title: Covid-19 Associated Hepatitis in children (CACH) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon.

abstract: Objective: While pediatric population has largely remained free of severe COVID-19, in some cases SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). We mention another unique presentation subsequent to asymptomatic infection of SARS-CoV-2, a unique form of hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The contrasting clinical presentations, temporal association and viral parameters of CAH-C cases, to the MIS-C cases are presented here. Methods: As a retrospective and follow-up observational study we reviewed all children testing positive for SARS-CoV-2 during study period. Children presenting with sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice, lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis or previous underlying liver disease (b) multi-system involvement were classified as CAH-C, are described here. Results: Among 475 children who tested positive, 47 patients presented with hepatitis, 37 patients who had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers and uneventful recovery following supportive treatment. Whereas remaining 10 MIS-C hepatitis had protracted illness, multiple system involvement, required admission to critical care, and had mortality of 30%. Conclusion: With the emergence of newer variants of concern (VOC) including the Delta variant which predominated the second wave of infections in India and has now spread to more than 142 countries with changing presentations, CAH-C might be one of them. Cases of such new entities need to be identified early and differentiated from other emerging syndromes in children during the ongoing pandemic for preventing adversities by timely intervention.

category: pediatrics


title: Covid-19 Associated Hepatitis in children (CAHC) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon.


title: Covid-19 Associated Hepatitis in children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon.


title: Effect of dialysis modality on the survival of end-stage renal disease patients starting dialysis in Sabah from 2007 to 2017: a retrospective cohort study

abstract:
BackgroundThe effect of dialysis modality on the survival of end-stage renal disease patients is a major public health interest.

MethodsIn this retrospective cohort study, all adult end-stage renal disease patients receiving dialysis treatment in Sabah between January 1, 2007 and December 31, 2017 as identified from the Malaysian Dialysis and Transplant Registry were evaluated and followed up through December 31, 2018. The endpoint was all-cause mortality. The observation time was defined as the time from the date of dialysis initiation after the onset of end-stage renal disease to whichever of the following that came first: date of death, date of transplantation, date of last follow-up, date of recovered kidney function, or December 31, 2018. Weighted Cox regression was used to estimate the effect of dialysis modality. Analyses were restricted to patients with complete data on all variables.

Results1,837 patients began hemodialysis and 156 patients started with peritoneal dialysis, yielding 7,548.10 (potential median 5.48 years/person) and 747.98 (potential median 5.68 years/person) person-years of observation. 3.1% of patients were lost to follow-up. The median survival time was 5.8 years (95% confidence interval: 5.4, 6.3) among patients who started on hemodialysis and 7.0 years (95% confidence interval: 5.9, indeterminate) among those who started on peritoneal dialysis. The effect of dialysis modality was not significant after controlling for confounders. The average hazard ratio was 0.80 (95% confidence interval: 0.61, 1.05) with hemodialysis as a reference.

ConclusionThere was no evidence of a difference in mortality between hemodialysis and peritoneal dialysis.

category: nephrology


title: Cross-frequency phase-amplitude coupling in repetitive movements in patients with Parkinson's disease

abstract: Bradykinesia is a cardinal motor symptom in Parkinsons disease whose pathophysiology is incompletely understood. When signals are recorded from the cortex or scalp at rest, affected patients display enhanced phase-amplitude coupling between {beta} (13-30Hz) and broadband {gamma} (50-150Hz) oscillatory activities. However, it remains unclear whether and how abnormal phase-amplitude coupling is involved in slowing Parkinsonian movements during their execution. To address these questions, we analyzed high-density EEG signals recorded simultaneously with various motor activities and at rest in 19 patients with Parkinsons disease and 20 healthy controls. The motor tasks consisted of repetitive index finger pressing, and slow and fast tapping movements. Individual EEG source signals were computed for the premotor cortex, primary motor cortex, primary somatosensory cortex, and primary somatosensory complex. For the resting condition and the pressing task, phase-amplitude coupling averaged over the 4 motor regions and the entire movement period was larger in patients than in controls. In contrast, in all tapping tasks, state-related phase-amplitude coupling was similar between patients and controls. These findings were not aligned with motor performance and EMG data, which showed abnormalities in patients for tapping but not for pressing, suggesting that the strength of {beta}-broadband {gamma} phase-amplitude coupling during the movement period does not directly relate to Parkinsonian bradykinesia. Subsequently, we examined the dynamics of oscillatory EEG signals during motor transitions. When healthy controls performed the pressing task, dynamic phase-amplitude coupling increased shortly before pressing onset and decreased subsequently. A strikingly similar motif of coupling rise and decay was observed around the offset of pressing and around the onset of slow tapping, suggesting that such transient phase-amplitude coupling changes may be linked to transitions between different movement states - akin to preparatory states in dynamical systems theory of motor control. In patients, the modulation of phase-amplitude coupling was similar in (normally executed) pressing, but flattened in slow (abnormally executed) tapping compared to the controls. These deviations in phase-amplitude coupling around motor action transients may indicate dysfunctional evolution of neuronal population dynamics from the preparatory state to movement generation in Parkinsons disease. These findings may indicate that cross-frequency coupling is involved in the pathophysiology of bradykinesia in Parkinsons disease through its abnormal dynamic modulation.

category: neurology


title: Consumption of multiple sources of protein is associated with gestational diabetes mellitus in the Chinese population

abstract:
BackgroundGestational diabetes mellitus (GDM) is a hyperglycemic state during pregnancy that results in disruptions of insulin sensitivity and secretion. It affects 7% of all pregnancies and lead to adverse maternal and offspring outcomes. GDM has many risk factors, such as ethnicity special, hereditary. However Nutritional factors offer key strategies against GDM, but this is less characterized for the Chinese population.

MethodsA case control study of GDM pregnant women (n=49, 29.88{+/-}3.92 years of age) and healthy pregnant women (n=77, 27.63{+/-}4.83 years of age) from 1st Affiliated Hospital of Fujian Medical University were studied. Diagnosis was made using oral glucose tolerance test. Dietary data were collected using food frequency questionnaires. Data for use of dietary supplements, occupation, education, income, meal expenditure and smoking history were also recorded.

ResultsNo differences were found between GDM and control subjects for their age, education, occupation, monthly income, grocery expenditure and smoking (p>0.05). GDM subjects were associated with higher quantities of dairy products (p<0.05) and seafood (p<0.01) intake. There were also higher number of GDM subjects using protein powder supplementation (p<0.05).

ConclusionsDietary recommendation guidelines for pregnant Chinese women should consider possible risks with excessive consumption of dairy products, seafood and protein powder. They should also assess the quality of the nutrition factor, other dietary interactions and their nutritional status further to minimize adverse outcomes caused by GDM.

category: nutrition


title: Parent attitudes about childhood vaccines: a vaccine hesitancy point prevalence study.

abstract:
ObjectivesThe aim of this study was to measure the prevalence of vaccine hesitancy using Parent Attitudes about Childhood Vaccines (PACV) survey regarding paediatric vaccines for their children, in a population of parents attending a STEM (Science, Technology, Engineering and Mathematics) outreach event in Cork, Ireland.

Study designCross-sectional survey study.

MethodsThis study was conducted in November 2018 at the "Community Festival of Science" STEM event. Eligible attendees were invited to read the participant information leaflet, provide written informed consent, and complete the validated Parent Attitudes about Childhood Vaccines (PACV) survey. Each of the 15 PACV survey items was scored. A score [≥]50 identified vaccine hesitant parents.

ResultsA total of 105 parents participated in the study. A small number of participants (6.7%, n = 7) were identified as vaccine hesitant. There were no statistically significant differences between the vaccine hesitant and non-hesitant groups based on age, education, or number of children. Parents had concerns around vaccine side effects (36.2%, n=38) and vaccine safety (20%, n=21). Parents trusted the information they received on vaccines (85.6%, n=90) and 81.9% (n=86) believed that the vaccine schedule was good for their child.

ConclusionsThe findings of this research indicate the presence of vaccine hesitancy in parents in Ireland regarding paediatric vaccines. Parents had concerns regarding vaccine side effects and the number of vaccines on the paediatric immunisation schedule. Further research is necessary to understand how these issues may contribute to vaccine hesitancy, and to develop evidence-based interventions to build on parents existing trust in the vaccination schedule.

Key pointsO_LIA low level of vaccine hesitancy regarding childhood vaccinations was reported in a sample of parents at a science outreach event in Ireland using the PACV survey.
C_LIO_LIAreas of parents concerns were around vaccine side effects and number of vaccines.
C_LIO_LIMost parents trusted their doctors regarding vaccines, trusted vaccines information and followed the vaccine schedule.
C_LIO_LIThe PACV survey could be used as a screening tool to identify vaccine hesitant parents by healthcare providers and provide them with additional information and support, to support public health vaccination campaigns.
C_LI

category: allergy and immunology


title: Outbreak of P.3 (Theta) SARS-CoV-2 emerging variant of concern among food service workers in Louisiana

abstract: In May, 2021, during routine oil and gas industrial quarantine/premobilization procedures, four individuals who recently arrived to Louisiana from the Philippines tested positive for SARS-CoV-2. Subsequent genomic analysis showed that all were infected with a Variant of Interest (P.3-Theta). This increases the number of known P.3 infections in the United States to eleven and highlights the importance of genomic surveillance within industries that are prone to rapidly spread the infection.

category: epidemiology


title: Outbreak of P.3 (Theta) SARS-CoV-2 emerging variant of concern among service workers in Louisiana


title: Excess morbidity and mortality among survivors of childhood acute lymphoblastic leukaemia: 25 years of follow-up from the United Kingdom Childhood Cancer Study (UKCCS)

abstract:
ObjectivesTo examine morbidity and mortality in survivors of childhood acute lymphoblastic leukaemia (ALL) across their teenage and young adult (TYA) years; comparing the patterns observed with individually matched general population controls.

