title: A novel immersive virtual reality environment for the motor rehabilitation of stroke patients: A feasibility study

abstract:
We designed and implemented an immersive virtual reality environment for upper limb rehabilitation, which possesses several notable features. First, by exploiting modern computer graphics its can present a variety of scenarios that make the rehabilitation routines challenging yet enjoyable for patients, thus enhancing their adherence to the therapy. Second, immersion in a virtual 3D space allows the patients to execute tasks that are closely related to everyday gestures, thus enhancing the transfer of the acquired motor skills to real-life routines. Third, in addition to the VR environment, we also developed a client app running on a PC that allows to monitor in real-time and remotely the patients routines thus opening the door to telerehabilitation scenarios.

Here, we report the results of a feasibility study in a cohort of 16 stroke patients. All our patients showed a high degree of comfort in our immersive VR system and they reported very high scores of ownership and agency in embodiment and satisfaction questionnaires. Furthermore, and notably, we found that behavioral performances in our VR tasks correlated with the patients clinical scores (Fugl-Meyer scale) and they can thus be used to assess improvements during the rehabilitation program. While further studies are needed, our results clearly support the feasibility and effectiveness of VR-based motor rehabilitation processes.

Significance statementApproximately 80% of stroke patients suffer from a hemiparesis of the contralateral upper limb. Motor rehabilitation has been proven to be of key importance to regain, partially or totally, the impaired motor skills. Rehabilitation techniques are based on the repetitive and intense execution of simple motor behaviors. As such they can become taxing and cumbersome for the patients. This often produces non-adherence issues with an obvious negative impact on motor recovery.

Here we describe a novel immersive virtual environment for upper limb motor rehabilitation and we report the results that we obtained in a cohort of 16 stroke patients. Our system was designed to turn rehabilitation routines into engaging games and to allow the remote monitoring of the patients exercises thus allowing telerehabilitation.

All our patients showed a high degree of comfort in our immersive VR system and they reported very high scores of ownership and agency in embodiment and satisfaction questionnaires. Furthermore, and notably, we found that behavioral performances in our VR tasks correlated with the patients clinical scores (Fugl-Meyer scale) and they can thus be used to assess improvements during the rehabilitation program.

category: rehabilitation medicine and physical therapy


title: Hematopoietic and Lung Platelet Biogenesis as a Prognostic Indicator in Idiopathic Pulmonary Fibrosis (IPF)

abstract:
Rationale and objectivesThe role of human lung megakaryocytes in homeostasis and their dynamics in disease states remain unknown. We sought to investigate whether megakaryocyte/platelet gene signatures are altered in IPF.

MethodsWe analyzed publicly available transcriptome datasets of lung tissue, bronchoalveolar lavage (BAL) cells, and peripheral whole blood from IPF patients and healthy controls. Enrichment of megakaryocyte and platelet gene signatures in those datasets were estimated using xCell, a novel computational method. Furthermore, we analyzed whether mean platelet volume (MPV) and platelet counts in peripheral blood are associated with lung transplant-free survival in our IPF cohort.

ResultsIn lung tissue, megakaryocyte scores were significantly lower in IPF than in controls. In BAL cells, platelet scores were significantly lower in IPF than in controls, and lower platelet scores were associated with lower lung transplant-free survival in IPF. In contrast, in blood, megakaryocyte scores were significantly higher in IPF than in controls, and higher megakaryocyte scores were associated with lower disease progression-free survival in IPF. Furthermore, higher MPV was associated with lower transplant-free survival in our IPF cohort, independent of age, sex, forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO).

ConclusionsIn IPF, megakaryocyte/platelet gene signatures were altered in a compartment-specific manner. Moreover, those signatures and MPV in blood were associated with important clinical outcomes such as transplant-free survival. These findings provide new insights into altered megakaryocyte/platelet biogenesis in IPF and suggest the potential utility of megakaryocyte/platelet-based biomarkers in IPF.

category: respiratory medicine


title: Patient Perceptions by Race of Educational Animations About Living Kidney Donation Made for a Diverse Population

abstract:
IntroductionThis qualitative study sought to identify potential design and delivery alterations to inform cultural adaptation of educational animations about living donor kidney transplantation (LDKT) - previously developed for a diverse population - to better fit Black Americans needs.

MethodsWe conducted a secondary analysis of 88 transcripts derived from interviews and focus groups conducted with diverse target users (62 kidney failure patients, 36 prior/potential donors, and 11 care partners) to develop 12 animations about LDKT, named KidneyTIME. Statements were abstracted and coded pertaining to cognitive and communication barriers to LDKT, and the perceived value of using the videos to learn and share the information with social network members using content analysis. Incidence counts of each content code were also calculated to assess differences between Black and non-Black patients.

ResultsCognitive barrier codes included lack of knowledge, ambivalence, and concern for donor. Communication barrier codes included reluctance and difficulty talking about LDKT. Cognitive facilitating codes included attention-getting, efficient learning, manageable content, emotional impact, and new knowledge. Communication facilitating codes included delivery through many dissemination channels and broadly shareable. Compared to non-black patients (n=33) Black patients (n=29) more often stated concern for donor and reluctance/difficulty talking about LDKT as barriers, and less often stated efficient learning and manageable content as facilitators.

ConclusionFindings highlight the value of LDKT informational content that is visually appealing, digestible, non-threatening, and highly shareable. Heterogeneity may exist when considering access and intervention preferences in using KidneyTIME videos and highlight a potential for further cultural targeting or tailoring.

category: transplantation


title: Effect of reduction in brain amyloid levels on change in cognitive and functional decline in randomized clinical trials: an updated instrumental variable meta-analysis

abstract:
ObjectiveTo update a recently published analysis exploring the causal association between positron emission tomography (PET)-measured change in brain {beta}-amyloid plaque and cognitive decline in patients with Alzheimers disease (AD) enrolled in randomized clinical trials (RCTs).

DesignUpdated instrumental variable meta-analysis.

SettingSixteen RCTs were included in this updated meta-analysis versus 14 in the original publication by Ackley et al.1 Data sources were ClinicalTrials.org, Alzheimer Research Forum (alzforum.org), PubMed and clinical study reports from 2015 to March 1, 2022. Three researchers extracted data from the data sources independently and subsequently resolved any discrepancy.

PopulationRCTs that evaluated {beta}-amyloid targeting therapies and enrolled adult patients with AD dementia or mild cognitive impairment due to AD with data on {beta}-amyloid as measured by PET and clinical outcome measures.

Main outcome measuresAn instrumental variable meta-analysis was performed to compute trial and drug-specific estimates and pooled estimates of the effect of change in PET {beta}-amyloid standard uptake value ratio (SUVR) on cognitive and functional decline with 95% confidence intervals (CIs) and associated p-values. This analysis updated and expanded a prior meta-analysis by Ackley et al.1 using the same methodology and clinical outcome measures: Clinical Dementia Rating-Sum of Boxes (CDR-SB), Alzheimers Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Mini-Mental State Examination (MMSE).

ResultsThe reduction of PET-measured {beta}-amyloid induced a statistically significant reduction in cognitive and functional decline. The effect size was characterized by an estimated change (95% CI) of 0.09 (0.034, 0.15) on the CDR-SB; 0.33 (0.12, 0.55) on the ADAS-Cog; and 0.13 (0.017, 0.24) on the MMSE for each decrease of 0.1-unit in PET {beta}-amyloid SUVR.

ConclusionThis updated instrumental variable meta-analysis of 16 RCTs provides statistically significant evidence of a causal relationship between the reduction in brain {beta}-amyloid plaque and the reduction in cognitive and functional decline in patients with Alzheimers disease.

category: neurology


title: Exploring the relationship between womens experience of postnatal care and reported staffing measures: an observational study

abstract:
BackgroundWomen have reported dissatisfaction with care received on postnatal wards and this area has been highlighted for improvement. Studies have shown an association between midwifery staffing levels and postnatal care experiences, but so far, the influence of registered and support staff deployed in postnatal wards has not been studied. This work is timely as the number of support workers has increased in the workforce and there has been little research on skill mix to date.

MethodsCross sectional secondary analysis including 13,264 women from 123 postnatal wards within 93 hospital Trusts. Staffing was measured at organisational level as Full Time Equivalent staff, and at ward level using Care Hours Per Patient Day. Womens experiences were assessed using four items from the 2019 national maternity survey. Multilevel logistic regression models were used to examine relationships and adjust for maternal age, parity, type of birth, medical staff and number of births per year in the Trust.

ResultsTrusts with higher levels of midwifery staffing had higher rates of women reporting positive experiences of postnatal care. However, when staffing was measured at a ward level, there was no evidence of an association between registered staffing and patient experience. Wards with higher levels of support worker staffing were associated with higher rates of women reporting they had help when they needed it and were treated with kindness and understanding.

ConclusionThe relationship between reported registered staffing levels on postnatal wards and womens experience is uncertain. Further work should be carried out to examine why relationships observed at an organisational level were not replicated closer to the patient, at ward level. It is possible that reported staffing levels do not reflect staff as deployed if midwives are floated to cover delivery units. This study highlights the potential contribution of support workers in providing quality care on postnatal wards.

category: nursing


title: Deep learning-based prognosis prediction among preeclamptic pregnancies using electronic health record data

abstract:
BackgroundPreeclampsia (PE) is one of the leading factors in maternal and perinatal mortality and morbidity worldwide. The only cure for PE to date is to deliver the placenta and stop gestation. However, the timing of delivery among PE patients is essential to minimize the risk of severe maternal morbidities, and at the same time ensure the survival of the baby.

MethodsIn this study, we constructed a series of deep learning-based models to predict the prognosis, or the time to delivery, since the initial diagnosis of PE using electronic health record (EHR) data. We extracted and processed 1578 pregnancies in Michigan Medicine at the University of Michigan in 2015-2021 as the discovery cohort. Using the Cox-nnet v2 algorithm, we built the baseline model with EHR information prior to diagnosis, as well as the full model including baseline information and lab testing results and vital signs at the time of diagnosis. We evaluated the models using the C-index and log-rank p-values in KM survival curves, using both 20% testing data of the Michigan cohort, as well as 1177 PE pregnancy EHR data from the Medical Center of the University of Florida.

