title: Impact of the early stages of the COVID-19 pandemic on coverage of RMNH interventions in Ethiopia

abstract:
BackgroundThe COVID-19 pandemic and response have the potential to disrupt access and use of reproductive, maternal, and newborn health (RMNH) services. Numerous initiatives aim to gauge the indirect impact of COVID-19 on RMNH.

MethodsWe assessed the impact of COVID-19 on RMNH coverage in the early stages of the pandemic using panel survey data from PMA-Ethiopia. Enrolled pregnant women were surveyed 6-weeks post-birth. We compared the odds of service receipt, coverage of RMNCH service indicators, and health outcomes within the cohort of women who gave birth prior to the pandemic and the COVID-19 affected cohort. We calculated impacts nationally and by urbanicity.

ResultsThis dataset shows little disruption of RMNH services in Ethiopia in the initial months of the pandemic. There were no significant reductions in women seeking health services or the content of services they received for either preventative or curative interventions. In rural areas, a greater proportion of women in the COVID-19 affected cohort sought care for peripartum complications, ANC, PNC, and care for sick newborns. Significant reductions in coverage of BCG vaccination and chlorohexidine use in urban areas were observed in the COVID-19 affected cohort. An increased proportion of women in Addis Ababa reported postpartum family planning in the COVID-19 affected cohort. Despite the lack of evidence of reduced health services, the data suggest increased stillbirths in the COVID-19 affected cohort.

DiscussionThe government of Ethiopias response to control the COVID-19 pandemic and ensure continuity of essential health services appears to have successfully averted most negative impacts on maternal and neonatal care. This analysis cannot address the later effects of the pandemic and may not capture more acute or geographically isolated reductions in coverage. Continued efforts are needed to ensure that essential health services are maintained and even strengthened to prevent indirect loss of life.

What is already known?O_LICOVID-19 pandemic and response have the potential to disrupt access and use of reproductive, maternal, and neonatal health services
C_LIO_LIAnecdotal evidence suggests some disruptions to health system staffing and resources, service access, and health campaigns in Ethiopia early in the pandemic
C_LI

What are the new findings?O_LIOur analysis of PMA-Ethiopia panel survey data shows little disruption of RMNH services in Ethiopia in the initial months of the pandemic
C_LIO_LICompared to immediately prior to the pandemic we observed an increase in care-seeking in rural areas, commodity-related intervention reductions in urban areas, and an increase in postpartum family planning in Addis Ababa
C_LIO_LIDespite the lack of evidence of a reduction in health services, the data suggest increased stillbirths in the COVID-19 affected cohort
C_LI

What do the new findings imply?O_LIThe government of Ethiopia successfully maintained continuity of most RMNCH services during the early stages of the COVID-19 pandemic
C_LIO_LIContinued efforts are needed to ensure that essential health services are maintained and even strengthened to prevent indirect loss of life
C_LI

category: public and global health


title: Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the PKC inhibitor ruboxistaurin.

abstract: Neutrophil extracellular traps (NETs) are web-like DNA and protein lattices which are expelled by neutrophils to trap and kill pathogens, but which cause significant damage to the host tissue. NETs have emerged as critical mediators of lung damage, inflammation and thrombosis in COVID-19 and other diseases, but there are no therapeutics to prevent or reduce NETs that are available to patients. Here, we show that neutrophils isolated from hospitalised patients with COVID-19 produce significantly more NETs in response to LPS compared to cells from healthy control subjects. A subset of patients were captured at follow-up clinics (3-4 month post-infection) and while LPS-induced NET formation is significantly lower at this time point, it remains elevated compared to healthy controls. LPS- and PMA-induced NETs were significantly inhibited by the protein kinase C (PKC) inhibitor ruboxistaurin. Ruboxistaurin-mediated inhibition of NETs in healthy neutrophils reduces NET-induced epithelial cell death. Our findings suggest ruboxistaurin could reduce proinflammatory and tissue-damaging consequences of neutrophils during disease, and since it has completed phase III trials for other indications without safety concerns, it is a promising and novel therapeutic strategy for COVID-19.

category: respiratory medicine


title: Twenty years review of probiotic meta-analyses articles: Effects on disease prevention and treatment

abstract: The study of the probiotic effect in the prevention or treatment of diseases has long attracted the attention of many researchers. Here, we collected close to 300 meta-analysis articles for 20 years, investigating the effect of probiotics in the prevention and treatment of diseases. The goal of this study is to provide an overview of all meta-analysis articles of the effects of probiotics on various human diseases. For this purpose, different online databases, Pubmed, ScienceDirect, and Google Scholar, were searched with the keywords "probiotics" + "disease" + "meta-analysis" in the title, abstract, and keywords. Papers studied and categorized and investigated in order to present valuable insights for researchers in the field. Some of main categories are based on publication year, publishing journals, gender, age, effect type, disease type, contradicting reports and etc. According to the results, most meta-analyses indicated probiotics were 79% effective in preventing or treating the diseases. Some articles have also reported no positive effects, but there is not any paper in our study confirming the detrimental influence of probiotic effect on human health. For the future works, Cochrane reviews, meta-analysis including dozens of articles (as e.g. for NEC and AAD) may be investigated.

category: nutrition


title: Data Preparation of the nuMoM2b Dataset

abstract: In 2010, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) started the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), a prospective cohort study of a racially/ethnically/geographically diverse population of nulliparous women with singleton gestation. The nuMoM2b is a very large dataset, consisting of data for 10,038 patients with over 4,600 features per patient, spread out over 80 files. In this report, we share our experience preparing and working with this dataset. We present our data preprocessing of the nuMoM2b dataset to get a deeper understanding of the data, extract the most relevant features, make the fewest assumptions when filling in unknown values, and reducing the dimensionality of the data. We hope this report is useful to researchers interested in building machine learning and statistical models from the nuMoM2b dataset.

category: obstetrics and gynecology


title: Motor Learning in Response to Different Experimental Pain Models among Healthy Individuals: A Systematic Review

abstract: Learning new movement patterns is a normal part of daily life, but of critical importance in both sport and rehabilitation. A major question is how different sensory signals are integrated together to give rise to motor adaptation and learning. More specifically, there is growing evidence that pain can give rise to alterations in the learning process. Despite a number of studies investigating the role of pain on the learning process, there is still no systematic review to summarize and critically assess investigations regarding this topic in the literature. Here in this systematic review, we summarize and critically evaluate studies that examined the influence of experimental pain on motor learning. Seventeen studies that exclusively assessed the effect of experimental pain models on motor learning among healthy individuals were included for this systematic review, carried out based on the PRISMA statement. The results of the review revealed there is no consensus regarding the effect of pain on the skill learning acquisition and retention. However, several studies demonstrated that participants who experienced pain continued to express a changed motor strategy to perform a motor task even one week after training under the pain condition. The results highlight a need for further studies in this area of research, and specifically to investigate whether pain has different effects on motor learning depending on the type of motor task.

category: pain medicine


title: COMORBIDITY ANALYSIS: OVERLAPPING SEMICIRCLES WITH WIGNER LAW AND RANDOM MATRIX THEORY

abstract: In December 2019 COVID-19 appeared as a new pandemic that has claimed the lives of millions of people around the world. This article presents a regional analysis of COVID-19 in Mexico. Due to the comorbidities of Mexican society, the new pandemic implies a higher risk for the population. The study period runs from April 12 to October 5, 2020 (761 665 Patients). In this proposal we apply a unique methodology of random matrix theory in the moments of a probability measure that appears as the limit of the empirical spectral distribution by the Wigner semicircle law. The graphical presentation of the results is done with Machine Learning methods in the SuperHeat maps. With this is possible to analyze the behavior of patients who tested positive for COVID-19 and their comorbidities. We conclude that the most sensitive comorbidities in hospitalized patients are the following three: COPD, Other Diseases and Renal Diseases.

category: health informatics


title: Monitoring socioeconomic inequalities across HIV knowledge, attitudes, behaviours and prevention: results from cross-sectional surveys in 18 sub-Saharan African countries

abstract:
ObjectivesSocioeconomic inequalities in HIV prevention services coverage constitute important barriers to global prevention targets, especially in sub-Saharan Africa (SSA). We aimed at monitoring these inequalities from population-based survey data in 18 SSA countries between 2010 and 2018.