DesignCase-control study with follow-up linkage to administrative healthcare databases for up to 25 years.

SettingThe study population comprises all children (0-14 years) registered for primary care with the National Health Service (NHS) in England 1992-1996.

Participants1082 five-year survivors of ALL diagnosed <15 years of age, and 2018 age- and sex-matched population-based controls; followed to 15 March 2020.

Main outcome measuresAssociations with hospital activity, cancer, and mortality were assessed using incidence rate ratios and absolute risk difference.

ResultsMortality 5-25 years after diagnosis was 20 times higher in cases than controls (Rate Ratio 21.3, 95% Confidence Interval 11.2-45.6), and cancer incidence 10 time higher (IRR 9.9 95% CI 4.1-29.1). Hospital activity was increased for many clinical specialties, the strongest effects being for endocrinology; outpatient IRR 36.7, 95% CI 17.3-93.4 and inpatient 19.7, 95% CI 1.9-25.5 for males, and 11.0, 95% CI 6.2-21.1 and 6.2 95% CI 3.1-13.5 respectively for females. Notable excesses were also evident for cardiology, neurology, ophthalmology, respiratory medicine and general medicine. Males were also more likely to attend gastroenterology, ENT (ear, nose and throat), urology, and dermatology; while females were more likely to be seen in plastic surgery and less likely in midwifery.

ConclusionsAdding to a large excess risk of death and cancer, survivors of childhood ALL experience excess outpatient and inpatient activity across their TYA years. Involving most clinical specialties, the observed effects are striking, showing no signs of diminishing over the first 25 years of follow-up. These findings underscore the need to take prior ALL drug and/or radiation treatment into account when interpreting seemingly unrelated symptoms in later life.


title: Major sex differences in migraine prevalence among occupational categories: a cross-sectional study using UK Biobank

abstract: Migraine represents one of the most prevalent neurological conditions worldwide. It is a disabling condition with high impact on the working situation of migraineurs. Interestingly, gender-related differences regarding an association of migraine with important occupational characteristics has been hardly studied. The current study scrutinizes gender-specific differences in the prevalence of migraine across a broad spectrum of occupational categories, shedding also light on associations with important job-related features such as shift work, job satisfaction, and physical activity. The study included data from 415 712 participants from the UK Biobank cohort, using the official ICD10 diagnosis of migraine and other health conditions as selection criteria. Prevalence ratios of migraineurs compared to healthy controls among different occupational categories and job-related variables were estimated using log-binomial regression analyses. Statistical models were adjusted for important sociodemographic features such as age, BMI, ethnicity, education and neuroticism. To better highlight specific differences between men and women we stratified by sex. We detected a differential prevalence pattern in relation to different job categories between men and women. Especially in men, migraine appears to be more prevalent in highly physically demanding occupations (PR 1.38, 95% CI [0.93, 2.04]). Furthermore, migraine is also more prevalent in jobs that frequently involve shift or night shift work compared to healthy controls. Interestingly, this prevalence is especially high in women (shift work PR 1.45, 95% CI [1.14, 1.83], night shift work PR 1.46, 95% CI [0.93, 2.31]). Our results show that higher migraine prevalence is associated with physically demanding jobs and shift working.


title: Efficacy and safety of non-invasive ventilation in pediatric care in low-income and middle-income countries: a systematic review

abstract:
BackgroundLower respiratory tract infections (LRTIs) are a leading cause of under-5 mortality in low-income and middle-income countries (LMICs) and interventions to reduce mortality are needed. Non-invasive ventilation has been shown to reduce mortality for neonates; however, data for children >1 month of age in LMICs are lacking. The objective of this study was to systematically review the available literature to determine if non-invasive ventilation as the primary modality of respiratory support is efficacious and safe for the management of respiratory distress in non-neonatal pediatric patients in LMICs.

MethodsWe systematically reviewed all studies assessing the endpoints of efficacy, effectiveness, and safety of non-invasive ventilation for pediatric LRTIs in LMICs. A comprehensive search of Medline, Embase, LILACS, Web of Science, and Scopus was performed on April 7, 2020. Included studies assessed the safety, efficacy or effectiveness of non-invasive ventilation (NIV) in the hospital setting for pediatric patients with respiratory distress from 1 month - 15 years of age in LMICs. All study types, including case reports and case series were included. Studies focusing exclusively on neonates (<28 days old) were excluded. Mortality and rates of adverse events were extracted using Covidence by two independent reviewers. Risk of bias was assessed using GRADE criteria for randomized control trials and a standardized risk of bias assessment tool for observational studies. The study protocol was registered on PROSPERO (CRD42018084278).

FindingsA total of 2174 papers were screened and 20 met criteria for inclusion. There were 5 randomized control trials (RCTs), including 3 large, well-designed RCTs. The first RCT, the  Bangladesh trial, found that children who received bubble continuous positive airway pressure (bCPAP) compared to low-flow oxygen had a significantly lower risk of failure (6% in CPAP and 24% in low-flow oxygen, p=0.0026) and mortality (4% in CPAP and 15% in low-flow oxygen, p=0.022). A second RCT, the  Ghana trial, found no decrease in all-cause mortality between the CPAP and control arms (3% and 4% respectively, p=0.11); however, an adjusted secondary analysis demonstrated decreased mortality for children under 1 year of age (3% in CPAP and 7% in control group, p=0.01). The third RCT, the  Malawi trial, compared bCPAP to low flow oxygen and found higher mortality in the bCPAP arm (17% and 11% respectively, p=0.036). Among the non-RCT studies, mortality rates ranged from 0-55%.

InterpretationThe evidence of efficacy, effectiveness, and safety is mixed regarding the use of NIV in children with respiratory failure in LMICs. Our review of the literature suggests that CPAP for non-neonatal pediatric patients should be considered only in well-controlled, high acuity units with high provider-to-patient ratios and direct physician supervision. Until further data are available, CPAP use in LMICs should be limited to children less than 1 year of age. Further research is needed to determine best practices for CPAP prior to wide-spread implementation.

FundingThere was no funding source for this study.


title: Potential Health Benefits of Eliminating Traffic Emissions in Urban Areas

abstract: Traffic is one of the major contributors to PM2.5 in cities worldwide. Quantifying the role of traffic is an important step towards understanding the impact of transport policies on the possibilities to achieve cleaner air and accompanying health benefits. We carried out a meta-analysis using the World Health Organisation (WHO) database of source apportionment studies of PM2.5 concentrations. Specifically, we used a Bayesian meta-regression approach, modelling both overall and traffic-related (tailpipe and non-tailpipe) concentrations simultaneously. We obtained the distributions of expected PM2.5 concentrations (posterior densities) of different types for 117 cities worldwide. For each city, we calculated the probabilities of exceeding the WHO-recommended concentration of PM2.5 if all of traffic emissions were removed. Using the non-linear Integrated Exposure Response (IER) function of PM2.5, we estimated percent reduction in different disease endpoints for a scenario with complete removal of traffic emissions. We found that this results in achieving the WHO-recommended concentration of PM2.5 only for a handful of cities that already have low concentrations of pollution. The percentage reduction in prevented mortality for cardiovascular and respiratory diseases increases up to a point (30-40 ug/m3), and above this concentration, it flattens off. For Diabetes-related mortality, the percentage reduction in mortality decreases with increasing concentrations--a trend that is opposite to other outcomes. For cities with high concentrations of pollution, the results highlight the need for multi-sectoral strategies to reduce pollution. The IER functions of PM2.5 result in diminishing returns of health benefits at high concentrations, and in case of Diabetes, there are even negative returns. The results show the significant effect of the shape of IER functions on health benefits. Overall, despite the diminishing results, a significant burden of deaths can be prevented by policies that aim to reduce traffic emissions even at high concentrations of pollution.

category: public and global health


title: Small Patient Datasets Reveal Genetic Drivers of Non-Small Cell Lung Cancer Subtypes using a Novel Machine Learning Approach

abstract: There are many small datasets of significant value in the medical space that are being underutilized. Due to the heterogeneity of complex disorders found in oncology, systems capable of discovering patient subpopulations while elucidating etiologies is of great value as it can indicate leads for innovative drug discovery and development. Here, we report on a machine intelligence-based study that utilized a combination of two small non-small cell lung cancer (NSCLC) datasets consisting of 58 samples of adenocarcinoma (ADC) and squamous cell carcinoma (SCC) and 45 samples from the gene expression analysis of human lung cancer and control samples series (GSE18842). Utilizing a novel machine learning approach, we were able to uncover subpopulations of ADC and SCC while simultaneously extracting which genes, in combination, were significantly involved in defining the subpopulations. An interactive hypothesis-generating interface designed to work with machine learning methods allowed us to explore the hypotheses generated by the unsupervised components of the system. Using these methods, we were able to uncover genes implicated by other methods and accurately discover known subpopulations without being asked, such as different levels of aggressiveness within the SCC and ADC subtypes. Furthermore, PIGX was a novel gene implicated in this study that warrants further study due to its role in breast cancer proliferation. Here we demonstrate the ability to learn from small datasets and reveal well-established properties of NSCLC. These machine learning techniques can reveal the driving factors behind subpopulations of patients altering the approach to drug discovery and development by making precision medicine a reality.

category: respiratory medicine


title: Genetic and neurophysiological biomarkers of neuroplasticity inform post-stroke language recovery

abstract:
BackgroundThere is high variability in post-stroke aphasia severity and predicting recovery remains imprecise. Standard prognostics do not include neurophysiological indicators or genetic biomarkers of neuroplasticity, which may be critical sources of variability.