ResultsThe baseline prognosis model for time to delivery since PE diagnosis achieved C-index values of 0.75 and 0.72 on the training and testing set respectively. While the full model reached C-indices of 0.77 and 0.74 in the same training and testing sets. Both models performed better than their Cox-PH model counterparts. The seven most important features in the baseline model in descending order were diagnosis gestational age, severe PE, past PE, age, parity, gravidity, and uncomplicated diabetes. Meanwhile, 14 most important features were selected and interpreted in the full model, including diagnosis gestational age, parity, severe PE, past PE, features in lab tests (white blood cell, platelet, and red blood cell counts, AST value), min respiratory rate, and features measuring blood pressure (minimum, mean and standard deviation of systolic blood pressure, and maximum and standard deviation of diastolic blood pressure).

ConclusionThe time to delivery predicting models provide clinicians valuable tools and options to quantify the delivery risks and make better decisions on the optimal delivery time of PE patients at the time of diagnosis. Implementation of these actionable models into PE clinical care practice is expected to significantly improve the management of PE patients.

category: obstetrics and gynecology


title: Workplace ventilation improvement to address coronavirus disease 2019 cluster occurrence in a manufacturing factory

abstract:
Aim and MethodsA coronavirus disease 2019 (COVID-19) cluster emerged in a manufacturing factory in early August 2021. In November 2021, a ventilation survey using tracer gas and data analysis was performed to reproduce the situation at the time of cluster emergence and verify that ventilation in the office increased the risk of aerosol transmission; verify the effectiveness of measures implemented immediately in August; and verify the effectiveness of additional measures when previously enforced measures proved inadequate.

ResultsAt the time of cluster emergence, the average ventilation frequency was 0.73 times/h, less than the 2 times/h recommended by the Ministry of Health, Labour, and Welfare; as such, the factorys situation was deemed to have increased the risk of aerosol transmission. Due to the measures already taken at the time of the survey, the ventilation frequency increased to 3.41 times/h on average. It was confirmed that ventilation frequency increased to 8.33 times/h on average, when additional measures were taken.

ConclusionTo prevent the re-emergence of COVID-19 clusters, it is necessary to continue the measures that have already been implemented. Additionally, introduction of real-time monitoring that visualizes CO2 concentrations is recommended. Furthermore, we believe it is helpful that external researchers in multiple fields and internal personnel in charge of health and safety department and occupational health work together to confirm the effectiveness of conducted measures, such as this case.

category: occupational and environmental health


title: Accurate genome-wide germline profiling from decade-old archival tissue DNA reveals the contribution of common variants to precancer disease outcome

abstract:
BackgroundInherited variants have been shown to contribute to cancer risk, disease progression, and response to treatment. Such studies are, however, arduous to conduct, requiring large sample sizes, cohorts or families, and more importantly, a long follow-up to measure a relevant outcome such as disease onset or progression. Unless collected for a dedicated study, germline DNA from blood or saliva are typically not available retrospectively, in contrast to surgical tissue specimens which are systematically archived.

ResultsWe evaluated the feasibility of using DNA extracted from low amounts of fixed-formalin paraffin-embedded (FFPE) tumor tissue to obtain accurate germline genetic profiles. Using matching blood and archival tissue DNA from 10 individuals, we benchmarked low-coverage whole-genome sequencing (lc-WGS) combined with genotype imputation and measured genome-wide concordance of genotypes, polygenic risk scores (PRS), and HLA haplotypes. Concordance between blood and tissue was high (r2>0.94) for common genome-wide single nucleotide polymorphisms (SNPs) and across 22 disease-related PRS (mean r=0.93). HLA haplotypes imputed from tissue DNA were 96.7% (Class I genes) and 82.5% (Class II genes) concordant with deep targeted sequencing of HLA from blood DNA. Using the validated methodology, we estimated breast cancer PRS in 36 patients diagnosed with breast ductal carcinoma in situ (11.7 years median follow-up time) including 22 who were diagnosed with breast cancer subsequent event (BSCE). PRS was significantly associated with BCSE (HR=2.5, 95%CI: 1.4-4.5) and the top decile patients were modeled to have a 24% chance of BCSE at 10 years, hence suggesting the addition of PRS could improve prognostic models which are currently inadequate.

ConclusionsThe abundance and broad availability of archival tissue specimens in oncology clinics, paired with the effectiveness of germline profiling using lc-WGS and imputation, represents an alternative cost and resource-effective alternative in the design of long-term disease progression studies.

category: oncology


title: Equally low blood metal ion levels at 10-years follow up of total hip arthroplasties with Oxinium, CoCrMo and stainless steel femoral heads. Data from a randomized clinical trial

abstract:
Background and purposeThe use of inert head materials such as ceramic heads has been proposed as a method of reducing wear and corrosion products from the articulating surfaces in total hip arthroplasty (THA), as well as from the stem-head taper connection. In the present study, we wanted to evaluate the blood metal ion levels of Oxinium modular femoral heads at 10 years postoperatively and compare with the CoCrMo modular femoral head counterpart, and the monoblock stainless steel Charnley prosthesis.

Patients and methods150 patients with osteoarthritis of the hip joint previously included in a randomized clinical trial that had the primary aim of examining polyethylene wear in cemented THAs were re-grouped according to femoral head material. One group (n=30) had received the Charnley monoblock stainless steel stem with 22.2 mm head (DePuy, UK). The other groups (n=120) received a Spectron EF CoCrMo stem with either a 28 mm CoCrMo or Oxinium modular head (Smith & Nephew, USA). After 10 years, 19 patients had died and 38 withdraw from the study. Five patients were revised due to infection in their hip and 7 were revised due to aseptic loosening of either the cup or stem or both. 81 patients with median age of 79 years (70-91) were available for whole blood metal ion analysis.

ResultsThe levels of Co, Cr, Ni and Zr in the blood were generally low with all head materials (medians <0.3 micrograms/L). We found no statistically significant difference in the concentration of metal ions between the group with Charnley prosthesis (n=17) and those with Spectron EF stems with either CoCrMo (n=32) or Oxinium heads (n=32) (p=0.18-0.81).

InterpretationIn this study of patients with non-revised THAs, no indication of severe trunnion corrosion was found. The blood ion levels with the use of ceramic Oxinium modular femoral heads were similar to CoCrMo or stainless steel heads at 10 years follow-up.

category: orthopedics


title: Age acquired skewed X Chromosome Inactivation is associated with adverse health outcomes in humans

abstract:
BackgroundAgeing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells, and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of XX,46 females to balance the gene expression with XY,46 males. Age acquired XCI-skew describes the preferential inactivation of one X chromosome across a tissue, which is particularly prevalent in blood tissues of ageing females and yet its clinical consequences are unknown.

MethodsWe assayed XCI in 1,575 females from the TwinsUK population cohort and employed prospective, cross-sectional, and intra-twin designs to characterise the relationship of XCI-skew with molecular, cellular, and organismal measures of ageing, and cardiovascular disease risk and cancer diagnosis.

ResultsWe demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10-year follow-up study, XCI-skew is predictive of future cancer incidence.

ConclusionsOur study demonstrates that age acquired XCI-skew captures changes to the haematopoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk.

FundingKSS acknowledges funding from the Medical Research Council (MR/M004422/1 and MR/R023131/1). JTB acknowledges funding from the ESRC (ES/N000404/1). MM acknowledges funding from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust in partnership with Kings College London. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guys and St Thomas NHS Foundation Trust in partnership with Kings College London.

category: genetic and genomic medicine


title: Low-dose IL-2 reduces IL-21+ T cells and induces a long-lived anti-inflammatory gene expression signature inversely modulated in COVID-19 patients

abstract: Despite early clinical success, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here, we examine the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) using high-resolution, single-cell multiomics. We confirmed that iLD-IL-2 selectively expands thymic-derived FOXP3+HELIOS+ Tregs and CD56br NK cells, and provide new evidence for an IL-2-induced reduction of highly differentiated IL-21-producing CD4+ T cells. We also discovered that iLD-IL-2 induces an anti-inflammatory gene expression signature, which was detected in all T and NK cell subsets even one month after treatment. The same signature was present in COVID-19 patients, but in the opposite direction. These findings indicate that the sustained Treg and CD56br NK cell increases induced by our 4-week iLD-IL2 treatment create a long-lasting and global anti-inflammatory environment, warranting further investigations of the potential clinical benefits of iLD-IL-2 in immunotherapy, including the possibility of reversing the pro-inflammatory environment in COVID-19 patients.


title: Digital health and quality of home-based primary care for older adults: A scoping review protocol

abstract:
IntroductionDigital health strategies have expanded in home care, particularly in home-based primary care (HBPC) following the increase in the older adult population and the need to respond to the higher demand of chronic conditions and health frailties of this population. There was an even greater demand with COVID-19 and subsequent isolation/social distancing measures for this group considered at risk. The objective of this study is to map digital health strategies and analyze their impacts on the quality of home-based primary care for older adults around the world.

Methods and analysisThis is a scoping review protocol which will enable a rigorous, transparent and reliable synthesis of knowledge. The review will be developed in the theoretical perspective of Arksey and Omalley, with updates by Levac et al. and Peters et al., based on the Joanna Briggs Institute manual, and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Data from white literature will be extracted from multidisciplinary health databases such as: the Virtual Health Library, LILACS, PubMed, Scopus, Web of Science, CINAHL and Embase; while Google Scholar will be used for gray literature. The quantitative data will be analyzed through descriptive statistics and qualitative data through thematic analysis. The results will be submitted to stakeholder consultation for preliminary sharing of study findings, identification of gaps, effective dissemination strategies and suggestions for future studies.

