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This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with concurrent chemotherapy and anti-EGFR monoclonal antibody in locally advanced nasopharyngeal carcinoma with induced chemotherapy resistance.~Eligibility criteria include histologically confirmed locally advanced NPC according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count (white blood cell counts ≥4×1012/L, hemoglobin level ≥100g/L and platelet counts ≥100×1012/L), normal hepatic function (total bilirubin level ≤1.5 mg/dl, alanine aminotransferase and aspartate aminotransferase levels ≤1.5 times the upper limit of normal) and normal renal function (creatinine ≤ 1.5 times the upper limit of normal).~Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to anti-EGFR monoclonal antibody; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement.~The full-set pretreatment evaluation will be performed to every patient.All patients in this study will receive intensity-modulated radiation therapy (IMRT).~In the induction chemotherapy phase, TP regimen (Docetaxel 75mg/m2, D1 + DDP 25mg/m2, D1-3, repeat every 3 weeks) or GP regimen (Gemcitabine 1.0g/m2, D1, 8 + DDP 25mg/m2 , D1-3, repeat every 3 weeks) will be used. Cetuximab 400mg/m2 will be used one week before radiotherapy and 250mg/m2/week during IMRT, or nimotuzumab 200mg/week; meanwhile, cisplatin 80mg/m2 will be used every 3 weeks.~Adverse events (AEs) will be evaluated every week during CCRT based on the evaluation criteria of adverse reactions of CTCAE V4.0. Tumor response is assessed at the end of CCRT according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. Radiation-related acute and late toxicities are graded according to the Radiation Therapy Oncology Group (RTOG). Late toxicities are evaluated beyond three months from the end of radiotherapy.~After the completion of CCRT, all patients will be followed up every 3 months during the first years, every 6 months for the following 2-5 years, and annually thereafter. Local recurrence is confirmed by nasopharynx MRI or histological biopsy. Regional recurrence is confirmed by fine needle aspiration or surgical biopsy. Distant metastases is detected by imaging examinations including PETCT, bone Emission Computed Tomography (ECT), CT, MRI or confirmed by histological confirmation of biopsy.~The primary endpoints of this study is adverse events (AE) rate and progression-free survival (PFS). PFS is calculated from the date of enrollment to the date of disease progression or the date of death for any cause. | This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with concurrent chemotherapy and anti-EGFR monoclonal antibody in locally advanced nasopharyngeal carcinoma with induced chemotherapy resistance.~Eligibility criteria include histologically confirmed locally advanced NPC according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count, normal hepatic function and normal renal function.~Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to anti-EGFR monoclonal antibody; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement.~The full-set pretreatment evaluation will be performed to every patient. All patients in this study will receive intensity-modulated radiation therapy (IMRT). The primary endpoints of this study is progression-free survival (PFS) and adverse events (AE) rate. |
This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with concurrent chemotherapy and anti-EGFR monoclonal antibody in locally advanced oropharyngeal carcinoma (OPC) with induced chemotherapy resistance.~Eligibility criteria include histologically confirmed locally advanced OPC with induced chemotherapy resistance according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count (white blood cell counts ≥4×1012/L, hemoglobin level ≥100g/L and platelet counts ≥100×1012/L), normal hepatic function (total bilirubin level ≤1.5 mg/dl, alanine aminotransferase and aspartate aminotransferase levels ≤1.5 times the upper limit of normal) and normal renal function (creatinine ≤ 1.5 times the upper limit of normal). Prior induction chemotherapy with platinum was allowed.~Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to anti-EGFR monoclonal antibody; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement.~The full-set pretreatment evaluation will be performed to every patient.All patients in this study will receive intensity-modulated radiation therapy (IMRT). In the induction chemotherapy phase, TP regimen (Docetaxel 75mg/m2, D1 + DDP 25mg/m2, D1-3, repeat every 3 weeks) or TPF regimen (Docetaxel 75mg/m2, D1 + DDP 25mg/m2, D1-3+5-FU 750mg/m2, CIV, 120h, repeat every 3 weeks) will be used. Cetuximab 400mg/m2 will be used one week before radiotherapy and 250mg/m2/week during IMRT, or nimotuzumab 200mg/week; meanwhile, cisplatin 80mg/m2 will be used every 3 weeks.~Adverse events (AEs) will be evaluated every week during CCRT based on the evaluation criteria of adverse reactions of CTCAE V4.0. Tumor response is assessed at the end of CCRT according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. Radiation-related acute and late toxicities are graded according to the Radiation Therapy Oncology Group (RTOG). Late toxicities are evaluated beyond three months from the end of radiotherapy.~After the completion of CCRT, all patients will be followed up every 3 months during the first years, every 6 months for the following 2-5 years, and annually thereafter. Local recurrence is confirmed by oropharyngeal MRI or histological biopsy. Regional recurrence is confirmed by fine needle aspiration or surgical biopsy. Distant metastases is detected by imaging examinations including PETCT, bone Emission Computed Tomography (ECT), CT, MRI or confirmed by histological confirmation of biopsy.~The primary endpoints of this study is adverse events (AE) rate and progression-free survival (PFS). PFS is calculated from the date of enrollment to the date of disease progression or the date of death for any cause. | This study is a prospective phase II trial which is designed to evaluate the efficacy and safety of IMRT combined with concurrent chemotherapy and anti-EGFR monoclonal antibody in locally advanced oropharyngeal carcinoma (OPC) with induced chemotherapy resistance.~Eligibility criteria include histologically confirmed locally advanced OPC according to the American Joint Committee on Cancer (AJCC) Staging System (the eighth edition); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1; normal complete blood count, normal hepatic function and normal renal function. Prior induction chemotherapy with platinum was allowed.~Exclusion criteria include previous radiotherapy, a history of any other type of malignancy; pregnancy or lactation; allergy to anti-EGFR monoclonal antibody; obvious dysfunction of liver, renal, cardiac or lung function; uncontrolled infection; systemic metastasis or distant metastasis; patients with severe gastrointestinal diseases, and patients with mental disorders affecting patient participation in trial judgement.~The full-set pretreatment evaluation will be performed to every patient. All patients in this study will receive intensity-modulated radiation therapy (IMRT). The primary endpoints of this study is progression-free survival (PFS) and adverse events (AE) rate. |
This is a single-arm prospective observational study aiming to explore the safety and efficacy of switching from direct oral anticoagulants (DOAC) to low molecular weight heparin (LMWH) in cancer patients with atrial fibrillation (AF) during antineoplastic therapy or for a maximum time period of 6 months.~AF is the most common sustained arrhythmia; it affects 1.5% to 2% of the general population, and this prevalence increases to 10% at 80 years of age and to 18% at 85 years of age. Given the increasing occurrence of malignancies in the elderly and the coexistence of other conditions predisposing to AF in cancer patients, an association between those 2 conditions would be expected. A study including 24,125 patients estimated a prevalence of AF of 2.4% at the time of cancer diagnosis. A recent prospective study of 34,691 middle-aged women without AF or cancer at baseline showed that new-onset AF was a risk marker of subsequent diagnosis of cancer (HR 1.48, 95% CI 1.25 to 1.75; p <0.001).~Moreover, patients with cancer are at significantly higher risk of developing venous thromboembolism (VTE) which sometimes may precede the diagnosis of the malignancy. The risk is even higher when the patient is poorly mobilized or hospitalized. On the other hand, some anticancer therapies and especially the novel angiogenesis inhibitors are associated with increased thrombogenicity.~According to current Guidelines, DOACs are preferred over vitamin K antagonist (VKA) therapy and LMWH in both AF and VTE in the general population. However, in the presence of active cancer the administration of LMWH is advised for patients who are hospitalized for any reason and/or receiving chemotherapy, unless there is a high bleeding risk. LMWH has more favorable outcomes in cancer patients than VKAs, both in the setting of primary or secondary thromboembolic prophylaxis while extended anticoagulation (beyond the first 6 months) may be considered for an indefinite period or until the cancer is cured. This is possibly related with the fact that LMWH present antitumour and antimetastatic effects and confer an increased survival benefit. It should be noted that currently there is no conclusive evidence regarding the safety and efficacy of DOACs in cancer patients and the first results seem contradictory.~A number of recent studies with the use of DOACs in cancer-associated venous thromboembolism have demonstrated that these drugs are effective with similar rates of recurrent VTE but higher rates of major bleeding compared to LMWH. However, there are particular disadvantages, especially during the period of chemotherapy, such as interactions between these agents and anticancer therapies (eg, potential interactions between DOACs and azole-antimycotic agents), as well as unknown pharmacokinetics from chemotherapy-related vomiting.~Putting things together, many patients who are under a DOAC due to AF or previous VTE/pulmonary embolism (PE) may be diagnosed with cancer. Moreover, the risk of VTE is 6-fold higher on intravenous chemotherapy. For this reason, current clinical practice suggests that LMWH is continued during treatment with intravenous chemotherapy. However, data on the efficacy and safety of this common approach is lacking. This is important, especially in the setting of gastrointestinal tumors (especially gastric and pancreatic disease) which pose a high bleeding risk and especially during the chemotherapy active period. | The primary objective is to assess the safety and efficacy of switching from direct oral anticoagulants to low molecular weight heparin in cancer patients during antineoplastic therapy |
Introduction: Refractory glaucoma is a complicated type of glaucoma difficult to be treated. This type is characterized by high IOP with a high resistance to be reduced by traditional medical or surgical therapy. Shunt surgery improve trabeculectomy poor long term outcomes in refractory glaucoma.1 AGV, a shunt device, is used either from the start or after conventional procedures failure in refractory glaucoma. It helps the aqueous humour flow direct in the silicone tube.2 AGV is effective in reducing the postoperative hypotony commonly seen in non valved implants however the presence of persistent hypotony is still a problem after AGV.3 Persistent hypotony after AGV is caused by over-priming the tube and excessive manipulation of the valve housing that may damage the valve mechanism, the outflow of aqueous humour around the silicone tube immediately post-operatorive after the utilization of a 22 or 23G needle in creation of the sclerostomy and ciliary body function failure post-surgery in complicated eyes in which AGV is used. 4-5 closure of the tube by ligation or stenting may be needed when postoperative ocular hypotony occurs. 6 Enough and expected outflow control may not be induced by ligation of the tube at a focal area. 7 postoperative ocular hypotony could be managed effectively by Ab interno tube stenting. 8-10 Patients and Methods: Thirty eyes with refractory glaucoma were included in randomized controlled clinical trial. Patients aged from 44 to 56 years old. Despite of tolerated medication after previous trabeculectomy surgery, those patients had high intraocular pressure (IOP). Approval of institutional research board committee was taken. Two groups were studied; AGV with intraluminal stenting group (n=15 eyes) and AGV with external ligation group (n=15 eyes). Follow- up to one year after the surgery was done. The primary outcome was Intraocular pressure (IOP) and its association with the number of postoperative glaucoma medications. IOP ≤ 21 mmHg without medications announced complete success while IOP ≤ 21 mmHg with medications indicated qualified success. IOP of <6 mmHg defined hypotony. All patients preoperatively were subjected to IOP measurement using Goldman applanation tonometer, visual acuity assessment (VA) using Snellen E chart, visual field analysis (VF) by Humphrey visual field analyzer, Angle examination by goniolens, optic disc examination by Volk+90 lens, sit lamp examination for assessment of corneal clarity and any corneal touch with the tube and anterior chamber depth. All patients had peribulbar anaesthesia. Operative technique: in group I, incision of superior-temporal conjunctiva was carried out, appropriate cauterization and approximately at 10 mm posterior to the corneal limbus, the valve body plate was placed. Forceps was used to insert A 7-0 prolene thread into the tube lumen; the prolene 7-0 thread was cut with scissors making it along the tube length to remove it when needed. (Figure 2) In group II, the same as in group I but 8-0 vicryl was used to ligate the tube with the underlying sclera in addition to usage of two interrupted prolene 7-0 sutures applied 2mm apart over the tube itself to make partial occlusion and then entered into the anterior chamber. (Figure 3) Postoperative treatment with combined antibiotic and steroid eye drops every four hours in the first week followed by 2 weeks gradual tapering. IOP, VA, VF, optic disc examination by Volk+90 lens, slit lamp examination were the follow-up parameters. Failure was considered if the patient needed to implant removal, added glaucoma surgery, or developed phthisis bulbi.~Statistical analysis: Data were statistically analyzed by SPSS version 22(SPSS Inc., Chicago, IL, USA). Non-paired t test and Mann-Whitney were applied to quantitative variables. Fisher's exact test was applied to qualitative variables. Correlation was used to assess strength and direction of association. Less than 0.05 P value was set to be significant.~Data Availability Statement:The data used to support the findings of this study are included within the article.~Compliance with Ethical Standards Funding Statement: None Conflicts of Interest: The author declares that there he has no conflict of interest regarding the publication of this paper.~Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.~Informed consent: Informed consent was obtained from all individual participants included in the study. | Objectives: To compare the intraluminal stenting and external ligation of Ahmed Glaucoma Valve (AGV) regarding refractory glaucoma management and postoperative hypotony prevention.~Patients and Methods: This randomized clinical trial included 30 eyes of 25 patients (age range: 44-56 y) with refractory glaucoma. This study was conducted during the period from September 2018 to January 2020. The study included two groups, AGV with intraluminal stenting group (n=15) and AGV with external ligation group (n=15). Follow up continued to a year post operation. The primary outcome was Intraocular pressure (IOP) and its association with the number of postoperative glaucoma medications. IOP ≤ 21 mmHg without medications announced complete success while IOP ≤ 21 mmHg with medications indicated qualified success. IOP of <6 mmHg defined hypotony.~Key Words: Stenting- ligation- Ahmed valve- Hypotony |
This is a two-part, multi-center, prospective longitudinal, exploratory study of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators and their impact in children with cystic fibrosis (CF) on endocrine growth factors and height, gastrointestinal function and gut microbiome, lung function and respiratory microbiome, liver and pancreatic function, sweat chloride, inflammatory markers, and bone health.~Total duration of the study is expected to be 6 years. Part A will be a prospective cross-sequential study to describe the natural history of hormonal growth factors in early childhood and assess the feasibility of additional measurements. In Part A, subjects will have up to 6 visits over a period of up to 3 years.~Part B will be a prospective longitudinal study to observe the effects of administration of either ivacaftor or elexacaftor/tezacaftor/ivacaftor (elex/tez/iva) on growth. In Part B, subjects will have one before ivacaftor or elex/tez/iva visit within 30 days before initiation of the therapy and five after ivacaftor or elex/tez/iva visits over a 24-month follow-up period. | This is a two-part, multi-center, prospective longitudinal, exploratory study of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators and their impact on children with cystic fibrosis (CF). |
The purpose of this study is to characterize patient pain and opioid use after an initial opioid prescription for acute pain. The investigators aim to enroll a total of 300 patients receiving a prescription for an opioid in primary and urgent care, inpatient care (child birth and total knee arthroplasty), and in the emergency department. Patients not currently using opioids who receive a new short-acting opioid prescription for acute pain will be recruited and followed prospectively for 180 days to assess pain trajectories, analgesic and non-pharmacologic treatment use, activity, and health care service use. The patient-centered health data sharing platform (Hugo) will be used to collect patient-reported outcomes and structured data from pharmacy and electronic health records patient portals as well as patient-generated data collected through personal digital devices (Fitbit).~Specific aims~To assess patients' pain and opioid use patterns in episodes of acute pain for which opioids were prescribed, characterizing pain severity and persistence, as well as other prescription and over-the-counter pain medication use~To examine associations between patient demographic, clinical and emotional characteristics and outcomes of pain severity and persistence, opioid and non-opioid treatment patterns, satisfaction with care, and barriers to care~To assess how patients handled unused opioids | This study will characterize patient pain and opioid use after an initial opioid prescription for acute pain. |
Migraine is a primary headache attack, specific, paroxysmal, with or without aura, with subjective manifestations both before and after the attack, a chronic type of headache with symptoms of recurrence, attacks at productive age and can cause a decrease in work productivity up to 80%, so that it will affect the quality of life, economic life and education globally which leads to losses for migraine sufferers and institutions where migraine sufferers attend school, work and in the lives of sufferers' families. With the high prevalence and disability rates for migraine sufferers, on the other hand, the right treatment for migraine has not yet been obtained to the maximum, it is necessary to deepen the treatment and prevention of migraine is needed, and until now there has been no definitive cure, both for prevention and treatment, so it is necessary to develop therapies that can provide more accurate relief for migraine sufferers. The purpose of this study is to assess the success in managing migraine in reducing the frequency of attacks, reducing the intensity of attacks and reducing the duration of attacks from weeks 0, 4 to 8 | Migraine is a primary headache attack, specific, paroxysmal, with or without aura, with subjective manifestations both before and after the attack, a chronic type of headache with symptoms of recurrence, attacks at productive age and can cause a decrease in work productivity up to 80%, so that it will affect the quality of life, economic life and education globally which leads to losses for migraine sufferers and institutions where migraine sufferers attend school, work and in the lives of sufferers' families. |
Rationale: Cancer cells express unique peptide antigens recognized by CD8+ cytotoxic T lymphocytes (CTL), which are typically 8-10 amino acids long and are presented in association with Class I MHC molecules. The peptides recognized by helper (CD4+) T-cells are presented in association with Class II MHC molecules and are usually longer (13-18 amino acids in length), although peptide elution studies have indicated no apparent restriction on peptide length. Selected peptides can induce circulating T cell responses in most patients, and that vaccination with a mixture of peptides is immunogenic in up to 100% of patients. The magnitude of T cell responses sometimes is substantial, with 1-5% of circulating CD8 T cells reactive to single antigens. T cell responses to vaccines may be durable for months or years, but are at least as likely to be transient, sometimes declining even while still receiving vaccines. However, T cells induced by vaccination can recognize and lyse cancerous cells expressing the relevant protein and MHC, and peptide vaccines induce promising immunogenicity.~Though MHC-restriction of individual peptides limits their use to a subset of patients, there are mixtures of a dozen peptides restricted by HLA-A1, A2, A3, or A11 can be prepared as a stable mixture and can induce immune responses in 85% of patients with cancer who express one or more of those MHC molecules, without negative effects from competition among the peptides. Other experience supports the ability to induce T cell responses to multiple peptides when vaccinating with peptide mixtures. Since antigenic peptides are easily degraded by proteases in the body, it is difficult for the receptors expressed on the immune cells to identify antigen epitopes, and they do not generate a strong immune response to pathogens. An epitope-based vaccine with a reasonable design is composed of epitope peptide/s, a delivery system, and an adjuvant. For multi-epitope vaccines, since the traditional carriers and adjuvants are associated with poor efficacy, vaccine designs with built-in adjuvants have been proposed. Therefore, a built-in adjuvant exhibiting both the functions of a transmission system and a traditional adjuvant, is constructed within the vaccine to improve the immunogenicity of epitope peptides by stimulating the innate immune response required for an adaptive immune response. To achieve this goal, the epitopes are regularly fused with adjuvant proteins or displayed on the surface of some particular biomaterials (e.g., liposomes, gold nanoparticles, and poly(lactic-co-glycolic acid) (PLGA)) and the immunogenicity of the epitopes are significantly increased by this immune complex.~Study design: This research is a pilot clinical trial using a personalized neoantigen peptide vaccine. Approximately 100 patients with cancer and whose sequencing studies show the presence of neoantigens will receive the personalized multi-peptide vaccine. Peptide vaccines will be given with an adjuvant (Montanide ISA-51 VG) by intradermal injection (~0.5 mg of each peptide) in the arm every week for a maximum of 8 weeks; the treatment will be discontinued if disease progresses or if there is deterioration of the patient's general condition. All patients will give written informed consent; their data will be coded and fully anonymized. The study was approved by the Ethics Committee of the Regenerative Medicine Institute and conformed to the ethical guidelines of the Declaration of Helsinki. | This research is a pilot clinical trial using personalized neoantigen peptide vaccines with an adjuvant (Montanide ISA-51 VG), in patients with different types of cancer |
Kawasaki disease is the most common systemic vasculitis in children. Coronary artery aneurysms may develop in 20-25% of untreated patients. Intravenous immune globulin (IVIG) can reduce coronary-artery aneurysms to 3-5%. Numerous studies and clinical trials had pointed out that corticosteroid treatment (pulse therapy or not) could lower the incidence of coronary artery abnormality in high-risk KD patients. However, the therapeutic effect of corticosteroid in KD patients with aneurysm formation after acute stage was never mentioned. There is no effective treatment for aneurysm formation available in KD after acute stage. Methylprednisolone pulse therapy (MP pulse) was used for treatment of KD during acute stage since more than 20 years ago. MP pulse plus IVIG seems not benefit for KD patients but benefit for IVIG resistant KD patients or for high-risk group of CAL formation/ IVIG resistance group. MP pulse therapy is well document used in autoimmune disease vasculitis such as SLE, rheumatoid arthritis, dermatomyosis...etc. Taking together, MP pulse is effective and safe for KD patients during acute stage. In this study, the investigators plan to use MP pulse in KD patients with CAL or aneurysm formation beyond acute stage to investigate the role of vasculitis of KD or regression of dilatation.~Methods: The investigators conducted a prospective study of methylprednisolone pulse therapy (MP pulse) for KD patients with coronary aneurysm or dilatation formation. The investigators will enroll these patients to receive methylprednisolone pulse (MP pulse, 30mg/kg, Max:1g/day for continue 3 days) for treatment. Together with other anti-inflammatory oral medicine including monteleukast, Dextromethorphan(DXM), prednisolone, and ketotifen as supplementary treatment.~The specific aim of this study is the regression of coronary artery aneurysm after MP pulse therapy.~Under the hypothesis and specific aim, the investigators plan to do in the following 3 years:~During the 1st year, the investigators will enroll for 5-10 cases for safety surveys including blood pressure monitoring, inflammatory markers, liver function, renal function, electrolyte imbalance, growth problems as Phase I study.~In the 2nd and 3rd year of this study, the investigators will enroll for 20-30 cases for an effective survey as Phase II study.~Results from this study will help clinicians to treat aneurysm formation or coronary artery dilatation in KD patients and reduce the activity limitation of patients, reduce the medical resource in those patients. The investigators may provide the first treatment for aneurysm in KD. | In this study, the investigator plan to prescribe Methylprednisolone pulse therapy in Kawasaki disease patients with coronary artery lesions or aneurysm formation beyond acute stage to investigate the role for vasculitis of KD or regression of dilatation. |
A randomized, controlled, single-center, exploratory clinical research method was used. In the treatment plan, the experimental group used basic treatment + Huperzine A, and the control group only used basic treatment, with a total of 20 cases. To evaluate the effectiveness and safety of Huperzine A injection in the treatment of brain injury in patients with hypertensive cerebral hemorrhage. | To evaluate the effectiveness of Huperzine A injection in the treatment of brain injury in patients with hypertensive cerebral hemorrhage；~To evaluate the safety of Huperzine A injection in the treatment of brain injury in patients with hypertensive cerebral hemorrhage。 |
Anemia in newborn babies is defined as the mean of hemoglobin values according to postnatal age is below 2 standard deviations. Disruption in tissue perfusion and oxygenation, hyperdynamic cardiac failure, increase in need of oxygen, increase in respiratory effort, inability to be separated from mechanical ventilation, failure to thrive, paleness, increase in frequency of morbidities of prematurity (necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage, etc.) may be seen as a result of progressive anemia. When critical hemoglobin values are reached in premature newborn babies with concomitant disruption of tissue oxygenation, transfusion is performed with erythrocyte suspensions. The main goal here is to correct impaired tissue oxygenation, provide perfusion in sufficient quantity, and prevent anemia-related morbidities. Although frequently applied, there is no consensus in our country and in the world regarding threshold hemoglobin values and supporting parameters for transfusions. As a result, there are no guidelines prepared for newborns based on evidence with clearly defined borders and accepted by everyone. Many countries and centers implement different transfusion protocols based on their experience. Given the risk of oxygen radical damage and associated diseases as a result of erythrocyte transfusions (infections, bone marrow suppression, necrotizing enterocolitis, retinopathy of prematurity, etc.), there is a need to develop new methods for taking and supporting transfusion decision, and to prepare more objective and more accepted guidelines. The origin of our study is the subsequent protective compensation mechanisms after deterioration in brain oxygenation due to symptomatic anemia in premature newborn babies. For these reasons, it is aimed to examine the changes in brain blood supply and oxygenation in neonatal premature babies who have anemia and who underwent erythrocyte suspension transfusion in the light of original guidelines by means of obtaining measurements with the help of cranial doppler ultrasonography and near-infrared spectroscopy. | It is aimed in this study to examine the changes in brain blood supply and oxygenation in neonatal premature babies who have anemia and who underwent erythrocyte suspension transfusion in the light of original guidelines by means of obtaining measurements with the help of cranial doppler ultrasonography and near-infrared spectroscopy. |