ObjectiveTo evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF) contributes to variability in post-stroke language recovery, and to assess whether BDNF polymorphism interacts with neurophysiological indicators of neuroplasticity to improve estimates of aphasia severity.

MethodsSaliva samples and motor-evoked potentials (MEPs) were collected from participants with chronic aphasia subsequent to left-hemisphere stroke. MEPs were collected prior to continuous theta burst stimulation (cTBS; index for cortical excitability) and 10 minutes following cTBS (index for stimulation-induced neuroplasticity) to the left primary motor cortex. Analyses assessed the extent to which BDNF polymorphism interacted with cortical excitability and stimulation-induced neuroplasticity to predict aphasia severity beyond established predictors.

ResultsVal66Val carriers showed less aphasia severity than Met allele carriers, after controlling for lesion volume and time post-stroke. Furthermore, Val66Val carriers showed expected effects of age on aphasia severity, and positive associations between both cortical excitability and stimulation-induced neuroplasticity and severity. In contrast, Met allele carriers showed weaker effects of age and negative associations between cortical excitability, stimulation-induced neuroplasticity and aphasia severity.

ConclusionsNeurophysiological indicators and genetic biomarkers of neuroplasticity improved ability to predict aphasia severity. Furthermore, BDNF polymorphism interacted with cortical excitability and stimulation-induced neuroplasticity to improve predictions. These findings provide novel insights into mechanisms of variability in stroke recovery and may improve aphasia prognostics.


title: Benefits and Challenges of Using Virtual Primary Care During the COVID-19 Pandemic: From Key Lessons to a Framework for Implementation

abstract:
BackgroundWith the onset of COVID-19, general practitioners (GPs) and patients worldwide swiftly transitioned from face-to-face to digital remote consultations. There is a need to evaluate how this global shift has impacted patient care, healthcare providers, patient and carer experience, and health systems.

ObjectiveWe explored GPs perspectives on the main benefits and challenges of using digital remote care.

MethodsGPs across 20 countries completed an online questionnaire between June - September 2020. GPs perceptions on main barriers and challenges were explored using free-text questions. Thematic analysis was used to analyse the data.

Results1,605 respondents participated in our survey. The benefits identified included reducing COVID-19 transmission risks, guaranteeing access and continuity of care, improved efficiency, faster access to care, improved convenience and communication with patients, greater work flexibility for providers, and hastening the digital transformation of primary care and the accompanying legal frameworks.

Main challenges included patients preference for face-to-face consultations, digital exclusion, lack of physical examinations, clinical uncertainty, delays in diagnosis and treatment, overuse and misuse of digital remote care, and unsuitability for certain types of consultations. Other challenges include the lack of formal guidance, higher workloads, remuneration issues, organisational culture, technical difficulties, implementation and financial issues, and regulatory weaknesses.

ConclusionAt the frontline of care delivery, GPs can provide important insights on what worked well, why, and how. Lessons learned during the emergency phase can be used to inform the stable adoption of virtual care solutions, and co-design processes and platforms that are technologically robust, secure, and supported by a strategic long-term plan.

category: health informatics


title: The Vaccination Threshold for SARS-CoV-2 Depends on the Indoor Setting and Room Ventilation

abstract:
BackgroundEffective vaccines are now available for SARS-CoV-2 in the second year of the COVID-19 pandemic, but there remains significant uncertainty surrounding the necessary vaccination rate to safely lift occupancy controls in public buildings and return to pre-pandemic norms. The aim of this paper is to estimate setting-specific vaccination thresholds for SARS-CoV-2 to prevent sustained community transmission using classical principles of airborne contagion modeling. We calculated the airborne infection risk in three settings, a classroom, prison cell block, and restaurant, at typical ventilation rates, and then the expected number of infections resulting from this risk at varying levels of occupant susceptibility to infection.

ResultsWe estimate the vaccination threshold for control of SARS-CoV-2 to range from a low of 40% for a mechanically ventilation classroom to a high of 85% for a naturally ventilated restaurant.

ConclusionsIf vaccination rates are limited to a theoretical minimum of approximately two-thirds of the population, enhanced ventilation above minimum standards for acceptable air quality is needed to reduce the frequency and severity of SARS-CoV-2 superspreading events in high-risk indoor environments.

category: infectious diseases


title: Genomic epidemiologic assessment implicates prolonged silent carriage, virulence factors and transmission between staff and patients in a NICU outbreak of MRSA.

abstract:
IntroductionMethicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in neonatal intensive care units (NICU) that carries significant morbidity and mortality. Improving our understanding of MRSA transmission dynamics, especially among high risk patients, is an infection prevention priority.

MethodsWe investigated a cluster of clinical MRSA cases in the NICU using a combination of epidemiologic review and whole genome sequencing (WGS) of isolates from clinical and surveillance cultures obtained from patients and healthcare personnel (HCP).

ResultsPhylogenetic analysis identified two genetically distinct phylogenetic clades and revealed multiple silent transmission events between HCP and infants. The predominant outbreak strain harbored multiple virulence factors. Epidemiologic investigation and genomic analysis identified a HCP colonized with the dominant MRSA outbreak strain who cared for the majority of NICU patients who were infected or colonized with the same strain, including one NICU patient with severe infection seven months before the described outbreak. These results guided implementation of infection prevention interventions that prevented further transmission events.

ConclusionSilent transmission of MRSA between HCP and NICU patients likely contributed to a NICU outbreak involving a virulent MRSA strain. WGS enabled data-driven decision making to inform implementation of infection control policies that mitigated the outbreak. Prospective WGS coupled with epidemiologic analysis can be used to detect transmission events and prompt early implementation of control strategies.

SummaryWhole genome sequencing identified a NICU outbreak of MRSA preceded by silent transmission between health care personnel and patients seven months prior to outbreak detection. This study suggests prospective genomic analysis may identify isolates with high virulence potential, offering an early opportunity for intervention.


title: Polygenic risk score and statin relative risk reduction for primary prevention in a real-world population

abstract:
AbstractsO_ST_ABSBackgroundC_ST_ABSRandomized-controlled trials demonstrate that high coronary heart disease (CHD) polygenic risk score modifies statin CHD relative risk reduction, but it is unknown if the association extends to statin users undergoing routine care.

ObjectivesThe primary objective was to determine how statin effectiveness is modified by CHD polygenic risk score in a real-world cohort of primary prevention participants.

MethodsWe determined polygenic risk scores in participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Cox regression models were used to compare the risk of the cardiovascular outcomes between statin users and matched nonusers.

ResultsThe hazard ratio (HR) for statin effectiveness on incident myocardial infarction was similar within 10-year atherosclerotic cardiovascular disease (ASCVD) risk score groups at 0.65 (95% confidence interval [CI] 0.39-1.08; P=0.10), 0.65 (95% CI 0.56-0.77; P=2.1E-7), and 0.67 (95% CI 0.57-0.80; P=4.3E-6) for borderline, intermediate, and high ASCVD groups, respectively. In contrast, statin effectiveness by polygenic risk was largest in the high polygenic risk score group (HR 0.62, 95% CI 0.50-0.77; P=1.4E-5), intermediate in the intermediate polygenic risk score group (HR 0.70, 95% CI 0.61-0.80; P=5.7E-7), and smallest in the low polygenic risk score group (HR 0.86, 95% CI 0.65-1.16; P=0.33). ASCVD risk and statin LDL-C lowering did not differ across polygenic risk score groups.

ConclusionsIn primary prevention patients undergoing routine care, CHD polygenic risk modified statin relative risk reduction of incident myocardial infarction independent of statin LDL-C lowering. Our findings extend prior work by identifying a subset of patients with attenuated clinical benefit from statins.

category: cardiovascular medicine


title: A Systems-Based Framework for Immunisation System Design: Six Loops, Three Flows, Two Paradigms

abstract: Despite massive progress in vaccine coverage globally, the region of sub-Saharan Africa is lagging behind and not on track for Sustainable Development Goal 3 by 2030. Sub-national under-immunisation, related to geographical and social heterogeneity, is part of the problem. System-wide changes could transform current immunisation systems to become more sustainable, resilient and inclusive. A framework is proposed that captures the complexity of immunisation systems and offers directions for sustainable redesign. Insights were extracted from literature, stakeholder workshops, and field research in Rwanda and Kenya. A conceptual model of the national immunisation system was co-developed and validated with stakeholders. Leverage points were suggested for intervention scenario building. The Immunisation System Diagram assembles the paradigms of planned and emergency immunisation in one system and emphasizes the synchronized flows of vaccine receiver, vaccinator and vaccine. Six feedback loops capture the main subsystems. Sustainability and resilience are assessed based on loop dominance and dependency on exogenous factors such as donor funding and vaccine stockpiles. In group model building workshops, the diagram invites stakeholders to share their mental models, to assess the systems performance and to trigger detection of root causes and leverage points. The framework provides a systems-approach for problem structuring and policy design.

category: health systems and quality improvement


title: FAIR-IFICATION OF STRUCTURED CLINICAL DATA

abstract: One of the common concerns in clinical research is improving the infrastructure to facilitate the reuse of clinical data and deal with interoperability issues. FAIR (Findable, Accessible, Interoperable and Reusable) Data Principles enables reuse of data by providing us with descriptive metadata, explaining what the data represents and where the data can be found. In addition to aiding scholars, FAIR guidelines also help in enhancing the machine-readability of data, making it easier for machine algorithms to find and utilize the data. Hence, the feasibility of accurate interpretation of data is higher and this helps in obtaining maximum results from research work. FAIR-ification is done by embedding knowledge on data. This could be achieved by annotating the data using terminologies and concepts from Web Ontology Language (OWL). By attaching a terminological value, we add semantics to a specific data element, increasing the interoperability and reuse. However, this FAIR-ification of data can be a complicated and a time-consuming process. Our main objective is to disentangle the process of making data FAIR by using both domain and technical expertise. We apply this process in a workflow which involves FAIR-ification of four independent public HNSCC datasets from The Cancer Imaging Archive (TCIA). This approach converts the data from the four datasets into Linked Data using RDF triples, and finally annotates these datasets using standardized terminologies. By annotating them, we link all the four datasets together using their semantics and thus a single query would get the intended information from all the datasets.


title: Prediabetes Blunts CD26/DPP4 Genetic Control of Postprandial Glycemia and Insulin Secretion

abstract:
Aims/hypothesisImbalances in glucose metabolism are hallmarks of clinically silent prediabetes representing dysmetabolism trajectories leading to type 2 diabetes (T2D). CD26/DPP4 is a clinically proven molecular target of diabetes-controlling drugs but the CD26 gene control of disglycemia is unsettled.