MethodsWe defined eight HIV indicators aimed at capturing uptake of HIV prevention services among adult participants. Country-specific wealth-related inequalities were measured using the Relative and Slope Index of Inequalities (RII and SII, respectively) and then pooled using random-effects meta-analyses. We compared inequalities between African regions using the Wilcoxon rank-sum test.

ResultsThe sample consisted of 358,591 participants (66% women). Despite variability between countries and indicators, the meta-analysis revealed significant levels of relative and absolute inequalities in 6 out of 8 indicators: HIV-related knowledge, positive attitudes toward people living with HIV (PLHIV), condom use at last sexual intercourse, participation to prevention of mother-to-child transmission programs, medical male circumcision and recent HIV testing. The largest inequalities were reported in condom use, with condom use reported 5 times more among the richest versus the poorest (RII=5.02, 95% Confidence interval, CI: 2.79-9.05) and in positive attitudes toward PLHIV, with a 32-percentage point difference between the richest and poorest (SII=0.32, 95% CI: 0.26-0.39). Conversely, no significant inequalities were observed in multi-partnership and HIV seropositivity among youth. Overall, inequalities tended to be larger in West and Central vs. East and Southern African countries.

ConclusionsDespite efforts to scale-up HIV-prevention programs, socioeconomic inequalities remain substantial over the continuum of HIV primary and secondary prevention in several SSA countries.

category: hiv aids


title: Monitoring socioeconomic inequalities across HIV knowledge, attitudes, behaviours and prevention in 18 sub-Saharan African countries


title: Use of HIV Recency Assays for HIV Incidence Estimation and Non-Incidence Surveillance Use Cases: A systematic review

abstract:
IntroductionHIV assays designed to detect recent infection, also known as "recency assays," are often used to estimate HIV incidence in a specific country, region, or subpopulation, alone or as part of recent infection testing algorithms (RITAs). Recently, many countries and organizations have become interested in using recency assays within case surveillance systems and routine HIV testing services, and in measuring other indicators beyond incidence, generally referred to as "non-incidence surveillance use cases."

MethodsTo identify best methodological and field implementation practices for the use of recency assays to estimate HIV incidence and trends in recent infections for key populations or specific geographic areas, we undertook: 1) a global Call for Information released from WHO/UNAIDS; and 2) a systematic review of the literature to: (a) assess the field performance characteristics of commercially available recency assays, (b) understand the use of recency testing for surveillance in programmatic and laboratory settings, and (c) review methodologies for implementing recency testing for both incidence estimation and non-incidence use cases.

Results and discussionAmong the 90 documents ultimately reviewed, 65 (88%) focused on assay/algorithm performance or methodological descriptions, with high-quality evidence of accurate age- and sex- disaggregated HIV incidence estimation at national or regional levels in general population settings, but not at finer geographic levels for prevention prioritization. The remaining 25 documents described field-derived incidence (n=14) and non-incidence (n=11) use cases, including integrating RITAs into routine surveillance and assisting with molecular genetic analyses, but evidence was generally weaker or only reported on what was done, without validation data or findings related to effectiveness of recency assays when used for these purposes.

ConclusionsHIV recency assays have been widely validated for estimating HIV incidence in age- and sex-specific populations at national and sub-national regional levels; however, there was a lack of evidence validating the accuracy and effectiveness of using recency assays for non-incidence surveillance use cases. The evidence identified through this review will be used in forthcoming technical guidance on the use of HIV recency assays for surveillance use cases by WHO and UNAIDS; further evidence on methodologies and effectiveness of non-incidence use cases is needed.


title: Community-Based Accompaniment for Adolescents Transitioning to Adult HIV Care in Urban Peru: a Pilot Study

abstract:
IntroductionAdolescents living with HIV (ALWH) face an elevated risk of poor health outcomes when transitioning into adult-oriented care; however, evidence-based interventions to support ALWH during this high-risk period are lacking, especially in Latin America. We conducted a pilot study of a community-based intervention designed to improve outcomes among ALWH transitioning to adult HIV care in Lima, Peru.

MethodsFrom October 2019 to January 2020, we enrolled adolescents transitioning to adult HIV care, either due to a recent diagnosis or having aged out of their pediatric clinic. ALWH previously lost from care during the transition process were also invited to participate. The nine-month intervention consisted of (1) logistical, adherence and social support delivered by entry-level health workers who accompanied adolescents during their transition to adult HIV care and (2) group sessions to improve health-related knowledge, skills and social support. We assessed intervention feasibility and effectiveness in improving medication adherence, psycho-social outcomes, and transition readiness after 6, 9, and 12 months.

ResultsWe enrolled 30 ALWH, ages 15-21 years; 11 were recently diagnosed and 19 had been living with HIV since infancy or early childhood. Participants included ten men who have sex with men, four young pregnant women and six adolescents who were previously lost during the transition to adult HIV care. Intervention participation was high with 90% of ALWH attending at least one in-person social support session and all attending at least one live online session. No ALWH withdrew from the intervention, study, or antiretroviral therapy. In transition readiness, we observed within-person improvements related to personal health (+1.9 points, p<0.001), healthcare usage (+2.4 points, p<0.001), knowledge (+3.3 points, p=0.001), and behavior (+3 points, p=0.003) at the end of the intervention, relative to baseline. We also observed strong evidence of improvements in medication adherence, social support, self-efficacy, and perceived stress, which were generally sustained three months after intervention cessation.

ConclusionWe identified a community-based intervention that is feasible and potentially effective for bridging the transition to adult HIV care among a diverse group of ALWH in Peru. A larger-scale effectiveness evaluation, including biological endpoints, is warranted.


title: Shared HIV envelope-specific B cell clonotypes induced by a pox-protein vaccine regimen

abstract: An effective HIV-1 vaccine will likely induce potent, broad neutralizing antibodies. No candidate vaccines have elicited these responses presumably because they fail to activate human B cell precursors that can affinity mature to generate broad neutralizing antibodies. To identify the B cell clonotypes that are elicited, we conducted in-depth analyses of the envelope-specific B cell repertoire in recipients of ALVAC-HIV vector (vCP2438) and bivalent subtype C gp120 protein (HVTN100). We observed high frequencies of envelope-specific IgG+ memory B cells with restricted immunogenetic diversity, relative to non-vaccine induced memory B cells, with preferential expansions of distinct variable genes but limited accumulation of mutations. Many envelope-specific clonotypes were shared across vaccinees, but did not overlap with the envelope-negative memory repertoire, within and across subjects. Single-cell sequencing of envelope-specific IgG+ memory B cells often revealed VH1-2*02 and VK3-20 sequence co-expression and in one case, contained a 5 amino acid CDRL3, the canonical signature of VRC01-class antibodies, confirming that these B cells are extremely rare but detectable. Our study provides evidence that immunogens play a critical role in selecting and restricting the responding B cell repertoire and supports the rational design of HIV vaccines targeting specific B cell lineages for induction of broadly-reactive neutralizing antibodies.


title: Evaluation of GENECUBE(R) HQ SARS-CoV-2 for anterior nasal samples and saliva samples with a new rapid examination protocol

abstract:
IntroductionGENECUBE(R) is a rapid molecular identification system, and previous studies demonstrated that GENECUBE(R) HQ SARS-CoV-2 showed excellent analytical performance for the detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with nasopharyngeal samples. However, other respiratory samples have not been evaluated.