Autism spectrum Disorder is a complex neuro- developmental, incurable disease with lifelong impacts.Epidemiological studies have shown a rapid increase in the prevalence of ASD throughout the world including Bangladesh. The World Health Organization (WHO) estimated every 1 in 160 children has an autism spectrum disorder. Various environmental, genetic ,biochemical, metabolic factors are presumed to be involved in the etiology of ASD. Researchers found Vitamin B6 with Magnesium has the potential effects to alleviate the core symptoms of autism. A possible association higher doses of vitamin B6-Magnesium supplementation may reduce biochemical abnormalities e.g. reduction of urinary excretion of homovanillic acid and improve neurobehavioral symptoms.Therefore the present study has been designed to assess the effects of high dose of vitamin B6 with magnesium along with standard care of treatment upon ASD patients. The study would be randomized, double blind placebo controlled trial to be conducted in the Department of Pharmacology and the Institute of Pediatric Neurodisoder and Autism(IPNA), BSMMU in between July 2019 to July 2020. A total 66 newly diagnosed ASD patients will be selected according to inclusion and exclusion criteria. The patients will be divided randomly into 2 groups: intervention and control. Intervention group would consist of 33 patients who wlill receive high dose of vitamin B6 with magnesium orally for three months. Vitamin B6 will be given 50 mg for 2- 3 years, 200 mg for ages 4-6 years, 300 mg for ages 7-8 years and Magnesium will be given 50 mg for 2-3 years, 100 mg for ages 4-8 years. Control group would also consist of 33 patients who will receive placebo in the same manners along with standard care of treatment for three months. Comparison between the two groups will be performed through urinary homovanillic acid estimation at baseline and three months after the intervention. Neurobehavioral status will be assess by Autism Diagnostic Checklist (ADCL) at baseline and after three months of intervention. Data would be analyzed by Scientific Package for Social Science and represented by tables and figures as applicable. Significance level would be set at 0.05, 0.01 and 0.001. Patients data will be recorded in a predetermined data sheet. Parents of the patient will be informed about the study in easy language and then written informed consent will be taken.This study has no potential risk to the patients. | Title:~The Neurobehavioral and Biochemical Effects of High Does of Vitamin B6 with Magnesium in Children with Autism spectrum Disorder: A Randomized, Double-Blind, Placebo Controlled Study.~Purpose of the Study:~This study aims to examine the effect of higher doses of vitamin B6-magnesium combination in modification of urinary homovanillic acid excretion and improving behavioral sign symptoms in a newly diagnosed autistic children.~Method:~This study will be a randomized,double blind placebo controlled trial to assess the effects of high dose of vitamin B6 with magnesium upon autistic children. This study will be conducted in the Department of Pharmacology and Institute of Pediatric Neurodisorder and Autism (IPNA) in between July 2019 to July 2020. A total 66 newly diagnosed autistic children will be selected according to inclusion and exclusion criteria. The patients will be divided randomly into 2 groups: Intervention group and Control group. Intervention group will consist of 33 patients who will receive vitamin B6-magnesium along with standard care of treatment for three months. Vitamin B6 will be given 150 mg for ages 2-3 years, 200 mg for ages 4-6 years, 300 mg for ages 7-8 years and Magnesium will be given 50 mg 2-4 years, 100 mg for ages 4-8 years. Control group consist of 33 patients who will receive placebo in the same manners along with standard care of treatment for three months. To see the effects of Vitamin B6 and Magnesium, Autism Spectrum Disorder would be assessed by Autism Diagnostic Checklist (ADCL) at baseline and three months after intervention. Urinary homovanillic acid level would also be performed at baseline and three months after intervention.~Ethical consideration:~The study will follow the principles of the Declaration of Helsinki and of the World Medical Assembly. Parents of the patient will be informed about the study in easy language and then informed written consent will be taken. This study has no potential risk to the patients. Confidentiality will be strictly maintained. |
Osteoporosis is a common condition found in postmenopausal women. Osteoporosis increases the risk of fractures: especially hip and vertebral fractures. These fractures increase the risk of morbidity and mortality. Falls and movements that incorporate trunk flexion or rotation can increase the risk of fractures in women with osteoporosis. Weight-bearing exercise and posture training are important adjunctive therapies to help decrease the risk of fractures and improve the function of individuals with osteoporosis. Often in Rheumatology and osteoporosis clinics, participant's will be given handouts concerning posture and exercise to complete, with little follow-up of their progress or evaluation of their technique. In this study, investigators will determine if the addition a video-based exercise intervention with handouts and limited physical therapist instruction and monitoring help this population increase adoption of a regular exercise program designed to improve lower extremity strength and dynamic posture.~The purpose of this study is to determine if the addition of computer-based video instructions with handouts and limited physical therapist (PT) instruction helps adoption and performance of an intervention designed to improve strength, dynamic posture, and balance in individuals with osteoporosis (OP). Investigators will perform all measurements and interventions via web-based and telecommunication technology. Twenty-four participants will be recruited for this feasibility study using flyers posted in the Rheumatology and Osteoporosis clinics at the University of Alabama at Birmingham (UAB). The investigators, who help staff these clinics, will also alert other clinic physicians of this study via flyers designed for these health care professionals to help recruit study participants. The participants will consent to participate in this study. The UAB Institutional Review Board will approve this study.~After consenting, a physical therapist (PT), blind to group assignment, will perform outcome measurements. Outcome measurements will be assessed at baseline and within a week after the 12-week intervention is completed. Measurements include five-time sit-to-stand-to sit (5xSTS), 4-stage balance test, and a dynamic posture test. Participants will also complete a questionnaire that examines demographics, medical history, exercise and fall perceptions, and functional activity performance. The pre- and post-intervention questionnaires will be similar except the post-intervention questionnaire will not include demographic, medical history questions, and perceived readiness to exercise item. SurveyMonkey will be used to deliver and collect all questionnaire data. The post-intervention questionnaire will contain items assessing intervention satisfaction.~Prior to enrolling participants, investigators will develop a script and checklist for the PT performing the measurements to increase consistency of outcome measurement. The PT will also practice these measurements using Zoom and intra-rater reliability will be determined. Intra-rater reliability will also be assessed from the data collected. Finally, investigators will perform quality control by reviewing recordings of the measurement sessions.~After baseline measurements, participants will be randomly assigned to one of two groups: one group will receive handouts that provide program instructions with PT coaching (HO) or a group who receives the same instructional delivery plus links to web-based videos instructing all elements of the program intervention (HO+). Participants will be asked to perform moderate level exercise/posture activity 5 sessions/week for 35 to 40 minutes per day (duration of activity/session by the end of the intervention). By email, the HO+ group participants will receive handouts with links to access the safe exercise posture instruction, posture warm-up, balance exercise resistance exercise and marching. The HO group will also receive an email that with the same attachments minus the video links. In both groups, the first intervention instruction email will instruct the participants to not start the program until the intervention PT (not the same PT who performs the measurements) guides them through the program via a Zoom videoconference. In week two, the intervention PT will finish the initial instructions in another 60-minute session. The PT will meet with participants during the third week of the intervention for a 15-minute meeting and will continue to meet with participants for 15-minutes every two weeks thereafter via Zoom. During these 15-minute sessions, the intervention PT will help individuals progress exercises, monitor symptoms, answer questions, and make performance recommendations. All participants will be instructed to track their posture and exercise activity by using a monitoring log provided by the research group. These logs will be shared with the investigators.~Both groups will perform marching in place five times a week. Participants will be instructed to slowly progress to a goal of performing 30 minutes of marching in place per session. They will be instructed to lift their knees to a height that is between their waist and knee when marching. Participants will start performing at 5 minutes of marching twice a day. Every two weeks they will progress the goal of marching time by 5 minutes. They will march two times per day until they reach 20 minutes. At this time, they will march one time per day. They will be instructed to march between a rating of 10 -14 on the 20-point Borg scale for rate of perceived exertion. The intervention PT will help participants in both groups progress safely when she teleconferences with each participant every two weeks.~Posture training will be performed daily. The participants will be taught how to hold good posture with activity over two 60-minute sessions by the intervention PT. In the first visit, the intervention PT will discuss holding dynamic posture basics, finding and holding good posture in sitting and sit to stand. In the next visit, she will teach them how to progress to standing activities while holding good posture. The PT will instruct the participant to use the posture activities as a warm-up on all days of exercise. She will also encourage participants to incorporate these skills in daily activities.~The intervention PT will use scripts and checklists developed prior to participant enrollment to ensure consistency of instruction between participants. The intervention PT will practice instructing participants prior to participant enrollment via Zoom with other investigators. These sessions will be taped so that they can be reviewed and scripts and checklists refined.~Demographic, satisfaction data, perception items and scales will be analyzed using appropriate descriptive statistics. Descriptive statistics, such as means and standard deviations, will also be used to describe data from 5xSTS and balance tests. These tests will also be analyzed using Cohen d to determine effect size. To determine within and between group differences over time, mixed-factor ANOVAs will be used. Finally, a Wilcoxon-Signed Rank test will be used to determine differences between the groups for the dynamic posture test. | Osteoporosis is a common condition found in postmenopausal women. Osteoporosis increases the risk of fractures: especially hip and vertebral fractures. These fractures increase the risk of morbidity and mortality. Falls and movements that incorporate trunk flexion or rotation can increase the risk of fractures in women with osteoporosis. Weight-bearing exercise and posture training are important complementary therapies to help decrease the risk of fractures and improve the function of individuals with osteoporosis. Often in Rheumatology clinic, patient's will be given handouts concerning bone building exercises and tips on holding safe postures with activities to complete, with little follow-up of their progress or evaluation of their technique. In this study, we will compare a video-based exercise intervention with printed handout group to a handout only group and will evaluate the effectiveness of these two different modalities using physical activity measures and overall outcomes of strength and posture. |
Anserine bursitis is a common etiology of medial knee pain. It could be severe enough to limit the patient's functional abilities with affection of the quality of life. The etiology of AB is unknown. It could be bursitis, tendinitis or other unknown etiology.~The treatment of AB includes conservative and surgical treatment. Conservative treatment consists of non-pharmacologic treatment and pharmacologic treatment. Their aim is pain relieve, with subsequent improvement of function and quality of life. The non-pharmacologic treatment consisted of activity modification with avoidance of precipitating activities and physiotherapy. The pharmacologic treatment consists of non-steroidal anti-inflammatory drugs, analgesics whether oral as acetaminophen or topical preparations; or local soft tissue injection of corticosteroid. Surgical treatment is indicated after failure of conservative treatment in chronic severe and resistant cases only.~Local corticosteroid injection is a treatment for refractory chronic anserine bursitis. The mechanism of action of corticosteroid is the suppression of the inflammatory process associated with anserine bursitis. Subsequently, improvement of anserine bursitis takes place.~Neural prolotherapy is the subcutaneous perineural injection of isotonic dextrose 5% in water solution at the fascial penetration point of the sensory nerve where it reaches the subcutaneous plane and along its course. It can be used for the treatment of chronic anserine bursitis.~The mechanism of action of neural prolotherapy in anserine bursitis could be due to stimulation the release of a group of growth factors that enhance soft tissue healing in response to isotonic dextrose 5% in water solution injection. Subcutaneous injection of isotonic dextrose 5% in water solution was found to stimulate human cells to start proliferation, increase in cell protein and DNA synthesis. It stimulates the release of a group of growth factors as transforming growth factor-β and other growth factors. Another mechanism of neural prolotherapy is the treatment of neurogenic inflammation.~This study aimed to determine the efficacy of neural prolotherapy subcutaneous perineural injection versus corticosteroid local soft tissue injection therapy for relieving pain and improvement of function among patients with chronic anserine bursitis. | Anserine bursitis is a common etiology of medial knee pain. It could be severe enough to limit the patient's functional abilities with affection of the quality of life. The etiology of AB is unknown. It could be bursitis, tendinitis or other unknown etiology.~The treatment of AB includes conservative and surgical treatment. Conservative treatment consists of non-pharmacologic treatment and pharmacologic treatment. Local corticosteroid injection is a treatment for refractory chronic anserine bursitis.~Neural prolotherapy is the subcutaneous perineural injection of isotonic dextrose 5% in water solution at the fascial penetration point of the sensory nerve where it reaches the subcutaneous plane and along its course. It can be used for the treatment of chronic anserine bursitis.~This study aimed to determine the efficacy of neural prolotherapy subcutaneous perineural injection versus corticosteroid local soft tissue injection therapy for relieving pain and improvement of function among patients with chronic anserine bursitis. |
This is a multicentre, open-label, single-arm, phase I/II clinical study with a dose-escalation stage (part 1) and a dose-expansion stage (part 2). In part 1, patients with treatment-naïve, relapsed/refractory extranodal natural killer/T-cell lymphoma (nasal type) will be assigned to receive sequentially higher doses of liposomal mitoxantrone hydrochloride plus a standard dose of pegaspargase every 21 days (a cycle). The dose escalation initially will follow an accelerated titration design for the first two dosing groups, then follow a classic 3+3 design. All dose-escalation decisions will be based on the safety data generated from the currently highest dose group. The maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of liposomal mitoxantrone hydrochloride will be determined in part 1. In part 2, additional patients will be recruited into two groups,the treatment-naïve group and the relapsed or refractory group, to receive liposomal mitoxantrone hydrochloride at the RP2D combined with a standard dose of pegaspargase. All patients will receive the treatment until disease progression, or observation of unacceptable grade 3 drug-related adverse events (a maximum of 6 cycles). | This is a multicentre, open-label, single-arm, phase I/II clinical study to evaluate the safety, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with pegaspargase in patients with extranodal natural killer/T-cell lymphoma, nasal type (NKTCL). |
Endoscopic ultrasound (EUS) was used firstly in 1980s as a diagnostic imaging technique for pancreatic lesions. It has the ability to detect the histological layers of the gastrointestinal (GI) tract wall as well as the periluminal structures.~EUS has been used to perform FNA from lesions that are difficult to access by conventional methods. EUS has the advantage of using both ultrasound and endoscopy to give the exact diagnostic features of the GI tract. The use of EUS was not limited to visualization only, but also in obtaining tissue biopsy for diagnostic purpose through EUS guided fine needle aspiration (FNA), and it has played a major role in revolutionizing the diagnosis of focal hepatic lesions as it is a minimally invasive procedure.~Abdominal imaging [CT, magnetic resonance imaging (MRI), and transabdominal ultrasonography (USG)] are the diagnostic tests of choice to detect hepatic lesions suspicious of metastasis.Unfortunately, these modalities are limited in their ability to detect hepatic lesions less than 1 cm.~In addition, although rare, percutaneous FNA for suspected metastatic lesions carries the risk of implantation metastasis. Although unable to completely visualize the entirety of the liver, EUS can detect small hepatic lesions that may be otherwise missed by conventional imaging. EUS can delineate detailed anatomy of the liver from the trans-gastric and trans-duodenal routes with the exception of the right posterior segments.~The prospect to obtain precise, ultrasound-guided biopsies of possible metastatic liver lesions can drastically alter the therapeutic conduct.~This, combined with limited adverse events, makes EUS an excellent modality to allow staging in malignant conditions. Due to the vicinity of the transducer to the liver, EUS provides detailed images of the liver segments and its vascular structures.~Based on the premise that EUS is more sensitive for the detection of small hepatic lesions then CT/MRI, Singh et al. proved that EUS was superior to CT scan (98% vs 92%, respectively) in diagnostic accuracy in its ability to detect the number of metastatic lesions in the liver and correctly diagnose the nature of the lesions .(Singh P etal.,2009) Endoscopic ultrasonography (EUS) has become an indispensable method for diagnosis and therapeutic procedures in gastroenterology and as experience with this technique is growing, new indications for EUS continue to emerge.~(Saraireh HA .,2017) Furthermore, the use of on-site cytopathology interpretation has further improved the diagnostic yield of EUS-FNA by helping to ensure that the samples obtained are representative of the target organ and adequate for diagnostic purposes.~Objectives: To assess the feasibility of EUS in detection of occult small hepatic focal lesions at the time of primary tumor staging, not seen by CT or MRI~All the patients will be subjected to:~Thorough history talking including;~Age~Sex~Comorbidity~Clinical general and local abdominal examination~Abdominal US & CT abdomen~laboratory investigations:~complete blood count (CBC)~Prothombin time ,INR~Ceatinine , Urea~Albumin~ALT , AST~Virological test for HIV, HCV and HBV~CA-19-9 and alfa fetoproteins.~EUS will be done to all patients. During EUS examination the liver will be examined thoroughly to detect hepatic focal lesions with possible EUS-FNA of any detected lesions.~All EUS examination with be done by EUS linear array Echoendoscope, Pentax EG-3870UTK attached to Hitachi Avius US machine under Propofol deep sedation.~The collected data will be organized and statistically analyzed.~Data collection tool:~Data including study design, participant demographics, stage and type of pancreatic and GI malignancy will be extracted and recorded on electronic data collection sheet. Data will be pooled for various arms in trials: Individual data for each outcome were entered into the Comprehensive analysis. Pooled effects with 95%CI will be reported. Data will be analyzed separately for each arm. | Liver metastasis may not be detected by CT and MRI due to their small size while they can be detected by EUS. Also, EUS-FNA has a great impact in improving the diagnostic accuracy of EUS. Objectives: To assess the feasibility of EUS in the detection of occult small hepatic focal lesions at the time of primary tumor staging, not seen by CT or MRI. |
The primary outcome of the study is to assess the effect of waterpipe smoking on periodontal health, it will be assessed by questions about smoking habits, including smoking mode as well as duration (heads smoked per day) and extent of use (age of initiation and number of sessions per week) of waterpipe smoking.~A full periodontal examination using UNC-15 periodontal probe will be done for all of the participants measuring the CAL, Probing Depth (PD), plaque index (PI), bleeding on probing (BOP) and gingival recession depth (GD). In subjects where attachment loss will be clinically detected, radiographic examination will be performed by digital periapical radiograph to detect the amount of bone loss, then staging will be done according to the new classification by the aid of radiographic examination. | The main objective of the study is to assess the effect of waterpipe smoking on periodontal health, which will be done using a well constructed validated questionnaire. Then a full periodontal examination and x-ray evaluation will be done for all of the participants. |
Higher DFI is correlated with poor embryo development, lower implantation rate in intracytoplasmic sperm injection (ICSI) cycles and higher miscarriage rate.~The effectiveness of micro nutrients (PROfortil™) has been proven in improving sperm quality including sperm cell density, progressive motility and normal morphology.~This randomized controlled trial includes male from infertile couples treated at the Center for Reproductive Endocrinology and Infertility, Hue University hospital, Vietnam from November 2019 to November 2020.~The semen samples were collected from the husband after 3-5 days of abstinence and then evaluated for sperm motility, vitality, concentration and morphology by the guideline of World Health Organization (WHO) 2010.~Sperm DNA fragmentation (SDF) was measured using a sperm chromatin dispersion (SCD) test (Halosperm® kit, Halotech, Madrid, Spain). A total of 500 sperms were examined by only one highly trained technician to decrease variability. DFI was expressed as the percentage of sperms with small halo, without halo and degraded sperms over total of 500 sperms.~Any case with high DNA fragmentation index (DFI >=30%) will be randomized indicated for (group 1) micro nutrient supplement (PROfortil™, twice daily) plus Vitamin E (Enat 400, once per day) in 3 months and (group 2) only Vitamin E (Enat 400 once per day) then checked again post-treatment for (DFI).~The IVF/ICSI cycles will then be analyzed for embryo quality, pregnancy outcomes including biochemical pregnancy rate, clinical pregnancy rate, on-going pregnancy, miscarriage. | Male from infertile couples are tested for semen analysis and sperm DNA fragmentation. Any case with high DNA fragmentation index (DFI) will be randomized indicated for multi-micro nutrient supplement (PROfortil™) in 3 months and then checked again post-treatment for (DFI). The IVF/ICSI cycles will be analyzed for pregnancy outcomes |
Eligible breast cancer patients will receive hypofractionated radiotherapy of 5.2 Gy in 5 fractions within one week and a sequential tumor bed boost of 5.2 Gy in 2 fractions to the conserved breast. The dose is prescribed to ipsilateral chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk). All patients are treated with intensity modulated radiation therapy (IMRT) technique. The primary endpoint is ≥2 grade any acute radiation induced toxicity event. patients will be followed for at least 1 years to evaluate the acute and late radiation-induced toxicity, locoregional recurrence, over survival, distant metastasis, and quality of life.~Calculation of the required number of cases based on an alpha of 0.05 and a power of 80% with a maximal tolerable toxicity difference of 10% during and within 6 months after RNI comparing to conventional radiotherapy and lost rate of follow up of 10%. In total 197 patients are needed to be recruited. | The purpose of this trial is to investigate the toxicities and efficacy of hypofractionated regional nodal radiotherapy (RNI) for one week in breast cancer patients treated with mastectomy or breast conserving surgery. Hypofractionated radiotherapy will be delivered to chest wall or whole breast and regional lymph regions (including supraclavicular/infraclavicular region, internal mammary nodes, and any part of the axillary bed at risk). Eligible breast cancer patients will be followed for at least 1 years to evaluate the acute and late radiation-induced toxicities, locoregional recurrence, over survival, distant metastasis, and quality of life. |
Airflow limitation is common exist in idiopathic bronchiectasis patients. Our previous studies showed that FEV1<50% is one of the major risk factors for poor prognosis and high incidence of acute exacerbation in patients with bronchiectasis. However, there are few evidence on the treatment of bronchodilator in bronchiectasis with airflow limitation, and there is no recommendation in bronchiectasis guidelines. Moreover, because of the high risk of infection and bacterial colonization in bronchiectasis, there is still unclear whether inhaled corticosteroids or bronchodilators affect the parameters of bronchiectasis. Thus, there is urgent need to optimize the treatment of bronchiectasis with airflow limitation. | Airflow limitation is common exist in idiopathic bronchiectasis patients. However, there are few evidence on the treatment of bronchodilator in bronchiectasis with airflow limitation. The efficacy and safety of dual bronchodilator in idiopathic bronchiectasis with airflow limitation are still unclear. Thus, the investigators conduct a multicenter, open-label randomized controlled trial to investigate the efficacy and safety of dual bronchodilator in idiopathic bronchiectasis with airflow limitation. |
The purpose of this study is to provide continued use of parsaclisib as monotherapy or in combination with itacitinib, ruxolitinib, or ibrutinib to participants who are currently enrolled in an Incyte-sponsored study and receiving the same treatment, who have at least stable disease, who are obtaining clinical benefit (in the opinion of the investigator) on the current study treatment, as defined by the parent Protocol, and who are unable to access parsaclisib as monotherapy or in combination with itacitinib, ruxolitinib, or ibrutinib outside a clinical study. Participants will continue on the same dose and schedule as the ones being administered in the Incyte-sponsored parent Protocol at the time of the rollover. The study will collect and assess safety information with regards to AEs. | This is a Phase 2, multicenter, open-label study to provide continued supply of parsaclisib as monotherapy or in combination therapy with itacitinib, ruxolitinib, or ibrutinib to participants from Incyte-sponsored studies of parsaclisib. |
Total Body Irradiation (TBI) continues to play an important role in myeloablative and non-myeloablative conditioning regimens for Allogeneic Stem Cell Transplant (ASCT). When TBI is used as part of a myeloablative regimen, it is combined with chemotherapy to eradicate malignant cells, as well as to immunosuppress the host to prevent rejection of donor hematopoietic progenitor cells (HPC).~This study is a single-institution study to assess the safety of linac based VMAT TBI for myeablative sreatment in hematologic malignancies. | Single institution study of safety of linac based VMAT TBI for myeloablative treatment in hematologic malignancies. |
The purpose of this study was to reveal the effects of CTM on pain severity, fatigue, sleep quality, general health status, systemic symptoms, anxiety and depression in women with primary dysmenorrhoea and to determine the effect of treatment time on recovery in a longterm period. Our primary outcome was intensity of menstrual pain. Secondary outcomes were intensity of sleep disturbance, fatigue, depression and anxiety status, general health and premenstrual symptoms. The participants included to this study were randomised into two groups with simple randomisation method. CTM was performed to participants in both groups included the basic region (Sacral and lumbar), lower thoracic (between T12-T7) and anterior pelvic regions. In Group 1, starting at the end of the menstrual cycle, CTM was applied for 5 days a week and for 1 cycle (approximately 3 weeks) until the beginning of the next period. Participants in the Group 2 CTM was started with the completion of menstrual cycle, 5 days a week and until the other menstrual cycles. At the end of the menstrual cycle, it was restarted and a total of 2 cycles were applied until the second menstrual cycle started (approximately 6 weeks). Both short and long strokes were used during manipulation. Each stroke was repeated for three times first on the right and then on the left side of all manipulated regions. All sessions were ended with bilateral long strokes to the iliac crest and subcostal regions. The treatment was started from the basic region and proceeded to other regions according to the vascular reaction of the connective tissue. Each session lasted 5 to 20 minutes, depending on the size of the treated region. During manipulation, the pad of the middle finger was in contact with the patient's skin. The finger was placed on the skin at 45° angle with distal interphalangeal joint in flexion and moved to cause traction. During back treatment, the participant was asked to sit erect, with hips, knees, and ankles at 90° flexion and thighs and feet are fully supported. During the treatment of anterior pelvic region, the patient was in a supine position with pillows placed under the head and knees. Treatment was performed by a trained physiotherapist. The participants' intensity of pain, fatigue and sleep quality were assessed with Visual Analogue Scale. Depressive symptoms and anxiety status, general health and premenstrual symptoms were assessed with Beck Depression Inventory, Beck Anxiety Inventory, General Health Questionnaire and Premenstrual Syndrome Scale, respectively. All measurements were repeated 5 times; baseline, after the first menstruation following the intervention period, 3th, 6th and 12th months after treatment. | The purpose of this study was to reveal the effects of connective tissue manipulation (CTM) on pain severity, fatigue, sleep quality, general health status, systemic symptoms, anxiety and depression in women with primary dysmenorrhoea and to determine the effect of treatment time on recovery in a longterm period. Our primary outcome was intensity of menstrual pain. Secondary outcomes were intensity of sleep disturbance, fatigue, depression and anxiety status, general health and premenstrual symptoms. |