Ethics and disclosureStakeholder consultation was approved by the Research Ethics Committee of Hospital Onofre Lopes, Federal University of Rio Grande do Norte, CAEE 54853921.0.0000.5292, and will not involve direct patient participation. It is registered in the Open Science Framework (OSF) (https://osf.io/vgkhy/). The results will be disseminated through publication in open access scientific journals, in scientific events and academic and community journals.

Scoping review registration OSF:https://osf.io/vgkhy/. DOI 10.17605/OSF.IO/VGKHY.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Strengths and limitations of this studyO_LIThis scoping review will be the first to explore the types, uses and impacts of digital health strategies on home-based primary care (HBPC) for older adults around the world.
C_LIO_LIThe geographic mapping of the studies will provide a global overview of the use of digital health strategies in providing home care.
C_LIO_LIThe search strategy for studies will be broad, including the main multidisciplinary health databases and gray literature.
C_LIO_LIThe expansion of the use of digital health strategies during COVID-19 may be a limiting factor to the scientific quality of studies.
C_LIO_LIA large number of publications in the gray literature may imply an important limitation of the study but also meaning that digital home care still lacks maturity.
C_LI

category: health informatics


title: Extraction of Sleep Information from Clinical Notes of Alzheimer's Disease Patients Using Natural Language Processing

abstract: Alzheimers Disease (AD) is the most common form of dementia in the United States. Sleep is one of the lifestyle-related factors that has been shown critical for optimal cognitive function in old age.. However, there is a lack of research studying the association between sleep and AD incidence. A major bottleneck for conducting such research is that the traditional way to acquire sleep information is time-consuming, inefficient, non-scalable, and limited to patients subjective experience. In this study, we developed a rule-based NLP algorithm and machine learning models to automate the extraction of sleep-related concepts, including snoring, napping, sleep problem, bad sleep quality, daytime sleepiness, night wakings, and sleep duration, from the clinical notes of patients diagnosed with AD. We trained and validated the proposed models on the clinical notes retrieved from the University of Pittsburgh of Medical Center (UPMC). The results show that the rule-based NLP algorithm consistently achieved the best performance for all sleep concepts.


title: Classification of Omicron BA.1, BA.1.1 and BA.2 sublineages by TaqMan assay consistent with whole genome analysis data

abstract:
ObjectiveRecently, the Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread and replaced the previously dominant Delta strain. Several Omicron sublineages (BA.1, BA.1.1 and BA.2) have been identified, with in vitro and preclinical reports showing that the pathogenicity and therapeutic efficacy differs between BA.1 and BA.2. We sought to develop a TaqMan assay to identify these subvariants.

MethodsA TaqMan assay was constructed for rapid identification and genotyping of Omicron sublineages. We analyzed three characteristic mutations of the spike gene, {Delta}69-70, G339D and Q493R, by TaqMan assay. The accuracy of the TaqMan assay was examined by comparing its results with the results of whole genome sequencing (WGS) analysis.

ResultsA total of 169 SARS-CoV-2 positive samples were analyzed by WGS and TaqMan assay. The 127 samples determined as BA.1/BA.1.1 by WGS were all positive for {Delta}69-70, G339D and Q493R by TaqMan assay. Forty-two samples determined as BA.2 by WGS were negative for {Delta}69-70 but positive for G339D and Q493R by TaqMan. The concordance rate between WGS and the TaqMan assay was 100% (169/169).

ConclusionTaqMan assays targeting characteristic mutations are useful for identification and discrimination of Omicron sublineages.

category: infectious diseases


title: Dengue-2 Cosmopolitan genotype detection and emergence in South America.

abstract:
We report the first confirmed case of DENV-2 Cosmopolitan genotype isolated from a male patient from Aparecida de Goiania, Goias state, Midwest Brazil. Using nanopore sequencing, and phylogenetic analyses our findings provide the first preliminary insight regarding the introduction of this emerging genotype in Brazil and South America.

Article Summary LineMolecular detection of Dengue virus type 2 Cosmopolitan genotype in South America


title: Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study

abstract:
BackgroundIn January 2022, United States guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown.

MethodsWe conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for RT-PCR and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by SARS-CoV-2 variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared to culture.

ResultsAmong 92 SARS-CoV-2 RT-PCR positive participants, all completed the initial vaccine series, 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For the 14 sub-study participants, sensitivity and specificity of RDT were 100% and 86% respectively.

ConclusionsThe majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though masking for a full 10 days is necessary to prevent transmission from the 17% of individuals who remain culture positive after isolation.

Main PointBeyond day 5, 17% of our Delta and Omicron-infected cohort were culture positive. We saw no significant impact of booster vaccination on within-host Omicron viral dynamics. Additionally, we found that rapid antigen testing may provide reassurance of lack of infectiousness.


title: Preliminary diagnostic performance of the VIDAS(R) TB-IGRA for the detection of Mycobacterium tuberculosis infection and disease

abstract:
ImportanceAccurate diagnosis of tuberculosis (TB) infection can be achieved with interferon-{gamma} release assays. Their performance can be improved by utilizing fully automated, single-patient formats.

ObjectiveEstablish clinical thresholds for a new interferon-{gamma} release assay, the VIDAS(R) TB-IGRA, and compare diagnostic performance in detecting tuberculosis infection and disease with the established QuantiFERON-TB Gold Plus (QFT-Plus).

DesignPreliminary diagnostic performance study (October 2nd, 2019-February 20th, 2020).

SettingMulticenter.

ParticipantsParticipants were divided into TB disease, high-risk, and low-risk populations. The confirmed TB disease population included 107 patients. The high-risk population included 162 individuals with flagged risk factors on a questionnaire but without objective clinical confirmation of TB. The Low-risk population included 117 healthy blood donors from the French National Blood Bank.

ExposuresTuberculosis.

Main Outcomes and MeasuresPositive and negative percent agreement (PPA, NPA) were determined between the VIDAS(R) TB-IGRA and QFT-Plus. In the TB disease and low-risk populations, sensitivity was also measured against bacterial culture and PCR.

ResultsThe VIDAS(R) TB-IGRA produced fewer indeterminate results than the QFT-Plus (1/107 vs. 23/107) in the TB disease population. One analysis included indeterminate results as false negatives (94 positives and 10 false negatives vs. 56 positives and 48 false negatives), and the VIDAS(R) TB-IGRA exhibited higher sensitivity than the QFT-Plus (90.4% vs. 53.8%) (p<0.0001). Another analysis excluded indeterminate results (76 positives and 4 false negatives vs. 55 positives and 25 false negatives), and the VIDAS(R) TB-IGRA again exhibited higher sensitivity than the QFT-Plus (95.0% vs. 68.8%) (p<0.0001). A 98.2% PPA was calculated between the two tests with this dataset.

In the high-risk population, the VIDAS(R) TB-IGRA exhibited a strong PPA (94.4%) with the QFT-Plus. However, a lower than expected NPA was observed (85.2%). In the low-risk population, the VIDAS(R) TB-IGRA demonstrated high specificity (94.9%) and a strong NPA (98.2%) with the QFT-Plus.

Conclusions and RelevanceThe fully automated VIDAS(R) TB-IGRA is a promising diagnostic test for both TB infection and disease. It exhibits higher sensitivity while maintaining specificity and produces fewer indeterminate interpretations. Its easy-to-use, single-patient format may lead to increased TB testing to help with the worldwide eradication of the disease.

KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat is the diagnostic performance of the VIDAS(R) TB-IGRA in detecting tuberculosis infection and disease?

FindingsThe VIDAS(R) TB-IGRA exhibited high sensitivity in individuals with tuberculosis disease (90.4-95.0%), high specificity in healthy blood donors (94.9%), a high positive percent agreement (PPA) in individuals with a high risk of tuberculosis infection (94.4%), and it produced a low number of indeterminate results (1/386).

MeaningThe VIDAS(R) TB-IGRA is a promising diagnostic test for both tuberculosis infection and disease.


title: Determinants of mortality among COVID-19 patients with diabetes mellitus in Addis Ababa, Ethiopia, 2022: An unmatched case-control study

abstract:
IntroductionCOVID-19 remains one of the leading causes of death seeking global public health attention. Diabetes mellitus is associated with severity and lethal outcomes up to death independent of other comorbidities. Nevertheless, information regarding the determinant factors that contributed to the increased mortality among diabetic COVID-19 patients is limited. Thus, this study aimed at identifying the determinants of mortality among COVID-19 infected diabetic patients.

MethodsAn unmatched case-control study was conducted on 340 randomly selected patients by reviewing patient records. Data were collected using a structured extraction checklist, entered into Epi data V-4.4.2.2, and analyzed using SPSS V-25. Then, binary logistic regression was used for bivariate and multivariable analysis. Finally, an adjusted odds ratio with 95% CI and a p-value of less than 0.05 was used to determine the strength of association and the presence of a statistical significance consecutively.

ResultsThe study was conducted on 340 COVID-19 patients (114 case and 226 controls). Patient age (AOR=4.90; 95% CI: 2.13, 11.50), severity of COVID-19 disease (AOR=4.95; 95% CI: 2.20, 11.30), obesity (AOR=7.78; 95% CI: 4.05, 14.90), hypertension (AOR=5.01; 95% CI: 2.40, 10.60), anemia at presentation (AOR=2.93; 95% CI: 1.29, 6.65), and AKI after hospital admission (AOR=2.80; 95% CI: 1.39, 5.64) had statistically significant association with increased mortality of diabetic patients with COVID-19 infection. Conversely, presence of RVI co-infection was found to be protective against mortality (AOR=0.35; 95% CI: 0.13, 0.90).

ConclusionPatient age (<65years), COVID-19 disease severity (mild and moderate illness), presence of hypertension, obesity, anemia at admission, and AKI on admission was independently associated with increased mortality of diabetic COVID-19 patients. Contrariwise, the presence of RVI co-infection was found to be protective against patient death. Consequently, COVID-19 patients with diabetes demand untiring efforts, and focused management of the identified factors will substantially worth the survival of diabetic patients infected with COVID-19.