MethodsWe dissected the genetic control of postprandial glycemic and insulin release responses by the CD26/DPP4 gene in an European/Portuguese population-based cohort that comprised individuals with normoglycemia and prediabetes, and in mouse experimental models of CD26 deficiency and hypercaloric diet.

ResultsIn individuals with normoglycemia, CD26/DPP4 single-nucleotide variants governed glycemic excursions (rs4664446, P=1.63x10-7) and C-peptide release responses (rs2300757, P=6.86x10-5) upon OGTT. Association with glycemia was stronger at 30min OGTT but the higher association of the genetic control of insulin secretion was detected in later phases of the postprandial response suggesting that CD26/DDP4 gene directly senses glucose challenges. Accordingly, in mice fed normal chow diet but not high fat diet, we found that under OGTT expression of CD26/DPP4 gene is strongly down-regulated at 30min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals indicating that postprandial glycemic control by CD26/DPP4 is abrogated in prediabetes. Furthermore, CD26 null mice provided concordant evidence that CD26/DPP4 modulates postprandial C-peptide release in normoglycemic but not in dysmetabolic states.

Conclusions/interpretationThese results unveiled CD26/DPP4 gene as a strong determinant of postprandial glycemia via glucose sensing mechanisms that are abrogated in prediabetes. We propose that impairments in CD26/DDP4 control of postprandial glucose-insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with T2D.

RESEARCH IN CONTEXTO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LICD26/DPP4 is a clinically proven molecular target of diabetes-controlling drugs
C_LIO_LIDPP4 enzymatic activity impacts in glycemia by degrading incretins
C_LIO_LIDPP4 represents a potential link between dysmetabolism and insulin resistance.
C_LI

What is the key question?O_LIIs CD26/DPP4 controlling postprandial glycemic and pancreatic responses?
C_LI

What are the new findings?O_LIFunctional link between postprandial glycemia excursions and subsequent insulin release is operational in NGT individuals but is altered in prediabetes.
C_LIO_LICD26/DPP4 gene is a robust component of mechanisms that control postprandial glycemia excursions and insulin secretion in NGT individuals.
C_LIO_LICD26/DPP4 gene controls postprandial glucose-insulin responses via glucose sensing mechanisms that are abrogated in prediabetes.
C_LIO_LIPostprandial reduction of hepatic CD26/DPP4 gene expression is abrogated in experimental diet-induced dysglycemia.
C_LIO_LICD26/DPP4 gene action in reducing post-prandial insulin release is not operating in experimental diet-induced dysglycemia.
C_LI

How might this impact on clinical practice in the foreseeable future?O_LIImpairments in the control of postprandial glucose-insulin responses by CD26/DDP4 are indicators of early metabolic disturbances and possible predictors of dysmetabolic trajectories leading to T2D.
C_LI

category: endocrinology


title: Estimating the genetically predicted effects of lifestyle risk factors, educational attainment and Alzheimer's disease liability on weight change during midlife

abstract:
BackgroundWeight change is a major indicator of adverse health outcomes. This study aims to examine factors contributing to weight change over a one-year interval in midlife.

MethodsObservational and one-sample Mendelian randomisation (MR) analyses were conducted to estimate effects on weight change compared to one year previously (mean age: 56.5 years) using data from the UK Biobank study (n=453,169). Risk factors included alcohol consumption, smoking intensity, body mass index (BMI), educational attainment and Alzheimers disease liability.

ResultsObservational analyses indicated strong evidence of an association between greater educational attainment and family history of Alzheimers disease with weight loss. In contrast, smoking intensity and higher BMI were associated with weight gain. MR analyses were consistent with observational estimates for educational attainment and Alzheimers disease liability on weight loss and provided strong evidence of a genetically predicted effect between higher overall BMI and weight gain. Whilst there was little evidence of a genetically predicted effect between smoking intensity and weight change in those who had ever smoked, when stratified, smoking intensity was associated with weight loss in current smokers and weight gain in previous smokers. There was little evidence of an association between alcohol consumption and weight change in the one-year period. Inverse probability weighting was used to account for non-random selection on smoking and alcohol status and further stratification by smoking status, indicating that our results were largely robust to collider bias.

ConclusionsIndividuals who have been in education for longer, may have more opportunity to reduce their weight in midlife. The effect of Alzheimers disease liability on weight loss could be indicative of early signs of dementia. The relationship between smoking intensity and weight change is complex, reinforcing the importance of combining interventions aimed at controlling weight and smoking cessation among cigarette smokers.

Key MessagesO_LIObservational and Mendelian randomisation analyses used in this study provide consistent evidence that educational attainment and Alzheimers disease liability have an effect on weight loss over one year during midlife.
C_LIO_LIThis suggests that individuals experiencing unintentional weight loss in midlife may be at high risk of developing Alzheimers disease in later life.
C_LIO_LIThese results additionally demonstrate the value of Mendelian randomisation in minimising spurious associations obtained through observational research when assessing lifestyle risk factors prone to residual confounding, such as smoking intensity.
C_LIO_LIOur findings show that the relationship between smoking and weight change is complex, endorsing the notion that strategies to tackle weight control and smoking cessation should be combined.
C_LI


title: On the mathematical modelling and analysis of Listeriosis from contaminated food products

abstract: Listeriosis is a food-borne disease caused by a bacterium known as Listeria monocytogens. Humans can be infected by consuming contaminated food products. A transmission can also occur through contact with infected animals or people, however to a less extent. In this paper, a mathematical model for Listeriosis dynamics was developed. The steady states and their stability of the model system were determined and analyzed. The result shows that the disease-free equilibrium is asymptotically stable if the bacterias growth rate is less than its removal rate, and also the growth rate of food contamination is less than its removal rate. It was further observed that we can still have Listeriosis driven by the contaminated food products even if the Listeria bacteria population in the environment is very small.The results indicate that Listeriosis can be effectively controlled by removing contaminated food products, which was the policy adopted by the South African government during the recent Listeriosis outbreak.


title: Measuring odds of various COVID-19 infection prevention & control measures among the contacts traced during trace test and quarantine activities at district Quetta (An un-matched case control study).

abstract:
BackgroundThe second wave of COVID-19 pandemic has started globally, right now globally 220 countries are infected and a total of 71351695 confirmed cases and 1612372 deaths due to COVID-19 has been reported so far1. As of today i.e. (16th Dec 2020) a total of 11430955 new COVID-19 confirmed cases have been reported across the south-east asia1. These cases are showing an increasing trend in all the Asian countries including Pakistan1. Across Pakistan till date 440787 new confirmed COVID-19 cases have been reported across the Pakistan showing a doubling time of 10.63 days (95% C.I 9.68-11.8), while a total of 8832 new deaths have been reported across the Pakistan making the double time for death as 11.11 days (95% C.I 4.04-14.86) 1. Till the development and availability of a vaccine the only tools that can help prevent the spread of COVID-19 are IPC measures violating them can result in a quick spread across the population3.

This study was conducted to assess the odds of various COVID-19 IPC measures among the Contacts of an index COVID-19 case traced by Provincial Disease Surveillance & Response unit Quetta.

MethodologyO_ST_ABSSample Size & Sampling techniqueC_ST_ABSUsing the detailed epidemiological reports of 600 COVID-19 contacts identified during the trace test and quarantine field activities form 1st October till 30th October 2020 in district Quetta, from this data a sample of 300 individuals was selected for this study using Simple random sampling technique.

Study DesignConsidering different exposure rates and pandemic situation an Un-matched Case control study study was conducted where Cases were defined as "Every PCR positive contact (Symptomatic or asymptomatic) for any index case" similarly Controls were defined as "Every PCR negative contact (Symptomatic or asymptomatic) for any index case who was home quarantined for 14 days based on suspicion by PDSRU team. A set ratio of 1:2 for cases & controls respectively was used for this study.