Background: Preliminary results from the Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial have reported a reduction in 28-day mortality with low-dose dexamethasone (6 mg) once daily versus no intervention in hospitalised patients with COVID-19; an effect that may have been more pronounced in patients with increasing hypoxia. Yet, higher doses of dexamethasone may be beneficial in patients with non-COVID-19 acute respiratory distress syndrome. At present, it is unclear what dose of dexamethasone is most beneficial in patients with COVID-19 and severe hypoxia, and clinical equipoise exists.~Objective: We aim to assess the effects of higher (12 mg) vs lower doses (6 mg) of intravenous dexamethasone on the number of days alive without life-support in adult patients with COVID-19 and severe hypoxia.~Design: International, parallel-group, centrally randomised, stratified, blinded, clinical trial.~Population: Adult patients with documented COVID-19 receiving at least 10 L/min of oxygen independent of delivery system OR mechanical ventilation.~Experimental intervention: Dexamethasone 12 mg once daily for up to 10 days in addition to standard care.~Control intervention: Dexamethasone 6 mg once daily for up to 10 days in addition to standard care.~Outcomes: The primary outcome is days alive without life support (i.e. mechanical ventilation, circulatory support, or renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions (i.e. anaphylactic reaction to hydrocortisone, new episode of septic shock, invasive fungal infection or clinically important gastrointestinal bleeding) at day 28; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, 90 and 180; and health-related quality of life at day 180.~Sample size: A total of 1000 participants will be randomised in order to detect a 15% relative reduction in 28-day mortality combined with a 10% reduction in time on life support among the survivors with a power of 85%. | We aim to assess the benefits and harms of higher (12 mg) vs lower doses (6 mg) of dexamethasone on patient-centered outcomes in patients with COVID-19 and severe hypoxia. |
This study consists of both single and multiple ascending doses in healthy subjects and in subjects with cholestatic or uremic pruritus.~Up to 48 healthy subjects will receive a single dose of EP547 or placebo. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days after dosing is completed.~24 healthy subjects will receive multiple doses of EP547 or placebo for 7 days. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days and then 14 days after dosing is completed.~6 subjects with cholestatic disease will receive a single dose of EP547. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days after dosing is completed.~Up to 16 subjects with cholestatic pruritus will receive multiple doses of EP547 or placebo for 7 days. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days and then 14 days after dosing is completed.~6 subjects with uremic disease will receive a single dose of EP547. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days after dosing is completed.~Up to 16 subjects with uremic pruritus will receive multiple doses of EP547 or placebo for 7 days. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days and then 14 days after dosing is completed.~12 healthy subjects will receive two doses of EP547 under fasted or fed condition. | This first in human, Phase 1/1b trial will evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of EP547 in healthy subjects and subjects with cholestatic or uremic pruritus. |
This study will establish a prospective cohort of pre-treatment tumor specimens with correlated de-identified clinical and demographic data and tissue histology from cancer patients who are undergoing treatment with PD-1/PD-L1 inhibitors. Patients who have undergone pre-anti-PD-1/PD-L1-treatment tumor biopsy or who are scheduled for tumor biopsy prior to anti-PD-1/PD-L1 treatment will be enrolled.~The study will not require a study-specific tumor biopsy; any biopsies taken prior to treatment as part of standard of care are eligible for this study. Biopsies must not have been taken after immunotherapy treatment began.~Participants will be asked to provide their consent for the potential use of their biospecimens in subsequent studies for the development and validation of a diagnostic test. | This study will collect de-identified tumor samples, with correlated clinical/demographic data and tissue histology, from patients selected or scheduled for pre-treatment tumor biopsy or who have had a recent pre-treatment tumor biopsy. These specimens and clinical data may be used in subsequent studies for the development and validation of a diagnostic test. |
Low hGH levels have been observed in approximately 1/3 of individuals with FM. Low hGH levels are hypothesized to contribute to inadequate treatment outcomes in many individuals with FM and several studies have demonstrated symptom improvement in individuals with FM and low hGH who received rhGH therapy. The amino acid-based blend represents a novel mechanism for increasing endogenous hGH production. It has been shown to produce an increase in endogenous hGH levels in healthy individuals by attenuating the inhibitory effect of somatostatin on hGH release. The amino acid-based blend may be a safe and effective treatment for FM in individuals with poorly controlled FM and low-normal hGH.~This study will investigate the effect of taking the amino acid blend on IGF-1 levels (a surrogate marker of the body's growth hormone levels), fibromyalgia symptoms, stress symptoms, body weight, and other cardiometabolic biomarkers in individuals with treatment-resistant FM and low-normal hGH.~After being informed about the study and potential risks, all eligible participants giving written informed consent will administer the amino acid-based blend daily. Standard care for fibromyalgia will continue. | The purpose of the study is to investigate the effect of the amino acid-based blend on growth hormone levels (measured by IGF-1) and clinical symptoms in individuals with treatment-resistant FM and low-normal hGH. |
Subjects enrolled in this study will be recruited from the population of adult patients with neuroendocrine tumors, including pheochromocytoma and paraganglioma, being treated at the University of Michigan Hospital.~The primary objective of the study is to obtain basic information on the biodistribution and pharmacokinetics of [18F]3F-PHPG in cancer patients with neuroendocrine tumors.~The secondary objective of the study is to compare the diagnostic performance of [18F]3F-PHPG in cancer patients with neuroendocrine tumors with the FDA approved radiopharmaceuticals [123I]metaiodobenzylguanidine ([123I]MIBG) and [68Ga]DOTA-TATE in the same patients. A group of approximately 12 of the subjects scanned with [18F]3F-PHPG will be recruited to undergo a whole-body [123I]MIBG scan using planar scintigraphy with a gamma camera, following the standard clinical protocol used at the University of Michigan. In addition, a single SPECT/CT scan of the primary neuroendocrine tumor will be acquired after the whole-body scan to provide a tomographic image for comparison with the positron emission tomography (PET) image acquired using [18F]3F-PHPG. Several subjects enrolled on this study will undergo [68Ga]DOTA-TATE scans off-study, as part of routine clinical management. Existing [68Ga]DOTA-TATE scans will be obtained from consenting subjects' medical records.~This is an exploratory study and thus all statistical data analyses will be exploratory in nature. | The goal of this exploratory study is to test whether [18F]3F-PHPG can be used reliably to map the locations of tumors in patients with neuroendocrine tumors. If so, the results of this study will be used to support further development of [18F]3F-PHPG as a clinical tool for neuroendocrine tumor localization and staging. |
Prediction of the neurological outcome in resuscitated post-cardiac arrest patients is important to tailor appropriate management plans. Brain imaging, electrophysiological evaluations, biomarkers all take part in neuroprognosis in cardiac arrest patients, however, these modalities are more expensive or not suitable to repeat in a short time. Optic nerve sheath diameter (ONSD) had been proved to be associated with increased intracranial pressure2 and can be used as one of the prognostic factors in cardiac arrest patients. It is simple, quick and can be measured repeatedly. Carotid duplex and transcranial duplex(TCD) provide rapid, noninvasive, real-time measures of cerebrovascular function. It can be used to assess the vascular territory by measuring blood flow, and to evaluate factors include brain perfusion, plaque morphology, and patency of intracranial collaterals.~Hence, it could act as a crucial role in neuroprognosis in post-arrest patients. In this study, the investigator aimed to analyze the ONSD diameters, ONSD/ETD ratio, carotid duplex and transcaranial duplex parameters in different stages of post-cardiac arrest care, demographic characteristics and resuscitation information with the neurological outcome of post-cardiac arrest patients. | Optic nerve sheath diameter (ONSD) had been proved to be associated with increased intracranial pressure and can be used as one of the prognostic factors in cardiac arrest patients. It is simple, quick and can be measured repeatedly. Carotid duplex and transcranial duplex(TCD) provide rapid, noninvasive, real-time measures of cerebrovascular function. It can be used to assess the vascular territory by measuring blood flow, and to evaluate factors include brain perfusion, plaque morphology, and patency of intracranial collaterals. Hence, it could act as a crucial role in neuroprognosis in post-arrest patients. In this study, the investigator aimed to analyze the ONSD diameters, ONSD/external transverse diameter (ETD) ratio, carotid duplex and transcaranial duplex parameters in different stages of post-cardiac arrest care, demographic characteristics and resuscitation information with the neurological outcome of post-cardiac arrest patients. The ONSD diameter, and ONSD/ETD ratio were compared with age-, and sex-matched normal volunteers. |
This is a single-arm, open-label, Phase 1b study to evaluate the efficacy and safety of oral single agent olmutinib administered to patients with T790M-positive NSCLC after treatment with an EGFR-TKI. | The purpose of this study is to evaluate the efficacy and safety of olmutinib 600 mg QD in patients with T790M-positive non-small cell lung cancer (NSCLC) after treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). |
The investigators will recruit adolescents with type 1 diabetes age 11-<13 years and one parent to participate in this 24-month study. While this is admittedly a long enrollment time, study commitments following enrollment will be limited to three in-person or video visits at yearly intervals and one virtual or in-person device training session to improve adherence. Participants must be pubertal, as puberty appears to contribute significantly to the insulin resistance that is likely related to worsened blood glucose control. Pubertal assessments will occur at yearly intervals.~The first of the two arms/substudies (Randomized substudy) is a longitudinal randomized controlled trial for which participants will be randomized to either continue their current diabetes therapy (with the addition of use of a Dexcom CGM, forming the Usual Care+CGM Control Group; this includes both adolescents using non-automated insulin delivery (AID) insulin pumps or multiple daily injections [MDI]). The Experimental Group will use an AP system (Tandem's Control-IQ system) during the two-year duration of the study. The primary outcome of the Randomized substudy will be HbA1c between intervention groups at the 24-month visit.~The second arm/substudy (Triple Label Surveillance substudy) is an observational study. Both arms/substudies perform a Triple Label mixed meal study assessing glucose flux and insulin resistance that requires visits to the Clinical Research Unit. All participants will undergo a Triple-Labeled Glucose Assessment at months 0, 12 and 24. This assessment evaluates the degree of insulin resistance including in the hepatic and peripheral compartments. During Visit 2, all participants (for both the Triple Label sub-study and the Glycemia-Only sub-study) will complete multiple questionnaires assessing aspects of adolescent psychology and sociology. HbA1c will also be collected using a local lab. The primary outcome of the study overall (combined Triple Label Surveillance and Randomized substudies) is the change in insulin resistance between baseline and the 24-month visit.~CGM glucose data will be collected continuously via remote connection during the entire study. At months 6 and 18, participants will be contacted to obtain insulin management information and will have HbA1c measures assessed at a local clinic or laboratory. Additional scheduled phone calls will occur in the month before the in-person study visits to request HbA1c and confirm body composition/Triple-Labeled Glucose Assessment scheduling and discuss use of CGM and activity tracker. Participants will be contacted in the event of insufficient CGM or AP system use. For the Randomized substudy, in the Eperimental Group, insufficient use is defined as <60% AP use over a 3-month period. For the Control Group, less than 1 month of CGM data over a 3-month period is considered insufficient. If participants do not meet minimum use criteria in 2 successive periods, the participant will be discontinued from the study.~The investigators are targeting completion of 42 child/parent dyads combined between the Randomized substudy and the Triple Label Surveillance sub-study. | This study designed to assess changes in control of Type 1 Diabetes in pubertal adolescents over a two year period. There are two arms/substudies, the first being a longitudinal randomized controlled trial and the second an observational study. |
Breast cancer is the most common cancers among women worldwide. Although chemotherapy and surgery have greatly improved the survival rate, most types of chemotherapy have been reported to have varying degrees of cardiotoxicity. We have focused on the field of chemotherapy-related cardiomyopathy. Using the unified magnetic resonance sequences and parameters, effect of chemotherapeutic drugs on the myocardium are studies. Our team's previous pilot study has found that chemotherapy-related cardiomyopathy (CMP) may be predicted within one week after chemotherapy initiation. The specific intervention timing, and the sensitivity and specificity of the early screening indicators are to be explored. At the same time, in patients with human epidermalgrowth factor receptor-2-positive breast cancer, our team observed the change of blood pressure, exercise tolerance and myocardial structure, function and tissue characteristics in patients who used tyrosine kinase inhibitors (pyrotinib and apatinib). This is a supplement to the existing drug knowledge. We are planning to further explore whether it is related to the patient's pre-existing cardiovascular diseases, drug type, dose or dosing. There are no published data addressing the above two research areas. The overall goal is to explore the commonness and specificity of myocardial changes after chemotherapy in breast cancer patients and to predict the development of CMP through multimodality imaging and clinical indices. We aim to propose the CMP time window in respective chemotherapy among more subjects. | Breast cancer is the most common cancers among women worldwide.Although chemotherapy and surgery have greatly improved the survival rate, most types of chemotherapy have been reported to have varying degrees of cardiotoxicity. The investigators will focus on the cardiotoxicity of pyrotinib and apatinib which belong to the new tyrosine kinase inhibitors in respective chemotherapy among more subjects. |
Background:~Recent pooled evidence indicates that the incidence of incisional hernia after stoma closure is of 7.4%, but this finding is limited by an important heterogeneity (reported incidences ranging from 0 to 48%). The pooled incidence of incisional hernia ranges from 4 to 10% according to the type of stoma, with the highest incidence reported after colostomy closure (10%). These incisional hernias at site of stoma generate patient discomfort, alteration of quality of life, complications such as bowel occlusion and increased costs for healthcare systems.~Several retrospective studies have investigated the impact of a prophylactic mesh during stoma closure on the incidence of incisional hernia. For instance, Liu et al. compared 47 patients who benefited from ileostomy closure with a synthetic non-resorbable mesh with 36 patients who underwent the same surgery without mesh, and found that incidences of incisional hernia (with a median follow-up of 18 months) were of 6.4% and 36.1%, respectively 3. Similarly, a retrospective case-control study compared 30 patients who had ileostomy closure with prophylactic biological mesh with 30 matched patients without mesh. At one year, the incidence of incisional hernia diagnosed with CTscan was of 3.3% in patients with mesh versus 40% in patients without mesh 4. A multicenter randomized controlled trial (RCT) is currently underway to evaluate whether an intra-abdominal mesh allows to prevent the one year incidence of CTscan-proven incisional hernia in patients undergoing ileostomy and colostomy closures 5. A preliminary feasibility study demonstrated the safety of the procedure 6. However, no specific techniques for mesh fixation and position are documented in the RCT protocol, which might introduce confusion factors in the final analysis. Further, applying an intra-abdominal mesh might potentially result in long-term complications due to bowel adhesion to the abdominal wall.~Therefore, we have planned to undertake a RCT aiming at determining whether a prophylactic non-resorbable mesh in the sublay position allows or not reducing the incidence of incisional hernia after ileostomy or colostomy closure.~Methods/Design:~Study design:~The study will be a randomized controlled single-blinded monocentric study determining the one year incidence of incisional hernia in patients undergoing ileostomy or colostomy closure with or without prophylactic mesh.~Study setting:~The study will take place at the Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland.~Population:~Adult patients undergoing ileostomy or colostomy closure after surgery for digestive cancer will be considered as eligible for the study.~Inclusion criteria:~Adult patient~Ileostomy or colostomy performed during surgery for digestive cancer~Planned elective closure of ileostomy or colostomy~Informed written consent~Exclusion criteria:~Allergy to mesh~Patients under corticosteroids or other immunosuppressive treatment~Inability/refusal to follow the procedures of the study~Drop-outs:~Stoma closure not performed~One-year follow-up not completed~Withdrawal of consent~Redo surgery at the site of stoma not related to the mesh and/or to incisional hernia~Violation of protocol~Intervention: Stoma closure with non-resorbable mesh in the sublay position~Antibioprophylaxis using cefuroxime and metronidazole~Standard disinfection and sterile draping~Circular incision around the stoma using the scalpel blade~Dissection around the stoma until entering the abdominal cavity~Closure of the stoma using a linear stapler~A midline laparotomy may be performed or not~Realization of an extra-corporeal or intra-corporeal side-to-side handsewn anastomosis~Closure of the posterior aponeurosis using separate Maxon 2-0 stitches~Application of an ULTRAPRO Advanced Mesh, Ethicon, Johnson & Johnson, with +2cm on the edges, secured by 4 stiches of Maxon 2-0~Closure of the anterior aponeurosis using separate Maxon 2-0 stitches~No subcutaneous stitches~Partial purse string skin closure using Monocryl 3-0~Standard wound dressing~Control: Stoma closure without mesh~Antibioprophylaxis using cefuroxime and metronidazole~Standard disinfection and sterile draping~Circular incision around the stoma using the scalpel blade~Dissection around the stoma until entering the abdominal cavity~Closure of the stoma using a linear stapler~A midline laparotomy may be performed or not~Realization of an extra-corporeal or intra-corporeal side-to-side handsewn anastomosis~Closure of the posterior aponeurosis using separate Maxon 2-0 stitches~Closure of the anterior aponeurosis using separate Maxon 2-0 stitches~No subcutaneous stitches~Partial purse string skin closure using Monocryl 3-0~Standard wound dressing~Outcomes:~Primary outcome:~The primary outcome will be the incidence of incisional hernia at site of stoma at one year after closure. The presence or not of an incisional hernia will be assessed clinically by a specialist in general surgery and radiologically by computed tomography realized in the setting of cancer follow-up. The investigator performing the one-year follow-up and the radiologist interpreting the CTscan will be blinded for the study group. Patients diagnosed with incisional hernia and/or reoperated for a complication related to stoma closure and/or mesh will be considered as treatment failure.~Secondary outcome:~The secondary outcome will be the incidence of surgical site infection (SSI) at site of stoma closure, evaluated at 7 and at 31 days after stoma closure according to the Center for Disease Control definition. Specialized nurses will record pictures of the stoma site for blinded evaluation by an investigator. In case of occurrence, SSI will be treated according to institutional guidelines.~Randomization, allocation concealment and blinding :~Patients will be recruited during the preoperative consultation. Patients will be given written information related to the study and will sign an informed consent form. Investigators will be contacted and perform randomization using the RedCap (Research Electronic Data Capture) software system on a 1:1 allocation ratio between study groups. The surgery planning form will be forwarded to the investigators, which will indicate if a mesh should be added or not to the stoma closure procedure. Patients will be blinded for the study group.~Sample size calculation:~Considering the results of existing studies comparing the incidence of incisional hernia after stoma closure with and without prophylactic mesh, we aimed reducing the incidence of incisional hernia from 30% to 5%. Using the two-sided Pearson's chi-squared test for proportions, with a power set at 0.8 and an alpha at 0.05, and considering a 1:1 allocation ratio, we will have to include 72 patients (36 with mesh and 36 without mesh).~Variables of interest:~Variables of interest will be recorded by the investigator into a case-report form generated in the RedCap software.~Variables related to stoma confection:~Date of stoma confection~Age~Gender~BMI~ASA class~Tobacco use~Pre-albumin concentration~Albumin concentration~Proteins concentration~Neo-adjuvant treatment~Surgery performed in emergency or elective setting~Diagnostic~Type of surgery performed~Type of stoma~Site of stoma~Length of stay~Variables related to stoma closure:~Date of stoma closure~Age~BMI~ASA class~Tobacco use~Pre-albumin concentration~Albumin concentration~Proteins concentration~Type of surgery performed~Presence or not of a parastomal hernia~Length of stay~Variables related to follow-up at 7 days after the stoma closure:~Date of early follow-up~Presence or not of a SSI~Pictures of the stoma site~Variables related to follow-up at 1 year after stoma closure:~Date of late follow-up~Age~BMI~Adjuvant treatment~Presence or not of an incisional hernia at the site of stoma closure (clinical examination)~Presence or not of an incisional hernia at the site of stoma closure (CTscan)~If appropriate, variables related to the management of the incisional hernia~Statistical analysis :~Continuous variables will be expressed as medians±SD. Categorical variables will be expressed as numbers (proportions). Continuous variables and outcomes will be compared using the two-sided Student's t test. Categorical variables and outcomes will be compared using the Chi-square test or the exact Fisher test, when appropriate. Subgroup analyses will be performed according to BMI class and type of stoma. An in interim analysis will be performed when 36 patients are included; if a difference >15% of SSI (the short-term outcome) between the 2 groups is put observed, the study will be terminated. A p-value <0.05 will be considered as significant. Analyses will be performed using GraphPad Prism version 15 and STATA version 13.~Discussion:~Existing literature reports heterogeneous incidences of incisional hernia at stoma site after stoma closure. Several systematic reviews and meta-analyses, however, documented clinically significant pooled incidences 1, 2. Considering that the incisional hernia usually requires surgery and hospitalization, we believe that this complication, in addition to altering patients' quality of life, also impairs healthcare systems budgets.~Preliminary studies have shown that insertion of a prophylactic mesh, resorbable or not, during stoma closure, reduces the incidence of incisional hernia at stoma site 3, 4. However, to date, no RCT has been released on the subject. Further, the procedure seems to be safe, with very few SSI reported.~The aim of the present RCT will be to determine whether application of a prophylactic non-absorbable mesh during stoma closure allows or not for the prevention of incisional hernia at one year. Subgroup analysis will be performed according to the type of stoma and to BMI class. Furthermore, secondary analysis of the results might allow us to gather enough data for an objective cost-benefit analysis of the technique.~The strengths of the present RCT will be the following : (1) Good external validity due to the representation of all types of stomas, (2) Mesh in the sublay position, where the risk of intra-abdominal complications is lower and application is the easiest (as compared to intra-abdominal mesh), (3) Use of an affordable mesh (as compared to biological mesh), (5) assessment of the presence or not of incisional hernia by CTscan.~Trial status:~The RCT protocol was accepted by the local ethical committee. | Background:~Preliminary studies have shown that application of a prophylactic mesh during stoma closure reduces the incidence of incisional hernia at site of stoma closure.~Methods/Design:~The study will be a randomized controlled single-blinded monocentric study determining the 1-year incidence of incisional hernia in cancer patients undergoing ileostomy or colostomy closure with or without prophylactic non-absorbable mesh applied in the sublay position.~Discussion:~Prevention of incisional hernia at site of stoma closure will lead to an improvement in patients' quality of life and generating savings for healthcare systems. To date, no randomized controlled trial assessing the effect of prophylactic mesh applied during stoma closure on the prevention of incisional hernia has been published. With the present randomized controlled trial, we expect to demonstrate that the application of a prophylactic mesh reduces the one-year incidence of incisional hernia at site of stoma closure. |
Purpose: To determine whether angiotensin II receptor blockers (ARBs) decrease severity or mortality in hospitalized COVID-19 infected adults.~Main Hypothesis: Modulation of ACE2 by ARBs decreases the need for hospitalization, severity (need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement therapy) or mortality of hospitalized COVID-19 infected adults.~Secondary Hypotheses:~Plasma angiotensin I and II and other biomarker levels are associated with effectiveness of ARBs in hospitalized COVID-19 adults~Modulation of ACE2 by angiotensin type I receptor blockers is associated with decreased rate of hospitalization for COVID-19~In patients already on ARBs when they are hospitalized continuing ARBs is associated with decreased World Health Organization (WHO) COVID-19 ordinal outcome scale~Justification: The COVID-19 epidemic continues to grow exponentially affecting over 71,429 individuals with 1775 deaths (February 17, 2020), mostly in China but also in other countries. The population mortality rate is 2% (lower than SARS (10%) and MERS (36%) but is 10% in hospitalized and 24% in ICU-admitted COVID-19 patients in China. Recent data from China (not yet public domain) suggest ICU mortality is higher (J. Marshall personal communication). Interventions to date include quarantine, isolation and usual clinical care. There are no proven antiviral or host modulating interventions for COVID-19. Notably, critically ill COVID-19 patients have similar mortality rates as sepsis and acute respiratory distress syndrome. Cohort studies have shown that patients already on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have lower sepsis mortality. Angiotensin II worsens lung injury in influenza models because ACE2 is downregulated in H1N1, H5N1, H7N9, and SARS viral infections leading to increased angiotensin II. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Preliminary data shows ARBs limits lung injury in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and organ injury in COVID-19.~Research Design:~Prospective clinical chart review: we will collect clinical data on the participant throughout their hospital stay. Includes collection of baseline characteristics such as age, sex, heart rate, respiratory rate, temperature, blood pressure, SaO2, respiratory (PaO2/FiO2), renal (creatinine) and hepatic (bilirubin) function, use of oxygen, vasopressors, ventilation and RRT. They will be followed daily throughout their hospital stay, until death or discharge. Using left over clinical blood collected upon admission to hospital, plasma angiotensin I and II and other biomarker levels will be measured in our research laboratories. | The coronavirus (COVID-19) pandemic continues to grow exponentially. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Preliminary data shows angiotensin II receptor blockers (ARBs) limits lung injury in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and organ injury in COVID-19. We will therefore collect clinical chart data and test angiotensin II levels of patients who are admitted to ICU with COVID-19 to determine whether there is a correlation between taking ARBs and clinical outcomes in these patients.~Other blood biomarkers and clinical risk factors for COVID-19 have come to light in recent weeks. We include these in our observational analysis to help generate an understanding of COVID-19 presentation and blood biomarker characterization of disease. |