MethodsThis prospective comparison between GENECUBE(R) HQ SARS-CoV-2 and reference real-time reverse transcriptase polymerase chain reaction (RT-PCR) was performed for the detection of SARS-CoV-2 using anterior nasal samples and saliva samples. Additionally, we evaluated a new rapid examination protocol using GENECUBE(R) HQ SARS-CoV-2 for the detection of SARS-CoV-2 with saliva samples. For the rapid protocol, in the preparation of saliva samples, purification and extraction processes were adjusted, and the total process time was shortened to approximately 35 minutes.

ResultsFor 359 anterior nasal samples, the total-, positive-, and negative concordance of the two assays was 99.7% (358/359), 98.1% (51/52), and 100% (307/307), respectively. For saliva samples, the total-, positive-, and negative concordance of the two assays was 99.6% (239/240), 100% (56/56), and 99.5% (183/184), respectively. With the new protocol, total-, positive-, and negative concordance of the two assays was 98.8% (237/240), 100% (56/56), and 98.4% (181/184), respectively. In all discordance cases, SARS-CoV-2 was detected by additional molecular examinations.

ConclusionGENECUBE(R) HQ SARS-CoV-2 provided high analytical performance for the detection of SARS-CoV-2 in anterior nasal samples and saliva samples.

category: infectious diseases


title: Longevity of SARS-CoV-2 Antibody in Health Care Workers: 6-Months Follow Up

abstract:
The prevalence and longevity of acquired immunity to coronavirus disease 2019 (COVID-19) in health care workers (HCWs) is of great interest, especially with the roll-out of vaccines for SARS-CoV-2. Determining such immunity may enhance knowledge about susceptibility of HCWs to COVID-19, frequency of vaccine administration, and degree of workplace risk, and may also support enactment of better workplace policies and procedures.

The present study reports on 6-months follow-up serosurveillance to determine the longevity of SARS-CoV-2 antibodies in HCWs.

Sub-sample (n=35) of the original serosurveillance in HCWs (n = 3,458) with baseline, 8-week, and 6-month blood sampling were analyzed. Information on job duties, location, COVID-19 symptoms, polymerase chain reaction test history, travel since January 2020, and household contacts with COVID-19 was collected.

Of 35 subjects, 13 were seropositive at baseline and maintained positivity at 8-week follow-up, with 3 losing positivity at 6-month follow-up. Among 22 subjects who were seronegative at baseline and seropositive at 8-week follow-up, all but one maintained positivity at 6-month follow-up. There was no significant effect of all factors (e.g., age, gender, job duties) examined at the .05 level on seropositivity at 6-month follow-up. The observed antibody longevity was 7.0+/-0.6 months for seropositive subjects (n=13), and 4.5+/-0.8 months for those seronegative subjects (n=22), at baseline. The longest duration of seropositivity observed in this cohort was 7.9 months (236 days).

With reported COVID-19-related symptoms up to 4.7 months prior to baseline blood sampling, possibly longer antibody presence is suggested. Similarly, seropositivity at 6-month follow-up further suggests greater antibody longevity than observed in this study.


title: A quantitative evaluation of aerosol generation during manual facemask ventilation

abstract: Manual facemask ventilation, a core component of elective and emergency airway management, is classified as an aerosol generating procedure. This designation is based on a single epidemiological study suggesting an association between facemask ventilation and transmission from the SARS 2003 outbreak. There is no direct evidence to indicate whether facemask ventilation is a high-risk procedure for aerosol generation. We conducted aerosol monitoring during routine facemask ventilation, and facemask ventilation with an intentionally generated leak, in anaesthetised patients with neuromuscular blockade. Recordings were made in ultraclean theatres and compared against the aerosol generated by the patients own tidal breathing and coughs. Respiratory aerosol from tidal breathing was reliably detected above the very low background particle concentrations (191 (77-486 [3.8-1313]) versus 2.1 (0.7-4.6 [0-12.9] particles.l-1 median(IQR)[range], n=11, p=0.002). The average aerosol concentration detected during facemask ventilation both without a leak (3.0 particles.l-1 (0 - 9 [0-43])) and with an intentional leak (11 particles.l-1 (7.0 - 26 [1-62])) was 64-fold and 17-fold lower than that of tidal breathing (p=0.001 and p=0.002 respectively). The peak particle concentration during facemask ventilation both without a leak (60 particles.l-1 (0 - 60 [0-120])) and with a leak (120 particles.l-1 (60 - 180 [60-480]) were respectively 20-fold and 10-fold lower than a cough (1260 particles (800 - 3242 [100-3682]), p=0.002 and p=0.001 respectively). This study demonstrates that facemask ventilation, even performed with an intentional leak, does not generate high levels of bioaerosol. On the basis of this evidence, facemask ventilation should not be considered an aerosol generating procedure.

category: anesthesia


title: The impact of studies with no events in both arms on meta-analysis of rare events: a simulation study using generalized linear mixed model

abstract:
ObjectiveThe common approach to meta-analysis with double-zero studies is to remove such studies. Our previous work has confirmed that exclusion of these studies may impact the results. In this study, we undertook extensive simulations to investigate how the results of meta-analyses would be impacted in relation to the proportion of such studies.

MethodsTwo standard generalized linear mixed models (GLMMs) were employed for the meta-analysis. The statistical properties of the two GLMMs were first examined in terms of percentage bias, mean squared error, and coverage. We then repeated all the meta-analyses after excluding double-zero studies. Direction of estimated effects and p-values for including against excluding double-zero studies were compared in nine ascending groups classified by the proportion of double-zero studies within a meta-analysis.

ResultsBased on 50,000 simulated meta-analyses, the two GLMMs almost achieved unbiased estimation and reasonable coverage in most of the situations. When excluding double-zero studies, 0.00% to 4.47% of the meta-analyses changed the direction of effect size, and 0.61% to 8.78% changed direction of the significance of p-value. When the proportion of double-zero studies increased in a meta-analysis, the probability of the effect size changed the direction increased; when the proportion was about 40% to 60%, it has the largest impact on the change of p-values.

ConclusionDouble-zero studies can impact the results of meta-analysis and excluding them may be problematic. The impact of such studies on meta-analysis varies by the proportion of such studies within a meta-analysis.

category: epidemiology


title: A community based case-control study to determine the risk factors of dengue fever in Bangladesh

abstract:
In a tropical country like Bangladesh where the climatic condition favors the growth of Aedes mosquito vectors, the success of dengue prevention depends largely on the proper identification and controlling of the socio-demographic and lifestyle-related risk factors. A case-control study including 150 cases and 150 controls were conducted aimed to explore the potential risk and protective factors and their association with dengue virus infection in the Chattogram district of Bangladesh. Cases were confirmed for dengue patients admitted in Chattogram medical college hospital and Bangladesh institute of tropical and infectious diseases during August and September 2019. Whereas, controls were non-dengue patients admitted in other departments of the same hospitals through gender age and location matching. The questionnaire data were collected through telephone-based interviews which included information regarding general demography, daily life activities, housing with its surroundings status. Chi-square and binary logistic regression were performed for identifying potential risk factors and their association with the occurrences of dengue fever.