ResultsThe odds for various IPC measures like Knowingly and intentionally Contacted with a COVID-19 positive case, Family member of the index COVID-19 case, Knowingly and intentionally received an object handed over by a COVID-19 Positive case, Touched the same surface/surfaces after it was touched by the index case, Not doing regular Hand washing, Knowingly and intentionally did not follow the government SOPs of Social Distancing During encounter with a positive symptomatic case, Knowingly and intentionallydid not Follow the government SOPs of Social Distancing During sharing of bedroom and toilet with positive symptomatic case, used the same vehicle after it was used by the COVID-19 index case, Spoke with Positive COVID-19 index case for more than 15mins few days before catching the disease, Individual did not use a face mask during all of his contact episodes with the positive index case, Participating in gathering or social events were all found to be poorly followed by the PCR positive contacts.


title: Data Analysis and Forecasting of COVID-19 Pandemic in Kuwait

abstract: The first COVID 19 case of Kuwait was announced on 24th February, 2020 and the daily new cases increases exponentially since then until May, 2020 when the first wave started to decline. The same exponential dynamics has been observed between January and March, 2021. The forecast of new cases and death recorded daily is crucial so that health experts and citizens can be guided in order to avoid escalation of the pandemic. We propose a deterministic method to predict the basic reproduction number Ro of first and second wave of COVID-19 cases in Kuwait and also to forecast the daily new cases and death of the pandemic in the country. Forecasting has been done using ARIMA model, Exponential smoothing model, Holts method, Prophet forecasting model and machine learning models like log-linear, polynomial and support vector regressions. The results presented aligned with other methods used to predict Ro in first and second waves and the forecasting clearly shows the trend of the pandemic in Kuwait. The deterministic prediction of Ro is a good forecasting tool available during the exponential phase of the contagion, which shows an increasing trend during the beginning of the first and second waves of the pandemic in Kuwait.


title: A regression discontinuity analysis of the social distancing recommendations for older adults in Sweden during COVID-19

abstract:
ObjectivesTo study the impact of non-mandatory, age-specific social distancing recommendations for older adults (70+ years) in Sweden on isolation behaviors and disease outcomes during the first wave of the COVID-19 pandemic.

MethodsOur study relies on self-reported isolation data from COVID Symptom Study Sweden (n = 96,053) and national register data on COVID-19 hospitalizations, deaths, and confirmed cases. We use a regression discontinuity design to account for confounding factors, exploiting the fact that exposure to the recommendation was a discontinuous function of age.

ResultsBy comparing individuals just above to those just below the age limit for the policy, our analyses revealed a sharp drop in the weekly number of visits to crowded places at the 70-year-threshold (-13%). Severe COVID-19 cases (hospitalizations or deaths) also dropped abruptly by 16% at the 70-year-threshold. Our data suggest that the age-specific recommendations prevented approximately 1,800 to 2,700 severe COVID-19 cases, depending on model specification.

ConclusionThe non-mandatory, age-specific recommendations helped control the COVID-19 pandemic in Sweden.


title: Amygdala connectivity as a predisposing neural feature of stress-induced behaviour during the COVID-2019 outbreak in Hubei

abstract: The amygdala plays an important role in the regulation of stress and anxiety. However, little is known about the relationship between amygdala connectivity and subsequent stress-induced behavior. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress-induced behavior while individuals face an emergent and unexpected event like the COVID-19 outbreak. Using an fMRI cohort established before the pandemic in Wuhan, Hubei, we found that resting-state functional connectivity (rsFC) of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress-induced behavior of these volunteers during the COVID-2019 outbreak in Hubei. Furthermore, the self-connection of the right amygdala, inferred using dynamic causal modeling, was negatively correlated with stress-induced behavior in this cohort. A significant correlation between the right amygdala-dmPFC rsFC and self-connection of the right amygdala was found. Additionally, after three months of the COVID-19 outbreak in Hubei when the stressor weakened - and in another cohort collected in regions outside Hubei where the individuals experienced a lower level of stress - the relationship between the amygdala-dmPFC rsFC and the stress-induced behavior disappeared. Our findings support that amygdala connectivity is a predisposing neural feature of stress-induced behavior in the COVID-19 outbreak in Hubei, suggesting the amygdala connectivity before stress predicts subsequent behavior while facing an emergent and unexpected event. And thus our findings provide an avenue for identifying individuals vulnerable to stress using intrinsic brain function before stress as an indicator.

category: psychiatry and clinical psychology


title: Evidence from imaging resilience genetics for a protective mechanism against schizophrenia in the ventral visual pathway

abstract:
IntroductionIlluminating neurobiological mechanisms underlying the protective effect of recently discovered common genetic resilience variants for schizophrenia is crucial for more effective prevention efforts. Current models implicate adaptive neuroplastic changes in the visual system and their pro-cognitive effects as a schizophrenia resilience mechanism. We investigated whether common genetic resilience variants might affect brain structure in similar neural circuits.

MethodUsing structural magnetic resonance imaging, we measured the impact of an established schizophrenia polygenic resilience score (PRSResilience) on cortical volume, thickness, and surface area in 101 healthy subjects and in a replication sample of 33,224 healthy subjects (UK Biobank).

FindingWe observed a significant positive whole-brain correlation between PRSResilience and cortical volume in the right fusiform gyrus (FFG) (r=0.35; p=.0004). Post-hoc analyses in this cluster revealed an impact of PRSResilience on cortical surface area. The replication sample showed a positive correlation between PRSResilience and global cortical volume and surface area in the left FFG.

ConclusionOur findings represent the first evidence of a neurobiological correlate of a genetic resilience factor for schizophrenia. They support the view that schizophrenia resilience emerges from strengthening neural circuits in the ventral visual pathway and an increased capacity for the disambiguation of social and non-social visual information. This may aid psychosocial functioning, ameliorate the detrimental effects of subtle perceptual and cognitive disturbances in at-risk individuals, and facilitate coping with the cognitive and psychosocial consequences of stressors. Our results thus provide a novel link between visual cognition, the vulnerability-stress concept and schizophrenia resilience models.


title: Frontal lobe fALFF measured from resting-state fMRI at baseline predicts acute treatment response in first episode psychosis

abstract: While antipsychotic medications have been utilized for decades, many patients experiencing psychosis do not demonstrate a satisfactory positive symptom response, even in the first episode of illness. Resting state functional magnetic resonance imaging (rs-fMRI) has increasingly been studied as a potential biomarker of antipsychotic treatment response, but studies to date remain limited in terms of sample size and brain regions examined. The present study examined fractional amplitude of low frequency fluctuations (fALFF) derived from rs-fMRI to search the whole brain, in a hypothesis-free manner, for regions that might predict response to 12 weeks of treatments with standard antipsychotic medications (risperidone or aripiprazole). To our knowledge, the present study represents the largest first episode psychosis treatment sample studied with rs-fMRI to date (N=126). At baseline, patients who would later meet strict criteria for clinical response demonstrated significantly greater baseline fALFF in bilateral orbitofrontal cortex compared to non-responders. In a subset of 62 patients who were scanned a second time at the end of treatment, responders and non-responders demonstrated significant increases in fALFF in differing brain regions. Specifically, responders demonstrated significant increases in fALFF, from baseline to follow-up, in bilateral dorsal prefrontal cortex; prefrontal changes were not observed in non-responders or in healthy individuals (n=45) scanned at two time points. Thus, spontaneous activity in orbitofrontal cortex may serve as a prognostic biomarker of antipsychotic treatment, while spontaneous activity in the dorsal prefrontal cortex may serve as a critical target of effective medication.


title: A comprehensive evaluation methodology for the publicly accessible AI services for medical diagnostics

abstract:
Online AI in telemedicine for radiology became widely available and valuable in the pandemic, particularly for chest CT analysis. On the other hand, the potentially harmful consequences of such services inappropriate usage cannot be neglected. Thus, a suitable methodology for quality assurance and quality control has to be established.

A studys purpose was to develop and test an original methodology for a complex evaluation of open-access AI services in teleradiology. The approach included assessing the user experience, accessibility, safety, and diagnostic accuracy on the independent reference dataset. The methodology was applied to assess seven AI services for the detection of COVID-19 on a CT scan. A comparative analysis of this assessment is presented in this work. The analysis allowed us to draw conclusions about AI services quality and their value for different users - patients, physicians, and healthcare data scientists. The originality of the findings, timeliness, and interdisciplinary approach make this quality assurance methodology of particular interest for further application and spreading.

HighlightsO_LIThe availability of diagnostic procedures increases each year with a corresponding increase of low-impact workload.
C_LIO_LIDuring pandemics, medical AI services have become valuable in reducing the workload on healthcare professionals.
C_LIO_LIQuality assurance for AI in healthcare requires an interdisciplinary approach - medicine, IT, and data science collaboration.
C_LIO_LISuggested methodology of AI quality assurance suits different target users groups, such as the general public, physicians, and data scientists.
C_LI

category: radiology and imaging


title: Quantifying the Utility of Low Resolution Brain Imaging:: Treatment of Infant Hydrocephalus

abstract: As low-field MRI technology is being disseminated into clinical settings around the world, it is important to assess the image quality required to properly diagnose and treat a given disease and evaluate the role of machine learning algorithms, such as deep learning, in the enhancement of lower quality images. In this post-hoc analysis of an ongoing randomized clinical trial, we assessed the diagnostic utility of reduced-quality and deep learning enhanced images for hydrocephalus treatment planning. CT images of post-infectious infant hydrocephalus were degraded in terms of spatial resolution, noise, and contrast between brain and CSF and enhanced using deep learning algorithms. Both degraded and enhanced images were presented to three experienced pediatric neurosurgeons accustomed to working in low- to middle-income countries (LMIC) for assessment of clinical utility in treatment planning for hydrocephalus. In addition, enhanced images were presented alongside their ground-truth CT counterparts in order to assess whether reconstruction errors caused by the deep learning enhancement routine were acceptable to the evaluators. Results indicate that image resolution and contrast-to-noise ratio between brain and CSF predict the likelihood of an image being characterized as useful for hydrocephalus treatment planning. Deep learning enhancement substantially increases contrast-to-noise ratio improving the apparent likelihood of the image being useful; however, deep learning enhancement introduces structural errors which create a substantial risk of misleading clinical interpretation. We find that images with lower quality than is customarily acceptable can be useful for hydrocephalus treatment planning. Moreover, low quality images may be preferable to images enhanced with deep learning, since they do not introduce the risk of misleading information which could misguide treatment decisions. These findings advocate for new standards in assessing acceptable image quality for clinical use.


title: Assessing the Utility of Low Resolution Brain Imaging: Treatment of Infant Hydrocephalus


title: Patient reported outcome on endourethrotomy combined with Amplatz dilatation for treatment of incompletely obliterated posterior urethral stricture following pelvic trauma: Validation in the era of urethroplasty

abstract:
IntroductionDirect vision internal urethrotomy (DVIU) is gaining revival among urologists, the procedure having the advantages of being minimally invasive as well as keeping continence and sexual function unaffected. The recurrence rate at 12 months was diminished by combination of DVIU with a Amplatz dilatation at the time of the procedure. Objectives are of present work is to present the outcome of the procedure.