Objectives:~To understand whether the implementation of warfarin dose management using NextDose (nextdose.org) at The First Affiliated Hospital of Soochow University (Suzhou, China) improves the quality of anticoagulation therapy.~Endpoint Primary~Percentage of time within the acceptable INR range estimated using linear interpolation during the 28 days after initiation of warfarin.~Secondary 2.1 Percentage of Time Measures~Percentage of time within the acceptable INR Range estimated using linear interpolation during the 90 days after initiation of warfarin.~Percentage of time spent above and below the acceptable INR range at day 28, and 90 after initiation of warfarin estimated by linear interpolation.~2.2 Time to Stable Dose a. Number of days to achievement of stable dose (defined as 3 consecutive INR measurements within acceptable range for the same mean daily dose).~2.3 Safety Outcomes a. Number of participants who experience at least one of the following safety events: major bleeding within 30 days, INR of 4 or greater within 30 days, death within 30 days, and symptomatic or asymptomatic VTE confirmed by objective testing within 60 days of surgery.~2.4 Acceptability of NextDose Recommendations~Percentage of prescribed doses within 0.625 mg of the NextDose proposed dose.~Mean difference between the prescribed dose and the NextDose proposed dose. Exploratory 3.1 Percentage of Time Measures~a. The percentage of time spent within, above and below the acceptable INR range estimated by numerical integration with the Bayesian parameter estimates of the PKPD model at day 28 and at day 90 after initiation of warfarin.~3.2 Time to Stable Dose a) Days to first INR measurement within the acceptable range. b) Days to second consecutive INR measurement within the acceptable range. c) Number of dose adjustments to achievement of stable dose (3 consecutive INR measurements within acceptable range for the same mean daily dose).~d) Total number of dose adjustments at day 90. e) Total number of INR measurements at day 90. 3.3 Safety Outcomes~a) Incidence of minor and major bleeding events. b) Incidence of thromboembolic events. c) 30 day all-cause mortality. d) 90 day all-cause mortality. e) 90 day cardiovascular mortality. f) Number of warfarin doses withheld due to high INR (as determined by the treating clinician).~3.4 Acceptability of NextDose Recommendations a) Percentage of prescribed doses within 20% of the NextDose proposed dose. 3.5 Model Evaluation~a) Predictive performance of the model for patients with steady-state warfarin doses below 2 or above 7 mg/day.~3.6 INR Variability~a) INR variability as described by Lind et al. (the standard deviation of transformed INR values).~Population:~240 participants of any sex between the age of 18 and 80 years. Patients requiring treatment with warfarin following cardiac surgery. | Objectives:~To understand whether the implementation of warfarin dose management using NextDose (nextdose.org) at The First Affiliated Hospital of Soochow University (Suzhou, China) improves the quality of anticoagulation therapy.~Endpoint Primary~1. Percentage of time within the acceptable INR range estimated using linear interpolation during the 28 days after initiation of warfarin.~Secondary 2.1 Percentage of Time Measures 2.2 Time to Stable Dose 2.3 Safety Outcomes 2.4 Acceptability of NextDose Recommendations Exploratory 3.1 Percentage of Time Measures 3.2 Time to Stable Dose 3.3 Safety Outcomes 3.4 Acceptability of NextDose Recommendations 3.5 Model Evaluation 3.6 INR Variability~Population:~240 participants of any sex between the age of 18 and 80 years. Patients requiring treatment with warfarin following cardiac surgery. |
This study will evaluate the impact InheRET™, an online family history gathering and risk assessment reporting tool, has on facilitating National Comprehensive Cancer Network(NCCN) guideline compliant referrals for cancer genetic counseling/genetic evaluation by decreasing and/or removing the barriers of 1) time-consuming in-clinic 3-generation family history collection, and 2) interpretation of the family and personal history in light of current NCCN guidelines.~This is a prospective study with a pre/post intervention analysis. The prior 6-months' genetic counseling referrals to Michigan Medicine will be collected for each site to serve as baseline data and compared to the intervention data to measure the difference made by InheRET utilization. Primary care sites are selected to offer the broadest range of patient populations to ensure the InheRET tool works well in diverse groups accessing varied clinical settings. The Cancer Genetics and MM Breast and Ovarian Cancer Risk Evaluation Clinics will allow us to measure the appropriateness of referrals and the impact of InheRET on genetic counseling workflows as patients from the primary care sites are referred for counseling from throughout the tri-state catchment areas and beyond. Similarly, investigators will review electronic health records for appropriateness of referrals to other counseling clinics at Michigan Medicine.~This will be accomplished by implementing InheRET in a variety of clinical settings to measure its acceptance by providers and patients as well as any changes made in referral patterns as a result of its use, compared to patterns of referral before it is implemented. Patients completing the InheRET online tool form will be followed longitudinally by surveys to discover their risk management actions (i.e. genetic counseling appointment, genetic testing, screenings, prophylaxis) and the reasons for or against undertaking such actions. Providers will also be surveyed to determine the impact InheRET has made to their workflow, the acceptability of this tool by their practice, and the usefulness of InheRET's features to accomplish its goals. This study has a goal enrollment of 2109 patients in Phase I (already enrolled) and at least 1023 patient subjects in Phase II (anticipated) to use the InheRET program for the purpose of this study and will also enroll six to twelve (6-12) physicians to obtain reflection on experience using InheRET for the purpose of this study. | This study will evaluate the impact InheRET™, an online family history gathering and risk assessment reporting tool, has on facilitating National Comprehensive Cancer Network(NCCN) guideline compliant referrals for cancer genetic counseling/genetic evaluation by decreasing and/or removing the barriers of 1) time-consuming in-clinic 3-generation family history collection, and 2) interpretation of the family and personal history in light of current NCCN guidelines.~Identifying individuals at increased risk for cancer has been shown to decrease morbidity and mortality in multiple clinical settings. Investigators hypothesize that InheRET will prove to be accurate, efficient, and accessible, and that its use will improve identification of individuals at risk for inherited susceptibility to cancer. The investigators propose also that using this tool will result in a reduction of inappropriate genetic counseling referrals and reduce unnecessary genetic testing in both primary and specialty care settings. InheRET will allow health care providers to focus resources on individuals at higher risk for developing cancer. |
Healthcare for older adults with multiple chronic conditions (MCCs) is burdensome and of uncertain benefit, resulting in unwanted and unhelpful care. Patient Priorities Care (PPC) is an approach that aligns care with patients' health priorities (i.e. the health outcomes most desired given the healthcare each is willing and able to receive). PPC offers the opportunity to increase value by improving both outputs (desired health outcomes) and inputs (healthcare preferences) for these major users of healthcare.~We will employ a quasi-experimental, usual care (UC) group design, involving 2 primary care sites (1 PPC and 1 UC. Patients are assigned to intervention or usual care arms based on their primary care practice location. We will use analytic techniques (e.g., inverse propensity score weighting) designed to reduce selection bias and balance PPC and UC sites in terms of baseline characteristics. Data collection will occur through quantitative and qualitative interviews and health encounter information in the Electric Health Record(EHR).~Patient Priorities Care requires the elicitation and documentation of patient health outcome goals and care preferences and the alignment of clinical care with goals and priorities to achieve patients' health outcome goals and reduce the burden of multi-morbidity. Participants will be enrolled in the Patient Priorities Care Program and speak with a trained health priorities facilitator to elicit their healthcare preferences and health outcome goals, which together constitute their health priorities. This information will be documented, entered into the EHR, and shared with the clinicians who will then use the Patient Priorities Care approach with patients to inform and guide treatment decisions. Patients will participate in the program and be followed for up to one year from the health priorities identification visit.~To determine the value of PPC, comparable primary care sites within the Cleveland Clinic will be assigned to PPC or Usual care (UC). Clinicians and staff at the PPC site will be trained to identify and align decision-making with the health priorities of older adults with MCCs. Value will be compared using patient and provider-reported outcomes, healthcare utilization, and possibly costs at PPC and UC sites.~The ultimate goal of our work is to implement and evaluate this approach to care for older adults with multiple chronic conditions that focuses on what matters most to them and is less fragmented and burdensome, resulting in better quality and outcomes at lower cost. This study will focus on evaluating practice change at test sites at the Cleveland Clinic. | Healthcare for older adults with multiple chronic conditions (MCCs) is burdensome and of uncertain benefit, resulting in unwanted and unhelpful care. Patient Priorities Care (PPC) aligns care with patients' health priorities (i.e. the health outcomes most desired given the healthcare each is willing and able to receive). The aim of this project is to test, using a parallel group design involving 2 matched primary care sites, whether PPC decreases patient treatment burden and unwanted and unnecessary health care as well as assess what the value of this program is for patients. |
The study is examining differences in central arterial stiffness, orthostatic changes in blood pressure, norepinephrine, and plasma renin in individuals with spinal cord injury compared with age-matched uninjured controls. Arterial stiffness and blood pressure will be collected in the laying down position. A blood sample of norepinephrine and plasma renin will also be collected. The participant will tilt to 30, 45 and 60 degrees for 10 minutes at each angel. Blood pressure and heart rate will be monitored at each angle. Another blood sample of renin and norepinephrine will be collected at the end of 10 minutes at 60 degrees. | The study is examining differences in central arterial stiffness, orthostatic changes in blood pressure, norepinephrine, and plasma renin in individuals with spinal cord injury compared with age-matched uninjured controls. |
PRIMARY OBJECTIVE:~I. To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between participants randomized to the triplet combination of encorafenib + binimetinib + nivolumab versus the doublet combination of ipilimumab + nivolumab among participants with BRAF-V600 mutant melanoma that has metastasized to the brain.~SECONDARY OBJECTIVES:~I. To estimate the overall survival (OS) of participants in each treatment arm. II. To estimate the objective response rate (ORR) (confirmed and unconfirmed, complete and partial responses) per RECIST 1.1 in each treatment arm.~III. To estimate the intracranial response rate (ICRR), defined as confirmed and unconfirmed complete and partial response per modified RECIST for brain metastases (mRECIST).~IV. To evaluate the duration of response, per RECIST 1.1 and the duration of ICRR per mRECIST, and per Response Assessment in Neuro-Oncology (RANO)-Brain Metastases (BM) (and immunotherapy [i]RANO) in each treatment arm.~V. To evaluate the toxicity profile of each treatment arm. VI. To evaluate current and emerging radiographic response criteria (modified RECIST 1.1, modified RANO-BM and iRANO) by a retrospective blinded independent centralized review (BICR) of banked images.~BANKING OBJECTIVE:~I. To bank tumor tissue, cerebral spinal fluid (CSF), stool and blood samples for future correlative studies.~OUTLINE: Patients are randomized to 1 of 2 arms.~ARM I: Patients receive encorafenib orally (PO) once daily (QD) on days 1-28, binimetinib PO twice daily (BID) on days 1-28, and nivolumab intravenously (IV) on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.~ARM II: Patients receive nivolumab IV on day 1 of all cycles and ipilimumab IV over 30 minutes on day 1 of cycles 1-4. Cycles repeat every 21 days for 4 cycles and then every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up every 6 months for 2 years, and then annually until 3 years after randomization. | This phase II trial compares the effect of encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab in treating patients with BRAF- V600 mutant melanoma that has spread to the brain (brain metastases). Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ipilimumab and nivolumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. This trial aims to find out which approach is more effective in shrinking and controlling brain metastases from melanoma. |
Acute myocardial infarction (AMI) is a life-threatening condition and a cause of functional disability, although reperfusion therapies and pharmacological strategies have been developed dramatically. Percutaneous coronary intervention（PCI）can effectively improve the myocardial blood supply of patients, However, various degrees of reduced exercise tolerance, anxiety and depression symptoms, impaired social function may occur after PCI and then lead to the decline of their quality of life. Exercise-based cardiopulmonary rehabilitation, which has beneficial effects on physical fitness, quality of life, cardiovascular risk factors and clinical outcome, is an important part of secondary prevention for patients after an acute myocardial infarction. Despite the evidence of these beneficial effects, cardiac rehabilitation programs are still largely underutilized and the exact benefits are still less well known. In this study, a randomized, controlled and prospective clinical trial is designed for patients with AMI to improve exercise capacity, cardiometabolic parameters, as well as quality of life by an individualized, low-cost exercise intervention we developed after evaluation by Cardiopulmonary Exercise Tests (CPET) . Serial CPET are performed to prospectively measure changes in aerobic exercise capacity, and the MOS item short form health survey（SF-36）are constructed to survey life quality. What's more, echocardiography and NT-proBNP are also assessed. | Acute myocardial infarction (AMI) is a life-threatening condition and a cause of functional disability. After reperfusion therapies and pharmacological strategies, patients suffered great pain physically and mentally. How to improve the quality of life and the prognosis in patients with AMI is a hot topic in the field of cardiac rehabilitation now. In this study, a randomized, controlled and prospective clinical trial is designed for patients with AMI to improve exercise capacity, cardiometabolic parameters, as well as quality of life by an individualized, low-cost exercise intervention we developed after evaluation by Cardiopulmonary Exercise Tests (CPET). Serial CPET are performed to prospectively measure changes in aerobic exercise capacity, and the MOS item short form health survey（SF-36）are constructed to survey life quality. What's more, echocardiography and NT-proBNP are also assessed. |
80 female patients evaluated for sexual function after receiving Mirabegron 50 mg once daily for 6 months for treatment of overactive bladder symptoms | 80 female patients evaluated for sexual function after receiving Mirabegron 50 mg once daily for 6 months for treatment of overactive bladder symptoms |
Background:~A substantial portion of patients in routine care suffer from a recurrent preoccupation with physical symptoms, which often leads to substantial suffering and impairment. Exposure-based treatment - where the patient systematically seeks out that which gives rise to unwanted sensations, cognitions, or behavior - has been found to lead to beneficial effects in several types of symptom preoccupation. Yet, this form of treatment is rarely offered in routine care. This may be partially because existing treatment protocols have been developed for specific symptom clusters (e.g., functional somatic syndromes such as irritable bowel syndrome and fibromyalgia) or specific unwanted responses to symptoms (e.g., the fear of having a severe illness), and that many clinics do not have the resources to offer all these specialized protocols in parallel. An alternative approach could be to base exposure treatment on a more general protocol that may be tailored to suit a larger variety of patient groups who suffer from a recurrent preoccupation with physical symptoms. However, it is yet unclear if the use of such a general treatment protocol for symptom preoccupation would be feasible, for example in terms of patient-reported credibility, adherence, identification with the rationale, and general client satisfaction.~Aim:~To investigate the feasibility of delivering exposure-based treatment using a general protocol for clinically significant symptom preoccupation, without selecting patients based on any specific symptom cluster (such as a functional somatic syndrome) or specific unwanted response to physical symptoms (such as a frequent fear of illness).~Design:~This is a prospective single-group feasibility study based at Karolinska Institutet, Stockholm, Sweden, where 40 adults with somatic symptom disorder according to the Diagnostic and statistical manual of mental disorders 5 (DSM-5) are enrolled in 8 weeks of therapist-guided exposure-based treatment that is delivered via the Internet. Various aspects of feasibility are assessed; most notably: patient-reported credibility and expectancy, adherence to the treatment protocol, client satisfaction, and negative events. Within-group effects are also quantified. | This study investigates the feasibility of a general exposure-based treatment protocol that is intended to work for a large variety of patient groups with a clinically significant preoccupation with physical symptoms. This is a prospective single-group study based at Karolinska Institutet, Stockholm, Sweden, where 40 adults with DSM-5 somatic symptom disorder are enrolled in 8 weeks of therapist-guided exposure-based treatment via the Internet. Exposure is based on general principles but tailored to suit the needs of each patient. Outcomes include patient-reported credibility and expectancy, adherence to the treatment protocol, client satisfaction, and negative events. Within-group effects will also be quantified and discussed in relation to the existing literature. |
A randomised placebo-control study of metformin in people with mild cognitive impairment and without diabetes mellitus to determine effects on cognitive decline, neuroimaging and biomarkers over 3 years. | A randomised control study of metformin in people with mild cognitive impairment and without diabetes mellitus to determine effects on cognitive decline and neuroimaging over 3 years. |
Diabetes is an important public health problem as the number of people with diabetes are increasing across the world and contributes to high mortality burden. Prediabetes is an intermediate stage between normal glucose tolerance and type 2 diabetes mellitus. Furthermore, people with prediabetes have higher risk to develop diabetes mellitus type 2.~There are several objectives in this study, such as primary objective, secondary objectives, and exploratory objectives.~Primary Objective:~To investigate the effect of a combination of Zinc, Chromium, Vitamin C, and Copper supplementation (ZCC supplementation) with standard healthy lifestyle intervention in improving glucose profile [Fasting Blood Glucose (FBG), 2-hour Oral Glucose Tolerance Test (OGTT), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)]) from prediabetes to normal (reducing the proportion of prediabetes and increasing the proportion to become normal) or reducing the risk of progression from prediabetes to Type 2-Diabetes Mellitus (T2DM) compared to placebo with standard healthy lifestyle intervention.~Secondary Objectives:~To investigate the level of Zinc and Chromium among the prediabetes, the safety of the ZCC supplementation, and the effect of a combination of Zinc, Chromium, Vitamin C, and Copper supplementation (ZCC supplementation) among prediabetic adults compared to the placebo supplementation on:~Lipid profile [Low-Density Lipoprotein (LDL), High-Density Lipoprotein (HDL), Triglyceride];~Hemoglobin A1c (HbA1c);~Dietary intake and physical activity~Body weight and composition (body weight, Body Mass Index (BMI), body fat).~Exploratory Objectives:~To determine cost effectiveness of intervention on prediabetic adults comparing two different intervention models~To determine the quality of life of prediabetes adults receiving a combination of zinc, chromium, vitamin C, and copper supplementation.~Level of hs-crp; TNF-alpha and Vitamin C will be assessed later if needed (optional)~Study Design:~This study is a double-blind, randomized, placebo-controlled trial in the community setting, with two arms of intervention involving a total of 670 people.~Study Duration:~This study is a two-year study with 1 year of intervention for each subject. | Currently, the incidence of diabetes mellitus is increasing worldwide. People with prediabetes have higher risk to develop diabetes mellitus type 2. Several studies have proven that Zinc and Chromium are minerals that contribute to decreasing the level of blood glucose and insulin resistance. In addition, vitamin C also contributes in decreasing Fasting Blood Glucose (FBG) and Hemoglobin A1c (HbA1c). However, the eficacy of a combined zinc, chromium, vitamin C, and copper (ZCC) in decreasing blood glucose in prediabetic people has never been performed.~The primary objective of this study is to investigate the effect of a combination of ZCC supplementation with standard healthy lifestyle counseling in improving glucose profile [Fasting Blood Glucose (FBG), 2-hour Oral Glucose Tolerance Test (OGTT), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)] from prediabetes to normal or reducing the risk of progression from prediabetes to Type 2-Diabetes Mellitus (T2DM) compared to placebo with standard healthy lifestyle intervention. |
This is a Phase 4, open label, single arm, multi-center, prospective clinical trial of dacomitinib that will be performed in India. This study will enroll a sufficient number of participants to ensure that 100 participants are treated with dacomitinib. The primary objective of this study is to assess the safety and tolerability of dacomitinib. The secondary objective is to evaluate antitumor activity of dacomitinib by objective response rate and duration of response. Drug administration: Dacomitinib will be supplied by Pfizer and administered in accordance with the India Local Product Document (LPD). The recommended dosage of dacomitinib is 45 mg taken orally once a day at approximately the same time each day, until disease progression, participant refusal/lost to follow-up, or unacceptable toxicity occurs.~STUDY PROCEDURES:~Screening: Participants will be screened within 28 days prior to first dosing of dacomitinib to confirm that they meet the eligibility criteria for the study.~Follow-up Visit: All participants will return to the study site up to 28 days after the last dose of study drug administration for assessment of potential AEs, recording of concomitant treatment use and to confirm appropriate contraception usage.~ASSESSMENTS Tumor Assessments: Tumor assessments will include all known or suspected disease sites. Computerized tomography (CT) or Magnetic resonance imaging (MRI) scans of Chest Abdomen and Pelvis and MRI of the brain will be performed at Screening and repeated every 12 weeks ±1 week until the end of treatment. For all tumor assessments, the method of assessment that was used at Screening will be used throughout the study. Tumor assessment will be repeated at the end of treatment if more than 6 weeks have passed since the last evaluation. Assessment of response will be made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Confirmation of response will be required ≥4 weeks after initial response is observed.~Safety Assessments: The following parameters will be assessed - Physical examination, vital signs, Eastern Cooperative Oncology Group Performance score (ECOG PS), safety lab data, 12 lead electrocardiogram (ECG). Unscheduled clinical laboratory measurements may be obtained at any time during the study to assess any perceived safety concerns.~Adverse event reporting: All observed or volunteered AEs regardless of treatment group or suspected causal relationship to the investigational product(s) will be reported as per regulatory requirements.~End of Study: The end of study is defined as 1 year after the last participant first visit (LPFV) date in the study. At the end of study, participants who are on treatment and benefiting from dacomitinib treatment will be switched to commercially available dacomitinib if considered appropriate by the investigator, as soon as feasible. | This is a Phase 4, open label, single arm, multi-center, prospective clinical trial of dacomitinib that will be performed in India. This study will enroll a sufficient number of participants to ensure that 100 participants are treated with dacomitinib. The primary objective of this study is to assess the safety and tolerability of dacomitinib. The secondary objective is to evaluate antitumor activity of dacomitinib by objective response rate and duration of response. |
Gastric cancer represents one of the common malignant tumors in China, with high incidence and mortality rates. Surgery is the conventional treatment option for early and intermediate stage gastric cancer, but the diagnosis in the early stage of gastric cancer remains a challenge to clinical practitioners. Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA with an average size of 166 bp, mixed with cell-free DNA (cfDNA) of other sources in blood circulation. ctDNA is reflecting the most up-to-date status of the tumor genome. Hence, it is considered as a novel biomarker for tumors, which can be qualitative, quantitative, and used for disease monitoring. This study is designed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) as a clinical index in the diagnosis and prognosis of gastric cancer. The primary purpose of this trial is to describe the profile of ctDNA methylation in gastric cancer. The second purpose is to demonstrate the correlation between the plasma ctDNA methylation status and the diagnosis and prognosis of patients with early and intermediate stage gastric cancer. | The primary purpose of this trial is to describe the profile of ctDNA methylation in gastric cancer. The second purpose is to demonstrate the correlation between the plasma ctDNA methylation status and the diagnosis and prognosis of patients with early and intermediate stage gastric cancer. |
Assertive community treatment (ACT) is a community-based, patient-centered, and rehabilitation-oriented model based on multidisciplinary service teams. It has been proved to be suitable for the management of patients with severe mental disorder in the community. In this study, we aimed to investigate the effectiveness of ACT in an urban district of Shanghai with a larger sample size and a 24-month duration of follow up. We hypothesized that patients assigned into ACT would show better improvement in psychiatric symptoms and social function.The study protocol was approved by the Institutional Review Board in Shanghai Mental Health Center.~Aim of the study: 1.1 To explore the effectiveness of assertive community treatment in patients with schizophrenia. 1.2 The patients were followed up for 24 months to explore the duration of ACT.~Introduction of the study: Patients who previously diagnosed as schizophrenia according to International Classification of Diseases 10th Revision (ICD-10) in the psychiatric hospitals would receive basic public health service in the community. The selected schizophrenic patients were randomly assigned into intervention group and control group by a computer randomization algorithm. During the following 2 years, the control group received basic public health services in the community while the intervention group received ACT. Clinical assessments were conducted at baseline and every 6 months till the end of the 2-year study. A single-blind method was used, in which all the assessments were independently completed by trained psychiatrists who didn't know the grouping.The Positive and Negative Symptoms Scale (PANSS) and the Personal and Social Performance Scale (PSP) were measured at baseline and every 6 months during the study. | Assertive community treatment (ACT) is a community-based, patient-centered, and rehabilitation-oriented model based on multidisciplinary service teams. It has been proved to be suitable for the management of patients with severe mental disorder in the community. In this study, we aimed to investigate the effectiveness of ACT in an urban district of Shanghai with a larger sample size and a 24-month duration of follow up. We hypothesized that patients assigned into ACT would show better improvement in psychiatric symptoms and social function. |
The investigators designed the Child-Caregiver Interaction Observation Scale（CCIOS）to assess social communication behaviors, stereotyped behaviors for children with autism spectrum disorder(ASD) via a 20-min video of interactions between a caregiver and a child. The original CCIOS coding scheme consists 23 items. The score range for each item is 0-4, with higher scores being indicative of more atypical behavior. The investigators conduct this study to determine items for inclusion in the final CCIOS coding scheme through exploration of item correlations, establish the cutoff score of CCIOS for ASD and evaluate the reliability and validity of CCIOS.~It is of importance to accurately distinguish children with ASD from those with Global Developmental Delay (GDD) and Language Disorder (LD) without ASD, sometimes, it's very difficult in children with mental ages below 2 years. This differentiation has strong implications for treatment recommendations and may also inform long-term prognosis. In this study, The investigators planned to recruit 60 children with ASD and 60 children with GDD/LD aged from 18 months to 48 months. The reliability evaluation include test-retest reliability and inter-rater reliability. DSM-5 criterion is used as the gold standard. Validity is assessed by determining the correlation and consistency between CCIOS and DSM-5 criterion. | The investigators designed the Child-Caregiver Interaction Observation Scale（CCIOS）to assess social communication behaviors, stereotyped behaviors for children with autism spectrum disorder(ASD) via a 20-min video of interactions between a caregiver and a child. The original CCIOS coding scheme consists 23 items. The score range for each item is 0-4, with higher scores being indicative of more atypical behavior. The aim of the study is to determine items for inclusion in the final CCIOS coding scheme through exploration of item correlations, establish the cutoff score of CCIOS for ASD and evaluate the reliability and validity of CCIOS. The reliability evaluation include test-retest reliability and inter-rater reliability. DSM-5 criterion is used as the gold standard. Validity is assessed by determining the correlation and consistency between CCIOS and DSM-5 criterion. |