What is already known on this topic?Diabetes mellitus is associated with severity and lethal outcomes up to death independent of other comorbidities. Previous studies indicated that diabetic patients have almost four times increased risk of severe disease and death due to COVID-19 infection. Consequently, with this increased mortality and other public health impacts, numerous reports have been evolved worldwide on the link between COVID-19 and DM, and diabetes management during the COVID-19 pandemic. However, information regarding the determinant factors that lead to the increased mortality among diabetic COVID-19 patients is not well-studied yet.

What this study adds?O_LIPatient age (<65years), COVID-19 disease severity (mild and moderate illness), presence of hypertension, obesity, anemia at admission, and AKI on hospital admission were independently associated with increased mortality of COVID-19 patients with DM.
C_LIO_LIIn addition, RVI co-infection was found to be protective against patient death.
C_LI


title: Combination of Baricitinib plus Remdesivir and Dexamethasone improves time to recovery and mortality among hospitalized patients with severe COVID-19 infection

abstract:
BackgroundThere seems to be a gap in the therapeutic options for severe Covid-19 pneumonia. Though the beneficial effect of combination treatment with baricitnib and remdesivir in accelerating clinical status improvement is described, the impact of the triple therapy with baricitinib + remdesivir/dexamethasone is not known.

MethodsA retrospective observational study comparing the effect of baricitinib plus standard treatment (remdesivir and dexamethasone) with standard therapy in patients requiring [≥] 5 L/min O2 was conducted. The primary outcome was to compared time to recovery in both groups, and the secondary outcomes was to determine mortality rate at discharge.

ResultsOf 457 patients hospitalized during the study period, 51 patients received standard treatment while 88 patients received baricitinib plus standard treatment. In baricitinib group, the rate ratio of recovery was 1.28 (95%CI 0.84-1.94, p=0.24) with a reduction in median time to recovery of 3 days compared to standard treatment group. Subgroup analysis based on Ordinal Scale showed reduction in median time to recovery by 4 and 2 days with rate ratio of recovery of 2.95 (1.03-8.42, p =0.04) and 1.80 (1.09-2.98, p=0.02) in Ordinal Scale 5 and 6 respectively. No benefit was found in the Ordinal Scale 7 subgroup. An overall decrease in rate (15.9% vs 31.4% p=0.03) a likelihood (OR 0.41, 95%CI 0.18-0.94, p=0.03) of mortality was observed in the baricitinib group. Bacteremia and thrombosis were noted in the Baricitinib group, but comparable with the Standard of care group.

ConclusionBaricitinib with standard therapy reduced time to recovery and offer mortality benefit in patients with severe COVID-19 pneumonia."

category: intensive care and critical care medicine


title: Hyperinflammatory ARDS is characterized by interferon-stimulated gene expression, T-cell activation, and an altered metatranscriptome in tracheal aspirates

abstract: Two molecular phenotypes of the acute respiratory distress syndrome (ARDS) with substantially different clinical trajectories have been identified. Classification as "hyperinflammatory" or "hypoinflammatory" depends on plasma biomarker profiling. Differences in the biology underlying these phenotypes at the site of injury, the lung, are unknown. We analyze tracheal aspirate (TA) transcriptomes from 46 mechanically ventilated subjects to assess differences in lung inflammation and repair between ARDS phenotypes. We then integrate these results with metatranscriptomic sequencing, single-cell RNA sequencing, and plasma proteomics to identify distinct features of each ARDS phenotype. We also compare phenotype-specific differences in gene expression to experimental models of acute lung injury and use an in silico analysis to identify candidate treatments for each phenotype. We find that hyperinflammatory ARDS is associated with increased integrated stress response and interferon gamma signaling, distinct immune cell polarization, and differences in microbial community composition in TA. These findings demonstrate that each phenotype has distinct respiratory tract biology that may be relevant to developing effective therapies for ARDS.


title: Effectiveness of Oral Health Education Interventions on Oral Health Literacy Levels in Adults; A Systematic Review

abstract:
BackgroundOral health literacy within the construct of health literacy may be instrumental in decreasing oral health disparities and promoting oral health. Even though current research links oral health literacy to oral health knowledge and education, the impact of educational intervention on oral health literacy remains controversial. We aimed to identify effective health education interventions delivered with a focus on oral health literacy.

MethodsAn electronic systematic search in PubMed, Scopus, Web of Science and Cochrane library and gray literatue was performed for relevant studies (1995-2021). Experimental study designs of randomized controlled trials, non-randomized controlled trials, and quasi-experimental studies in which adults aged 18 years or older, male, or female (participants) trained under a health education intervention (intervention) were compared with those with no health education or within the usual care parameters (comparison). An assessment of oral health literacy levels (outcome) were included according to the PICO question. The search was conducted by applying filters for the title, abstract and methodological quality of the data, and English language. Study screening, extraction and critical appraisal was performed by two independent reviewers. Data was extracted from the included studies whereas a meta-analysis was not possible since findings were mostly presented as a narrative format.

ResultsEight studies out of the 2783 potentially eligible articles met the selection criteria for this systematic review. The aim of interventions in these studies was 1) improving oral health literacy as the first outcome or 2) improving oral health behavior and oral health skills as the first outcome and assessing oral health literacy as the second outcome. The strength of evidence from the reviewed articles was high and there was an enormous heterogeneity in the study design, OHL measurement instruments and outcomes measure. Interventions were considerably effective in improving oral health literacy.

ConclusionHealth education that is tailored to the needs and addresses patients barrier to care can improve their oral health literacy level.

category: dentistry and oral medicine


title: What (if anything) is going on? Examining longitudinal associations between social media use and mental ill-health among young people

abstract:
ObjectivesIn mid-adolescence, to 1) examine cyclical associations between social media use and mental ill health by investigating longitudinal and bidirectional associations, dose response relationships, and changes in social media use and in mental health; 2) assess potential interaction effects between social media use and mental health with pre-existing early life vulnerabilities.

MethodsLongitudinal data on 12,114 participants from the Millennium Cohort Study on social media use, depressive symptoms, self-harm and early life risk factors were used.

ResultsWe found little support for the existence of cyclical relationships between social media use and mental health. Where detected, effect sizes were small. Dose response associations were seen in the direction of mental health to social media (depressive symptoms 1 time OR=1.22, 2 times OR=1.71; self-harm 1 time OR=1.17, 2 times OR=1.53), but not for social media to mental health. Changes in social media use and changes in mental health were not associated with each other. We found no evidence to suggest that either social media use or mental health interacted with pre-existing risk for mental ill health.

ConclusionsFindings highlight the possibility that observed longitudinal associations between social media use and mental health might reflect other risk processes or vulnerabilities and/or the precision of measures used. More detailed and frequently collected prospective data about online experiences, including those from social media platforms themselves will help to provide a clearer picture of the relationship between social media use and mental health.

category: epidemiology


title: Cohort profile: The Pregnancy, Arsenic, and Immune Response (PAIR) Study, a longitudinal pregnancy and birth cohort in rural northern Bangladesh

abstract:
PurposeArsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the fetus, and maternal and infant acute morbidity. The Pregnancy, Arsenic, and Immune Response (PAIR) Study is a longitudinal pregnancy and birth cohort designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal or newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy.

ParticipantsWe enrolled 784 pregnant women in rural Gaibandha District in northern Bangladesh between October 2018 and March 2019. Women received a quadrivalent seasonal inactivated influenza vaccine at enrollment in the late first or early second trimester between 11 and 17 weeks of gestational age. Follow-up included up to 13 visits between enrollment and three months postpartum as well as weekly telephone surveillance to ascertain influenza-like illness and other acute morbidity symptoms in women and infants. Tube well drinking water and urine specimens were collected to assess arsenic exposure. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visit to three months postpartum.

Findings to DateArsenic was [≥]0.02 {micro}g/L in 97.9% of water specimens collected from participants at enrollment. The medians (interquartile ranges) of water and urinary arsenic were 5.1 (0.5-25.1) {micro}g/L and 33.1 (19.6-56.5) {micro}g/L, respectively. Water and urinary arsenic were strongly correlated (Spearmans {rho}=0.72) among women with water arsenic [≥] median but weakly correlated ({rho}=0.18) among women with water arsenic < median.

Future PlansThe PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants.

RegistrationNCT03930017


title: Reconstructing long-term dengue virus immunity in French Polynesia

abstract:
BackgroundUnderstanding the underlying risk of infection by dengue virus from surveillance systems is complicated due to the complex nature of the disease. In particular, the probability of becoming severely sick is driven by serotype-specific infection histories as well as age; however, this has rarely been quantified. Island communities that have periodic outbreaks dominated by single serotypes provide an opportunity to disentangle the competing role of serotype, age and changes in surveillance systems in characterising disease risk.

MethodologyWe develop mathematical models to analyse 35 years of dengue surveillance (1979-2014) and seroprevalence studies from French Polynesia. We estimate the annual force of infection, serotype-specific reporting probabilities and changes in surveillance capabilities using the annual age and serotype-specific distribution of dengue.

Principal FindingsEight dengue epidemics occurred between 1979 and 2014, with reporting probabilities for DENV-1 primary infections increasing from 3% to 5%. The reporting probability for DENV-1 secondary infections was 3.6 times that for primary infections. Reporting probabilities for DENV-2-DENV-4 were 0.1-2.6 and 0.7-2.3 times that for DENV-1, for primary and secondary infections, respectively. Reporting probabilities declined with age after 14 y.o. Between 1979 and 2014, the proportion never infected declined from 70% to 23% while the proportion infected at least twice increased from 4.5% to 45%. By 2014, almost half of the population had acquired heterotypic immunity. The probability of an epidemic increased sharply with the estimated fraction of susceptibles among children.

Conclusion / SignificanceBy analysing 35 years of dengue data in French Polynesia, we characterised key factors affecting the dissemination profile and reporting of dengue cases in an epidemiological context simplified by mono-serotypic circulation. Our analysis provides key estimates that can inform the study of dengue in more complex settings where the co-circulation of multiple serotypes can greatly complicate inference.