The study found that travel history to the high incidence area, the place of staying most of the time, living in 21 to 40 years old houses, and the temporary residence of the city were statistically significant risk factors for getting the dengue infection. On contrary, Quality of indoor daylight, ventilation, bus stand/garage, stagnant water, and any construction site around 250 meters of the house did not show significant association with dengue fever.


title: Anti-GM-CSF autoantibodies promote a pre-diseased state in Crohns Disease.

abstract:
Background & AimsAnti-GM-CSF autoantibodies (aGMAb) are detected in ileal Crohns Disease (CD) patients. Their induction and mode of action impacting homeostasis during, or prior to disease are not well understood. We aimed to investigate the underlying mechanisms leading to the induction of aGMAb, from functional orientation to recognized epitopes, for their impact on intestinal immune homeostasis and use as predictive biomarker for complicated CD.

MethodsUsing longitudinally collected sera from active component US personnel, we characterize naturally occurring aGMAb in a subset of CD patients years before disease onset. We employed biochemical, cellular, and transcriptional analysis to uncover a mechanism that governs the impaired immune balance in CD years prior to diagnosis.

ResultsNeutralizing aGMAb are specific to posttranslational glycosylations on GM-CSF, detectable years prior to diagnosis, and associated with complicated CD at presentation. Glycosylation and production of GM-CSF change in CD patients, altering myeloid homeostasis and destabilizing group 3 innate lymphoid cells. Perturbations in immune homeostasis precede the inflammation and are detectable in the non-inflamed CD mucosa of patients presenting with anti-GM-CSF autoantibodies.

ConclusionsAnti-GM-CSF autoantibodies predict the diagnosis of complicated CD, have unique epitopes, and impair myeloid cell homeostasis across the ILC3-GM-CSF-myeloid cell axis, altering intestinal immune homeostasis long before the diagnosis of disease.

category: gastroenterology


title: Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis

abstract:
BackgroundMost people with cystic fibrosis (pwCF) suffer from gastrointestinal symptoms and are at risk of gut complications. Gut microbiota dysbiosis is apparent within the CF population across all age groups, with evidence linking dysbiosis to intestinal inflammation and other markers of health. This pilot study aimed to investigate the potential relationships between the gut microbiota and gastrointestinal physiology, transit, and health.

Study DesignFaecal samples from 10 pwCF and matched controls were subject to 16S rRNA sequencing. Results were combined with clinical metadata and MRI metrics of gut function to investigate relationships.

ResultspwCF had significantly reduced microbiota diversity compared to controls. Microbiota compositions were significantly different, suggesting remodelling of core and rarer satellite taxa in CF. Dissimilarity between groups was driven by a variety of taxa, including Escherichia coli, Bacteroides spp., Clostridium spp., and Faecalibacterium prausnitzii. The core taxa were explained primarily by CF disease, whilst the satellite taxa were associated with pulmonary antibiotic usage, CF disease, and gut function metrics. Species-specific ordination biplots revealed relationships between taxa and the clinical or MRI-based variables observed.

ConclusionsAlterations in gut function and transit resultant of CF disease are associated with the gut microbiota composition, notably the satellite taxa. Delayed transit in the small intestine might allow for the expansion of satellite taxa resulting in potential downstream consequences for core community function in the colon.

HighlightsO_LIFaecal microbiota significantly differs between pwCF and healthy controls
C_LIO_LIKey SCFA producers contributed to microbiota dissimilarity between groups
C_LIO_LIPulmonary antibiotic treatment heavily impacted gut microbiota
C_LIO_LIIntestinal physiology and transit impacted satellite microbiota composition
C_LI


title: Survivors of SARS-CoV-2 Infection Show Neuropsychiatric Sequelae Measured by Surveys, Neurocognitive Testing, and Magnetic Resonance Imaging: Preliminary Results

abstract: A significant number of individuals experience physical, cognitive, and mental health symptoms in the months after acute infection with SARS-CoV-2, the virus that causes COVID-19. This study assessed depressive and anxious symptoms, cognition, and brain structure and function in participants with symptomatic COVID-19 confirmed by PCR testing (n=100) approximately three months following infection, leveraging self-report questionnaires, objective neurocognitive testing, and structural and functional neuroimaging data. Preliminary results demonstrated that over 1/5 of our cohort endorsed clinically significant depressive and/or anxious symptoms, and >40% of participants had cognitive impairment on objective testing across multiple domains, consistent with  brain-fog. While depression and one domain of quality of life (physical functioning) were significantly different between hospitalized and non-hospitalized participants, anxiety, cognitive impairment, and most domains of functioning were not, suggesting that the severity of SARS-CoV-2 infection does not necessarily relate to the severity of neuropsychiatric outcomes and impaired functioning in the months after infection. Furthermore, we found that the majority of participants in a subset of our cohort who completed structural and functional neuroimaging (n=15) had smaller olfactory bulbs and sulci in conjunction with anosmia. We also showed that this subset of participants had dysfunction in attention network functional connectivity and ventromedial prefrontal cortex seed-based functional connectivity. These functional imaging dysfunctions have been observed previously in depression and correlated with levels of inflammation. Our results support and extend previous findings in the literature concerning the neuropsychiatric sequelae associated with long COVID. Ongoing data collection and analyses within this cohort will allow for a more comprehensive understanding of the longitudinal relationships between neuropsychiatric symptoms, neurocognitive performance, brain structure and function, and inflammatory and immune profiles.

category: psychiatry and clinical psychology


title: White matter disruption as a cause or consequence of schizophrenia: A Mendelian randomization study

abstract: Brief abstractSchizophrenia is hypothesized to be caused by impaired functional integration in the brain, and this could hypothetically be caused by white matter disruptions, synaptic dysfunction, or both. Neuroimaging studies consistently show reduced fractional anisotropy, a measure of white matter integrity, in patients with schizophrenia. Using Mendelian randomization, we show that these white matter changes are likely to be the consequence of a primary synaptopathy in schizophrenia.


abstract:
Athletes are advised to receive the COVID-19 vaccination to protect them from SARS CoV-2 infection during major competitions. Despite this, many athletes are reluctant to get the COVID-19 vaccine due to concerns that symptoms of vaccinosis may impair athletic performance.

OBJECTIVETo determine the effects of COVID-19 vaccination on the physiological responses to graded exercise.

METHODSHealthy participants completed a 20-minute bout of graded cycling exercise before and ~21 days after COVID-19 vaccination (2 dose Pfizer mRNA or 1 dose Johnson & Johnson).

RESULTSOxygen uptake, CO2 production, respiratory exchange ratio, ventilation, heart rate, serum noradrenaline, and rating of perceived exertion were significantly elevated in the post vaccine trial. However, vaccination did not affect serum lactate, adrenaline, cortisol, predicted [Formula], and ventilatory threshold. Post-vaccine effects on heart rate and noradrenaline remained significant in non-infected participants that received the Pfizer vaccine. No significant effects in respiratory gas exchange parameters were found after vaccination in those previously exposed to SARS-CoV-2, but exercise adrenaline levels were significantly lower and serum lactate levels trending (p= 0.10) lower after vaccination. No changes in any physiological responses to exercise were found in control participants who completed two bouts of exercise separated by ~5 weeks without vaccination.