Materials and methodsThis is an observational study with a cross-sectional approach. Patients underwent combined endo-urethrotomy and Amplatz dilation for posterior urethral strictures between February 2015 and January2020 were purposively recruited. We performed a retrospective review of the records of 48 patients who completed 12 months follow-up. Patient-reported outcome measures for urethral stricture surgery (USS-PROMs) and sexual function were assessed at 12 months follow-up. A questionnaire was used to assess quality of life, patients in the study filled a questionnaire. Correlation between status before and after treatment were analyzed using simple statistical analysis to evaluate the effect of treatment on quality of life. Clinician-driven outcome were uroflowmetry, retrograde urethrogram, and reporting of complications.

ResultsMean length of stricture segment was 2 cm (range 1-2.5 cm). At 12 months follow up patients reported very satisfactory. Restenosis that was treated with redo was reported in 2%. Mild stenosis that was treated with Amplatz dilatation was in 3%. Patients reported very satisfactory or satisfactory for USS-PROSMs, sexual function in comparison to pre-trauma status.

ConclusionsEndourethrotomy combined with Amplatz dilation is an effective treatment for short segment passable posterior urethral stricture and it has a place in the era of endourethrotomy.

category: urology


title: The final blink: intact cerebellar associative learning in isolated dystonia

abstract:
Structured AbstractO_ST_ABSBackgroundC_ST_ABSImpaired eyeblink conditioning is often cited as evidence for cerebellar dysfunction in isolated dystonia yet the results from individual studies are conflicting and underpowered.

ObjectiveTo systematically examine the influence of dystonia, dystonia subtype and clinical features over eyeblink conditioning within a statistical model which controlled for the covariates age and sex.

MethodsOriginal neurophysiological data from all published studies were shared to an age and sex matched control group. Two raters blinded to participant identity scored all recordings (6732 trials). After higher inter-rater agreement was confirmed, mean conditioning per block was entered into a mixed repetitive measures model.

ResultsMuch variability of eyeblink conditioning was seen in both groups. All dystonia versus controls showed no difference in conditioning (p=0.517). Analysis of dystonia subgroup, with age and sex as covariates did not reveal evidence that eyeblink conditioning is impaired in specific subtypes (cervical dystonia, DYT-TOR1A, DYT-THAP1 or focal hand dystonia). The presence of tremor did not significantly influence levels of eyeblink conditioning.

ConclusionsCollaborative efforts such as this article allow larger number of patients to be evaluated and provide more balanced estimates of disease effects over experimental outcomes. Intact eyeblink conditioning is against a global cerebellar learning deficit in isolated dystonia. Precise mechanisms for how the cerebellum interplays mechanistically with other key neuroanatomical nodes within the dystonic network remains an open research question.


title: Estimated Veterans Health Administration costs for Alzheimer's disease treatment with aducanumab

abstract: The approval of aducanumab for the treatment of Alzheimers disease has been met with significant public concern. Projections of annual cost across United States Medicare beneficiaries are in the tens of billions of dollars. Here, we performed an electronic health record review of Veterans Affairs beneficiaries, identifying 151,921 individuals (1.7%) with diagnosis codes for Alzheimers disease. We estimate that treatment for this cohort will cost in excess of $4 billion annually with further expenditures for associated screening, consultations, imaging, and therapeutic monitoring. The magnitude of projected expenditures necessitates early assessment of drug cost effectiveness.


title: Ergonomics knowledge, attitude, and practice among biomedical scientists

abstract: Biomedical scientists (BMSs) are important professionals for healthcare services as they help in the detection, diagnosis, and treatment of numerous diseases. To the best of our knowledge, this is the first study to assess ergonomics knowledge, attitude, and practice among BMSs. A cross-sectional study was carried out among BMSs using a self-constructed questionnaire. The association between these parameters and various risk factors was measured using the Chi-square test. The study included 110 BMSs. Females represented 68.2% and 45.5% were in the age of 25-34. Good ergonomics knowledge showed in 54.5% and 82.7% showed high positive attitude. However, poor ergonomics showed in 83.5%. There was no significant interrelation between the three parameters. A significant association was found between the male gender (0.040), more than 20 working experience (0.016), and good ergonomics practice. Biomedical scientists have good knowledge, high attitude but the poor practice of ergonomics. Ergonomics training and practice should be firmly enhanced among these healthcare professionals.

category: occupational and environmental health


title: Distinct pancreatic and neuronal Lung Carcinoid molecular subtypes revealed by integrative omic analysis

abstract: Lung Carcinoids (L-CDs) are uncommon low-grade neuroendocrine tumours that are only recently becoming characterised at the molecular level. Notably data on the molecular events that precipitate altered gene expression programmes are very limited. Here we have identified two discrete L-CD subtypes from transcriptomic and whole-genome DNA methylation data, and comprehensively defined their molecular profiles using Whole-Exome Sequencing (WES) and Single Nucleotide Polymorphism (SNP) genotyping. Subtype (Group) 1 features upregulation of neuronal markers (L-CD-NeU) and is characterised by focal spindle cell morphology, peripheral location (71%), high mutational load (P=3.4x10-4), recurrent copy number alterations and is enriched for Atypical Lung Carcinoids. Group 2 (L-CD-PanC) are centrally located and feature upregulation of pancreatic and metabolic pathway genes concordant with promoter hypomethylation of beta cell and genes related to insulin secretion (P<1x10-6). L-CD-NeU tumours harbour mutations in chromatin remodelling and in SWI/SNF complex members, while L-CD-PanC tumours show aflatoxin mutational signatures and significant DNA methylation loss genome-wide, particularly enriched in repetitive elements (P<2.2 x 10-16). Our findings provide novel insights into the distinct mechanisms of epigenetic dysregulation in these lung malignancies, potentially opening new avenues for biomarker selection and treatment in L-CD patients.

category: genetic and genomic medicine


title: A Proteogenomic Signature of Age-related Macular Degeneration in Blood

abstract: Age-related macular degeneration (AMD) is one of the most frequent causes of visual impairment in the elderly population. The overall etiology of AMD is complex and still poorly understood, though age, obesity, smoking, and high-density lipoprotein are known risk factors. In one of the first successful reported genome-wide association studies (GWAS), common genetic variants were strongly associated with AMD, including variants within the complement factor H (CFH) gene. To date, 34 genomic regions have been linked to AMD; however, the genes that mediate the risk remain largely unknown, indicating that novel approaches to identifying causal candidates are needed. Recent advances in proteomic technology have exposed the serum proteomes depth and complexity. In the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), a broad population-based study of the elderly (N = 5764), levels of 4137 human serum proteins and associated networks were integrated with established genetic risk loci for AMD, revealing many predicted as well as novel proteins and pathways, linked to the disease. Serum proteins were also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study of five proteins associated with AMD found CFHR1, CFHR5, and FUT5 to be causally related to the disease, all of which were directionally consistent with the observational estimates. This study provides a robust and unique framework for elucidating the pathobiology of AMD.


title: Genetic influences on the intrinsic and extrinsic functional organizations of the cerebral cortex

abstract: The human cerebral cortex plays a crucial role in brain functions. However, genetic influences on the human cortical functional organizations are not well understood. Using a parcellation-based approach with resting-state and task-evoked functional magnetic resonance imaging (fMRI) from 40,253 individuals, we identified 47 loci associated with functional areas and networks at rest, 15 of which also affected the functional connectivity during task performance. Heritability and locus-specific genetic effects patterns were observed across different brain functional areas and networks. Specific functional areas and networks were identified to share genetic influences with cognition, mental health, and major brain disorders (such as Alzheimers disease and schizophrenia). For example, in both resting and task fMRI, the APOE {varepsilon}4 locus strongly associated with Alzheimers disease was particularly associated with the visual cortex in the secondary visual and default mode networks. In summary, by analyzing biobank-scale fMRI data in high-resolution brain parcellation, this study advances our understanding of the genetic determinants of cerebral cortex function and prioritizes genetically associated fMRI traits for clinical applications of specific brain disorders.


title: Semantic modelling of Common Data Elements for Rare Disease registries, and a prototype workflow for their deployment over registry data

abstract:
BackgroundThe European Platform on Rare Disease Registration (EU RD Platform) aims to address the fragmentation of European rare disease (RD) patient data, scattered among hundreds of independent and non-coordinating registries, by establishing standards for integration and interoperability. The first practical output of this effort was a set of 16 Common Data Elements (CDEs) that should be implemented by all RD registries. Interoperability, however, requires decisions beyond data elements - including data models, formats, and semantics. Within the European Joint Programme on Rare Disease (EJP RD), we aim to further the goals of the EU RD Platform by generating reusable RD semantic model templates that follow the FAIR (Findable, Accessible, Interoperable, and Reusable) Data Principles.

ResultsThrough a team-based iterative approach, we created semantically grounded models to represent each of the CDEs, using the SemanticScience Integrated Ontology (SIO) as the core framework for representing the entities and their relationships. Within that framework, we mapped the concepts represented in the CDEs, and their possible values, into domain ontologies such as the Orphanet Rare Disease Ontology, Human Phenotype Ontology and National Cancer Institute Thesaurus. Finally, we created an exemplar, reusable ETL pipeline that we will be deploying over these non-coordinating data repositories to assist them in creating model-compliant FAIR data without requiring site-specific coding nor expertise in Linked Data or FAIR.