Author summaryCharacterising the true extent of dengue circulation and the level of population immunity is essential to assess the burden of disease, evaluate epidemic risk and organise prevention strategies against future epidemics. However, this is difficult in a context where most people who are infected by dengue virus (DENV) only have mild symptoms which may not be reported to surveillance systems. In this article, we develop a mathematical model to evaluate the fraction of unreported dengue infections from case data. The key idea is to introduce reporting probabilities that depend on the infecting serotype and the infection history of patients. These factors are known to contribute to variations in the severity of symptoms and hence the reporting probabilities, but have rarely been taken into account in model frameworks to study population immunity from the case data. Using the developed model, we study long-term dengue virus immunity in French Polynesia.


title: Estimating the allele frequency threshold of the pathogenic mtDNA variant m.3243A>G tolerated by human myofibres

abstract: Cells are thought to tolerate the presence of heteroplasmic pathogenic mitochondrial (mt)DNA variants, up to a threshold proportion with little or no functional consequence, only developing a detectable oxidative phosphorylation (OXPHOS) defect once this threshold is exceeded. We hypothesised that, given the highly variable phenotypic presentation and severity of disease caused by the most common heteroplasmic pathogenic mtDNA variant m.3243A>G, this threshold may vary between patients. To estimate this threshold we examined the relationship between m.3243A>G level and deficiency of respiratory complexes I and IV in hundreds of single skeletal muscle fibres captured by laser microdissection from 17 patients carrying the m.3243A>G variant. We confirmed that tissue homogenate m.3243A>G level is a poor surrogate for the broad and complex distributions of m.3243A>G level in single cells from individual patients. We used unsupervised machine learning to characterise the biochemical status of muscle fibres, based on immunocytochemical measurements and estimate that the m.3243A>G threshold proportion above which myofibres develop a respiratory complex defect is 82.8% (IQR:2.7%). We do not find any significant difference in threshold between individuals, however we demonstrate that the pattern of respiratory complex defect and the distribution of m.3243A>G varies considerably between patients. This observation suggests that the pathogenesis of m.3243A>G is more diverse than previously thought.

category: pathology


title: Quantifying phenotype and genotype distributions in single muscle fibres from patients carrying the pathogenic mtDNA variant m.3243A>G


title: EARLY OUTPATIENT TREATMENT OF COVID-19: A RETROSPECTIVE ANALYSIS OF 392 CASES IN ITALY

abstract:
IntroductionThe pandemic of severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) disease 2019 (COVID-19) was declared in march 2020. Knowledge of COVID-19 pathophysiology soon provided a strong rationale for the early use of anti-inflammatory, antiplatelet and anticoagulant drugs, however the evidence was only slowly and partially incorporated into institutional guidelines. Unmet needs of COVID-19 outpatients were soon taken care of by networks of physicians and researchers, using pharmacotherapeutic approaches based on the best available experiences.

MethodsObservational retrospective study investigating characteristics, management and outcomes in COVID-19 patients taken care of in Italy by physicians volunteering within the IppocrateOrg Association, one of the main international assistance networks, between 1st november 2020 and 31st march 2021.

ResultsTen doctors took part in the study and provided data about 392 consecutive COVID-19 patients. Patients mean age was 48,5 years (range: 0,5-97). They were 51,3% females and were taken care of when in COVID-19 stage 0 (15,6%), 1 (50,0%), 2a (28,8%), 2b (5,6%). Many patients were overweight (26%) or obese (11,5%), with chronic comorbidities (34,9%), mainly cardiovascular (23%) and metabolic (13,3%). Drugs most frequently prescribed included: vitamins and supplements (98,7%), aspirin (66,1%), antibiotics (62%), glucocorticoids (41,8%), hydroxychloroquine (29,6%), enoxaparin (28,6%), colchicine (8,9%), oxygen therapy (6,9%), ivermectin (2,8%). Hospitalization occurred in 5,8% of total cases, mainly in patients taken care of when in stage 2b (27,3%). Altogether, 390 patients (99,6%) recovered, one patient (0,2%) was lost at follow up, and one patient (0,2%) died after hospitalization. One doctor reported one grade 1 adverse drug reaction (ADR) (transient or mild discomfort), and 3 doctors reported in total 8 grade 2 ADR (mild to moderate limitation in activity).

ConclusionsThis is the first study describing attitudes and behaviors of physicians caring for COVID-19 outpatients, and the effectiveness and safety of COVID-19 early treatment in the real world. COVID-19 lethality in our cohort was 0,2%, while the overall COVID-19 lethality in Italy in the same period was between 3% and 3,8%. The use of individual drugs and drug combinations described in this study appears therefore effective and safe, as indicated by the few and mild ADR reported. Present evidence should be carefully considered by physicians caring for COVID-19 patients as well as by political decision makers managing the current global crisis.

category: pharmacology and therapeutics


title: Cannabis potential effects to prevent or attenuate SARS-COV2 contagion

abstract: Medical cannabis has gained an exponential interest in recent years. Therapeutic targets have been broadened from specific applications over pain control, chemotherapy side effects, treatment-resistant epilepsies and multiple sclerosis, among others. Several in vitro and animal studies, along with few human controlled studies, suggest cannabinoids have a potential therapeutic role over medical conditions comporting inflammatory mechanisms. Given the tremendous world-wide impact of the COVID-19 pandemic, research efforts are converging towards the use of cannabinoids to attenuate severe or fatal forms of the disease. The present survey aims to explore possible correlations between cannabis use, either recreational or medical, over the presence of SARS-COV-2 contagion, along with the symptoms severity. 4026 surveys were collected via electronic form. Results suggest a relation between any type of cannabis use and a lower risk of SARS-COV-2 contagion (p=0,004; OR=0,689, IC95% 0,534-0,889). Despite several methodological limitations, the present survey steps up the urge to expand our understanding on cannabinoids potential use on human controlled studies, that can better arm us in the fight against the current COVID-19 pandemic.


title: Voice patterns as markers of schizophrenia: building a cumulative generalizable approach via cross-linguistic and meta-analysis based investigation

abstract:
Background and HypothesisVoice atypicalities are potential markers of clinical features of schizophrenia (e.g., negative symptoms). A recent meta-analysis identified an acoustic profile associated with schizophrenia (reduced pitch variability and increased pauses), but also highlighted shortcomings in the field: small sample sizes, little attention to the heterogeneity of the disorder, and to generalizing findings to diverse samples and languages.

Study DesignWe provide a critical cumulative approach to vocal atypicalities in schizophrenia, where we conceptually and statistically build on previous studies. We aim at identifying a cross-linguistically reliable acoustic profile of schizophrenia and assessing sources of heterogeneity (symptomatology, pharmacotherapy, clinical and social characteristics). We relied on previous meta-analysis to build and analyze a large cross-linguistic dataset of audio recordings of 231 patients with schizophrenia and 238 matched controls (>4.000 recordings in Danish, German, Mandarin and Japanese). We used multilevel Bayesian modeling contrasting meta-analytically informed and skeptical inferences.

Study ResultsWe found only a minimal generalizable acoustic profile of schizophrenia (reduced pitch variability), while duration atypicalities replicated only in some languages. We identified reliable associations between acoustic profile and individual differences in clinical ratings of negative symptoms, medication, age and gender. However, these associations vary across languages.

ConclusionsThe findings indicate that a strong cross-linguistically reliable acoustic profile of schizophrenia is unlikely. Rather, if we are to devise effective clinical applications able to target different ranges of patients, we need first to establish larger and more diverse cross-linguistic datasets, focus on individual differences, and build self-critical cumulative approaches.

category: psychiatry and clinical psychology


title: Modeling behavior change and underreporting in the early phase of COVID-19 pandemic in Metro Manila, Philippines

abstract: When the Philippine government eased the community quarantine restrictions on June 2020, the healthcare system was overwhelmed by the surge in coronavirus disease 2019 (COVID-19) cases. In this study, we developed an SEIQR model considering behavior change and unreported cases to examine their impact on the COVID-19 case reports in Metro Manila during the early phase of the pandemic. We found that if behavior was changed one to four weeks earlier, then the cumulative number of cases can be reduced by up to 74% and the peak delayed by up to four weeks. Moreover, a two- or threefold increase in the reporting ratio can decrease the cumulative number of cases by 29% or 47%, respectively, at the end of September 2020. Results of our finding are expected to guide healthcare professionals to mitigate disease spread and minimize socioeconomic burden of strict lockdown policies during the start of an epidemic.

category: public and global health


title: Automated method to extract and purify RNA from wastewater enables more sensitive detection of SARS-CoV-2 markers in community sewersheds

abstract: Wastewater based epidemiology (WBE) has emerged as a strategy to identify, locate, and manage outbreaks of COVID19, and thereby possibly prevent surges in cases, which overwhelm local to global health care networks. The WBE process is based on assaying municipal wastewater for molecular markers of the SARS-CoV-2 virus. The standard process for sampling municipal wastewater is both time-consuming and requires the handling of large quantities of wastewater, which negatively affect throughput and timely reporting, and can increase safety risks. We report on a method to assay multiple sub-samples of a bulk wastewater sample. We document the effectiveness of this new approach by way of comparison of technologies for automating RNA purification from wastewater samples. We compared processes using the Perkin-Elmer Chemagic 360 to a PEG/NaCl/Qiagen protocol that is used for detection of N1 and N2 SARS-CoV-2 markers by the majority of 19 pandemic wastewater testing labs in the State of Michigan. Specifically, we found that the Chemagic 360 lowered handling time, decreased the amount of wastewater required by 10-fold, increased the amount of RNA isolated per {micro}l of final elution product by approximately five-fold, and had no deleterious effect on subsequent ddPCR analysis. Moreover, for detection of markers on the borderline of detectability, we found that use of the Chemagic 360 enabled the detection of viral markers in a significant number of samples for which the result with the PEG/NaCl/Qiagen method was below the level of detectability. This improvement in detectability of the viral markers might be particularly important for early warning to public health authorities at the beginning of an outbreak.


title: Changing patterns of SARS-CoV-2 infection through Delta and Omicron waves by vaccination status, previous infection and neighbourhood deprivation: A cohort analysis of 2.7M people.

abstract:
ObjectiveTo examine if SARS-CoV-2 infections vary by vaccination status, if an individual had previously tested positive and by neighbourhood socioeconomic deprivation across the Delta and Omicron epidemic waves of SARS-CoV-2.