The therapeutic hypothesis for the use of losmapimod in COVID-19 disease is that increased disease severity and consequent increased mortality is caused by p38 mitogen-activated protein kinase (MAPK)-mediated exaggerated acute inflammatory response resulting from SARS-CoV-2 infection.~It is anticipated that the early initiation of p38α/β inhibitor therapy in patients with moderate COVID-19 will prevent further clinical deterioration and reduce the need for both increased respiratory support as well as mortality. This is the main hypothesis for this study.~To address this hypothesis, Fulcrum Therapeutics is conducting a Phase 3, multicenter, randomized, double-blind, placebo-controlled study that will evaluate the safety and efficacy of losmapimod versus placebo in subjects with COVID-19 disease.~Losmapimod is currently in Phase 2 clinical trials for the treatment of facioscapulohumeral dystrophy (FSHD) and has previously been administered to more than 3600 adult healthy volunteers and subjects including participants in a large Phase 3 trial which looked at clinical outcomes and safety after major cardiovascular events.~Patients will participate in this study for approximately 34 days. The total treatment duration will be 14 days. Subjects will be evaluated during a 3 day pre-treatment period (Screening and Baseline Visits) to establish pre-treatment baseline assessments and eligibility. Subjects will then be randomized to treatment with losmapimod or placebo for 14 days and assessed frequently for changes from pre-treatment in various clinical outcome assessments. Patients must have a confirmed diagnosis of COVID-19 by viral PCR prior to randomization and first dosing. Patients will receive 15 mg of losmapimod, or placebo twice daily given as two 7.5 mg tablets per dose by mouth: for a total of 4 pills or 30 mg daily for 14 consecutive days. All study visits during the first week of treatment are anticipated to be conducted in the inpatient setting while later visits are anticipated to be conducted as outpatient.~The primary endpoint of the study is to assess the efficacy of losmapimod tablets compared with placebo for the treatment of COVID-19 when administered concurrently with the local standard of care. Secondary endpoints include evaluating the effect of losmapimod compared with placebo on clinical outcomes, clinical status, effect on survival, safety, and tolerability and to characterize changes in the levels of SARS-CoV-2 infection. | The therapeutic hypothesis for the use of losmapimod in COVID-19 disease is that increased mortality and severe disease is caused by p38 mitogen-activated protein kinase (MAPK)-mediated exaggerated acute inflammatory response resulting from SARS-CoV-2 infection.~The study Sponsor hypothesize's that the early initiation of p38α/β inhibitor therapy in patients hospitalized with moderate COVID-19 who are at increased risk of a poor prognosis based on older age and elevated systemic inflammation will reduce clinical deterioration including progression to respiratory failure and death.~To address this hypothesis, Fulcrum Therapeutics is conducting a Phase 3, multicenter, randomized, double-blind, placebo-controlled study that will evaluate the safety and efficacy of losmapimod versus placebo in subjects 50 and older who are hospitalized with moderate COVID-19 disease. |
The cause of cryptogenic organizing pneumonia (COP) was unknown, but studies had shown that certain bacteria, viruses, or specific pathogens could be detected in bronchoalveolar lavage fluid (BALF) in some patients, and these pathogenic microorganisms may be the cause of COP. Specimens were obtained by conventional methods (sputum, blood, BALF or lung puncture fluid) for microbiological detection. Due to the influence of the quality of acquired specimens, specimen preservation and transportation which were influenced by external factors, many patients did not get good test results, which affected the diagnosis and subsequent treatment of patients. Next-generation sequencing (NGS) which could determine hundreds of thousands to millions of DNA molecules in parallel at one time, and efficiently sequence or fragment of pathogenic microorganisms. NGS had greatly improved the detection rate of pathogenic microorganisms. This study aimed to screen pathogenic microorganisms in BALF and lung puncture fluid of COP patients by NGS, and further clarify the correlation between occurrence of COP and pathogenic microorganisms. | The etiology of cryptogenic organizing pneumonia (COP)was not clear, but previous studies have shown that in some patients, some pathogen could be detected in bronchoalveolar lavage fluid (BALF), and may be one of the causes of COP. This study aimed to screen the pathogenic microorganisms in BALF and lung puncture fluid of the patients with COP through the next-generation sequencing to further clarify the correlation between the incidence of COP and pathogenic microorganisms. |
Mucus hypersecretion plays an essential role in bronchiectasis. It has been deduced that reducing the production of mucus or improving the clearance of sputum in the airway is the key to break down this vicious cycle and enhance the therapeutic efficacy for bronchiectasis.~The investgators aimed to assess whether the long-term use of oral An'Ningpai Enteric Soft Capsules (300 mg, three times daily) might reduce the rate of exacerbations and improve the quality of life in patients with bronchiectasis. | The objective of this study was to assess whether the long-term use of oral An'Ningpai Enteric Soft Capsuleson (300 mg, three times daily, 12 months) might reduce the incidence of exacerbations and improve the quality of life in patients with Non-CF bronchiectasis. |
Multi-center, double-masked, randomized trial of microcurrent stimulation for the treatment of patients affected with dry age-related macular degeneration. | Evaluate the safety and efficacy of microcurrent stimulation therapy for patients with dry age-related macular degeneration. |
The main purpose of this study is to assess the efficacy of TAS-303 in female patients with stress urinary incontinence (SUI) compared with placebo as measured by the percent change in the average SUI episode frequency per 24 hours from baseline at week 12. | The purpose of this study is to evaluate the efficacy and safety of TAS-303 in female patients with stress urinary incontinence. |
The number of elderly patients (>80 years) is increasing and a large proportion of these patients will require surgery and anesthesia within the next decades. Elderly patients are at higher risk of major morbidity and mortality and are characterized by a reduction in cardiac output, liver function and renal function. These physiological changes influence pharmacodynamics and pharmacokinetics of drugs administered during anesthesia.~Rocuronium is a nondepolarizing neuromuscular blocking drug with an onset time of approximately 70 s and a clinical duration of action of approximately 50 min. according to previous studies. During anesthesia rocuronium is administered to facilitate intubating conditions and reduce the trauma to the larynx and vocal cords. Rocuronium is primarily metabolized in the liver (70 % unmetabolized via the bile) and excreted via the kidneys.~Onset time and duration of action of rocuronium should be assessed by objective neuromuscular monitoring. Also, this reduces the risk of residual neuromuscular block which is defined as a train of four (TOF) ratio less than 0.9. Especially elderly patients have a high incidence of residual neuromuscular block.~The collected data regarding the effect of rocuronium in elderly patients may change the treatment so these patients receive the correct dose for optimal intubating conditions. Also, detection of duration of action of different doses of rocuronium may reduce the risk of residual block and postoperative respiratory complications~The aim of this study is to determine the onset time, duration of action and effect on intubating conditions after rocuronium 0.3 mg/kg and 0.9 mg/kg in patients with age ≥ 80 years. | The number of elderly patients above 80 years is increasing and a large proportion of these patients will require surgery and anesthesia.~During anesthesia neuromuscular blocking agents (NMBA) are administered to facilitate intubating conditions and reduce the trauma to the larynx and vocal cords. There is a risk of residual neuromuscular block when using NMBAs like rocuronium.~The aim of this study is to determine the onset time, duration of action and effect on intubating conditions after rocuronium 0.3 mg/kg and 0.9 mg/kg in patients with age ≥ 80 years. |
In China, the incidence of esophageal cancer has declined in recent years, but the mortality rate has been ranked fourth. Morbidity and mortality were ranked sixth and fourth in all malignancies, respectively. Therefore, esophageal cancer has always been a major malignant tumor that threatens the health of our residents. We designed a multi-center, randomized controlled, phase II clinical study of camrelizumab with or without radiotherapy for the treatment of recurrent or metastatic esophageal cancer that has progressed after chemotherapy. The purpose of this study is to observe and evaluate the efficacy and safety of camrelizumab with or without radiotherapy for advanced esophageal cancer. | The purpose of this study is to observe and evaluate the efficacy and safety of Camrelizumab combined with or without radiotherapy for the treatment of recurrent or metastatic esophageal cancer that has progressed after chemotherapy |
Asthma is a chronic disease and affects approximately 300 million people worldwide. Of these patients 3-10% have severe asthma which is defined as asthma remaining uncontrolled despite treatment with high-dose inhaled glucocorticoids combined with other controllers (long-acting β2-agonist, long-acting antimuscarinic agent, leukotriene receptor antagonist or theophylline) and/or treatment with systemic glucocorticoids for at least 6 months. Severe asthma causes a high amount of medical expenses in asthma. For patients suffering from severe uncontrolled asthma, an IL-5 antibody (mepolizumab) has been approved for therapy when a type 2 inflammation was present. Treatment is well tolerated and a significant reduction of exacerbations, oral glucocorticoid use was reported. Another IL-5 antibody (reslizumab) and an IL-5 receptor antibody (benralizumab) are available now.~Patients with severe eosinophilic asthma will be placed on biologics if they continue to be uncontrolled under maximal therapy or if they are only controlled under oral corticosteroids. Among biologics, 80% of patients improve, 20% are non-responders, but there is no way to identify them early. Among the responders, about 30% respond very well (so-called super responders), the rest shows moderate improvements. The main problems at the moment are that lung function improvements are only delayed, the response (or non-response) can only be reliably estimated after 4 to 12 months. This leads on the one hand to prolonged use of medication in non-responders (overtreatment), on the other hand to unjustified and premature termination of therapy (undertreatment) (GINA report 2019).~Study Rationale Functional lung MRI has the potential to show early changes in lung microstructure, regional ventilation and perfusion and thus has the potential for early detection of therapy response. Very promising results of dynamic regional ventilation and perfusion mapping using phase resolved functional lung (PREFUL) MRI have been shown recently. This technique holds the promise to mature into a patient friendly sensitive MRI spirometry test, with novel clinically relevant information to guide clinical decision making and improve patient monitoring. PREFUL MRI typically uses standard 1.5T or 3T MRI equipment and is based on a routine gradient echo fast low angle shot (FLASH) sequence. PREFUL is well suited also for children, because it is a free breathing exam without the need for i.v. contrast and has a relatively short examination time. The ventilation, perfusion and dynamic flow-volume loop maps are reconstructed entirely after the image acquisition using complex registration and post processing algorithms developed and validated at Hannover Medical School. Preliminary unpublished data show that PREFUL MRI may detect changes in regional ventilation 3 months after anti IL 5 antibody therapy treatment.~However, if functional lung MRI can reliably detect changes at 3 months of Mepolizumab treatment and can predict long term patient outcome is still unknown, which is of high clinical relevance for future clinical decision making.~The aim of this study is to examine if early treatment changes of Mepolizumab treatment can be detected at 3 months measured by functional lung MRI and predict clinical outcome at 12 months of treatment. | Patients with severe eosinophilic asthma will be placed on biologics if they continue to be uncontrolled despite maximized inhalation therapy or if they are only controlled under oral corticosteroids. Among biologics, 80% of patients respond to treatment and improve clinically, but approximately 20% are non-responders and up to date no established predictive factors for treatment response exist. Among the responders, about 30% respond very well (so-called super responders), the rest shows moderate improvements. As the lung function, one main criterion to evaluate treatment response improves in most patients with delay, the response (or non-response) to treatment can only be reliably estimated after 4 to 12 months. This can lead to prolonged use of medication in non-responders (overtreatment) on one hand and to unjustified and premature termination of therapy (undertreatment) on the other hand (GINA report 2019).~Functional lung MRI has the potential to show early changes in lung microstructure, regional ventilation and perfusion and thus has the potential for early detection of therapy response. Very promising results of dynamic regional ventilation and perfusion mapping using phase resolved functional lung (PREFUL) MRI have been shown recently.~However, if functional lung MRI can reliably detect treatment effects under Mepolizumab therapy and can help to predict a long-term patient outcome is still unknown. As these findings could directly influence clinical decision making this question is of high clinical relevance. |
The third most common cancer in both male and female is colorectal carcinoma (CRC) worldwide. In India, it is the fourth most common cause of cancer in males and third most common cancer in females. The age - standardized rates of CRC in India have been estimated to be 4.2 and 3.2/100000 for males and females, respectively. Age, smoking and colonic adenoma along with family history is considered as traditional risk factors for CRC. The US National Polyp study demonstrated that colonoscopy and polypectomy could prevent 76% to 90% of colorectal cancers. The vast majority of CRC result from malignant transformation from adenomas. This is called adenoma - carcinoma sequence, these adenomatous polyps grows slowly over many years and malignant transformation eventually occurs. The time span for this transformation is on an average 10 years. So, the detection and removal of polyp at early stage on adenoma - carcinoma sequence should benefit in preventing CRC.~The prevalence of adenoma, utilization of colonoscopy for its detection and subsequent reduction in CRC has been well studied and established in western population. This has led to formulation of national screening colonoscopy programs elsewhere. However, data from Indian subcontinent is scanty. In current study, at a large tertiary care center, we aimed to study prevalence of colonic polyps and adenoma who are undergoing diagnostic colonoscopy using high definition colonoscopy and characterizing with Narrow Band Imaging and to find associated demographic, social, personal and family related risk factors in patients with adenomas.~Methodology:~This will be a prospective, single center, observational study. All subjects referred for diagnostic colonoscopy will be prospectively enrolled.~Enrollment:~All subjects referred for the diagnostic colonoscopy will be enrolled. A member of the research team will approach each subject to discuss participation in the study, including background of the proposed study, inclusion and exclusion criteria, benefits and risks of the procedures and follow-up. If this is of interest to the subject, the informed consent form is discussed and presented. The subject must sign the consent form prior to enrollment. This form will have prior approval of the study site's Institutional Review Board (IRB). Failure to obtain informed consent renders the subject ineligible for the study.~Study equipment~Colonoscope:~Olympus HDWL colonoscope will be used to perform colonoscopies. Technical specifications include outer diameter 13.2 mm, instrument channel diameter 3.7 mm, air-water suction channels, field of view 170 degrees, 4-way angulations (180 degrees up and 180 degrees down, 160 degrees right and left), working length, 168 cm.~Colonoscopy procedure and definitions~For all patients, either moderate sedation with intravenous midazolam or conscious sedation with intravenous propofol will be administered in a standard fashion prior to undergoing colonoscopy.~The colonoscope will be inserted and cecum will be intubated. Photo documentation of the cecum will be performed. The colonic mucosa will be carefully visualized upon withdrawal of the colonoscope.~The time from the point of insertion of the colonoscope into the rectum to the intubation of cecum will be recorded with a stop watch by a research coordinator and will be documented as the insertion time.~The time spent in inspecting the mucosa during withdrawal of the colonoscope will be documented as the withdrawal time. During withdrawal of the colonoscope the stop watch will be stopped whenever mucosa is being cleaned, fluid/solid debris is suctioned or a polyp is being removed to ensure that the withdrawal time is the actual representation of the mucosal inspection time. Meticulous technique will be employed during the withdrawal phase with special efforts to visualize portions of colonic mucosa on the proximal aspects of haustral folds, flexures and valves.~All polyps detected will be documented: size, location, and morphology (using the Paris classification - Appendix A and Narrow Band Imaging classification - NICE and JNET). Photo documentation of the polyps will be performed.~Polyps will then be removed with a biopsy forceps or snare and sent for histopathological evaluation, each in a separate jar and labeled accordingly.~The bowel preparation will be evaluated and graded according to previously reported criteria using the Boston Bowel Preparation Scale. Complications including post colonoscopy pain, perforation or gastrointestinal bleeding (requiring intervention) will be recorded.~Adverse events:~The primary investigator at each site will monitor any adverse events reported to the study staff and determine if it's related to the study procedures including standard colonoscopy at the respective site. All adverse events will be monitored until a satisfactory resolution and will be reported to the local IRB within 5 days of knowledge. A table will be maintained for the adverse events in each arm and in case of any statistically significant adverse even rate in any arm, the primary investigator will make the decision to remove the treatment arm or stop the study. Because the risks of this proposed study are low, this program will not require a Data Safety and Monitoring Board. Instead, the Principal Investigator and clinical Site Investigators performing the endoscopies will be responsible for implementing a detailed Data and Safety Monitoring plan in compliance with the IRB guidelines.~Data integrity and safety:~All paper charts pertaining to the patient will be kept under lock and key in coordinators office away from the endoscopy area. The data will be entered in to a data base weekly after collection of histology reports. The data is password protected and stored on the AIG internal server where it will remain throughout the study. Computers and/or files will be password-protected. Only approved personnel by the IRB will have access to the file storage.~To protect subject confidentiality, each subject will be assigned a case study number. The subject's name is not to appear anywhere on the Case Report Forms (CRF's) or supporting documentation. A study log with the identifiable information will be kept in a separate folder to enable the investigators to assist in any research audit. No procedural data except the date of examination will be entered in to this log. | Colorectal carcinoma (CRC) is the third most common cancer in male and female worldwide. In India, it is the fourth most common cause of cancer in males and third most common cancer in female. Age, smoking, colonic adenomatous polyp, family history are traditional risk factor for CRC. The vast majority of CRC results from malignant transformation from adenoma, which is called as adenoma carcinoma sequence. These adenomatous polyps grows slowly over many years and malignant transformation eventually occurs over 10 years. So, the early detection and removal of polyp at early stage should benefit in preventing CRC. |
The objective of this study is to evaluate the ability of HVNI next generation nasal cannula designs to effect ventilation and related physiological responses relative to the current cannula design, with which there are published clinical outcomes data. It is hypothesized that next generation nasal cannula designs (Prosoft and Unicorn) will be comparable at relieving patient dyspnea while on HVNI, when compared to the conventional (Legacy) cannula. | This study will evaluate the ability of High Velocity Nasal Insufflation [HVNI] next generation nasal cannula designs to effect ventilation and related physiological responses relative to the conventional legacy cannula design. |
Comparison of Ventricular Tachycardia Ablation Strategies in Patients With Ischemic Cardiomyopathy (EPI VT) is a prospective multicenter randomized controlled study that is planned as a pilot study to include 100 patients. The aim of our study is to assess whether endocardial or endocardial-epicardial ablation is superior to the standard approach (i.e., Antiarrhythmic drugs) in the achievement of long-term ventricular tachycardia (VT) treatment success. Patients will be stratified into two groups depending on the history of taking antiarrhythmic medications (AAD) and each group will be further randomized 1:1 for endocardial and epicardial ablation vs endocardial only ablation in group who failed AAD. And in the group who didn't fail AADs patients will be randomized 1:1:1 into 3 groups: endocardial and epicardial ablation, endocardial only ablation or antiarrhythmic medications. Follow up planned at 3, 6 and 12 months, if VT recurrence is noted, repeated procedure (according to initially allocated group) or adjustment of medications (if AAD group) will be performed. Follow up at 3, 6 and 12 months is also planned after a repeat procedure/ medications adjustment.~Primary endpoints include freedom from documented VT episodes (> 30 seconds) at 12 months after the first ablation procedure or on antiarrhythmic medication and freedom from documented VT episodes (>30 seconds) at 12 months after the second ablation procedure or on two antiarrhythmics combined. | This is a prospective multicenter randomized open-label study aiming to assess whether endocardial or endocardial-epicardial ablation is superior to the standard approach (i.e., Antiarrhythmic drugs) in achievement of long-term ventricular tachycardia (VT) treatment success. |
PRG Science & Technology Co., Ltd. (PRG S&T) is developing Progerinin (SLC-D011) for the treatment of the rare aging diseases Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner Syndrome (WS).~Progerin, an abnormal splice variant of the inner nuclear membrane protein lamin A is implicated in the pathology of HGPS and WS. It is believed that the extremely strong binding between lamin A and progerin is responsible for the nuclear abnormality phenotype observed in HGPS. WS is caused by functional defect of WRN, RecQ4L DNA helicase and rapid accumulation of progerin in WRN deficient condition is thought to be the cause of premature aging in WS. PRG S&T has shown that Progerinin binds specifically to progerin reduces its expression in both HGPS and WS cells, Progerinin further prevents progerin-lamin A in HGPS cells. In a progeria mouse model (LmnaG609G/G609G), treatment with Progerinin via intraperitoneal (i.p) injection (20 mg/kg, twice per week) could increase the body weight and extend the life span of LmnaG609G/G609G mice up to 21 weeks. In the LmnaG609G/+ mouse model, improved morphology such as status of coat hair and body size, increased body weight and extended life span for about 16 weeks was noted following Progerinin treatment. In addition, Progerinin can suppress muscle weakness including the heart muscle. Safety pharmacology studies did not indicate any Progerinin-related effects on vital organs and systems including respiratory, cardiovascular and central nervous system.~Prior to studies in the disease states, this study PRG-PRO-001, an initial first-in-human study, will be conducted in healthy volunteers to assess the safety, tolerability and pharmacokinetics of Progerinin. PRG-PRO-001 is a Phase I, Randomized, Double-blind, Placebo-Controlled, Single Ascending Dose (SAD) Study including a food interaction study, followed by a Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Profile of Progerinin in Healthy Volunteers. This is a first-in-human study. The study aims to determine the safety and tolerability of Progerinin after single and multiple doses in healthy volunteers and to evaluate the pharmacokinetics (PK) of Progerinin after single and multiple dose administrations in healthy volunteers. The estimated enrollment is around 56 healthy volunteers, with 40 subjects estimated for the SAD phase and 16 subjects for the MAD Phase at one site in the USA.~Expanded Access Program is available. For more details, please use the link in the References Section below to access our company's main webpage on Expanded Access Program. | PRG-PRO-001 is a Phase I, Randomized, Double-blind, Placebo-Controlled, Single Ascending Dose (SAD) Study including a food interaction study, followed by a Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Profile of Progerinin in Healthy Volunteers. This is a first-in-human study. The study aims to determine the safety and tolerability of Progerinin after single and multiple doses in healthy volunteers and to evaluate the pharmacokinetics (PK) of Progerinin after single and multiple dose administrations in healthy volunteers. |
As the population ages and medical progress is made, many elderly patients that previously would not have been candidates for surgery are now undergoing operations. In this group of older patients, brain dysfunction after anesthesia and surgery is well recognized, naming post-operative cognitive dysfunction.~Post-operative cognitive dysfunction (POCD) is a term used to describe subtle changes in cognition, such as memory and executive function. The most commonly seen problems are memory impairment and impaired performance on intellectual tasks. In severe cases, it can lead to inability to perform daily living functions. The reported incidence figures for postoperative cognitive dysfunction vary depending on the group of patients studied, the definition of POCD used, the tests used to establish the diagnosis and their statistical evaluation, the timing of testing, and the choice of control group. The diagnosis of POCD relies on the availability of the neuropsychological tests. In a large prospective multicenter cohort study, it was found that the presence of cognitive dysfunction 3 months after noncardiac surgery was associated with an increased mortality. Furthermore, patients with cognitive decline at 1 week had an increased risk of leaving the labor market prematurely and a higher prevalence of time receiving social transfer payments. The mechanisms leading to cognitive impairment after anesthesia and surgery are not yet fully clear. The risk factors for developing POCD are related to patient characteristics, type of operation and anesthetic management.~Cardiovascular, respiratory, hepatic, and renal insufficiency are all associated with impaired brain performance. It is theoretically obvious that an adequate intraoperative oxygen supply for all vital organs is essential if postoperative cerebral dysfunction is to be avoided. Casai et al found that brain desaturation (rSO2 decrease <75% of baseline) occurred in 40% of elderly patients after noncardiac surgery, and the cerebral desaturation was linked with a high incidence of POCD. A recent systematic review shows that reductions in cerebral oxygen saturation (rSO2) during cardiac surgery may indicate CPB cannula malposition, particularly during aortic surgery. However, only weak evidence links low rSO2 during cardiac surgery to POCD.~POCD is a well-recognized clinical phenomenon of multifactorial origin; emboli, hypoperfusion, inflammation, and patient's preoperative cerebral dysfunction. Meticulous surgical and anesthesiological techniques are important for preventing complications and keeping the risk of POCD to a minimum.~The EEG is an electrophysiological monitoring method used to record electrical activity of the brain, including normal and abnormal activity. In recent years, numerous clinical studies were performed to evaluate whether the use in intraoperative electroencephalography (EEG) to control the depth of anesthesia has any effect on POCD.~Recently it was confirmed that intraoperative neuro-monitoring for depth of anesthesia is associated with a lower incidence of delirium. However it is unrelated to the incidence of POCD. The most common available monitor for depth of anesthesia is the Bispectral index, developed more than 20 years ago. The device's output is based on electroencephalographic (EEG) signals from the frontal lobe (monitors brain activity) in combination with electromyographic (EMG) waves (monitors muscle activity). The BIS produces a number ranging from 0 -100, which matches the patient's level of consciousness (awake, sedated or unconscious) under GA.~Despite its limitations, over-anesthesia as monitored by BIS, was at-least correlative with POD (but not with POCD). Therefore, it is hopeful that an even more precise evaluation of the level of anesthesia will improve POD prediction (and thereby prevention) even further. On the other hand the measure of depth of anesthesia by itself does not provide sufficient prediction for POCD.~The investigators have recently that brain injury is demonstrated by interhemispheric desynchronization, which is recognized by our new algorithm, which monitors electrophysiological markers of attention and of perception. This algorithm was based on a previous set of studies, which showed the ability to decompose the entire multi-electrode EEG/ ERP sample to a superposition of attention and perception processes, spread in space (over the scalp) and time (hundreds of milliseconds). Our algorithm is unique in the ability to extract the needed perceptual and attentional information indicating depth of anesthesia and hemispheric damage (manifested by interhemispheric desynchronization) in real time every 30 seconds and with a minimal electrodes' setup.~The aims of this proof of concept study are: (i) to find-out whether attention processes might be in association with brain frailty. (ii) to find our whether brain injury which is expressed by interhemispheric synchronization is is associated with POCD; (iii) to find out whether the level of anesthesia, as measured electrophysiological by perception might be linked primary to POCD. | As the population ages and medical progress is made, many elderly patients that previously would not have been candidates for surgery are now undergoing operations. In this group of older patients, brain dysfunction after anesthesia and surgery, naming post-operative cognitive dysfunction, is well known.~Post-operative cognitive dysfunction (POCD) is a term used to describe subtle changes in cognition, such as memory and executive function. The most commonly seen problems are memory impairment and impaired performance on intellectual tasks. In severe cases, it can lead to inability to perform daily living functions. It was previously found that the presence of cognitive dysfunction 3 months after non-cardiac surgery was associated with increased mortality. The mechanisms leading to cognitive impairment after anesthesia and surgery are not yet fully clear. The risk factors are related to patient characteristics, type of operation and anesthetic management.~The investigators have recently shown that using different electrophysiological markers, they can monitor attention and perception which might be associated with brain frailty and brain injury.~The aims of this proof of concept study are: (i) to find-out whether attention processes might be in association with brain frailty. (ii) to find our whether brain injury which is expressed by interhemispheric synchronization is is associated with POCD; (iii) to find out whether the level of anesthesia, as measured electrophysiological by perception might be linked primary to POCD. |