ConclusionsWithin the EJP RD project, we determined that creating reusable, expert-designed templates reduced or eliminated the requirement for our participating biomedical domain experts and rare disease data hosts to understand description logic semantics. This enabled them to publish highly expressive FAIR data using tools and approaches that were already familiar to them.


title: Purifying selection determines the short-term time dependency of evolutionary rates in SARS-CoV-2 and pH1N1 influenza

abstract: High throughput sequencing enables rapid genome sequencing during infectious disease outbreaks and provides an opportunity to quantify the evolutionary dynamics of pathogens in near real-time. One difficulty of undertaking evolutionary analyses over short timescales is the dependency of the inferred evolutionary parameters on the timespan of observation. Here, we characterise the molecular evolutionary dynamics of SARS-CoV-2 and 2009 pandemic H1N1 (pH1N1) influenza during the first 12 months of their respective pandemics. We use Bayesian phylogenetic methods to estimate the dates of emergence, evolutionary rates, and growth rates of SARS-CoV-2 and pH1N1 over time and investigate how varying sampling window and dataset sizes affects the accuracy of parameter estimation. We further use a generalised McDonald-Kreitman test to estimate the number of segregating non-neutral sites over time. We find that the inferred evolutionary parameters for both pandemics are time-dependent, and that the inferred rates of SARS-CoV-2 and pH1N1 decline by [~]50% and [~]100%, respectively, over the course of one year. After at least 4 months since the start of sequence sampling, inferred growth rates and emergence dates remain relatively stable and can be inferred reliably using a logistic growth coalescent model. We show that the time-dependency of the mean substitution rate is due to elevated substitution rates at terminal branches which are 2-4 times higher than those of internal branches for both viruses. The elevated rate at terminal branches is strongly correlated with an increasing number of segregating non-neutral sites, demonstrating the role of purifying selection in generating the time-dependency of evolutionary parameters during pandemics.


title: regentrans: a framework and R package for using genomics to study regional pathogen transmission

abstract:
Increasing evidence of regional pathogen transmission networks highlights the importance of investigating the dissemination of multidrug-resistant organisms (MDROs) across a region to identify where transmission is occurring and how pathogens move across regions. We developed a framework for investigating MDRO regional transmission dynamics using whole-genome sequencing data and created regentrans, an easy-to-use, open source R package that implements these methods (https://github.com/Snitkin-Lab-Umich/regentrans). Using a dataset of over 400 carbapenem-resistant Klebsiella pneumoniae isolates collected from patients in 21 long-term acute care hospitals over a one-year period, we demonstrate how to use our framework to gain insights into differences in inter- and intra-facility transmission across different facilities and over time. This framework and corresponding R package will allow investigators to better understand the origins and transmission patterns of MDROs, which is the first step in understanding how to stop transmission at the regional level.

Impact statementIncreasing evidence suggests that pathogen transmission occurs across healthcare facilities. Genomic epidemiologic investigations into regional transmission shed light on potential drivers of regional prevalence and can inform coordinated interventions across healthcare facilities to reduce transmission. Here we present a framework for studying regional pathogen transmission using whole-genome sequencing data, and a corresponding open-source R package, regentrans, that implements these methods to streamline analyses and make them more accessible to other researchers and public health practitioners. We also discuss how these methods can be extended to study transmission in other settings.

Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

O_LIThe regentrans R package can be downloaded from GitHub: https://github.com/Snitkin-Lab-Umich/regentrans/
C_LIO_LIThe manuscript figures are generated from regentrans example data and can also be found on GitHub: https://github.com/Snitkin-Lab-Umich/regentrans/tree/master/vignettes/manuscript_figures
C_LIO_LIThe example data used in the package and manuscript is from BioProject accession no. PRJNA415194. The specific SRA accession numbers can be found in supplementary file S1. The metadata corresponding to these sequences can be found on the SRA Run Selector (isolate column) and as example data in the regentrans package.
C_LIO_LIThe KPNIH1 sequence was used as the reference genome (SRA accession number SRZ080789)
C_LI


title: Modelling the effect of infection prevention and control measures on rate of Mycobacterium tuberculosis transmission to clinic attendees in primary health clinics in South Africa

abstract:
BackgroundElevated rates of tuberculosis in health care workers demonstrate the high rate of Mycobacterium tuberculosis (Mtb) transmission in health facilities in high burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on Mtb transmission to patients and other clinic attendees.

MethodsAn individual-based model of patient movements through clinics, ventilation in waiting areas, and Mtb transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa. Seven interventions - co-developed with health professionals and policy-makers - were simulated: 1. queue management systems with outdoor waiting areas, 2. ultraviolet germicidal irradiation systems (UVGI), 3. appointment systems, 4. opening windows and doors, 5. surgical mask wearing by clinic attendees, 6. simple clinic retrofits, and 7. increased coverage of long antiretroviral therapy prescriptions and community medicine collection points through the CCMDD service.

ResultsIn the model, 1. outdoor waiting areas reduced the transmission to clinic attendees by 83% (interquartile range [IQR] 76-88%), 2. UVGI by 77% (IQR 64-85%), 3. appointment systems by 62% (IQR 45-75%), 4. opening windows and doors by 55% (IQR 25-72%), 5. masks by 47% (IQR 42-50%), 6. clinic retrofits by 45% (IQR 16-64%), and 7. increasing the coverage of CCMDD by 22% (IQR 12-32%).

ConclusionsThe majority of the interventions achieved median reductions in the rate of transmission to clinic attendees of at least 45%, meaning that a range of highly effective intervention options are available, that can be tailored to the local context. Measures that are not traditionally considered to be IPC interventions, such as appointment systems, may be as effective as more traditional IPC measures, such as mask wearing.


title: Assessment of knowledge, attitude, and practices of Tuberculosis patients towards DOTs regimen in Jimma health center, Jimma zone, southwest Ethiopia

abstract:
ObjectiveGlobally, tuberculosis (TB) is one of a chronic infectious disease, which has a major health burden. Thus, 9.4 million incidents and 14 million prevalent cases were reported in 2010. The high burden of TB is common in sub-Saharan Africa countries, including Ethiopia. The purpose of conducting this study was to assess the knowledge, attitude, and practices of TB patients towards DOTs regimen. The other objective of the study was to assess the attitude of patients towards causative factor and its treatment.

ResultsThe result of the study showed that 103 (68.7%) of patients scored high knowledge status, whereas 47 (31.3%) of them scored low. 25(16.7%) governmental employee had overall high knowledge status. 101 (67.3%) of the patient scored high overall attitude, while 49 (32.7%) of them scored low overall attitude. 85 (56.7%) of patients scored high overall practices, whereas 65(43.3%) of them scored low overall practices.In this study, the knowledge and attitude of patients about TB and its treatment was found within low level of perception. Therefore, implementation of health education and awareness creation are required to avoid the problem of patients.


title: Statistical Analysis Plan for the Helmet Non-Invasive Ventilation for COVID-19 Patients (Helmet-COVID) Randomized Controlled Trial

abstract:
Background and objectiveNoninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation having multiple advantages over other support modalities but data about effectiveness are limited.

MethodsIn this multicenter randomized trial of helmet non-invasive ventilation for COVID-19 patients (Helmet-COVID), 320 adult ICU patients with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (with a ratio of arterial oxygen partial pressure to fraction (percent) of inspired oxygen (PaO2/FiO2) <200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate >10 L/min or above) will be randomized to helmet-noninvasive ventilation with usual care or usual care alone. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction from 40% to 25%.

ConclusionConsistent with international guidelines, we developed a detailed plan to guide the analysis of the Helmet-COVID trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes to facilitate unbiased analyses of clinical data.

Trial registrationClinicaltrials.gov: NCT04477668 (registered on July 20, 2020)

category: intensive care and critical care medicine


title: Predictors of Premature Discontinuation of Opioid Use Disorder Treatment in the United States

abstract: Over the last few decades, opioid use disorder (OUD) and overdose have dramatically increased. Evidence shows that treatment for OUD, particularly medication for OUD, is highly effective; however, despite decreases in barriers to treatment, retention in OUD treatment remains a challenge. Therefore, understanding key risk factors for OUD treatment discontinuation remains a critical priority. We built a machine learning model using the Treatment Episode Data Set - Discharge (TEDS-D). Included were 2,446,710 treatment episodes for individuals in the U.S. discharged between January 1, 2015 and December 31, 2018 (the most recent available data). Exposures contain 32 potential risk factors, including treatment characteristics, substance use history, socioeconomic status, and demographic characteristics. Our findings show that the most influential risk factors include characteristics of treatment service setting, geographic region, primary source of payment, referral source, and health insurance status. Importantly, several factors previously reported as influential predictors, such as age, living situation, age of first substance use, race and ethnicity, and sex had far weaker predictive impacts. The influential factors identified in this study should be more closely explored to inform targeted interventions and improve future models of care.

category: addiction medicine


title: COVID-19 in Londrina-PR-Brazil: SEIR Model with Parameter Optimization

abstract: The first cases of COVID-19 in Londrina-PR were manifested in March 2020 and the disease lasts until the present moment. We aim to inform citizens in a scientific way about how the disease spreads. The present work seeks to describe the behavior of the disease over time. We started from a compartmental model of ordinary differential equations like SEIR to find relevant information such as: transmission rates and prediction of the peak of infected people. We used the data released by city hall of Londrina to carry out simulations in periods of 14 days, applying a parameter optimization technique to obtain results with the greatest possible credibility.