DesignCohort study using electronic health records

SettingCheshire and Merseyside, England (3rd June 2021 to 1st March 2022)

Participants2.7M residents

Main Outcome measureRegistered positive test for SARS-CoV-2

ResultsSocial inequalities in registered positive tests were dynamic during the study. Originally higher SARS-CoV-2 rates in the most socioeconomically deprived neighbourhoods changed to being higher in the least deprived neighbourhoods from the 1st September 2021. While the introduction of Omicron initially reset inequalities, they continued to be dynamic and inconsistent. Individuals who were fully vaccinated (two doses) were associated with fewer registered positive tests (e.g., between 1st September and 27th November 2021: (i) individuals engaged in testing - Hazards Ratio (HR) = 0.48, 95% Confidence Intervals (CIs) = 0.47-0.50; (ii) individuals engaged with healthcare - HR = 0.34, 95% CIs = 0.33-0.34). Individuals with a previous registered positive test were also less likely to have a registered positive test (e.g., between 1st September and 27th November 2021: (i) individuals engaged in testing - HR = 0.16, 95% CIs = 0.15-0.18; (ii) individuals engaged with healthcare - HR = 0.14, 95% CIs = 0.13-0.16). However, Omicron is disrupting these associations due to immune escape resulting in smaller effect sizes for both measures.

ConclusionsChanging patterns of SARS-CoV-2 infections during the Delta and Omicron waves reveals a dynamic pandemic that continues to affect diverse communities in sometimes unexpected ways.


title: Sustained patient use and improved outcomes with digital transformation of a COPD service: RECEIVER trial and DYNAMIC-SCOT COVID-19 scale-up response.

abstract:
IntroductionLenusCOPD has been co-designed to enable digital transformation of COPD services for proactive preventative care. Patient-facing progressive web application, clinician dashboard and support website integrate patient-reported outcomes (PROs), self-management resources, structured clinical summary, wearable and home NIV data with asynchronous patient-clinician messaging. We commenced the implementation-effectiveness observational cohort RECEIVER trial in September 2019, with the primary endpoint of sustained patient usage and secondary endpoints including admissions, mortality, exacerbations, service workload and quality of life. We paused recruitment in March 2021 and provided LenusCOPD as routine care in the "DYNAMIC-SCOT" COVID-19 response service scale-up.

Methods83 RECEIVER trial participants and 142 DYNAMIC-SCOT participants had completed minimum 1 year follow-up when we censored data on 31st August 2021. We established a control cohort with 5 patients matched per RECEIVER participant from de-identified contemporary routine clinical data.

ResultsSustained patient app utilisation was noted in both cohorts. Median time to admission or death was 43 days in control, 338 days in RECEIVER and 400 days in DYNAMIC-SCOT participants who had had a respiratory-related admission in the preceding year. The 12-month risk of admission or death was 74% in control patients, 53% in RECEIVER and 47% in the DYNAMIC-SCOT sub-cohort participants. There was a median of 2.5 COPD exacerbations per patient per year with stable quality of life across follow up and a manageable workload for clinical users.

ConclusionsA high proportion of people continued to use the co-designed LenusCOPD application during extended follow-up. Outcome data supports scale-up of this digital service transformation.

Key messages

What is the key question?Can sustained patient interaction and improved patient outcomes be achieved with digital transformation of a COPD service?

What is the bottom line?Participants continue to use the LenusCOPD patient app, with an average of 3-3.5 interactions per person per week sustained >1-year post-onboarding. COPD- related hospital admissions and occupied bed days were reduced following LenusCOPD onboarding in participants with a history of a severe exacerbation in the previous year, with a median time to readmission of 380 days compared with 50 days in a contemporary matched control patient cohort.

Why read on?Feasibility and utility results support scale-up adoption of these digital tools, to support optimised co-management of COPD and other long-term conditions within a continuous implementation-evaluation framework. This will establish a test-bed infrastructure for additional innovations including artificial intelligence-insights for MDT decision support.

category: respiratory medicine


title: Nonutility of procalcitonin for diagnosing bacterial pneumonia in COVID-19

abstract: Patients hospitalized with COVID-19 are at significant risk for superimposed bacterial pneumonia. However, diagnosing superinfection is challenging due to its clinical resemblance to severe COVID-19. We therefore evaluated whether the immune biomarker, procalcitonin, could facilitate the diagnosis of bacterial superinfection. To do so, we identified 185 patients with severe COVID-19 who underwent lower respiratory culture; 85 had superinfection. Receiver operating characteristic curve analysis showed that procalcitonin at the time of culture was incapable of distinguishing patients with bacterial infection (AUC, 0.52). We conclude that static measurement of procalcitonin does not aid in the diagnosis of superinfection in severe COVID-19.


title: Comparing phrenic nerve stimulation using three rapid coils: implications for mechanical ventilation

abstract:
RationaleRapid magnetic stimulation (RMS) of the phrenic nerves may serve to attenuate diaphragm atrophy during mechanical ventilation. With different coil shapes and stimulation location, inspiratory responses and side-effects may differ.

ObjectiveTo compare the inspiratory and sensory responses of three different RMS-coils either used bilaterally on the neck or on the chest, and to determine if ventilation over 10min can be achieved without muscle fatigue and coils overheating.

MethodsHealthy participants underwent 1-s RMS on the neck (RMSBAMPS) (n=14) with three different pairs of magnetic coils (parabolic, D-shape, butterfly) at 15, 20, 25 and 30Hz stimulator-frequency and 20% stimulator-output with +10% increments. The D-shape coil with individual optimal stimulation settings was then used to ventilate participants (n=11) for up to 10min. Anterior RMS on the chest (RMSaMS) (n=8) was conducted on an optional visit. Airflow was assessed via pneumotach and transdiaphragmatic pressure via esophageal and gastric balloon catheters. Perception of air hunger, pain, discomfort and paresthesia were measured with a numerical scale.

Main resultsInspiration was induced via RMSBAMPS in 86% of participants with all coils and via RMSaMS in only one participant with the parabolic coil. All coils produced similar inspiratory and sensory responses during RMSBAMPS with the butterfly coil needing higher stimulator-output, which resulted in significantly larger discomfort ratings at maximal inspiratory responses. Ten of 11 participants achieved 10min of ventilation without decreases in minute ventilation (15.7{+/-}4.6L/min).

ConclusionsRMSBAMPS was more effective than RMSaMS, and could temporarily ventilate humans seemingly without development of muscular fatigue.


title: Predicting Clinical Endpoints and Visual Changes with Quality-Weighted Tissue-based Histological Features

abstract:
Two common obstacles limiting the performance of data-driven algorithms in digital histopathology classification tasks are the lack of expert annotations and the narrow diversity of datasets. Multi-instance learning (MIL) can be used to address the former challenge for the analysis of whole slide images (WSI) but performance is often inferior to full supervision. We show that the inclusion of weak annotations can significantly enhance the effectiveness of MIL while keeping the approach scalable.

An analysis framework was developed to process periodic acid-Schiff (PAS) and Sirius Red (SR) slides of renal biopsies. The workflow segments tissues into coarse tissue classes. Handcrafted and deep features were extracted from these tissues and combined using a soft attention model to predict several slide-level labels: delayed graft function (DGF), acute tubular injury (ATI), and Remuzzi grade components. A tissue segmentation quality metric was also developed to reduce the adverse impact of poorly segmented instances. The soft attention model was trained using 5-fold cross-validation on a mixed dataset and tested on the QUOD dataset containing n=373 PAS and n=195 SR biopsies.

The average ROC-AUC over different prediction tasks was found to be 0.598{+/-}0.011, significantly higher than using only ResNet50 (0.545{+/-}0.012), only handcrafted features (0.542 {+/-} 0.011), and the baseline (0.532 {+/-} 0.012) of state-of-the-art performance. Weighting tissues by segmentation quality in conjunction with the soft attention has led to further improvement (AUC = 0.618 {+/-} 0.010). Using an intuitive visualisation scheme, we show that our approach may also be used to support clinical decision making as it allows pinpointing individual tissues relevant to the predictions.

category: transplantation


title: Influence of Illustrators Intentions and Visual Description Techniques of Medical Illustrations on Generating Interest and Boosting Comprehension of Medical Information

abstract:
In this study, an exploratory online survey was conducted to clarify points that have not been clarified so far in the medical illustration research field. If several illustrators make an illustration of the same information, does a match of intentions and techniques affect the impression or comprehension of the information? The aim is to further the utilization of medical illustration in actual practice (n=1104).

First, we selected Autosomal Dominant Polycystic Kidney Disease (ADPKD) as the medical condition about which information had to be disseminated. Then, we asked 32 art professionals to make six illustrations with three detail types (high, middle, and low) and two purposes ("getting interested" and "boosting comprehension"). Thereafter, we selected six different types of art professionals illustrations for the questionnaire to ask the participants about the intentions of the illustrations and comprehension of the content. We found that if the illustrators intentions and visual description techniques match with the recipients, the match of intentions could help generate interest in the content, and the match of visual description techniques could enhance the comprehension of the information.

category: medical education


title: Trans-border transfer of human biological materials in collaborative biobanking research: Perceptions and experiences of researchers in Uganda

abstract:
IntroductionThe study aimed to explore researchers perceptions and experiences on the transfer of human biological materials in international collaborative research.

MethodsThis was a descriptive convergent parallel survey that randomly recruited 187 researchers involved in biobanking and/or genetics research. Data were collected using a self-administered tool that had both open and closed ended questions.