This is a clinical pilot study using oral beta-glucan on patients with advanced stage III-IV melanoma without evidence of disease receiving adjuvant Pembrolizumab. The aim is to see whether beta-glucan treatment in combination with Pembrolizumab may provide augmented immunologic phenotypes such as decreased peripheral MDSCs, enhanced T effector cell function, or enhanced cytokine production in the peripheral blood or plasm of enrolled subjects. Secondary outcome measures will include clinical endpoints such as recurrence, progression free survival and overall survival. | The purpose of this study is to determine how beta-glucan affects the immune system in subjects with melanoma. |
Aim: This study was conducted as a randomized controlled experimental study to examine the effect of abdominal massage with ginger and lavender oil on constipation in elderly individuals.~Design: The study was completed with 40 elderly individuals in Kayseri nursing home, including 20 in intervention and 20 in control group who met the criteria for inclusion in the study. In the study, written informed volunteer consent was obtained from the individuals with the approval of the ethics committee and the permission of the institution. The data were collected by the researcher using the Questionnaire Form, Bristol Stool Scale, Rome IV Criteria, Constipation Severity Scale and Mini Mental Test.~The elderly individuals in the intervention group underwent aromatherapy massage with ginger and lavender oils for a period of five days and 15 minutes on weekdays for four weeks according to the abdominal massage application protocol. No application was made to individuals in the control group. The Bristol Stool Scale and Constipation Severity Scale were re-applied to the individuals in the intervention and control group before, during the second week of practice and at the end of practice (fourth week). | Aim: This study was conducted as a randomized controlled experimental study to examine the effect of abdominal massage with ginger and lavender oil on constipation in elderly individuals.~Design: The study was completed with 40 elderly individuals in Kayseri nursing home, including 20 in intervention and 20 in control group who met the criteria for inclusion in the study. In the study, written informed volunteer consent was obtained from the individuals with the approval of the ethics committee and the permission of the institution.~The elderly individuals in the intervention group underwent aromatherapy massage with ginger and lavender oils for a period of five days and 15 minutes on weekdays for four weeks according to the abdominal massage application protocol. No application was made to individuals in the control group. |
Liver cancer is the fourth leading cause of cancer-related deaths globally. Hepatocellular carcinoma (HCC) accounts for 70% to 85% of primary HCC and is the leading cause of death in patients with cirrhosis. We developed a novel no-touch combined directional perfusion radiofrequency ablation system.By inserting two or more electrodes around the tumor and activating them simultaneously.The hypertonic saline solution can be directed into the focal tissue from a lateral pore through a tube within the electrode to provide more uniform and thorough necrosis.The maximum ablation volume was increased while the loss of normal tissue in the non-injection direction was reduced, thus reducing the incidence of postoperative complications. Therefore, the purpose of this study was to evaluate the short-term efficacy of novel no-touch combined directional perfusion radiofrequency ablation in the treatment of small hepatocellular carcinoma with cirrhosis. | To evaluate the short-term efficacy of novel no-touch combined directional perfusion radiofrequency ablation in the treatment of small hepatocellular carcinoma with cirrhosis. |
Following the administration of one unit (approximately 200 mL) of convalescent plasma over one hour, the study proposes to determine the therapeutic efficacy (response rate) of convalescent plasma infusion in patients at high risk for mortality when infected by SARS-CoV-2 (COVID-19) by prevention of progression to severe or life threatening COVID-19 during the current hospitalization as determined by evaluating if the patient experienced the following the following: respiratory rate >30/min, Blood oxygen saturation <93%, partial pressure of arterial oxygen to fraction of inspired oxygen ration <300, or received a medical diagnosis of respiratory failure, septic shock or multiple organ dysfunction/failure. This will be captured from the daily physical exam/clinical assessment done as part of routine care and at discharge.~The study also proposes to determine the immunologic effects of convalescent plasma infusion as measured by serial SARS-CoV-2 Ag levels through RT-PCR measured by CoV PCR collected at enrollment, day 7 and discharge.~Finally, the study intends to measure normalization of laboratory parameters for risk which will be documented every 3 days while the patient is hospitalized until the time that lab value returns to within the institution's normal range. | This study proposes to evaluate the therapeutic efficacy, immunologic effects and normalization of laboratory parameters for patients at high risk for mortality when infected by SARS-CoV-2 (COVID-19) when administered one unit (approximately 200 mL) of convalescent plasma administered over a period of one hour. Following administration of the convalescent plasma, physical exam/clinical assessment information is collected daily and routine lab result data is collected every three days. |
Covid-19 pneumonia became the worldwide, serious health problem, affecting nearly 20 million people and causing nearly one million deaths. The health systems of many countries are overwhelmed with the increased need of medical care, of the number of available hospital beds, intensive care beds and ventilators. The proper management of available resources becomes now critical. Ultrasound can reliably detect morphologic changes associated with pneumonia, especially in Covid-19 pneumonia, where the involvement of superficial parts of the lungs predominates. Additionally, protocols were elaborated which unify the investigation procedure and improve the intra- and interrater reliability. Moreover, ultrasound is a time and cost-effective and widely available method. Finally, it is much easier to take measures, which minimize the risk of viral transmission between patients for ultrasound equipment than for other lung imaging devices such as x-ray or computer tomography. The aim of this study is to evaluate the efficacy of the ultrasound of the lungs in predicting the length of hospitalization, of intensive care and of mechanical ventilation in Covid-19 pneumonia. Further aims are the evaluation of the efficacy of the ultrasound of the lungs in predicting the risk of death and of the long-term pulmonary complications as consequences of Covid-19 pneumonia. The study will include repeated ultrasound investigations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients admitted to the University Hospital in Cracow (Poland) performed during hospitalization and after discharge. The relation of severity and the course of pneumonia revealed by ultrasound to clinical condition, long term complications, use of mechanical ventilation, admission to intensive care and results of laboratory tests will be examined. | Ultrasound can reliably detect morphologic changes associated with pneumonia. Additionally, protocols were elaborated which unify the investigation procedure and improve the intra- and interrater reliability. Moreover, ultrasound is a time and cost-effective and widely available method. The aim of this study is to evaluate the efficacy of the ultrasound of the lungs in predicting the length of hospitalization, of intensive care and of mechanical ventilation in Covid-19 pneumonia. Further aims are the evaluation of the efficacy of the ultrasound of the lungs in predicting the risk of death and of long-term pulmonary complications as consequences of Covid-19 pneumonia. |
This is one of two replicate randomized, double-blind, placebo-controlled, parallel arm trials to determine the safety and efficacy of two different dose levels of SEL-212 compared to placebo. 112 and 153 patients, stratified as to the presence or absence of tophi, were randomized in a 1:1:1 allocation ratio prior to Baseline to receive treatment with one of two dose levels of SEL-212 or placebo every 28 days for approximately 6 months in each trial respectively (SEL-212/301 and SEL-212/302). The SEL-212 doses differed as to the SEL-110.36 component. Participants received SEL-037 administered at a dose of 0.2 mg/kg via intravenous (IV) infusion immediately after receiving SEL-110.36 at a dose of either 0.1 mg/kg (SEL-212 low-dose) or 0.15 mg/kg (SEL-212 hig-dose) via IV infusion. The placebo consisted of normal saline.~Upon completion of the 6-month double-blinded, placebo-controlled portion of the study, SEL-212/301 continued in a blinded, placebo-controlled 6-month extension. This provided up to 12 months of continuous treatment with SEL-212 in a placebo controlled fashion.~Placebo subjects who completed both phases of the study will be offered enrollment in an open-label extension study for treatment with SEL-212 (SEL-212/303).~Efficacy assessments were conducted at intervals that are appropriate to determine treatment effect with samples for the primary endpoint drawn during Treatment Period 6. Safety was monitored throughout the study with an independent data safety monitoring board (DSMB). | This is one of two replicate randomized, double-blind, placebo-controlled, parallel arm trials to determine the safety and efficacy of two different dose levels of SEL-212 compared to placebo. 112 and 153 patients, stratified as to the presence or absence of tophi, were randomized in a 1:1:1 allocation ratio prior to Baseline to receive treatment with one of two dose levels of SEL-212 or placebo every 28 days for approximately 6 months in each trial respectively (SEL-212/301 and SEL-212/302). Analysis of primary and key efficacy will be performed at Day 28 of Treatment Period 6. Safety was monitored throughout the study. |
Esophageal cancer ranks the fourth in mortality and the sixth in incidence among cancers in China according to the latest report of cancer epidemiology. Although the development of neoadjuvant therapy and radical esophagectomy have improved the prognosis of esophageal cancer patients, dysphagia and digestive tract reconstruction can cause malnutrition and infection-related complications. Postoperative enteral and parenteral nutrition have proved to be effective in improving outcomes after esophagectomy. However, whether to provide a preoperative nutritional support for patients with resectable esophageal cancer remains controversial.~This prospective randomized controlled trial will evaluate the effects of preoperative enteral immunonutrition in esophageal cancer patients undergoing neoadjuvant therapy. The purpose of this study is to determine whether preoperative immune-modulating diet before surgery can improve the rate of complications and other perioperative outcomes.~The sample size is estimated with the hypothesis that preoperative immunonutrition during the neoadjuvant therapy can reduce postoperative nutrition and immune-related complications after esophagectomy. According to the previously published articles, the required sample size of interventional and control arm (ratio=2:1) was calculated as 137 cases and 69 cases to detect the reduction in related complications from 50% to 30% based on a bilateral significance level (α) of 0.05 and a power of test (1-β) of 0.80. Considering an estimated drop rate of 15%, the minimum sample size of this study is 244 patients, 162 cases in the interventional group and 82 in the control group. After signing the informed consent, every eligible participant will be randomized into either group based on a computer-generated random number. Blinding will not be applied to patients and surgeons due to the difficulty in clinical practice but outcomes assessor will be masked. | This randomized controlled trial will evaluate the effects of preoperative enteral immunonutrition in esophageal cancer patients undergoing neoadjuvant therapy. The purpose of this study is to determine whether preoperative immune-modulating diet before surgery can improve the rate of complications and other perioperative outcomes. |
Study Rationale~COVID-19, the name given to the clinical syndrome associated with the newly recognized virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become pandemic with a mortality estimated based on reports from China between 1-3% and complications among hospitalized patients leading to up to 15-25% admissions to the Intensive Care Unit (ICU). The clinical presentation includes both upper and lower respiratory tract infection, but patients may also be asymptomatic.~The term cytokine storm calls up vivid images of an immune system gone awry and an inflammatory response flaring out of control. The term has captured the attention of the public and the scientific community alike and is increasingly being used in both the popular media and the scientific literature. Indeed, a few publications have indicated an important part of the complications in COVID-19 are related to a cytokine storm.~In that regard, the investigators have recently completed a successful phase 1b clinical trial of immune-modulation in patients with sepsis (NCT03925857).~Taken together, in patients with moderate to severe COVID-19, there may be a comparable underlying immunological mechanism of action that may be similar to the one that was recently shown by us in sepsis, which is a hyper-inflammatory pathway associated with increased death. 40 previous trials using monoclonal antibodies against a single cytokine in septic patients have failed in sepsis pointing out that there is a need to modify the cytokine storm rather than treating with a single anti-cytokine.~This solution is provided by Allocetra-OTS, which targets macrophages and dendritic cells that produce most of the cytokine storm.~Study Design This is a multi-center, open-label study evaluating the safety of Allocetra-OTS, in five subjects with severe COVID-19 and respiratory dysfunction. Subjects, who will be identified as suffering from COVID-19, will be recruited.~After signing an informed consent by the patient and, within 24+6 hours following the time of eligibility (time 0), on Day 1, eligible recipient subjects will receive single intravenous (IV) administration of investigational product as described below:~● Allocetra-OTS treatment at 140 x 106 ±20% cells/kg body weight (screening body weight) in 375 mL of Ringer's lactate solution.~Subjects will be followed for efficacy and safety assessments over 28 days following investigational product administration.~Subjects will be hospitalized for COVID-19, and later as medically indicated. Following IP administration (Day 1), subjects will be followed for efficacy and safety assessments through 28 days. The number of visits for subjects participating in this study will be on Days 3, 5, 7, 14, and 28.~Study Intervention, Route of Administration, and Dosage Form Allocetra-OTS is a cell-based therapeutic composed of donor early apoptotic cells.~Patient Classification [National Institutes of Health (NIH)]- www.covid19treatmentguidelines.nih.gov/overview/management-of-covid-19/~In general, adults with COVID-19 can be grouped into the following severity of illness categories:~Asymptomatic or Pre-symptomatic Infection: Individuals who test positive for SARS-CoV-2 by virologic testing using a molecular diagnostic (e.g., polymerase chain reaction) or antigen test, but have no symptoms.~Mild Illness: Individuals who have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain) without shortness of breath, dyspnea, or abnormal chest imaging.~Moderate Illness: Individuals who have evidence of lower respiratory disease by clinical assessment or imaging and saturation of oxygen (SpO2) ≥94% on room air at sea level.~Severe Illness: Individuals who have respiratory frequency >30 breaths per minute, SpO2 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg, or lung infiltrates >50%~Critical Illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.~Standard of Care (SOC) The SOC for COVID-19 will be according to institutional standards. Institutional SOC may include Clexane, anti-viral agents such as Remdesivir, Dexamethasone, or other agents.~Concomitant Medications Prohibited medications: Significant immune-suppressing agents including Azathioprine, Cyclosporine, Cyclophosphamide, and any biological treatment.~Concomitant Medical Conditions Apart from patients with a tumor or end-stage organ condition, chronic diseases like cardiovascular or diabetes are allowed. | This is a multi-center, open-label study evaluating the safety of Allocetra-OTS, in 5 subjects with severe COVID-19 and respiratory dysfunction. Subjects, who will be identified as suffering from COVID-19, will be recruited.~After signing an informed consent by the patient and, within 24+6 hours following the time of eligibility (time 0), on Day 1, eligible recipient subjects will receive single intravenous (IV) administration of investigational product as described below.~Subjects will be hospitalized for COVID-19, and later as medically indicated. Following investigational product (IP) administration (Day 1), subjects will be followed for efficacy and safety assessments through 28 days. |
Traditional risk factors for AF were established from the original Framingham Heart Study cohort which showed aging, hypertension, congestive heart failure, coronary artery disease, valvular heart disease and diabetes mellitus (DM) as independent risk factors. In the past decade, several important risk factors not encompassed in previous studies have also been found to have a link with AF. One of these newly-identified risk factors is obstructive sleep apnea (OSA), which has been listed as one of the risk factor needed to be assessed and treated in AF patients.~OSA and AF often co-exist and indeed share some risk factors, such as hypertension. AF Patients are more likely to have OSA, with reported prevalence rates of OSA (apnea-hypopnea index [AHI] ≥15) as high as 62% in AF cohorts from hospital-based studies. In community-based cohort studies, a cross-sectional analysis from sleep heart health study (SHSS) found those with sleep-disordered breathing(SDB)/sleep apnea (SA) (respiratory disturbance index [RDI] ≥ 30) had four times the odds of a polysomnography (PSG)-detected nocturnal AF as compared to those without SDB/SA after adjusting confounders. Following from this, a cross-sectional study on Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep Study) showed a dose-response association between RDI and AF.~There are several pathophysiological mechanisms by which OSA could potentially increase the risk of development of new AF, or trigger a recurrence of AF in a patient with an established history of AF. OSA is characterized by repetitive collapse of the upper airway (UA) during sleep. The UA collapses when sleep-related loss in UA dilator muscle tone is superimposed upon a narrow and/or collapsible airway. These obstructive apneas or hypopneas, characterized by unsuccessful inspiratory efforts against an occluded airway, lead to 1) exaggerated negative intrathoracic pressure swings 2) hypoxia, and 3) co-activation of sympathetic and parasympathetic systems, all of which have been shown to potentiate a pro-arrhythmic state. Given that these mechanisms are pro-arrhythmic, CPAP (continuous positive airway pressure), the gold standard therapy for OSA, works by splinting the upper airway open during sleep with subsequent abolition of swings in pressure, hypoxia and arousals, can potentially modify the risk of development of AF or recurrence of AF in OSA patients.~There is a growing body of literature supporting that OSA being as a risk factor for recurrence of AF after cardioversion or ablation and treatment of OSA with CPAP decreased the risk of recurrence of AF. Nevertheless, all of the aforementioned studies are observational or retrospective in nature. Recently, Caples et al. conducted the first randomized control trial using CPAP in patients with AF and OSA but failed to find a difference of recurrence of AF between those treated with CPAP versus usual care. Notably, there are several issues in the study design and methodology that do not allow for firm conclusion from the results of this study. It was a single-center study, enrolling very small number of patients, and used a low cut-off AHI>5/h as inclusion criteria. More importantly, only patients with persistent AF scheduled for cardioversion were included. Given the natural time-course from paroxysmal AF to persistent AF, long-term remodeling or established atrial arrythmogenic substrate in persistent AF may be less or not reversible even when the initial risk factor is removed. In this regard, early intervention with CPAP in patients with paroxysmal AF and OSA, which has never been done in previous studies, should confer a better antiarrythmic effect. Therefore, the investigators aim to test the hypothesis that treatment of OSA with CPAP would reduce the burden of AF in patients with paroxysmal AF. | Obstructive sleep apnea is associated with atrial fibrillation. This study is to evaluate the effect of continuous positive airway pressure on the burden of atrial fibrillation in the patients with obstructive sleep apnea and paroxysmal atrial fibrillation. |
The investigators hypothesize that participants with earlier stages (NYHA Class I and Class II) of ATTR wild type and ATTR mutant will demonstrate stabilization of ATTR following 1 year of Tafamidis.~The investigators propose to pursue the following specific aims:~Utilize cardiac magnetic resonance to assess stabilization of ATTR after Tafamidis therapy based on extracellular volume mapping.~Investigate left ventricular myocardial mass, native T1, T2, and extracellular volume mapping after 12 month follow-up.~Utilize cardiac magnetic resonance feature tracking at baseline and at 12 month follow-up.~The investigators will enroll 131 participants with confirmed ATTR. Participants will be screened to exclude light chain amyloidosis by either measuring the proportion of kappa: lambda light chains with the serum free light chain assay, and tested for immunofixation electrophoresis of serum and urine. Once participants has confirmed diagnosis of ATTR (pyrophosphate scan positive scoring >1.5 ratio) and undergone baseline testing participants will be ask to enroll in the study. Genetic testing will performed to further distinguish between mutation and wild type. All participants will be required to sign informed consent agreeing to follow up testing at 1 year.~Participants will undergo a baseline cardiac magnetic resonance imaging for the purpose of evaluating native T1, T2, first pass perfusion, and extracellular volumes for patients with glomerular filtration rate >30. Patients with glomerular filtration rate <30 will only have native T1 and T2 values evaluated. If participants undergo implanted cardiac device during Tafamidis therapy, follow up cardiac magnetic resonance imaging will only evaluate featuring tracking and left ventricular mass. Left ventricular mass and cardiac magnetic feature tracking values will be extracted from all cardiac magnetic resonance imaging studies. After one year of Tafamidis therapy, participants will return to initial facility where testing was preformed to undergo a follow up cardiac magnetic resonance imaging study.~There is emerging evidence that there may be biomarkers yet identified for earlier detection of this disease. Henceforth, investigators propose to collect and store blood samples for all participants for future analyses. | The study will investigate the stabilization effects of Tafamidis utilizing cardiac imaging cardiac magnetic resonance imaging (CMR). The investigators propose to pursue the following specific aims:~Utilize cardiac magnetic resonance to assess stabilization of ATTR after Tafamidis therapy based on extracellular volume mapping.~Investigate left ventricular myocardial mass, native T1, T2, and extracellular volume mapping after 12 month follow-up.~Utilize cardiac magnetic resonance feature tracking at baseline and at 12 month follow-up. |
This is a prospective, single-arm, open-label, multi-center registry of the CorPath GRX System to evaluate its real-world performance during peripheral vascular interventions. | This study will evaluate real-world performance of the CorPath GRX System in peripheral vascular interventions. |
This is an Intermediate-Size Expanded Access, Open-Label Study for Use of Mino-Lok Therapy (MLT) in Combination with Systemic Antibiotics in the Treatment of Central Line Associated Bloodstream Infection.~Mino-Lok Therapy is being developed as an adjunctive therapy for the treatment of catheter-related or central line associated bloodstream infection (CRBSI/CLABSI) in combination with appropriate systemic antibiotic(s), to preserve central venous access and to avoid the complications and morbidities associated with catheter removal and reinsertion.~This is an expanded access program (EAP). This program is designed to provide access to Mino-Lok. A physician must decide whether the potential benefit outweighs the risk of receiving an investigational therapy.~To learn more about this study, please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02901717 | This is an Intermediate-Size Expanded Access, Open-Label Study for Use of Mino-Lok Therapy (MLT) in Combination with Systemic Antibiotics in the Treatment of Central Line Associated Bloodstream Infection. Mino-Lok may be made available for patients who otherwise do not qualify for the phase 3 clinical trial (NCT02901717 ) |
This Expanded Access Program (EAP) is designed to provide access to an unlicensed drug that is approved in the United States for the treatment of a serious or life-threatening condition. This EAP will be sponsored by SK Life Science Inc. and managed by WEP Clinical. Cenobamate is approved for the treatment of partial onset seizures in adults in United States. The attached US Label (appendix 1) provides the most recent guidance for use of cenobamate.~The objective of this EAP is to continue providing treatment with Cenobamate (YKP3089) to patients with partial-onset epilepsy that were enrolled in the SK Life Science clinical trial YKP3089C013, YKP3089C017 or YKP3089C021. Access to Cenobamate under this guideline is considered a treatment scenario and is not a clinical trial.~Epilepsy is a symptom of a neurological problem that causes sudden, brief seizures. It leads to an increased risk of injury from accidents, an increased rate of mortality, and has a significant impact on quality of life. Epilepsy can occur as a result of a neurological injury, a structural brain lesion, as a part of many systemic medical diseases or may be generic in origin. The incidence of having epilepsy during a lifetime is between 2-5%. Available medications control seizures in 50% of patients and decrease seizure incidence in 75%. The remainder continued to have unacceptable number of seizures, side effects, and psychiatric symptoms. The high treatment failure may be the result of inadequate efficacy or intolerable side effects that lead to poor compliance.~Cenobamate is a novel small molecule that is an antiepileptic agent for partial onset seizures. The precise mechanism by which cenobamate exerts its therapeutic effects in patients with partial-onset seizures is unknown. Cenobamate has been demonstrated to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents. It is also a positive allosteric modulator of the γ-aminobutyric acid (GABAA) ion channel. | This Cenobamate Expanded Access Program (EAP) is designed to continue providing treatment with Cenobamate (YKP3089) to patients with partial-onset epilepsy that were enrolled in the SK Life Science clinical trial YKP3089C013, YKP3089C017 or YKP3089C021. |