CONCLUSIONRecent COVID-19 vaccination is associated with modest increases in the physiological demands to graded exercise in non-infected healthy people but may actually improve metabolic responses to exercise in those previously infected with SARS-CoV-2. Whether or not these small effects could impact athletic performance at the elite level warrants investigation.

category: sports medicine


title: Altered cerebellar oscillations in Parkinson's disease patients during cognitive and motor tasks

abstract: Structural and functional abnormalities in the cerebellar region have been shown in patients with Parkinsons disease (PD). Since the cerebellar region has been associated with cognitive and lower-limb motor functions, it is imperative to study cerebellar oscillations in PD. Here, we evaluated cerebellar electroencephalography (EEG) during cognitive processing and lower-limb motor performances in PD. Cortical and cerebellar EEG were collected from 74 PD patients and 37 healthy control subjects during a 7-second interval timing task, 26 PD patients and 13 controls during a lower-limb pedaling task, and 23 PD patients during eyes-open/closed resting conditions. Analyses were focused on the mid-cerebellar Cbz electrode and further compared to the mid-occipital Oz and mid-frontal Cz electrodes. Increased alpha-band power was observed during the eyes-closed resting-state condition over Oz, but no change in alpha power was observed over Cbz. PD patients showed higher dispersion when performing the 7-second interval timing cognitive task and executed the pedaling motor task with reduced speed compared to controls. PD patients exhibited attenuated cue-triggered theta-band power over Cbz during both the interval timing and pedaling motor tasks. Connectivity measures between Cbz and Cz showed theta-band differences, but only during the pedaling motor task. Cbz oscillatory activity also differed from Oz across multiple frequency bands in both groups during both tasks. Our cerebellar EEG data along with previous magnetoencephalography and animal model studies clearly show the alteration in the cerebellar oscillations during cognitive and motor processing in PD.

category: neurology


title: Unexplained longitudinal variability in COVID-19 antibody status by Lateral Flow Immuno-Antibody testing

abstract:
BackgroundCOVID-19 antibody testing allows population studies to classify participants by previous SARS-CoV-2 infection status. Home lateral flow immune-antibody testing devices offer a very convenient way of doing this, but relatively little is known about how measurement and antibody variability will affect consistency in results over time. We examined consistency by looking at the outcome of two tests three months apart while COVID-19 infection rates were low (summer 2020 in the UK).

MethodsThe KCL-Coronavirus Health and Experiences in Colleagues at Kings is an occupational cohort of staff and postgraduate research students. Lateral flow immune-antibody testing kits were sent to participants homes in late June 2020 and late September 2020. Participants also completed regular surveys that included asking about COVID-19 symptoms and whether they thought they had been infected.

ResultsWe studied 1489 participants returned valid results in both June and September (59% of those sent kits). Lateral flow immune-antibody test was positive for 7.2% in June and 5.9% in September, with 3.9% positive in both. Being more symptomatic or suspecting infection increased the probability of ever being positive. Of those positive in June, 46% (49/107) were negative in September (seroreversion), and this was similar regardless of symptom characteristics, suspicion, and timing of possible infection. A possible outlier was those aged over 55 years, where only 3 of 13 (23%) had seroreversion.

DiscussionThese results do not follow the pattern reported from studies specifically designed to monitor seropositivity, which have found greater consistency over time and the influence of presence, timing and severity of symptoms on seroreversion. We suggest several factors that may have contributed to this difference: our low bar in defining initial seropositivity (single test); a non-quantitative test known to have relatively low sensitivity; participants carrying out testing. We would encourage other studies to use these real-world performance characteristics alongside those from laboratory studies to plan and analyse any antibody testing.

category: occupational and environmental health


title: The Yale Department of Medicine COVID-19 Data Explorer and Repository (DOM-CovX): An Innovative Approach to Promoting Collaborative Scholarship During a Pandemic

abstract:
BackgroundThe COVID-19 pandemic has led to an explosion of research publications spanning epidemiology, basic and clinical science. While a digital revolution has allowed for open access to large datasets enabling real-time tracking of the epidemic, detailed, locally-specific clinical data has been less readily accessible to a broad range of academic faculty and their trainees. This perpetuates the separation of the primary missions of clinically-focused and primary research faculty resulting in lost opportunities for improved understanding of the local epidemic; expansion of the scope of scholarship; limitation of the diversity of the research pool; lack of creation of initiatives for growth and dissemination of research skills needed for the training of the next generation of clinicians and faculty.

ObjectivesCreate a common, easily accessible and up-to-date database that would promote access to local COVID-19 clinical data, thereby increasing efficiency, streamlining and democratizing the research enterprise. By providing a robust dataset, a broad range of researchers (faculty, trainees) and clinicians are encouraged to explore and collaborate on novel clinically relevant research questions.

MethodsWe constructed a research platform called the Yale Department of Medicine COVID-19 Explorer and Repository (DOM-CovX), to house cleaned, highly granular, de-identified, continually-updated data from over 7,000 patients hospitalized with COVID-19 (1/2020-present) across the Yale New Haven Health System. This included a front-end user interface for simple data visualization of aggregate data and more detailed clinical datasets for researchers after a review board process. The goal is to promote access to local COVID-19 clinical data, thereby increasing efficiency, streamlining and democratizing the research enterprise.

Expected OutcomesO_LIAccelerate generation of new knowledge and increase scholarly productivity with particular local relevance
C_LIO_LIImprove the institutional academic climate by:
O_LIBroadening research scope
C_LIO_LIExpanding research capability to more diverse group of stakeholders including clinical and research-based faculty and trainees
C_LIO_LIEnhancing interdepartmental collaborations
C_LI
C_LI

ConclusionsThe DOM-CovX Data Explorer and Repository have great potential to increase academic productivity. By providing an accessible tool for simple data analysis and access to a consistently updated, standardized and large-scale dataset, it overcomes barriers for a wide variety of researchers. Beyond academic productivity, this innovative approach represents an opportunity to improve the institutional climate by fostering collaboration, diversity of scholarly pursuits and expanding medical education. It provides a novel approach that can be expanded to other diseases beyond COVID 19.


title: Long-term immunogenicity of BNT162b2 vaccination in the elderly and in younger health care workers

abstract:
COVID-19 mRNA vaccine BNT162b2 is highly immunogenic and effective, but recent studies have indicated waning anti-SARS-CoV-2 immune responses over time. Increasing infection rates has led authorities in several countries to initiate booster campaigns for vulnerable populations, including the elderly. However, the durability of vaccine-induced immunity in the elderly is currently unknown. Here, we describe interim results of a prospective cohort study comparing immune responses in a cohort of vaccinated elderly persons to those in healthcare workers (HCW), measured six months after first immunisation with BNT162b2. Anti-SARS-CoV-2 S1-, full Spike- and RBD-IgG seropositivity rates and IgG levels at six months were significantly lower in the elderly compared to HCW. Serum neutralization of Delta VOC measured by pseudovirus neutralisation test was detectable in 43/71 (60.6%, 95%CI: 48.9-71.1) in the elderly cohort compared to 79/83 in the HCW cohort (95.2%, 95%CI: 88.3-98.1) at six months post vaccination. Consistent with the overall lower antibody levels, SARS-CoV-2-S1 T cell reactivity was reduced in the elderly compared to HCW (261.6 mIU/ml, IQR:141.5-828.6 vs 1198.0 mIU/ml, IQR: 593.9-2533.6, p<0.0001).