ResultsMajority of respondents were male scientists (53.5%) with a mean research experience of 12.2 (SD 6.75) years. About 89% had ever worked in international collaborative research and 42% had ever participated in material transfer agreement (MTA) development. There were several areas of agreement in regard to the rights of local researchers and institution in collaborative biobanking research, and what details should be included in material transfer agreements. There was overwhelming support for collaborative partnership in biobanking research with 90.4% of researchers agreeing that local scientists should be involved in decisions making regarding the future use of samples. A majority (85.6%) opined that there should be fair sharing of research benefits with local researchers and populations or country from which the human biological materials were taken. Researchers felt that most MTAs tend to favour international collaborators. Several trust issues in the MTA development and implementation process were also highlighted and these included: lack of transparency and dishonesty of receiving scientists; lack of mechanisms to monitor the use of exported samples; ownership and intellectual property disputes; exploitation and inequitable sharing of research benefits; and authorship challenges. Several researchers seemed not to be conversant with the guidance provided by the Ugandan national ethics guidelines on the cross-border exchange of human biological specimens.

ConclusionLocal researchers had a positive attitude towards the export of human biological materials in collaborative research. However, there were several governance and trust concerns. There is a need for collaborative partnership in biobanking research.

category: medical ethics


title: Classifying REM Sleep Behavior Disorder through CNNs with Image-Based Representations of EEGs

abstract:
ObjectiveRapid Eye Movement Sleep Behavior Disorder (RBD) is a parasomnia with a high conversion rate to -synucleinopathies such as Parkinsons Disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). The objective of this paper is to classify RBD in patients through a convolutional neural network utilizing imagebased representations of electroencephalogram (EEG) channels.

MethodsAnalysis was conducted on polysomnography data from 22 patients with RBD and 12 healthy controls acquired from the Cyclic Alternating Pattern (CAP) Sleep Database. EEG channels were split into four frequency bands (theta, alpha, beta, and gamma). Power spectrum density was calculated through a Fast Fourier Transformation (FFT) and converted into 2D images through bicubic interpolation. RBD classification was accomplished through a pre-trained VGG-16 CNN with layer weights being fine-tuned.

ResultsThe model was successful in classifying RBD patients over non-RBD patients and achieved 97.92% accuracy over 40 epochs. Accuracy increased dramatically with increased data generated from FFT and interpolation (62.63% to 97.92%).

ConclusionsThis project proposes a novel approach toward an automatic classification of RBD and highlights the importance of deep learning models in the field. The proposed transfer learning model outperforms state-of-the-art models and preliminarily accounts for the lack of computational resources in clinical spaces, thereby increasing the accessibility of automatic classification.

SignificanceBy leveraging transfer learning and raw data, the results demonstrate that a similar model for the classification of RBD patients could easily be translated to the clinical atmosphere, drastically accelerating the classification pipeline. The proposed methods are also applicable to -synucleinopathies, including PD, DLB, and MSA.

category: neurology


title: Cardiovascular diseases worsen the maternal prognosis of COVID-19

abstract: Cardiovascular diseases are a risk factor for severe cases of COVID-19. There are no studies evaluating whether the presence of CVD in pregnant women and in postpartum women with COVID-19 is associated with a worse prognosis. In an anonymized open database of the Ministry of Health, we selected cases of pregnant and postpartum women who were hospitalized due to COVID-19 infection. Among the 1,876,953 reported cases, 3,562 confirmed cases of pregnant and postpartum women were included, of which 602 had CVD. Patients with CVD had an older age (p<0,001), a higher incidence of diabetes (p<0,001) and obesity (p<0,001), a higher frequency of systemic (p<0,001) and respiratory symptoms (p<0,001). CVD was a risk factor for ICU admission (p<0,001), ventilatory support (p=0.004) and orotracheal intubation in the third trimester (OR 1.30 CI95%1.04-1.62). The group CVD had a higher mortality (18.9% vs. 13.5%, p<0,001), with a 32% higher risk of death (OR 1.32 CI95%1.16-1.50). Moreover, the risk was increased in the second (OR 1.94 CI95%1.43-2.63) and third (OR 1.29 CI95%1.04-1.60) trimesters, as well as puerperium (OR 1.27 IC95%1.03-1.56). Hospitalized obstetric patients with CVD and COVID-19 are more symptomatic. Their management demand more ICU admission and ventilatory support and the mortality is higher.

category: obstetrics and gynecology


title: Automated Enhancement and Curation of Healthcare Data

abstract: Social and behavioral aspects of our lives significantly impact our health, yet minimal social determinants of health (SDOH) data elements are collected in the healthcare system. In this study we developed a repeatable SDOH enrichment and integration process to incorporate dynamically evolving SDOH domain concepts from consumers into clinical data. This process included SDOH mapping, linking compiled consumer data, data quality analysis and preprocessing, storage, and visualization. Our preliminary analysis shows commercial consumer data can be a viable source of SDOH factor at an individual-level for clinical data thus providing a path for clinicians to improve patient treatment and care.


title: Evaluation of Eight Lateral Flow Tests For The Detection Of Anti-SARS-CoV-2 Antibodies In A Vaccinated Population

abstract: With the distribution of COVID-19 vaccinations across the globe and the limited access in many countries, quick determination of an individuals antibody status could be beneficial in allocating limited vaccine doses in low- and middle-income countries (LMIC). Antibody lateral flow tests (LFTs) have potential to address this need as a quick, point of care test, they also have a use case for identifying sero-negative individuals for novel therapeutics, and for epidemiology. Here we present a proof-of-concept evaluation of eight LFT brands using sera from 95 vaccinated individuals to determine sensitivity for detecting vaccination generated antibodies. All 95 (100%) participants tested positive for anti-spike antibodies by the chemiluminescent microparticle immunoassay (CMIA) reference standard post-dose two of their SARS-CoV-2 vaccine: BNT162b2 (Pfizer/BioNTech, n=60), AZD1222 (AstraZeneca, n=31), mRNA-1273 (Moderna, n=2) and Undeclared Vaccine Brand (n=2). Sensitivity increased from dose one to dose two in six out of eight LFTs with three tests achieving 100% sensitivity at dose two in detecting anti-spike antibodies. These tests are quick, low-cost point-of-care tools that can be used without prior training to establish antibody status and may prove valuable for allocating limited vaccine doses in LMICs to ensure those in at risk groups access the protection they need. Further investigation into their performance in vaccinated peoples is required before more widespread utilisation is considered.


title: Developing a model for predicting impairing physical symptoms in children 3 months after a SARS-CoV-2 PCR-test: The CLoCk Study

abstract:
ImportancePredictive models can help identify SARS-CoV-2 patients at greatest risk of post-COVID sequelae and direct them towards appropriate care.

ObjectiveTo develop and internally validate a model to predict children and young people most likely to experience at least one impairing physical symptom 3 months after a SARS-CoV-2 PCR-test and to determine whether the impact of these predictors differed by SARS-CoV-2 infection status.

DesignPotential pre-specified predictors included: SARS-CoV-2 status, sex, age, ethnicity, deprivation, quality of life/functioning (5 EQ-5D-Y items), physical and mental health, and loneliness (all prior to SARS-CoV-2 testing), and number of physical symptoms at testing. Logistic regression was used to develop the model. Model performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting.

SettingNational cohort study of SARS-CoV-2 PCR-positive and PCR-negative participants matched according to age, sex, and geographical area.

ParticipantsChildren and young people aged 11-17 years who were tested for SARS-CoV-2 infection in England, January to March 2021.

Main outcome measureone or more physical symptom 3 months after initial PCR-testing which affected physical, mental or social well-being and interfered with daily living.

ResultsA total of 50,836 children and young people were approached; 7,096 (3,227 test-positives, 3,869 test-negatives) who completed a questionnaire 3 months after their PCR-test were included. 39.6% (1,279/3,227) of SAR-CoV-2 PCR-positives and 30.6% (1,184/3,869) of SAR-CoV-2 PCR-negatives had at least one impairing physical symptom 3 months post-test. The final model contained predictors: SARS-COV-2 status, number of symptoms at testing, sex, age, ethnicity, self-rated physical and mental health, feelings of loneliness and four EQ-5D-Y items before testing. Internal validation showed minimal overfitting with excellent calibration and discrimination measures (optimism adjusted calibration slope:0.97527; C-statistic:0.83640).

Conclusions and relevanceWe developed a risk prediction equation to identify those most at risk of experiencing at least one impairing physical symptom 3 months after a SARS-CoV-2 PCR-test which could serve as a useful triage and management tool for children and young people during the ongoing pandemic. External validation is required before large-scale implementation.

Key PointsO_ST_ABSQuestionC_ST_ABSWhich children have impairing physical symptoms during the COVID-19 pandemic?

FindingsUsing data from a large national matched cohort study in children and young people (CYP) aged 11-17 years (N=7,096), we developed a prediction model for experiencing at least one impairing physical symptom 3 months after testing for SARS-COV-2. Our model had excellent predictive ability, calibration and discrimination; we used it to produce a risk estimation calculator.