This is a prospective, open-label, multicentric phase II single-arm trial in which patients with initially unresectable and previously untreated RAS wild-type mCRC will receive induction treatment with mFOLFOXIRI plus cetuximab and avelumab up to 12 cycles followed by maintenance with 5-FU/LV plus cetuximab plus avelumab until disease progression, unacceptable toxicity or patient's refusal. The second- and subsequent lines of treatment will be at investigators' choice. | The aim of this study is to evaluate the efficacy of mFOLFOXIRI plus cetuximab and avelumab as first line treatment of patients with initially unresectable and previously untreated RAS wild-type metastatic colorectal cancer (mCRC), in terms of Progression-free Survival. |
PRIMARY OBJECTIVE:~I. To evaluate the clinical performance of a novel point-of-care diagnostic test for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the disease called coronavirus disease 19 (COVID-19).~SECONDARY OBJECTIVES:~I. To compare the clinical performance of provider-collected nasopharyngeal samples with self-collected nasal swab, cheek swab, and saliva sample using the novel SARS-CoV-2 diagnostic test.~II. To measure viral load and evaluate the role of viral load in COVID-19 severity.~OUTLINE:~Participants undergo collection of nasopharyngeal (back of the nose) samples by a medical provider and self-collection of oral, saliva, and nasal samples.~After completion of study, participants are followed up at 1 month. | This study investigates a new diagnostic test in detecting SARS-CoV-2, the virus that causes the disease COVID-19. This may help to improve testing for COVID-19. |
This is a cluster randomized controlled trial (CRCT) to evaluate the efficacy of Wolbachia-infected A. aegypti mosquito releases in reducing the burden of ARBV infection in Brazil over threefour years. The intervention will be the release of Wolbachia-infected A. aegypti mosquitoes. Standard control measures routinely established by the Belo Horizonte City Hall as recommended by the PNCD, will continue to be performed by the Belo Horizonte Health Department (Zoonoses Management) in all clusters, that is, the standard control measures will be carried out throughout the city of Belo Horizonte, independent of this clinical study. Wolbachia-infected A. aegypti will be deployed by releasing adult mosquitoes in pre-determined, thoroughly spaced release points in easily accessible roads described in a release map. A release map will be generated for each cluster and the numbers of release points will be determined by population density, surface area and mosquito abundance. Wolbachia-infected A. aegypti mosquitoes will be deployed across intervention clusters in two stages: 1) a 4 month establishment stage in which most of the releases will occur and 2) followed by an 8 month consolidation stage in which the abundance of Wolbachia-infected mosquitoes will be measured and remedial deployments will be completed, if needed, with the aim of achieving a high prevalence of Wolbachia amongst A. aegypti mosquitoes in intervention clusters within 12 months from the start of the release. The goal is to reach a Wolbachia prevalence of 60% or higher. Monitoring of Wolbachia prevalence in the cluster will continue throughout the study period, but no further mosquito deployments will occur after the consolidation stage is complete. The primary objective is to evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of ARBV infection compared to standard Aedes vector control measures alone. The Secondary objectives are 1.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of ARBV infection, inferred from model-based reconstruction of serological dynamics compared to standard Aedes vector control measures alone; 2.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of FLAV or CHIKV infection amongst individuals who are seronegative to each of these viruses, respectively, at study entry, compared to standard Aedes vector control measures alone; 3.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the overall sero-incidence of FLAV (DENV + ZIKV) infection; 4.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of DENV infection; 5.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of ZIKV infection; 6.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of CHIKV infection among those who are CHIKV seronegative at baseline; 7.) To evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of DENV infection amongst individuals who are seropositive to any DENV serotype(s) at study entry, compared to standard Aedes vector control measures alone; 8.) To evaluate the extent to proportion of Wolbachia-infected Aedes aegypti mosquitoes in intervention clusters during the study period; 9.) To evaluate the proportion of Wolbachia-infected Aedes aegypti mosquitoes in control clusters during the study period. | This is a cluster randomized controlled trial (CRCT) to evaluate the efficacy of Wolbachia-infected A. aegypti mosquito releases in reducing the burden of ARBV infection in Brazil over threefour years. The intervention will be the release of Wolbachia-infected A. aegypti mosquitoes. Standard control measures routinely established by the Belo Horizonte City Hall as recommended by the PNCD, will continue to be performed by the Belo Horizonte Health Department (Zoonoses Management) in all clusters, that is, the standard control measures will be carried out throughout the city of Belo Horizonte, independent of this clinical study. Wolbachia-infected A. aegypti will be deployed by releasing adult mosquitoes in pre-determined, thoroughly spaced release points in easily accessible roads described in a release map. A release map will be generated for each cluster and the numbers of release points will be determined by population density, surface area and mosquito abundance. Wolbachia-infected A. aegypti mosquitoes will be deployed across intervention clusters in two stages: 1) a 4 month establishment stage in which most of the releases will occur and 2) followed by an 8 month consolidation stage in which the abundance of Wolbachia-infected mosquitoes will be measured and remedial deployments will be completed, if needed, with the aim of achieving a high prevalence of Wolbachia amongst A. aegypti mosquitoes in intervention clusters within 12 months from the start of the release. The goal is to reach a Wolbachia prevalence of 60% or higher. Monitoring of Wolbachia prevalence in the cluster will continue throughout the study period, but no further mosquito deployments will occur after the consolidation stage is complete. The primary objective is to evaluate whether release of Wolbachia-infected Aedes aegypti mosquitoes plus standard Aedes vector control measures reduces the sero-incidence of ARBV infection compared to standard Aedes vector control measures alone. |
Chronic rhinosinusitis (CRS) is a prevalent inflammatory disorder of the nasal passages and sinuses associated with detrimental effects on quality of life and productivity as well as billions of dollars in healthcare expenses and lost productivity each year. Numerous endoscopic scoring systems have been developed to assess CRS disease severity such as the popular Modified Lund-Kennedy (MLK) score which assesses sinus cavities only based on 3 criteria (polyps, edema, and discharge) with small 0-2 integer scales. Yet, such systems at best have reported good to moderate reliabilities and weak to no correlation with patient-reported outcome measures (PROMs) which should motivate further research to develop a more reliable and clinically valid CRS endoscopic scoring system, especially one which can better align the observed endoscopic signs of disease with the severity of symptoms reported by patients. In this study we propose a more descriptive Alsaleh-Javer Endoscopic Sinus Score (AJESS) system which assesses all sinuses and nasal passages with a numerical score of inflammation severity, alphabetical score for presence of CRS features, and an aggregated numerical score of overall disease severity. Our mixed-methods clinical study of 100 stable post-operative CRS patients and 30 post-operative CRS patients experiencing an exacerbation who are visiting St. Paul's Sinus Centre will gather both cross-sectional (1 visit, CRS stable) and prospective (2 follow-up visits approximately 2-4 weeks apart each, CRS flares) clinical data including two PROMs (SNOT-22, VAS) and an objective olfactory sensation test (Sniffin' Sticks TDI Score) to assess AJESS and MLK scores in terms of inter-rater reliability, test-retest reliability, correlation with clinical data, and responsiveness to changes in clinical data. Pending validation and head-to-head analysis with the MLK score, the AJESS system may be a more reliable and valid endoscopic scoring system for clinical practice and outcomes research in CRS.~Study goals and objectives~Assess the test-retest and inter-rater reliability of the AJESS and MLK scores.~Assess the correlation of AJESS and MLK scores with cross-sectional PROMs (SNOT-22, VAS) and Sniffin' Sticks TDI Score~Assess the reactivity of AJESS and MLK scores with prospective PROMs (SNOT-22, VAS) in patients experiencing CRS exacerbations~Research design~Participants visiting St. Paul's Sinus Centre who meet inclusion criteria and no exclusion criteria who are stable (N=100) and who are experiencing an exacerbation (N=30) will be approached at random and consented to the study. Encounters are expected to be 30 minutes each and participants experiencing a CRS or AFRS exacerbation will be expected to present for follow-up after 3 weeks (+/- 1 week) intervals for a second and a third encounter until their exacerbation are settled. The first encounter will collect relevant clinical data, endoscopic photos of 10 anatomic sites, patient-reported outcomes measures (PROMs, eg.SNOT-22, VAS) and olfactory sense test results (Sniffin' Sticks TDI score). Subsequent visits for exacerbated participants will collect the same endoscopic photos, PROMs and olfactory sense test results. | Several endoscopic scores have been developed to assess Chronic Rhinosinusitis severity like the Modified Lund-Kennedy (MLK). This is a simple score only based on endoscopic signs. We proposed a more descriptive Alsaleh-Javer Endoscopic Sinus Score (AJESS) system which assesses all sinuses and nasal passages based on participant's severity of symptoms too. This would be a more reliable and clinically valid CRS endoscopic score. We aim to study thE AJESS system in 100 participants with stable CRS and 30 participants CRS who are experiencing an exacerbation (worsening of CRS). |
Different types of anesthetics have different effects on heart rate variability. However It has not yet been reported whether this difference in effect remains at recovery time after anesthesia.~Several studies have been reported that preoperative heart rate variability predicted the occurence of postoperative nausea and vomiting. However, whether the difference in heart rate variability after anesthesia is related to the difference in postoperative nausea and vomiting has not been studied. Therefore, this study aims to observe whether propofol and sevoflurane have differences during recovery period after anesthesia in heart rate variabiliy. In addition, we want to examine that these differences during recovery period in heart rate variability can predict the occurrence of nausea and vomiting within 24 hours after surgery. | Propofol and sevoflurane have different effects on heart rate variability. It has not yet been reported whether this difference in effect remains at recovery time after anesthesia and the difference is related to postoperative nausea and vomiting has not been studied. The aim of this study is observe whether propofol and sevoflurane have different effects on heart rate variability during recovery and the differences can predict the occurrence of postoperative nausea and vomiting. |
The objective of this study is to evaluate the effects of intravenous ANX005 administered for up to 22 weeks in subjects with, or at risk for, manifest Huntington's Disease.~Subjects will receive induction dosing of ANX005 administered by IV infusion on Days 1 and 5 or 6, followed by maintenance dosing every 2 weeks through Week 22, with follow up visits on Weeks 24, 28, and 36.~All subjects will be contacted (in clinic visit or phone call) 6 months after study completion. | This study is a multi-center, open-label study of intravenous (IV) ANX005 in subjects with, or at risk for, manifest Huntington's Disease (HD). |
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal Non-Hodgkin Lymphoma. Induction treatment of PCNSL in most reported single-arm or randomized trials includes high-dose methotrexate (HD-MTX)-based therapy, temozolomide, with or without cytarabine and the anti-CD20 antibody rituximab. A better combination remains undefined. Treatment is associated with considerable morbidity and disease recurrences with a 5-year survival of approximately 40%.~The BTK inhibitor ibrutinib has shown antitumor activity in patients with recurrent or refractory PCNSL. However, tumor responses to single-agent ibrutinib in CNS lymphoma are often incomplete or transient. Efficacy and safety of ibrutinib in combination with cytotoxic agents are worth to be discovered. Grommes et al.have shown ibrutinib in combination with methotrexate and rituximab are safe and shows promising activity in recurrent/refractory CNS lymphoma. In comparison to their prior study with single-agent ibrutinib, the radiographic response of r/r PCNSL was higher with the ibrutinib/HD-MTX/rituximab combination regimen and PFS was longer with the combination therapy. The study has shown that ibrutinib combined with chemotherapy were superior to ibrutinib single agent and overcome the transient effect of ibrutinib in relapsed PCNSL. However, there are some limitations in interpreting Grommes' study results, especially the heterogeneous patient population with inclusion of both PCNSL and SCNSL. Most recently, the role of rituximab in PCNSL has become clearly. In the HOVON 105/ALLG NHL 24 study, the addition of rituximab to a methotrexate-based regimen did not demonstrate a significant benefit on clinical outcome. We therefore initiate this study aim to evaluate the activity and safety of ibrutinib in combination with Methotrexate and temozolomide (MIT regimen) in newly diagnosed PCNSL patients. | The purpose of the study is to test the efficacy and tolerability of a combination treatment of methotrexate, ibrutinib, and temozolomide (MIT regimen) in treating patients who have newly-diagnosed primary CNS lymphoma. |
A multicenter, randomized, double-blind, positive drug parallel control design was used. The trial included screening period (4 weeks) and treatment period (4 treatment cycles, at least 12 weeks). All eligible subjects were randomly divided into experimental group (hs627 treatment group) and control group (pertuzumab) treatment group. After 4 treatment cycles, the subjects arranged surgical treatment, and then conducted the last visit. | The trial included screening period (4 weeks) and treatment period (4 treatment cycles, at least 12 weeks). |
Data from clinical trials suggest that pharmacological therapies prescribed at appropriate doses will lead to dramatic improvements in survival and hospitalization rates in patients with heart failure with reduced ejection fraction (HFrEF). Consequently, major cardiovascular societies assign the highest level of recommendation to use these therapies in all eligible patients. However, data from several registries over the last three decades has failed to see use of these evidence based therapies at levels noted in clinical trials, despite aggressive guideline recommendations and promotion by thought leaders in the field.~It remains unclear as to why many patients with HFrEF are not on evidence-based therapies, and why the percentages are consistent across national registries over time. One explanation might be that providers know the data regarding evidence-based therapies, but the therapies only benefit a narrow population. Another factor might be a lack of knowledge among providers about the appropriate management of HFrEF patients. A simple way to test this hypothesis is to examine whether electronic health record (EHR) based best practice advisories (BPAs) can increase use of evidence based therapies. If found to be effective, these low cost interventions can be rapidly applied across large healthcare systems.~This study will conduct a randomized controlled trial across outpatient clinics within a single health system comparing the effectiveness of an EHR-based alerting system that informs practitioners about what evidence-based medications they can prescribe for HFrEF patients versus usual care (no alert). One hundred eligible unique providers will be randomized to an intervention in which an alert will appear for all eligible patients with HFrEF, or to a control group in which no alert appears and usual care will continue, with a target patient enrollment of 1,310. The primary outcome for the trial will be the proportion of patients with HFrEF with an increase in evidence based medical therapies for HFrEF (beta-blockers, ACE-I/ARB/ARNI, MRA, SGLT2i). Secondary outcomes will include 30-day hospital admission rates, 30-day ED visits, one year all-cause mortality, and total 6 month healthcare costs. | A randomized controlled trial to compare the efficacy of an electronic health record-based alert informing providers about evidence-based medications for HFrEF versus usual care (no alert) in outpatient clinics across a single health system. |
Arthritis is a term used to mean any disorder that affects the joints. The two most common forms of arthritis are osteoarthritis and rheumatoid arthritis.Rheumatoid arthritis is an autoimmune chronic inflammatory disease of unknown etiology and is characterized by chronic inflammation of the joint capsule's synovial membrane. This chronic inflammation ultimately destroys the underlying cartilage and bone. Activated fibroblast-like synoviocytes (FLS) line the synovial membrane and are a prominent cell type responsible for inflammation and joint destruction. Osteoarthritis is characterized by degradation of joint cartilage. Studies demonstrate chondrocytes expressed FAP and that chondrocyte FAP expression was elevated in patients with osteoarthritis. Other researches identified FAP expression in synovial samples taken from both rheumatoid arthritis and osteoarthritis patients. However, FAP expression was greater in samples taken from refractory rheumatoid arthritis patients in comparison to end-stage osteoarthritis patients.68Ga-FAPI has been developed as a tumor-targeting agent as fibroblast activation protein is overexpressed in cancer-associated fibroblasts and some inflammation, such as IgG4-related disease and inflammatory bowel disease. Recently the investigators have published an article of the application of 68Ga-FAPI in IgG4-related disease which showed it was more sensitive than FDG in detecting a certain type of inflammations. Thus this prospective study is going to investigate whether 68Ga-FAPI PET/CT may be superior for diagnosis, therapy response assessment and follow-up of arthritis than 18F-FDG PET/CT. | 68Ga-FAPI has been developed as a tumor-targeting agent as fibroblast activation protein is overexpressed in cancer-associated fibroblasts and some inflammation, such as IgG4-related disease and inflammatory bowel disease. Some researches identified FAP expression in synovial samples taken from both rheumatoid arthritis and osteoarthritis patients.Thus this prospective study is going to investigate whether 68Ga-FAPI PET/CT may be superior for diagnosis, therapy response assessment and follow-up of arthritis than 18F-FDG PET/CT. |
Overview of the study Research design: prospective, single-arm blind randomized control study, non-inferiority study Study Period: 12 months since IRB approval date Subject: Patients with benign prostatic hyperplasia Number of study subjects: 90 Vulnerable Subjects: None~Background and purpose of the study~1) Research background~Overview and main symptoms of prostatic hyperplasia (BPH)~-The prostate is a male reproductive organ located in the lower bladder. Benign prostatic hyperplasia (BPH) causes lower urinary tract symptoms (LUTS) due to bladder outlet obstruction.~The prevalence of prostatic hyperplasia is known to reach 37% in the 50s, 49% in the 60s, and 70% in the 70s; a disease with a very high incidence in long-aged men.~BPH is a disease directly related to the quality of life that interferes with the patient's social life, sexual life, and daily life. If it persists for a long time, it may cause bladder stones, hematuria, and even renal dysfunction, so timely treatment is absolutely necessary.~Surgical Treatment of BPH~-Surgical treatment is recommended for an enlarged prostate that is not treated with drugs, and transurethral surgery using an endoscope is recommended for standard surgery for an enlarged prostate.~Transurethral surgery for BPH varies from traditional transurethral resection of the prostate (TURP) to holmium laser enucleation of the prostate (HoLEP).~HoLEP has a sharp increase in the number of surgeries worldwide due to its low recurrence rate, high efficiency, and high patient satisfaction;~Since its first introduction in 2008 in Korea, the number and rate of surgeries have been steadily increasing. The total number of surgery for BPH is equivalent to about 10,000 cases per year. TUR-P and KTP laser surgery are on a decreasing trend, while HoLEP is on an increasing trend.~The importance of HoLEP~-HoLEP is a surgery to completely remove prostate tumors using a Holmium-YAG Laser of 2100nm wavelength.~-The tissue penetration depth of the Holmium laser is less than 0.44mm, enabling sharp incisions, and has the advantage of less bleeding than traditional transurethral prostatectomy.~-The surgery principle of HoLEP is fundamentally different from TUR-P and KTP laser prostate vaporization. TUR-P and KTP laser prostatectomy aim to remove part of the prostate tumor, whereas HoLEP performs complete removal of the prostate tumor according to the anatomical structure.~-HoLEP consists of two steps, and the first step consists of an enucleation step in which the prostate tumor is completely removed and placed in the bladder, and a morcellation step in which the enucleated adenoma tissue is morcellated and removed.~HoLEP is relatively safe compared to other transurethral surgery and can completely remove prostate adenoma, so it has a low recurrence rate and the patient's satisfaction with surgery is over 90%, making it the next-generation standard treatment for BPH.~Low energy HoLEP related research and clinical status -HoLEP is mainly applied to treatment with 80-100 Watt high energy equipment. High-energy HoLEP has the advantage of removing prostate tumors in a short time, but there are problems of frequent laser fiber damage, device shutdown problems, and possible bladder damage due to scattered lasers.~In 2008, Rassweiller et al. proposed the possibility of clinical application of low energy HoLEP by applying a 40 Watt Holmium laser. Since then, prospective studies have been published sporadically. In 2018, a prospective randomized study that compared and analyzed the prostate removal efficiency of 50 Watt laser and 100 Watt laser in a total of 121 patients was the latest and largest study and confirmed that low-energy prostatectomy is not inferior to the high-energy procedure. And proved its clinical safety.~In theory, low-energy HoLEP reduces dysuria immediately after surgery and storage symptoms after surgery. It is estimated to be advantageous in preserving erectile function.~The research team is the first in the world to compare the safety and usefulness of 30 Watt HoLEP with 100 Watt HoLEP through prospective, non-inferiority studies.~2) Research goal The final purpose of the study: To prove that the low-energy (30Watt) HoLEP is not inferior to the high-energy (100Watt) HoLEP in short-term and mid-term surgical results (safety and effectiveness).~Detailed research objectives:~Compare short-term (2 weeks-1 months) surgical outcomes/surgical complications of low energy HoLEP with high energy HoLEP.~Compare the mid-term (3, 6 months) surgical outcomes/surgical complications of low-energy HoLEP with high-energy HoLEP.~3) Selection criteria, exclusion criteria, the target number of subjects and basis for calculation~Selection criteria Men over 50 Patients receiving HoLEP due to an enlarged prostate Patients who fully understood and agreed to the study~Exclusion criteria Patients with neuropathy that may adversely affect the urination function (Parkinson's disease, dementia, etc.) Patients with acute urinary retention within the last month Patients with symptomatic urinary tract infection In case there are other factors that can significantly affect treatment results at the discretion of the researcher~(2) Number of research subjects About 90 patients~The basis for calculating the number of subjects This study aims to prospectively enroll and randomize prostatectomy patients, and then compare the results of the treatment at 6 months after the maximum operation to confirm non-inferiority.~The current standard is a method using a high-energy holmium laser, and the treatment results for 6 months after surgery have been published through many studies. The research team wants to confirm the surgical outcome as a decrease in the International Prostate Symptom Score (IPSS). After 6 months of predicted high-energy HoLEP, IPSS in other literature (5.1 ± 5.0), 6 months after the expected of low-energy HoLEP. IPSS is estimated from the most recently published academic paper (5.0 ± 5.0).~Alpha (0.15) and Beta (0.8) were calculated, and the non-inferior margin was set to 3. The estimated number of subjects is calculated by considering the 20% drop-out rate. Statistics for calculating the number of subjects are calculated using PASS 2019.~Considering drop-out 20%, it is necessary to recruit 25-114 patients (total 50-114) per group to conduct the study.~This organization is an organization that implements about 20-30 HoLEP cases per month, and a follow-up period of up to 6 months is required to announce short-term and mid-term results. Therefore, the actual patient enroll period is estimated to be up to 6 months. It is expected that 120-180 patients can undergo surgery during the recruitment period of up to 6 months, and assuming that only 60% of patients will participate in the study based on the median of about 150, a total of 90 patients, about 45 for each group. It is judged realistic to conduct a study with 3 patients.~4. Research method~Specific research method Since the researchers have already published dozens of studies related to HoLEP surgery, we are securing a systematic preoperative examination/postoperative follow-up process. The preoperative examination/postoperative follow-up protocol of high energy HoLEP surgery, which was previously performed, will be used as it is, but the study will be conducted by adding only the preoperative randomization process.~-Pre-screening: After making operation in the outpatient clinic, before hospitalization, it is checked whether it is subject to enroll according to the patient record.~-Random allocation: Using R package (RandomizeR), low energy HoLEP, and high energy HoLEP is randomly assigned.~-Pre-Op work-up & Operation: This item is irrelevant to Randomization and is a situation where you do not know who will undergo surgery, so it is considered a normal treatment process and proceeds according to the existing process.~Monitoring: It is planned to perform research ethics, safety, and monitoring work independently from the researcher by requesting the Medical Device Innovation Center.~Clinical trial insurance: In case of adverse side effects to patients, the company plans to subscribe to clinical trial liability insurance through the Medical Device Innovation Center to notify the patient of the procedures and details of the clinical trial damage relief.~Compensation: There is no monetary incentive for research participants, and the research team will pay 30,000 won of transportation and inspection costs (160,000 won) per visit during the participation period of visit #1-#3.~Test drug administration/dosage, administration/use method, combination therapy, reasons for selection when using a reference drug None~Observation items, clinical test items and observation test methods Primary endpoint: 3-6 month questionnaire (International Prostate Symptom Score, IPSS) total score~Secondary endpoint:~1) Surgery day: surgery time, total energy, resected prostate volume, immediate complication~1) 2 weeks after surgery: questionnaire (IPSS-subscore, IPSS-QoL, OABSS total score), Qmax, 2) post voided residual urine volume, Clavian-Dindo complication classification 3) 3, 6 months after surgery: questionnaire (IPSS-total, IPSS subscore, IPSS-QoL, OABSS total score), Qmax, post voided residual urine volume, Clavian-Dindo complication classification, urine test (urinalysis, urine microscopy), serum PSA level~4) Effect evaluation criteria, evaluation method Efficacy~Statistical analysis of low-power HoLEP is not inferior in short-term (2wk/1month) and mid-term (3-6 months) IPSS.~Uroflowmetry (UFM) and non-inferiority of post voided residual (PVR) were verified in urinalysis.~3 months/6 months U/A, micro, 6 months PSA~Non-inferiority was verified in terms of improving the patient's QoL.~To verify the non-inferiority of the storage symptom subscore after the patient's surgery.~Safety:~The safety of HoLEP has been revealed to some extent through overseas research results, so animal testing is not required. For the safety, all safety issues that occurred using the Clavian-Dindo grade, which are commonly used clinically in human studies, were recorded and compared and analyzed.~If adverse events that occurred immediately after surgery and during up to 3 visits were recorded and there was a statistically significant difference in complications of Grade III-IV, it was judged that there was a safety problem.~4) The difference between existing treatment and research Existing studies comparing low energy HoLEP surgery and high energy HoLEP are mostly retrospective studies, and two prospective studies have been performed.~One of the two prospective studies involved 54 patients and had no active control group.~The most recent study was RCT with 121 subjects, but it was a study comparing 50W laser and 100W laser.~This study is the first in the world to compare 30W laser and 100W laser, and it is a prospective, RCT that recruits 90 patients, and it is judged that the results of the study can provide important medical evidence for the safety and effectiveness of low-energy HoLEP surgery. | The purpose of this study is to prove that low-energy (30W) Holmium laser prostatectomy (Holeb) is not inferior to high-energy (100W) Holmium laser prostatectomy (safety and effectiveness) |