Collectively, these findings suggest that the established two-dose vaccination regimen elicits less durable immune responses in the elderly compared to young adults. Given the recent surge in hospitalisations, even in countries with high vaccination rates such as Israel, the current data may support booster vaccinations of the elderly. Further studies to determine long-term effectiveness of COVID-19 vaccines in high-risk populations and the safety and effectiveness of additional boosters are needed.


title: Disruption of spatiotemporal dependence in dengue transmission by wMel Wolbachia in Yogyakarta, Indonesia

abstract: AO_SCPLOWBSTRACTC_SCPLOWDengue exhibits focal clustering in households and neighborhoods, driven by local mosquito population dynamics, human population immunity, and fine scale human and mosquito movement. We tested the hypothesis that spatiotemporal clustering of homotypic dengue cases is disrupted by introduction of the arbovirus-blocking bacterium Wolbachia (wMel-strain) into the Aedes aegypti mosquito population. We analysed 318 serotyped and geolocated dengue cases (and 5,921 test-negative controls) from a randomized controlled trial in Yogyakarta, Indonesia of wMel deployments. We find evidence of spatial clustering up to 300m among the 265 dengue cases (3,083 controls) in the untreated trial arm. Participant pairs enrolled within 30 days and 50m had a 4.7-fold increase (compared to 95% CI on permutation-based null distribution: 0.1, 1.2) in the odds of being homotypic (i.e. potentially transmission-related) as compared to pairs occurring at any distance. In contrast, we find no evidence of spatiotemporal clustering among the 53 dengue cases (2,838 controls) resident in the wMel-treated arm. Introgression of wMel Wolbachia into Aedes aegypti mosquito populations interrupts focal dengue virus transmission leading to reduced case incidence; the true intervention effect may be greater than the 77% efficacy measured in the primary analysis of the Yogyakarta trial.


title: Disruption of spatiotemporal clustering in dengue cases by wMel Wolbachia in Yogyakarta, Indonesia


title: Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots

abstract: For any given level of overall adiposity - as commonly quantified by body mass index (BMI) within clinical practice - individuals vary considerably in fat distribution. We and others have noted that increased visceral fat (VAT) is associated with increased cardiometabolic risk, while gluteofemoral fat (GFAT) may be protective. Familial partial lipodystrophy (FPLD) - often caused by rare variants in the LMNA gene - represents an extreme example of this paradigm, leading to a severe shift to visceral fat with subsequent insulin resistance and adverse metabolic profile. By contrast, the inherited basis of body fat distribution in the broader population is not fully understood. Here, we studied up to 38,965 UK Biobank participants with VAT, abdominal subcutaneous (ASAT), and GFAT volumes precisely quantified using abdominal MRI. Because genetic associations with these raw depot volumes were largely driven by variants known to affect BMI, we next studied six phenotypes of local adiposity: VAT adjusted for BMI (VATadjBMI), ASATadjBMI, GFATadjBMI, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 178 unique loci associated with at least one adiposity trait, including 29 newly-identified loci. Rare variant association studies extend prior evidence of association for PDE3B as an important modulator of fat distribution. Sex-specific analyses of local adiposity traits noted overall higher estimated heritability in females, increased effect sizes for identified loci, and 25 female-specific associations. Individuals in the extreme tails of fat distribution phenotypes were highly enriched for predisposing common variants, as quantified using polygenic scores. Taking GFATadjBMI as an example, individuals with extreme values were 3.8-fold (95%CI 2.8 to 5.2) more likely to have a polygenic score within the top 5% of the distribution. These results - using more precise and BMI-independent measures of local adiposity - confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.

category: endocrinology


title: Global disparities in SARS-CoV-2 genomic surveillance

abstract:
Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.

One-Sentence SummarySocioeconomic inequalities impacted the SARS-CoV-2 genomic surveillance, and undermined the global pandemic preparedness.


title: Toward Using Twitter for PrEP-Related Interventions: An Automated Natural Language Processing Pipeline for Identifying Gay or Bisexual Men in the United States

abstract:
BackgroundPre-exposure prophylaxis (PrEP) is highly effective at preventing the acquisition of Human Immunodeficiency Virus (HIV). There is a substantial gap, however, between the number of people in the United States who have indications for PrEP and the number of them who are prescribed PrEP. While Twitter content has been analyzed as a source of PrEP-related data (e.g., barriers), methods have not been developed to enable the use of Twitter as a platform for implementing PrEP-related interventions.

ObjectiveMen who have sex with men (MSM) are the population most affected by HIV in the United States. Therefore, the objective of this study was to develop and assess an automated natural language processing (NLP) pipeline for identifying men in the United States who have reported on Twitter that they are gay, bisexual, or MSM.

MethodsBetween September 2020 and January 2021, we used the Twitter Streaming Application Programming Interface (API) to collect more than 3 million tweets containing keywords that men may include in posts reporting that they are gay, bisexual, or MSM. We deployed handwritten, high-precision regular expressions on the tweets and their user profile metadata designed to filter out noise and identify actual self-reports. We identified 10,043 unique users geolocated in the United States, and drew upon a validated NLP tool to automatically identify their ages.

ResultsBased on manually distinguishing true and false positive self-reports in the tweets or profiles of 1000 of the 10,043 users identified by our automated pipeline, our pipeline has a precision of 0.85. Among the 8756 users for which a United States state-level geolocation was detected, 5096 (58.2%) of them are in the 10 states with the highest numbers of new HIV diagnoses. Among the 6240 users for which a county-level geolocation was detected, 4252 (68.1%) of them are in counties or states considered priority jurisdictions by the Ending the HIV Epidemic (EHE) initiative. Furthermore, the majority of the users are in the same two age groups as the majority of MSM in the United States with new HIV diagnoses.

ConclusionsOur automated NLP pipeline can be used to identify MSM in the United States who may be at risk for acquiring HIV, laying the groundwork for using Twitter on a large scale to target PrEP-related interventions directly at this population.


title: The relationship between autoantibodies targeting GPCRs and the renin-angiotensin system associates with COVID-19 severity

abstract: The coronavirus disease 2019 (COVID-19) can evolve to clinical manifestations resembling systemic autoimmune diseases, with the presence of autoantibodies that are still poorly characterized. To address this issue, we performed a cross-sectional study of 246 individuals to determine whether autoantibodies targeting G protein-coupled receptors (GPCRs) and renin-angiotensin system (RAS)-related molecules were associated with COVID-19-related clinical outcomes. Moderate and severe patients exhibited the highest autoantibody levels, relative to both healthy controls and patients with mild COVID-19 symptoms. Random Forest, a machine learning model, ranked anti-GPCR autoantibodies targeting downstream molecules in the RAS signaling pathway such as the angiotensin II type 1 and Mas receptor, and the chemokine receptor CXCR3 as the three strongest predictors of severe disease. Moreover, while the autoantibody network signatures were relatively conserved in patients with mild COVID-19 compared to healthy controls, they were disrupted in moderate and most perturbed in severe patients. Our data indicate that the relationship between autoantibodies targeting GPCRs and RAS-related molecules associates with the clinical severity of COVID-19, suggesting novel molecular pathways for therapeutic interventions.