title: Predictive modelling of highly multiplexed tumour tissue images by graph neural networks

abstract: The progression and treatment response of cancer largely depends on the complex tissue structure that surrounds cancer cells in a tumour, known as the tumour microenvironment (TME). Recent technical advances have led to the development of highly multiplexed imaging techniques such as Imaging Mass Cytometry (IMC), which capture the complexity of the TME by producing spatial tissue maps of dozens of proteins. Combining these multidimensional cell phenotypes with their spatial organization to predict clinically relevant information is a challenging computational task and so far no method has addressed it directly. Here, we propose and evaluate MULTIPLAI, a novel framework to predict clinical biomarkers from IMC data. The method relies on attention-based graph neural networks (GNNs) that integrate both the phenotypic and spatial dimensions of IMC images. In this proof-of- concept study we used MULTIPLAI to predict oestrogen receptor (ER) status, a key clinical variable for breast cancer patients. We trained different architectures of our framework on 240 samples and benchmarked against graph learning via graph kernels. Propagation Attribute graph kernels achieved a class-balanced accuracy of 66.18% in the development set (N=104) while GNNs achieved a class-balanced accuracy of 90.00% on the same set when using the best combination of graph convolution and pooling layers. We further validated this architecture in internal (N=112) and external test sets from different institutions (N=281 and N=350), demonstrating the generalizability of the method. Our results suggest that MULTIPLAI captures important TME features with clinical importance. This is the first application of GNNs to this type of data and opens up new opportunities for predictive modelling of highly multiplexed images.

category: pathology


title: Duchenne muscular dystrophy patients lacking the dystrophin isoforms Dp140 and Dp71 and mouse models lacking Dp140 have a more severe motor phenotype

abstract:
BackgroundDuchenne muscular dystrophy (DMD) is caused by DMD mutations leading to dystrophin loss. Full length Dp427 is the primary dystrophin isoform expressed in skeletal muscle and is also expressed in the central nervous system (CNS). Two shorter isoforms, Dp140 and Dp71, are highly expressed in the CNS. While a role for Dp140 and Dp71 on DMD CNS co-morbidities is well known, relationships between lack of Dp140 and Dp71 and DMD motor outcomes are not. We have conducted a series of investigations addressing this.

MethodsFunctional outcome data from 387 DMD boys aged 4.0-15.4 years was subdivided by DMD mutation expected effect on isoform expression; Group 1 (Dp427 absent, Dp140/Dp71 present, n=201); group 2 (Dp427/Dp140 absent, Dp71 present, n=152); and group 3 (Dp427/Dp140/Dp71 absent, n=34). Relationships between isoform group and North Star ambulatory assessment (NSAA) scores, 10m walk/run and rise times were explored using regression analysis. We used Capillary Western immunoassay (Wes) analysis to study Dp427, Dp140 and Dp71 production in wild-type and DMD skeletal muscle and myogenic cultures. Grip strength was studied in wild-type, mdx (Dp427 absent, Dp140/Dp71 present), mdx52 (Dp427/Dp140 absent, Dp71 present) and DMD-null (lacking all isoforms) mice.

ResultsIn DMD boys, we found a strong association between isoform group and motor function. In DMD boys, mean NSAA scores at 5 years of age were 6.1 points lower in group 3 than group 1 (p<0.01) and 4.9 points lower in group 3 than group 2 (p=0.05). Mean peak NSAA scores were 4.0 points lower in group 3 than group 1 (p<0.01), 2.4 points lower in group 3 than group 2 (p=0.09) and 1.6 points lower in group 2 than group 1 (p=0.04).

Average grip strength in peak force at 3 months of age was higher in mdx than mdx52 mice (p=0.01).

Dp427, but not Dp71, was produced in normal skeletal muscle; low levels of Dp71 were detected in DMD skeletal muscle. High Dp71 levels were present in wild-type and DMD myogenic cultures.

ConclusionsDMD boys lacking Dp140 and Dp140/Dp71 displayed worse motor function with a cumulative effect of isoform loss. DMD mouse models lacking Dp427 and Dp140 had lower grip strength than those lacking Dp427 but not Dp140. Our results highlight the importance of considering the effects of dystrophin isoform loss on DMD motor impairment, with important implications for understanding the complex relationship between brain and muscle function in DMD and patient stratification for clinical trials.

category: pediatrics


title: Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of highly active anti-retroviral therapy

abstract: HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to disease caused by encapsulated bacteria in the first year of life. The mechanism of this increased risk is still poorly understood. We therefore investigated if HIV exposure dysregulates HEU infant immunity and if this is amplified by human herpes virus infection (HHV). Here, we compared monocyte enzymatic function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HUU infants. We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HUU infants. There was no difference in the prevalence of HHV infection between HEU and HUU infants. Our findings suggest that even in the era of antiretroviral therapy (ART)-mediated viral suppression, HIV exposure dysregulates monocyte and B cell function during a vulnerable period of immune maturation in infancy. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.


title: Stakeholders' perception of possible integration pathways for eye health into school health programme in Zanzibar: a qualitative health system research

abstract:
PurposeTo scope the potential for eye health programme to be integrated into Zanzibar School Health programme, through the lenses of stakeholders

MethodsEmbedded into an operational research project integrating eye and School health, we elicited responses from 83 participants, purposefully selected from the Ministry of Health (n=7), Ministry of Education and Vocational Training (n=7), hospitals/eye centres (n=5), master trainers (4) and schools (n=60) participated in in-depth interviews. Their responses were analysed and grouped into four pre-determined themes of Human Resource Training, Resources Mobilisation, Acceptability, and Leadership and Governance. Quotations are presented to illustrate the findings.

ResultsIn line with the four research themes, i) The integrated school eye health programme training was satisfactory, with room for improvement, ii) Child eye health screening conducted by teachers was well-received, with concerns and suggestions to improve its effectiveness and efficiency, iii) Integration of eye health into the school health programme is perceived as a good initiative, but to increase referral, service uptake and spectacle usage, primary care units must be equipped, and eye health awareness needs to be improved, iv) Departmental roles, resources, gaps and synergies to ensure eye health is successfully integrated into the school health programme.

ConclusionThe concept of integrated school eye health delivery is generally well-received by beneficiaries and stakeholders within an operational research project in Zanzibar, with the caveat that investment is required for effective referral and update.


title: Development of a High-Performance Multiparametric MRI Oropharyngeal Primary Tumor Auto-Segmentation Deep Learning Model and Investigation of Input Channel Effects: Results from a Prospective Imaging Registry

abstract:
Background and PurposeOropharyngeal cancer (OPC) primary gross tumor volume (GTVp) segmentation is crucial for radiotherapy. Multiparametric MRI (mpMRI) is increasingly used for OPC adaptive radiotherapy but relies on manual segmentation. Therefore, we constructed mpMRI deep learning (DL) OPC GTVp auto-segmentation models and determined the impact of input channels on segmentation performance.

Materials and MethodsGTVp ground truth segmentations were manually generated for 30 OPC patients from a clinical trial. We evaluated five mpMRI input channels (T2, T1, ADC, Ktrans, Ve). 3D Residual U-net models were developed and assessed using leave-one-out cross-validation. A baseline T2 model was compared to mpMRI models (T2+T1, T2+ADC, T2+Ktrans, T2+Ve, all 5 channels [ALL]) primarily using the Dice similarity coefficient (DSC). Sensitivity, positive predictive value, Hausdorff distance (HD), false-negative DSC (FND), false-positive DSC, surface DSC, 95% HD, and mean surface distance were also assessed. For the best model, ground truth and DL-generated segmentations were compared through a Turing test using physician observers.

ResultsModels yielded mean DSCs from 0.71 (ALL) to 0.73 (T2+T1). Compared to the T2 model, performance was significantly improved for HD, FND, sensitivity, surface DSC, and 95% HD for the T2+T1 model (p<0.05) and for FND for the T2+Ve and ALL models (p<0.05). There were no differences between ground truth and DL-generated segmentations for all observers (p>0.05).

ConclusionDL using mpMRI provides high-quality segmentations of OPC GTVp. Incorporating additional mpMRI channels may increase the performance of certain evaluation metrics. This pilot study is a promising step towards fully automated MR-guided OPC radiotherapy.


title: Association of acute kidney injury with the risk of dementia: A meta-analysis protocol

abstract: Acute kidney injury (AKI) is a complex disorder characterized by an abrupt decline in kidney function over a short period of time. Published epidemiological studies linked AKI with the development of dementia. This meta-analysis aims to understand the pooled risk of dementia in AKI patients compared to non-AKI patients. MEDLINE and Embase databases, and the grey literature in five sources were searched to identify the studies assessing the association of AKI with dementia. The Newcastle-Ottawa scale (NOS) will be used to determine the quality of included studies. The primary outcome of this study will be the risk of dementia among AKI patients compared to non-AKI patients. Subgroup analysis and sensitivity analysis will also be performed. Review Manager version 5.4.1 will be used to perform the meta-analysis.

category: nephrology


title: Coronavirus vaccination rates in cultural areas in Germany

abstract: Vaccination rates can provide useful information about potential risks of infection in a given population. In this study, the vaccination rates and attitudes toward vaccination in cultural sectors, i.e. music areas, have been investigated. In total, 4341 persons in four different areas including visitors of classical music and musicals as well as professional and amateur musicians participated in this survey. Results showed rates of 86% recovered or vaccinated at least once and 54.5% fully vaccinated. These vaccination rates were considerably higher compared to the general population. Vaccination hesitancy was half that of the general population at 6.4%. The findings of this large sample indicate that in the field of music culture there is a high vaccination rate and a low rejection of vaccination on the part of the audience and the performers. The risk of infection can therefore be assumed as very low and the opening of cultural events can thus be recommended.