studies will be obtained to address cardiac output and flow characteristics at the level of the aorta and the main pulmonary artery, as previously described.~Patient reported outcomes will be assessed using the COPD assessment test (CAT) to measure health status and the transition dyspnea index to measure dyspnea.~External data monitorization and Adverse Event Reporting shall be contracted to an independent CRO, following current standards of clinical investigation~Primary objective:~To address the effect (compared with placebo) of umeclidinium/vilanterol 55/22 μg on the increase in exercise stroke volume (from baseline).~Secondary objectives:~To address the effect (compared with placebo) of umeclidinium/vilanterol 55/22 μg on the reduction of dynamic hyperinflation (from baseline).~To address the effect (compared with placebo) of umeclidinium/vilanterol 55/22 μg on resting cardiac function (from baseline).~To address the effect (compared with placebo) of umeclidinium/vilanterol 55/22 μg on PROMs (patient-reported outcomes measurement) from baseline. | Double-blind, randomized, two-period crossover, placebo-controlled, single-center study, to determine the effect of umeclidinium/vilanterol 55/22 μg compared with placebo on the increase in left systolic chamber function during exercise in patients with COPD, lung hyperinflation and mild to moderate left ventricular dysfunction. |
This study is a 1:1 randomized controlled trial with an intervention for 18 months and a follow up period of 12 months.~The study will explore if treatment with recombinant human parathyroid hormone (PTH) improves bone turnover and bone mineral density (BMD), and thereby prevents the high risk of fracture in patients with chronic kidney disease (CKD).~Disturbed bone metabolism is related to increased risk of cardiovascular disease in patients with CKD. This study also wishes to examine of treatment with recombinant PTH improves cardiovascular parameters. | This study is a 1:1 randomized controlled trial with an intervention for 18 months and a follow up period of 12 months. The purpose of the study is to assess the safety and efficacy of recombinant human parathyroid hormone for treatment of adynamic bone disorder in patients with chronic kidney disease. |
Background:~Depression and the common anxiety disorders are highly prevalent and associated with disability and reduced quality of life. There is reason to believe that the majority of these patients are found in primary care. Official Swedish guidelines dictate that primary care clinics are responsible for treating mild to moderate cases, but access to treatment is limited. Transdiagnostic psychological interventions have been found to be efficacious for anxiety and mood disorders, and require a relatively rudimentary pre-treatment assessment. A large-group transdiagnostic course based on cognitive-behavioral principles may constitute an effective use of limited resources to improve access to treatment, and offer a sufficiently effective intervention, for most primary care patients with mild to moderate mental health problems.~Aim:~To investigate the feasibility and preliminary efficacy of a large-group transdiagnostic intervention for depression and clinically significant anxiety in Swedish primary care.~Design:~This is a prospective single-group feasibility study where 68 adults with clinically significant symptoms of depression or anxiety, and up to 25 adults with subclinical symptoms, are recruited from Liljeholmen primary care clinic, Stockholm, and offered 6 weekly structured transdiagnostic large-group course sessions which focus on evidence-based strategies to reduce psychiatric symptoms and increase wellbeing. If necessary, due to the covid-19 pandemic, the course will be held online. The primary outcome is patient satisfaction. Secondary outcomes include within-group effects on psychiatric symptoms (response rates), adherence rates, need for additional treatment, and adverse events. | This study investigates the feasibility of a transdiagnostic course that is intended to work for a large variety of patient groups with clinically significant depression or anxiety in primary care. This is a prospective single-group study where 68 adults with clinically significant symptoms of depression or general anxiety, and up to 25 adults with subclinical symptoms, attend up to 6 weekly structured large-group course sessions which focus on evidence-based strategies to reduce psychiatric symptoms and increase wellbeing. If necessary, due to the covid-19 pandemic, the course will be held online. |
This open-label clinical trial will explore the safety and potential efficacy of peripheral blood derived autologous CD34+ cells for the repair of COVID-19 induced pulmonary damage in adults. Eligible subjects will receive a single administration of CLBS119. | This clinical trial will explore the safety and potential efficacy of CLBS119 for the repair of COVID-19 induced pulmonary damage in adults. |
T2D is a condition that combines insulin resistance and relative insulin deficiency. The T2D naturally progresses towards an increasingly pronounced insulin deficiency that leads to the need for pancreatic replacement, by administering insulin.~Type 1 diabetes (T1D) requires a complete and immediate substitution of pancreatic insulin secretion. Currently, patients need to be involved in managing their disease by deciding how much insulin to administer based on the results of glucose monitoring. Artificial intelligence, thanks to a self-learning algorithm, enables the automation and customization of insulin administration. These devices, known as closed loops, bring real benefit to the patients included in the studies, by improving glycemic balance, by decreasing the number of hypo- and hyperglycemia but also by decreasing the mental load associated with the disease, improving their quality of life.~These very significant benefits in the T1D treatment open the possibility of obtaining similar benefits in the T2D treated by the basal-bolus type insulin regimen. This study aims to develop a specific algorithm of T2D to meet its particular characteristics.~The objective of this study is to collect the evolution of blood glucose levels in T2D patients under different conditions of their daily life: physical activity, meals, sleep, etc. This data will be used to develop a test bench to evaluate insulin delivery algorithms to treat patients with insulin-resistant T2D using a closed loop. | The objective of this study is to collect the evolution of blood glucose levels in type 2 diabetes (T2D) patients under different conditions of their daily life: physical activity, meals, sleep, etc. This data will be used to develop a test bench to evaluate insulin delivery algorithms to treat patients with insulin-resistant T2D using a closed loop. |
This is a prospective, open label, single arm, multi-centre phase II trial aiming to evaluate the safety and efficacy of Enasidenib (investigational product) as prophylactic consolidation in patients with IDH2-mutated MDS, CMML and AML in remission after allo-SCT.~Study Design:~interventional~prospective, open-label, single arm, multicenter phase-II trial~total patients sample size: 50 patients~number of trial sites: 11 all located in Germany and members of the EBMT~Patients with AML, MDS and CMML, in whom an IDH2 mutation has been detected at diagnosis prior allo-SCT, are eligible for consolidation therapy, if they are in complete hematological remission after first allo-SCT. IDH2 mutation might be absent at this time (CRMRDnegative), or might be detectable at submicroscopical levels (CRMRDpositive) given the high sensitivity of detection methods nowadays available. Remission will be evaluated within a screening period between day +25 and day +35. Evaluation of remission will be performed locally with IDH2 mutation analysis performed at an experienced local laboratory of the respective center. The report about IDH2 mutation testing at diagnosis has to be sent to the principle investigator for review at screening to include the patient; a BM sample will be stored for central retesting, which will be performed in batch during the course of the study. Having a documented hematological CR, patients will enter the treatment phase within 30 days after this BM evaluation (latest time point day +65) and start treatment with Enasidenib. They are envisaged to receive Enasidenib (100 mg per day, day 1-28) for up to 12 cycles (=12 months). Patients will go off protocol prematurely in case of relapse, intolerability of study treatment and in case of withdrawal of consent. In those patients who relapse during study treatment subsequent therapy for relapse will be performed according to the choice of the individual treating physician. Patients who finish study as planned or prematurely will be regularly followed for one year, lost to follow up, death or withdrawal of consent. | This is a prospective, open label, single arm, multi-centre phase II trial aiming to evaluate the safety and efficacy of Enasidenib (investigational product) as prophylactic consolidation in patients with IDH2-mutated MDS, CMML and AML in remission after allo-SCT. |
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