title: Sensitivity of wastewater-based epidemiology for detection of SARS-CoV-2 RNA in a low prevalence setting

abstract:
To assist public health responses to COVID-19, wastewater-based epidemiology (WBE) is being utilised internationally to monitor SARS-CoV-2 infections at the community level. However, questions remain regarding the sensitivity of WBE and its use in low prevalence settings. In this study, we estimated the total number of COVID-19 cases required for detection of SARS-CoV-2 RNA in wastewater. To do this, we leveraged a unique situation where, over a 4-month period, all symptomatic and asymptomatic cases, in a population of approximately 120,000, were precisely known and mainly located in a single managed isolation and quarantine facility (MIQF) building. From 9 July to 6 November 2020, 24-hr composite wastewater samples (n = 113) were collected daily from the sewer outside the MIQF, and from the municipal wastewater treatment plant (WWTP) located 5 km downstream. New daily COVID-19 cases at the MIQF ranged from 0 to 17, and for most of the study period there were no cases outside the MIQF identified. SARS-CoV-2 RNA was detected in 54.0% (61/113) at the WWTP, compared to 95.6% (108/113) at the MIQF. We used logistic regression to estimate the shedding of SARS-CoV-2 RNA into wastewater based on four infectious shedding models. With a total of 5 and 10 COVID-19 infectious cases per 100,000 population (0.005 % and 0.01% prevalence) the predicated probability of SARS-CoV-2 RNA detection at the WWTP was estimated to be 28 and 41%, respectively. When a more realistic proportional shedding model was used, this increased to 58% and 87% for 5 and 10 cases, respectively. In other words, when 10 individuals were actively shedding SARS-CoV-2 RNA in a catchment of 100,000 individuals, there was a high likelihood of detecting viral RNA in wastewater. SARS-CoV-2 RNA detections at the WWTP were associated with increasing COVID-19 cases. Our results show that WBE provides a reliable and sensitive platform for detecting infections at the community scale, even when case prevalence is low, and can be of use as an early warning system for community outbreaks.

HighlightsO_LIOver 4 months, all 0-17 new daily cases in one quarantine building, catchment 120,000 population
C_LIO_LIWastewater tested daily at quarantine building and downstream wastewater treatment plant, WWTP
C_LIO_LISARS-CoV-2 RNA detected in 95.6% (108/113) at the MIQF and 54.0% (61/113) at the WWTP
C_LIO_LISARS-CoV-2 RNA detections at the WWTP associated with increasing COVID-19 cases
C_LIO_LIProbability of SARS-CoV-2 RNA detection of 87% with 0.01% total case prevalence
C_LI

Graphical Abstract

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title: Using telehealth consultations for healthcare provision to patients from racial/ethnic minorities: A systematic review

abstract:
ObjectiveThe COVID-19 pandemic has seen a rapid adoption of telehealth consultations, potentially creating new barriers to healthcare access for racial/ethnic minorities. This systematic review explored the use of telehealth consultations for people from racial/ethnic minority populations in relation to health outcomes, access to care, implementation facilitators and barriers, and satisfaction with care.

Materials and MethodsThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and the JBI Manual for Evidence Synthesis. Five major databases were searched to identify relevant studies. Screening, full-text review, quality appraisal and data extraction were all completed independently and in duplicate. A convergent integrated approach to data synthesis was applied with findings reported narratively.

ResultsA total of 28 studies met the inclusion criteria. Telehealth-delivered interventions were mostly effective for the treatment/management of physical and mental health conditions including depression, diabetes and hypertension. In several studies, telehealth improved access to care by providing financial and time benefits to patients. Technological difficulties were the main barriers to effective telehealth consultation, although overall satisfaction with telehealth-delivered care was high.

DiscussionTelehealth-delivered care for racial/ethnic minorities offers promise across a range of conditions and outcomes, particularly when delivered in the patients preferred language. However, telehealth may be problematic for some due to cost and limited digital and health literacy.

ConclusionThe development and implementation of guidelines, policies and practices in relation to telehealth consultations for racial/ethnic minorities should consider the barriers and facilitators identified in this review to ensure existing health disparities are not exacerbated.


title: Facility-based HIV self-testing strategies may substantially increase number of men and youth tested for HIV in Malawi: results from a data-driven individual-based model

abstract:
BackgroundMalawi is rapidly closing the gap in achieving the UNAIDS 95-95-95 targets, with 90% of people living with HIV in Malawi aware of their status. As we approach epidemic control, interventions to improve coverage will become more costly. There is therefore an urgent need to identify innovative and low-cost strategies to maintain and increase testing coverage without diverting resources from other HIV services.

MethodsA data-driven individual-based model was parameterized with data from a community-representative survey (sociodemographic, health service utilization, HIV testing history) of men and youth in Malawi (data collected 08/2019). 79 different strategies for the implementation of HIV self-testing (HIVST) and provider-initiated-testing-and-counselling at the outpatient department (OPD) were evaluated. Outcomes included percent of men/youth tested for HIV in a 12-month period, cost-effectiveness, and human resource requirements. Testing yield was assumed to be constant across the scenarios.

FindingsFacility-based HIVST offered year-round resulted in the greatest increase in proportion of men and youth tested in the OPD (from 45% to 72%-83%), was considered cost-saving for HIVST kit priced at $1.00, and generally reduced required personnel as compared to the status quo. At higher HIVST kit prices, and more relaxed eligibility criteria, all scenarios that considered year-round HIVST in the OPD remained on the cost-effectiveness frontier.

InterpretationFacility-based HIVST is a cost-effective strategy to increase the proportion of men/youth tested for HIV and decreases the human resource requirements for HIV testing in the OPD-providing additional health care worker time for other priority health care activities.

FundingFCDO; USAID


title: Differentials and predictors of hospitalization among the elderly people in India: Evidence from 75th round of National Sample Survey (2017-18)

abstract:
IntroductionThere are limited evidences on the determinants of hospitalization and its causes in India. We examined the differential in the hospitalization rates and its socio-economic determinants. We also examined the causes of diseases in hospitalization among the elderly ([≥]60 years) in India.

MethodsWe used data from 75th round of the National Sample Survey Organizations (NSSO), collected from July 2017 to June 2018. The elderly samples in this survey are 42759, where 11070 were hospitalized, and 31,689 were not hospitalized in the last year or 365 days. We estimated hospitalization rates and carried out binary logistic regression analysis to examine the associations of hospitalization with the background variables. The cause of diseases in hospitalizations were also calculated.

ResultsHospitalization rate was lower among female elderly compared to male elderly. Elderly who belongs to middle-old aged groups, non-married, North-Eastern region, Southern region, general caste, health insurance, partially & fully economically dependent elderly have a higher chance of being hospitalized. About 38% elderly were hospitalized due to communicable diseases (CDs), 52% due to non-communicable diseases (NCDs) and 10% due to Injuries & others. Nearly 40% elderly were hospitalized in public hospitals due to CDs, while 52% were hospitalized in private hospitals due to NCDs and 11% due to Injuries & others.

ConclusionsRaising awareness, promoting a healthy lifestyle, and improving the quality of good healthcare provisions at the primary level is necessary. Early screening and early treatment for NCDs are needed, which is non-existent in almost all parts of India.


title: Attitudes to health promotion among teaching staff in South West England: a qualitative study

abstract:
BackgroundYoung people spend much of their formative years in education, making schools appealing environments for health promotion. The World Health Organisations Health Promoting Schools framework has been proposed as a useful model. We sought to explore secondary school teachers experiences of implementing this model and their attitudes to health promotion.