Chronic wounds (CWs) are common and carry out an important and often neglected burden not only to the individual, the family but also to the society as a whole. A wound becomes chronic when they fail to progress through a timely sequence of repair resulting in anatomic and functional integrity within a period of approximatively three months. CWs affect a large segment of the world population (3) with a prevalence of mixed aetiologies of 2.21 per 1000. The annual costs of care of patients with CWs is estimated to be £6 billion for 2.2 million in the United Kingdom (UK).~In CWs a massive production of matrix molecules resulting from underlying cellular dysfunction and dysregulation can be found. Fibrinogen and fibrin are also common in chronic wounds and it is thought that these and other macromolecules scavenge growth factors and other molecules involved in promoting wound repair. Chronic wound fluid is also biochemically distinct from acute wound fluid; it slows down, and can block the proliferation of cells, which are essential for the wound healing process. The therapeutic approach to enhance the wound healing process include wound bed preparation or wound dressing management. Wound bed preparation as a concept allows the clinician to focus systematically on all of the critical components of a non-healing wound to identify the cause of the problem, and implement a care programme so as to achieve a stable wound that has healthy granulation tissue and a well vascularised wound bed. Debridement is an integrated part of wound bed preparation, achieving certain goals and, thus, creating a healthy wound bed, margins and peri-wound skin with the objective to promote and accelerate healing (8). Debridement is defined as the removal of foreign material and necrotic tissue from a wound and it can also help to stimulate wound healing (8). However, not all methods of debridement are the same. Each method has advantages and disadvantages that must be clearly understood.~In the present clinical practice, there are several methods of wound debridement: autolytic, enzymatic, mechanical, surgical (sharp) and biologic. The most common method is the mechanical debridement. Autolytic, chemical, and surgical methods are considered to be selective techniques, whereas mechanical methods are considered to be nonselective. Selective modalities remove mainly necrotic tissue, whereas nonselective modalities remove both necrotic and viable tissue. In practice, selective modalities can also remove or damage healthy tissue. The most selective modalities are autolytic and biologic techniques. Instrument debridement is the most used debridement method from many years. It has been shown to improve wound healing and its main advantages are the low cost of treatment and the speed of dead tissue removal. This method is done with the intention of removing small amounts of visible devitalized tissue. However, residual nonviable tissue may remain at the microscopic level resulting in slowing healing process. On the contrary, the risk of exaggerated / mismanaged excision is not non-existent and can lead to damage to healthy tissue or even damage to deeper structures (blood vessels, nerves, tendons or even bones), resulting in delayed healing too. Instrument debridement can be painful. Patient's fear about this approach is a reality that can also be problematic. Autolytic or enzymatic debridement, which are more selective and less prone to patient's reluctance could remediate to this situation. However, time for complete dead tissue removal is considerably increased, requiring multiple applications and stringent patient compliance. While this type of debridement does not damage healthy tissue and causes little or no pain, it can cause contact sensitization. Water-jet debridement systems seems to pose a valid alternative to other methods. The approach is based on mechanical and homogenous wound cleansing and stimulation by a micro-jet of water. It uses an ultra-fine, powerful and adjustable micro-jet of water that precisely removes soft to fibrous deposits from the wound. It is usually fast. Softness of the treatment depends on the speed and intensity of the water jet according to wound condition. Adequate pain control should be performed and surface anaesthesia may be required. Water jet debridement promotes natural wound healing by inducing micro-bleeding from the wound bed and minimizes scarring. While there is ample anecdotal evidence about the efficacy of such method to preserve healthy tissue, the investigators propose here to document this ability by measuring precisely wound depth before and after debridement using Debritom+ micro water jet technology. The investigators propose to systematically assess patient's apprehension regarding this technique too. | Chronic wounds are common and carry out an important and often neglected burden not only to the individual, the family but also to the society as a whole. The therapeutic approach to the management of chronic wounds include wound bed preparation or wound dressing management. Wound bed preparation is a concept emphasizing a holistic and systematic approach to evaluate and remove barriers to the healing process to allow the wound healing process to progress normally. Debridement is an integrated part of wound bed preparation, achieving certain goals and, thus, creating a healthy wound bed, margins and peri-wound skin with the objective to promote and accelerate healing. Debridement is defined as the removal of foreign material and necrotic tissue from a wound and it can also help to stimulate wound healing. However, not all methods of debridement are the same. Each method has advantages and disadvantages that must be clearly understood. In the present clinical practice, there are several methods of wound debridement: autolytic, enzymatic, mechanical, surgical (sharp) and biologic. The most common method is the mechanical debridement. Currently a micro-water jet technique was introduced into clinical practice. The micro-water jet technique Debritom+ is an effective alternative to traditional instrument interventions performed with the scalpel and/or curette. A sterile liquid is expelled from a nozzle at a selected intensity and accurately sprayed onto the wound surface. The desired effect is the generation of targeted micro-bleedings to stimulate regeneration and healing processes while preserving the underlying healthy tissue.~Today, there is no clinical evidence quantitatively comparing one debridement method over the other. Therefore the invesitgators propose a pilot study to measure the extent of tissue loss after debridement using Debritom+ micro-water jet technology versus traditional instrument debridement procedure using scalpel and curette. |
In China, the incidence of esophageal cancer has declined in recent years, but the mortality rate has been ranked fourth. Morbidity and mortality were ranked sixth and fourth in all malignancies, respectively. Therefore, esophageal cancer has always been a major malignant tumor that threatens the health of our residents.We designed a single-arm, open-label, phase II trial of Sintilimab for consolidation therapy after radical concurrent chemoradiotherapylocally advanced esophageal squamous cell carcinoma.The purpose of this study is to observe and evaluate the efficacy and safety of Sintilimab for consolidation therapy after radical concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma. | The purpose of this study is to observe and evaluate the efficacy and safety of Sintilimab for Consolidation Therapy After Radical Concurrent Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma |
This is a single center study of 60 subjects. The investigators will enroll 30 subjects with asthma who demonstrate mucus plugging on a screening CT lung scan, 15 subjects with asthma without mucus plugging, and 15 healthy controls. The healthy controls and subjects with asthma but without mucus plugging with also undergo CT scans to confirm that their lungs aren't obstructed by mucus.~Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria will participate in image-guided bronchoscopy (virtual navigation bronchoscopy [VNB]) to sample airway biospecimens in mucus plugged and control airways. Subjects will participate in up to 5 study visits at the Airway Clinical Research Center. | This is a single center study of 60 subjects including those with asthma and mucus plugging, those with asthma and without mucus plugging, and healthy controls. Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria will participate in image-guided bronchoscopy (virtual navigation bronchoscopy [VNB]) to sample airway biospecimens in mucus plugged and control airways. |
Asthma is a common disease affecting 5 - 10% of the population. The main underlying pathology is airway inflammation, which in a majority of patients is characterized by upregulation of type 2 cytokines and infiltration of the airway mucosa with type 2 inflammatory cells. Despite incomplete understanding of mechanisms by which these molecules and cells initiate and propagate the inflammatory process, several new therapies have been developed and even approved to target type 2 cytokines like IL-4, IL-5 and IL13 in asthmatics.~While mechanistic understanding lags behind therapeutic advance, the emergence of these new therapeutics and increase use in treatment of asthmatic patients provides a unique opportunity to better understand how these medicines alter inflammation and ameliorate disease activity. The over-arching goal of this project is to advance understanding of how these new therapeutic proteins modulate inflammation in peripheral blood. A better understanding of these mechanisms will allow for tracking of cellular and molecular biomarkers that may inform treatment regimens with these new therapeutics in patients with asthma.~Through this observational, clinic-based, single center study of 120 subjects, investigators will compare blood lymphocytes as well as other molecular biomarkers associated with inflammation in healthy controls, asthmatic patients not on therapeutic proteins and asthmatics treated with therapeutic proteins. Participants will be comprised of patients seen in the outpatient faculty practice in ambulatory care at the UCSF Parnassus campus. Participants will be seen at 1 to 3 visits and provide blood samples at each visit. It is anticipated that this study will help uncover mechanisms of response to these novel therapeutic interventions in asthma. | This is an observational, clinic-based, single center study of 120 subjects. Participants will be comprised of patients seen in the outpatient faculty practice in ambulatory care at the UCSF Parnassus campus. Study investigators will enroll 20 healthy participants with no history of lung disease, 50 asthmatics who are newly prescribed therapeutic proteins for their asthma, and 50 asthmatics already being treated with therapeutic proteins for their asthma. Participants will be seen at 1 to 3 visits and provide blood samples at each visit. |
Glaucoma is a group of optic nerve diseases characterized by progressive and irreversible degeneration of retinal ganglion cells and their axons. Retinal ganglion cells, RGCs is a kind of central nervous system neuron whose cell bodies are located in the retina and axons make up the optic nerve. When antihypertensive drugs or laser therapy can not reach the target intraocular pressure, trabeculectomy (TRAB) is still the standard surgical method for glaucoma. The scarring of the operative area is a common reason for the failure of trabeculectomy. After trabeculectomy, maintaining the shape and function of the filtering bleb is an important aspect to maintain the surgical effect. The increase in the number of blood vessels on the filtering bleb and the morphological curvature are often the manifestations of decompensation of the filtering bleb. Angiogenesis in the filtering bleb region plays an important role in surgical incision healing and is related to the accompanying scar formation. Therefore, the evaluation of vascular distribution of filtering blebs is an important index and early parameter to evaluate the success or failure of surgery. With the improvement of detection methods, it is possible to use AS-OCTA to evaluate the function and prognosis of filtering bleb after trabeculectomy. Antimitotic drugs such as 5-fluorouracil (5-FU) or mitomycin C (MMC) have always been the most commonly used clinical drugs, but the side effects caused by their use are not satisfactory. It is still the research direction of glaucoma to find new targets for regulating wound healing and more safe and effective drugs. | When antihypertensive drugs or laser therapy can not reach the target intraocular pressure, trabeculectomy (TRAB) is still the standard surgical method for glaucoma. The scarring of the operative area is a common reason for the failure of trabeculectomy. After trabeculectomy, maintaining the shape and function of the filtering bleb is an important aspect to maintain the surgical effect. The increase in the number of blood vessels on the filtering bleb and the morphological curvature are often the manifestations of decompensation of the filtering bleb. Angiogenesis in the filtering bleb region plays an important role in surgical incision healing and is related to the accompanying scar formation. Therefore, the evaluation of vascular distribution of filtering blebs is an important index and early parameter to evaluate the success or failure of surgery. With the improvement of detection methods, it is possible to use AS-OCTA to evaluate the function and prognosis of filtering bleb after trabeculectomy. Antimitotic drugs such as 5-fluorouracil (5-FU) or mitomycin C (MMC) have always been the most commonly used clinical drugs, but the side effects caused by their use are not satisfactory. It is still the research direction of glaucoma to find new targets for regulating wound healing and more safe and effective drugs. |
Glaucoma is a group of optic nerve diseases characterized by progressive and irreversible degeneration of retinal ganglion cells and their axons. There are different opinions on the pathogenesis of glaucoma, which further reflects that the mechanism of glaucoma optic nerve injury is still in the exploratory stage, and there is still a long way to go to develop effective drugs to prevent or reverse the visual function damage in patients with glaucoma. Therefore, on the basis of previous studies, our research group explored and expanded whether there were similar pathological changes in patients with clinical glaucoma not only in aqueous humor, but also in blood and tear samples, and further studied the mechanism. Three kinds of samples (aqueous humor, blood and tears) were collected from patients with primary glaucoma and age-related cataract treated in Sun Yat-sen Eye Center of Sun Yat-sen University. Normal people with matched age and sex were recruited as normal control group (normal control group only collected blood and tear samples). Three methods of inductively coupled plasma mass spectrometry (FI-ICP-MS), metabonomics and genomics were used to study the concentration changes of patients with primary glaucoma in three kinds of body fluid samples, and the related factors were analyzed combined with clinical data, so as to provide a new theoretical basis for studying the pathogenic mechanism and new prevention pathway of primary glaucoma. | Trace elements are one of the indispensable substances in human body and play an important physiological role. Zinc is a trace element second only to iron in organisms, which is widely distributed in various systems and organs and plays an important biological role, and interacts with other trace elements such as copper and iron. With the improvement of detection methods, it is possible to detect the concentration of zinc and other trace elements in liquid samples. It is reported in the existing literature that there are significant changes in the concentration of trace elements in a variety of eye diseases. Our group intends to collect three kinds of samples (aqueous humor, blood and tears) of patients with primary glaucoma and age-related cataract who were treated in Sun Yat-sen Eye Center of Sun Yat-sen University from March 2020 to March 2021. Normal people with matched age and sex were recruited as normal control group (normal control group only collected blood and tear samples). Three methods (FI-ICP-MS, metabonomics and genomics) were used to study the concentration changes of patients with primary glaucoma in three kinds of body fluid samples, and the related factors were analyzed combined with clinical data, so as to provide a theoretical basis for studying the pathogenic mechanism and new prevention pathway of primary glaucoma. |
This is a prospective, open label, single arm, intervention study to examine the safety and feasibility of water-only fasting to treat hypertensive patients. Additional aims include describing mean changes in resting blood pressure as well as markers of cardiovascular health and inflammation between baseline and end of fast, end of refeed, 6-weeks post departure, and 12-months after 6-weeks follow-up. | This purpose of this study is to examine the safety and feasibility of water-only fasting to treat hypertensive patients. |
This randomized, open label, multi-centre, non-inferiority study aims to compare that the combination of thermotherapy (one application, 50⁰C for 30) and 3 weeks of miltefosine (2.5 mg/kg/day for 21 days orally) (here after referred to as combination), is non-inferior to the current recommended first line treatments, meglumine antimoniate (20 mg/kg/day for 20 days parenterally) or miltefosine monotherapy (2.5 mg/kg/day for 28 days orally), for uncomplicated CL cases in the New World.~Primary Objective~• To determine the non-inferior efficacy of the combination in comparison to the standard first line treatment (meglumine antimoniate) and/or to miltefosine monotherapy as measured by the percentage of patients with initial clinical cure at Day 90.~Secondary objectives~Assess the proportion of patients who show clinical improvement at D90 (have more or equal of 75% and less than 100% re-epithelization) and achieve 100% re-epithelization at D105 (late responders).~Assess the proportion of relapses at D180.~Assess the safety and tolerability profile for each regimen (percentage of treatment discontinuation, frequency and severity, causality with each study drug and seriousness of Adverse Events (AEs)).~Assess the time to achieve 100% re-epithelialization/ flattening of ulcerated/ non ulcerated lesions by Leishmania species.~A computer-generated randomization code will be used for patient treatment allocation to one of the three arms indicated and utilizing a 1:1:1 allocation ratio.~Patients assigned to the combination treatment will start treatment at Day 1 and have a follow-up visit on 24 hours to assess safety of thermotherapy. Hereafter, these patients are required to return at Days 7, 14, 21, 45, 63, 90, 105 (late responders only) and 180 after the beginning of treatment to assess safety and efficacy.In Brazil, women of childbearing potential are required to also return on D120 and D150 to perform blood pregnancy tests. Women with irregular menstrual cycle, should return for blood pregnancy tests every two weeks until D150.~Patients assigned to the meglumine antimoniate treatment are required to come at Days 1, 7, 14, 21, 45, 63, 90, 105 (late responders only) and 180 after the beginning of treatment to assess safety and efficacy.~Patients assigned to the miltefosine monotherapy are required to come at Days 1, 7, 14, 21, 28, 45, 63, 90, 105 (late responders only) and 180 after the beginning of treatment to assess safety and efficacy. In Brazil, women of childbearing potential are required to also return on D120 and D150 to perform blood pregnancy tests. Women with irregular menstrual cycle, should return for blood pregnancy tests every two weeks until D150.~Patients who have 100% re-epithelization at D90 are declared cured and appointed to come to their D180 assessment. If at D90 re-epithelization of the ulcer(s) is more or equal to 75% but less than 100%, patients will be defined as having clinical improvement and will be asked to return to D105 for a late responder assessment. | This study evaluates if the combination of thermotherapy (one application, 50⁰C for 30) and 3 weeks of miltefosine is safe and have a comparable cure rate with the current recommended first line treatments comprising meglumine antimoniate for 3 weeks or miltefosine monotherapy for 4 weeks, for the treatment of uncomplicated cutaneous leishmaniasis cases in the New World. |
In the CLL2-BZAG trial will be included a total of 40 patients with relapsed or refractory CLL in need of treatment. This trial will evaluate a debulking with two cycles bendamustine (only for patients with a high tumor load), followed by an induction and maintenance treatment with obinutuzumab, zanubrutinib and venetoclax in patients with relapsed/refractory CLL. Thus, this trial combines one established (chemotherapy) and three novel, synergistic (antibody, Bruton's tyrosine kinase(BTK)-inhibitor and Bcl-2 antagonist) principles of action in order to achieve deep and long lasting remissions with a short duration of treatment. Additionally, this trial has an extensive accompanying scientific program aiming at a better understanding of the kinetics of response and clonal evolution of CLL. | CLL2-BZAG is a prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by obinutuzumab (GA101), zanubrutinib (BGB-3111) and venetoclax (ABT-199) in patients with relapsed/refractory CLL. |
Gum arabic is a heteropolysaccharide (molecular weight 350-850 kDa) harvested from Acacia seyal or Acacia senegal. It is highly soluble and broadly used in numerous solid and liquid food matrices.~For the assessment of non-digestible carbohydrates as dietary fiber, it is eminent to demonstrate that its consumption is related to a specific beneficial physiological effect shown in an appropriate clinical study. The aim of the present trial was to expand the clinical evidence with respect to beneficial effects of gum acacia on post-prandial blood glucose levels, post-prandial insulin levels and prospective ad libitum food intake, in normal-weight and overweight subjects.~The present double-blind, randomized, controlled, three-way cross-over study was to evaluate the effect of gum acacia versus no treatment on post-prandial glucose (PPG) levels in normal-weight and overweight subjects during a 2-7 weeks intervention period.~Additionally, post-prandial insulin (PPI) levels, prospective ad libitum food intake, as well as the safety and tolerability of gum acacia were assessed. | Study to evaluate the effect of gum acacia (FibregumTM) on post-prandial glucose and insulin levels and food intake in normal-weight and overweight subjects during a 2-7 weeks intervention period. In addition, tolerability and safety of gum acacia (FibregumTM) will be assessed. |
Sarcopenia is a condition diagnosed from different clinical findings such as low muscle mass, low muscle strength and possibly also poor physical performance. In the general population, the risk of fall and bone fracture increases, when sarcopenia is also present.~Sarcopenia is known to occur in patients with chronic kidney disease, but whether, and if so, how this differs from the incidence in patients without kidney disease has not previously been described.~Patients with chronic kidney disease have a 3 times higher risk of bone fracture compared to the Danish background population, and they also have an increased risk of falls.~The association between sarcopenia, risk of falls and osteoporosis in patients with kidney disease is until now sparsely described, and because of this, the investigators want to explore this further in this cross-sectional study. | This study is a cross-sectional study that wishes to investigate whether there is an increased incidence of sarcopenia in patients with chronic kidney disease compared to the Danish background population. A possible association between sarcopenia and fall, as well as the incidence of osteoporosis in patients with chronic kidney disease will also be described. |
Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as oscillopathies. Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances.~Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory.~On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease.~In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether a single stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with Mild Cognitive Impairment due to Alzheimer's disease.~Subjects will be randomized in two groups, one receiving a single treatment with gamma tACS (40 Hz) first and the other receiving sham stimulation. After one week the treatments will be exchanged. Patients will be evaluated with neuropsychological tests and neurophysiological measures of cholinergic transmission. | Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as oscillopathies. Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances.~Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory.~On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease.~In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether a single stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with Mild Cognitive Impairment due to Alzheimer's disease. |
Persistent pain and fatigue are prevalent and disabling symptoms in people with Rheumatoid Arthritis, even in the absence of active inflammation. The investigators believe that these symptoms may be a result of abnormal pain processing by the Central Nervous System (CNS), in a process called central sensitization.~The investigators have developed a short, self-report questionnaire to measure central pain mechanisms in people with RA. It is called Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA), and was adapted from a pre-existing questionnaire called CAP-Knee (which measures central sensitization in people with chronic knee pain).~This study aims to measure the psychometric properties of CAP-RA, and the ability of the questionnaire to predict worse pain in the RA population. Secondary objectives of the study include predicting worse fatigue in people with RA, deriving CAP-RA scoring recommendations, investigating other factors associated with persistent RA pain, the association between central sensitization and pain, and investigating the course of pain and fatigue in RA.~Participants will be recruited from a Rheumatology clinic. At baseline and 12 weeks these participants will undergo quantitative sensory testing (QST, pain tests), ultrasound for synovitis, clinical assessments, laboratory tests for systemic inflammation and, complete a questionnaire booklet, including the CAP-RA questionnaire.~Some participants will complete the CAP-RA questionnaire 1 week after the baseline visit to assess the test-retest reliability of the questionnaire.~In addition, participants will provide weekly pain and fatigue self-report via text message (SMS) for 12 weeks. | This study seeks to measure the psychometric properties of a newly developed Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, and investigate the ability of this questionnaire to measure central mechanisms of pain and also to predict worse pain and fatigue outcomes in people with Rheumatoid Arthritis (RA). |
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with the incidence of about 70/100,000 in China. Recurrent relapses of disease and development of long-term organ damage are two key unsolved clinical problems. Its pathogenesis is still unclear, but B cells have been confirmed to play a vital role in it. Belimumab, a B-lymphocyte stimulating factor (Blys) inhibitor, was the only FDA-approved biological agent for SLE. BLISS-52 showed that more active lupus patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 10 mg/kg (58% vs 46%, p=0·0024) than with placebo. But there was limited data about belimumab in SLE patients with low disease activity. Our previous study indicated that even these patients still have an annual flare rate of 30-40%. Therefore, we try to explore whether low-dose of belimumab could prevent the disease flares in SLE patients with low disease activity. | Systemic lupus erythematosus (SLE) is a chronic inflammatory systemic autoimmune disease. Recurrent relapses of disease and development of long-term organ damage are two key unsolved clinical problems. Belimumab is the only FDA-approved biological agent for SLE. Data showed that treatment with belimumab on the background of standard therapy was effective in active SLE patients. However, the efficacy of low-dose belimumab for prevention of disease flares in SLE patients with low disease activity is to be explored. |
Starting in 2001, the Look AHEAD study randomized 5145 patients with type 2 diabetes to an intensive lifestyle intervention (ILI) focused on weight loss versus a control group receiving diabetes education (Diabetes Support and Education).The Look AHEAD study tested whether participants with type 2 diabetes assigned to an intensive lifestyle intervention (ILI) for weight loss exhibited reductions in cardiovascular morbidity and mortality, relative to a control group receiving usual care and diabetes support and education. During the 12-year intervention period, the ILI led to persistent reductions in weight, waist circumference, and hemoglobin A1c and improvements in physical fitness, among other clinical benefits. After the conclusion of the intervention in 2012, participants were consented to be linked with administrative data. The investigators attempted to link 3188 consenting participants with Social Security Administration databases. Of these, the investigators were able to successfully link 3093 participants. In this study, the investigators will compare participation in federal disability insurance programs including Social Security Disability Insurance (SSDI) and disability-related Supplemental Security Income (SSI) between the linked ILI and the control group during and after the intervention period (2001-2017). The investigators will investigate ILI-versus-control differences in whether participants ever applied or received benefits from SSDI and SSI. The investigators will also investigate ILI-versus-control differences in applications and benefit receipt in each year after randomization, relative to a pre-randomization assessment period. The investigators will use both multivariate regression controlling for baseline participant characteristics and clinic site and also survival analyses that estimate whether the time until SSDI or SSI application or benefit receipt differs between the ILI and control groups. | Starting in 2001, the Look AHEAD study randomized patients with type 2 diabetes to an intensive lifestyle intervention (ILI) focused on weight loss versus a control group receiving diabetes education (Diabetes Support and Education). The ILI successfully reduced weight, improved diabetes control, and functional status, among other outcomes. In this study, the investigators will compare participation in federal disability insurance programs between the ILI and the control group during and after the intervention period (2001-2017). |
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