MeaningOur developed risk calculator could serve as a useful tool in the early identification and management of CYP at risk of persisting physical symptoms in the context of the COVID-19 pandemic.


title: Long- and short-term effects of cross-immunity in epidemic dynamics

abstract: The vertebrate immune system is capable of strong, focused adaptive responses that depend on T-cell specificity in recognizing antigenic sequences of a pathogen. Recognition tolerance and antigenic convergence cause cross-immune reactions that extend prompt, specific responses to rather similar pathogens. This suggests that reaching herd-immunity might be facilitated during successive epidemic outbreaks (e.g., SARS-CoV-2 waves with different variants). Qualitative studies play down this possibility because cross-immune protection is seldom sterilizing. We use minimal quantitative models to study how cross-immunity affects epidemic dynamics over short and long timescales. In the short scale, we investigate models of sterilizing and attenuating immunity, finding equivalences between both mechanisms--thus suggesting a key role of attenuating protection in achieving herd immunity. Our models render maps in epidemic-parameter space that discern threatening variants depending on acquired cross-immunity levels. We illustrate this application with SARS-CoV-2 data, including protection due to vaccination rates across countries. In the long-time scale, we model sterilizing cross-immunity between rolling pathogens to characterize statistical properties of successful strains. We find that sustained cross-immune protection alters the regions of epidemic-parameter space where large outbreaks happen. Our results suggest an optimistic revision concerning prospects for herd protection based on cross-immunity, including for the SARS-CoV-2 pandemics.


title: Severity and Correlates of Mental Fog in People with Traumatic Brain Injury

abstract:
ObjectiveAlongside objective performance declines, self-reported cognitive symptoms after traumatic brain injury (TBI) abound. Mental fog is one symptom that has been underexplored. The current project investigated mental fog across two studies of individuals with mild traumatic brain injury and moderate-to-severe traumatic brain injury to close our knowledge gap about differences in severity. We then explored the cognitive and affective correlates of mental fog within these groups.

MethodsUsing between-groups designs, the first study recruited individuals with acute mild TBI (n = 15) along with a healthy control group (n = 16). Simultaneously, a second study recruited persons with post-acute moderate-to-severe TBI, a stage when self-reports are most reliable (n = 15). Measures across the studies were harmonized and involved measuring mental fog (Mental Clutter Scale), objective cognition (Cogstate(R) and UFOV(R)), and depressive symptoms. In addition to descriptive group difference analyses, nonparametric correlations determined associations between mental fog, objective cognition, and depressive symptoms.

ResultsResults revealed higher self-reported mental fog in acute mild TBI compared to healthy controls. And though exploratory, post-acute moderate-to-severe TBI also appears characterized by greater mental fog. Correlations showed that mental fog in mild TBI corresponded to greater depressive symptoms (r = .66) but was unrelated to objective cognition. By contrast, mental fog in moderate-to-severe TBI corresponded to poorer working memory (r = .68) and slowed processing speed (r = -.55) but was unrelated to depressive symptoms.

ConclusionAs a common symptom in TBI, mental fog distinguishes individuals with acute mild TBI from uninjured peers. Mental fog also appears to reflect challenges in recovery, including depressive symptoms and objective cognitive problems. Screening for mental fog, in addition to other cognitive symptoms, might be worthwhile in these populations.


title: Domain specific need assessment for Disaster Preparedness: a systematic review and critical interpretative synthesis

abstract:
BackgroundDuring disasters, the most pressing demands are those related to health, and hospital preparedness is an area that require special attention. Hospitals are viewed as resources that must be proactively utilized in the event of a disaster. If national and local systems, particularly health systems, are unprepared to deal with disasters, the vulnerability of both individuals and communities is amplified. The unexpected surge in demand for important health services caused by disasters frequently overwhelms health systems and institutions, leaving them unable to perform the life-saving measures that are required. This study aims to understand various domains of hospital disaster preparedness by critically synthesizing qualitative evidence from selected research on the topic.

MethodsElectronic data base from PubMed, Google Scholar, key hospital disaster related journals was explored with search syntax focusing on hospital related disaster preparedness. Peer reviewed English articles published from January 2011 were systematically selected and critical interpretative qualitative synthesis was done to have comprehensive understanding of the said phenomenon.

ResultsA total of 29 articles were included in the systematic review. Major resultant domains describing disaster preparedness were Human Resource, Logistics And Finance, Response, Communication, Coordination, Patient Care, Evacuation and Personal Protection. Some domains were more emphasised than others, this information can help prioritizing the action based on need especially in the times of disaster.

ConclusionDisaster preparedness needs a comprehensive approach including context specific optimization with the effective use of available resources.


title: Physical activity-correlated changes in plasma enzyme concentrations in fragile sarcolemmal muscular dystrophies

abstract:
STRUCTURED ABSTRACTO_ST_ABSBackground and ObjectivesC_ST_ABSMuscular dystrophies associated with decreased sarcolemma integrity lack validated clinical measures of sarcolemma fragility that can be used to assess disease progression and the effects of therapies designed to reduce sarcolemma fragility. We conducted a pilot study to test the hypothesis that physical activity leads to significant changes in muscle-derived plasma enzymes in participants with "fragile sarcolemmal muscular dystrophies" (FSMD).

MethodsWe enrolled ambulatory individuals clinically affected with genetically confirmed FSMD neither taking anti-inflammatory medications nor having relevant co-morbidities for an inpatient study. Over five days, blood samples at 20 time points were obtained. Plasma enzymes alanine and aspartate aminotransferase (ALT, AST), creatine kinase (CK), and lactate dehydrogenase (LDH), all found in muscle, were measured before and after routine morning activities and motor function testing. Analysis of Z-transformed time series data led to feature and kinetic models that revealed activity-dependent feature and kinetic parameters.

ResultsAmong the 11 enrolled participants, (LGMD Type 2B/R2 Dysferlin-related (4F/1M), LGMD Type 2L/R12 Anoctamin-5-related (3F/2M), LGMD Type 2I/R9 FKRP-related (1M)), plasma enzymes increased with activity. The average % change +/- SEM with morning activity across all participants was ALT 12.8 {+/-} 2.8%, AST 11.6 {+/-} 2.9%, CK 12.9 {+/-} 2.8%, and LDH 12.2 {+/-} 3.9%, suggesting the increases originate from the same stimulated source, presumably skeletal muscle. For ALT, AST, CK, and LDH, characteristic kinetic features include (a) elevated enzyme activities on arrival that decreased overnight; (b) a longer decay trend observed over the week, and (c) for ALT, AST, and CK, a similar decay trend observed with post-morning activity blood draws.

DiscussionControlled activity-dependent changes in plasma ALT, AST, and CK on time scales of days to weeks can serve as common outcome measures for sarcolemma integrity and may be efficient and effective tools for monitoring disease progression and treatment efficacy for both individuals and patient populations. In addition, this study provides data that may benefit patient management as it can inform guidance on duration and type of activity that minimizes muscle damage.


title: Effectiveness of mHEALTH Application at Primary Health Care to Improve Maternal and New-born Health Services in Rural Ethiopia: Comparative study

abstract:
Ethiopia has recently implemented mHealth technology on a limited scale to help increase the uptake of health services, including intervention for maternal and new-born health service utilisation. In this study, the effectiveness of the mHealth intervention was assessed by measuring the level of maternal health service utilization in 4 Health Centers in Ethiopia.

The study was comparative by design employing comparison of maternal and newborn health service utilization before and after initiation of mHealth implementation. Follow-up data of 800 clients were randomly selected and included in the study, to determine the magnitude of maternal and new-born health service utilization. Data analysis included comparison of pre-mHealth (baseline) with mHealth follow-up data, using independent t-test to compare magnitude of maternal and new-born health service utilization.

The mean of antenatal care follow-up during their recent pregnancy was 2.21(SD{+/-}1.02) and 3.43(SD{+/-}0.88) for baseline and intervention, respectively. Antenatal visit of four or more was reached for 55(13.8%) of the baseline and 256(64%) of pregnant women in the mHealth intervention group. Pregnant womens timeliness to start ANC follow-up at baseline and intervention groups was 44.5% and 77.3%, respectively. Institutional delivery at baseline and intervention groups were 35.0% and was 71.2%, respectively. Of women who gave birth, 23.8% at baseline received first postnatal care within 6 hours, 11.3% within 6 days, and 6.8% within 6 weeks. In the intervention group, 84% delivered women received first postpartum within 6 hours after delivery, 70.8% after 6 hours, and 46% made their third postpartum visit within 6 weeks after delivery. Penta-3 vaccination coverage at baseline and mHealth intervention groups was 61.5% and 70.4%, respectively.

The study result suggest that the introduction of a low-cost mHealth technologies contributed to the observed improvement of maternal and new-born health service utilization. This intervention shows promise for scale up as well as to be applied to other health interventions beyond maternal and newborn health services.

category: health systems and quality improvement


title: Interleukin-6 as a predictor of early weaning from invasive mechanical ventilation in patients with acute respiratory distress syndrome

abstract:
BackgroundTherapeutic effects of steroids on acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) have been reported. However, predictive indicators of early weaning from MV post-treatment have not yet been defined, making treating established ARDS challenging. Interleukin (IL)-6 has been associated with the pathogenesis of ARDS.

ObjectiveOur aim was to clarify clinical utility of IL-6 level in ventilated patients with established ARDS.

MethodsClinical, treatment, and outcome data were evaluated in 119 invasively ventilated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated ARDS. Plasma levels of IL-6 and C-reactive protein (CRP) were measured on days 1, 4, and 7 after intubation.

ResultsFifty-two patients were treated with dexamethasone (steroid group), while the remaining 67 patients were not (non-steroid group). Duration of MV use was significantly shorter in the steroid group compared to non-steroid group (11.5{+/-}0.6 vs. 16.1{+/-}1.0 days, P = 0.0005, respectively) along with significantly decreased levels of IL-6 and CRP. Even when restricted to the steroid group, among variables post-MV, IL-6 level on day 7 was most closely correlated with duration of MV use (Spearmans rank correlation coefficient [{rho}] = 0.73, P < 0.0001), followed by CRP level on day 7 and the percentage change in IL-6 or CRP levels between day 1 and day 7. Moreover, among these variables, IL-6 levels on day 7 showed the highest accuracy for withdrawal from MV within 11 days (AUC: 0.88), with optimal cutoff value of 20.6 pg/mL. Consistently, the rate of MV weaning increased significantly earlier in patients with low IL-6 ([≤] 20.6 pg/mL) than in those with high IL-6 (> 20.6 pg/mL) (log-rank test P < 0.0001).

ConclusionsIn invasively ventilated patients with established ARDS due to SARS-CoV-2, plasma IL-6 levels served as a predictor of early withdrawal from MV after dexamethasone administration.