ObjectivesTo explore teachers experiences and perceptions of health promotion and compare practice with the HPS framework for school health.

DesignQualitative study with semi-structured interviews

SettingNine state comprehensive schools in Bristol and surrounding areas.

Participants25 teaching staff from school senior leadership teams, those working in health education and other subject teachers.

AnalysisThematic analysis using NVivo 10.

ResultsTeachers largely described educational approaches with less emphasis on school ethos or environment. Staff supported a role for schools in promoting health but felt restrained by limited family engagement, contradictory school practices, resource constraints and conflicting government policies.

ConclusionsFuture reforms should ensure health is mainstreamed across school strategies, if we are to create the conditions that promote future generations health. Public health must build alliances with educationalists to support the priority-setting of health in school inspections, policy and practice.

Strengths and limitations of the studyO_LIIn-depth exploration with teachers from different schools, levels of seniority and with varying experience of health promotion
C_LIO_LIPurposive sampling to ensure representation from schools of different geography, Ofsted rating and proportions of students from disadvantaged backgrounds
C_LIO_LIPossibility that schools with greater enthusiasm for health promotion disproportionately participated
C_LIO_LITrend towards schools in more affluent areas participating
C_LI


title: Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients

abstract:
BackgroundChronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts.

ResultsExosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and [~]2.95 x 1010 particles/mL. Lung-derived exosomes were [~]146.04 nm in size and [~]2.38 x 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.

ConclusionsOverall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.


title: Results publications are inadequately linked to trial registrations: An automated pipeline and evaluation of German university medical centers

abstract:
ObjectiveTo evaluate links between registration and publication across clinical trials led by German university medical centers (UMCs) and registered in either ClinicalTrials.gov or the German Clinical Trials Registry (DRKS). Inadequate links make trial publications and registrations less findable and compromise evidence synthesis and health policy decision making. The World Health Organization (WHO) and others call for better adoption of this straightforward transparency practice.

DesignCross-sectional bibliographic study

SettingGerman UMC clinical trials

MethodsWe used automated strategies to download and extract data from trial registries, PubMed, and trial publications for a cohort of all registered, published clinical trials conducted across German UMCs and completed between 2009 and 2017. We implemented regular expressions to detect and classify publication identifiers (DOI and PMID) in registrations, and trial registrations numbers (TRNs) in publication metadata, abstract, and full-text.

Main outcome measuresThe proportion of trial registrations that reference a known results publication. The proportion of results publications that report the known TRN in the metadata, abstract, and full-text.

Secondary analysesWe constructed exploratory logistic regression models to investigate the relationship between trial completion date, registry, and registration-publication linking.

ResultsOnly 20% (373/1,895) of trials have a linked publication (DOI or PMID) in the registration as well as the TRN in the publication full-text, abstract, and metadata, and only 25% (477) of trials met the CONSORT and ICMJE guidelines to include TRNs in both the full-text and the abstract. 17% (327) of trials had no links. The most common link was TRN reported in the full-text (60%, 1,137). ClinicalTrials.gov trials were overall better linked than DRKS trials, and this difference appears to be driven by PubMed and registry infrastructure, rather than by trialists. Of trials reporting a TRN in the abstract, trials in ClinicalTrials.gov were more likely than trials in DRKS to have the TRN captured in the PubMed metadata. Most (78%, 662/849) ClinicalTrials.gov registrations with a publication link were automatically indexed from PubMed metadata, which is not possible in DRKS.

ConclusionGerman UMCs have not comprehensively linked trial registrations and publications by both including a structured reference to the publication in the registration, and reporting TRNs in results publications. In addition to improved linking by trialists, changes in the PubMed TRN capturing process (such as automated strategies like those developed in this study) and automated indexing of publications in DRKS would make trial registrations and results more findable.

Open Data and CodeAll code and the final analysis data for this study are available at https://github.com/maia-sh/reg-pub-link. Raw data is available at https://github.com/maia-sh/intovalue-data.

category: medical ethics


title: Comparative Analysis of the Chemotherapy-related Cognition Impairments in Patients with Breast Cancer: a Community-based Research

abstract:
PurposeWith increasing breast cancer (BC) survival rates, the survivors quality of life (QoL) has become an important issue. Chemotherapy-induced cognitive impairment, known as "chemobrain" has been addressed recently. Therefore, cognitive function as one of the determinants of QoL should be considered while prescribing chemotherapeutics. In this study, we aimed to evaluate the effects of two common chemotherapy regimens on BC survivors cognition.

MethodsThe participants comprised 35 BC patients who underwent two common chemotherapy regimens, AC-T and TAC, and 24 matched healthy volunteers. The participants were assessed regarding anxiety, depression, general health status, and cognitive function including aspects of concentration, verbal ability, reasoning, memory, and visuospatial skill through Addenbrookes Cognitive Examination (ACE-P) and Cambridge Brain Science (CBS) tests.

ResultsRegarding depression and anxiety, there were no significant differences between the three groups. However, BC patients significantly complained of chronic fatigue compared to healthy volunteers (P-value = 0.027). Besides, ACE-P revealed the language domain to be affected in the AC-T group in comparison with the TAC-treated cases (P-value = 0.036). Moreover, the patients receiving the AC-T regimen had worse performance in visuospatial working memory and attention domains compared to the TAC group considering CBS tests (P-value = 0.031 and 0.008, respectively).

ConclusionThe results represent the AC-T regimen to be more toxic than the TAC in domains of language, concentration, and visuospatial working memory.

Implications for cancer survivorsThe AC-T regimen should be prescribed with caution in BC patients suffering from baseline cognitive impairments to improve post-chemotherapy QoL.

Graphical Abstract

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title: Comparative Analysis of the Chemotherapy-related Cognitive Impairments in Patients with Breast Cancer: a Community-based Research


title: Predicting COVID-19 Incidences from Patients Viral Load using Deep-Learning

abstract: The transmission of the contagious COVID-19 is known to be highly dependent on individual viral dynamics. Since the cycle threshold (Ct) is the only semi-quantitative viral measurement that could reflect infectivity, we utilized Ct values to forecast COVID-19 incidences. Our COVID-19 cohort (n=9531), retrieved from a single representative cross-sectional virology test center in Lebanon, revealed that low daily mean Ct values are followed by an increase in the number of national positive COVID-19 cases. A subset of the data was used to develop a deep neural network model, tune its hyperparameters, and optimize the weights for minimal mean square error of prediction. The final models accuracy is reported by comparing its predictions with an unseen dataset. Our model was the first to capture the interaction of the previously reported Ct values with the upcoming number of COVID-19 cases and any temporal effects that arise from population dynamics. Our model was deployed as a publicly available and easy-to-use estimator to facilitate prospective validation. Our model has potential application in predicting COVID-19 incidences in other countries and in assessing post-vaccination policies. Aside from emphasizing patient responsibility in adopting early testing practices, this study proposed and validated viral load measurement as a rigid input that can enhance outcomes and precision of viral disease predicting models.


title: An in-depth statistical analysis of the COVID-19 pandemic's initial spread in the WHO African region

abstract:
During the first wave of the COVID-19 pandemic, sub-Saharan African countries experienced comparatively lower rates of SARS-CoV-2 infections and related deaths than in other parts of the world, the reasons for which remain unclear. Yet, there was also considerable variation between countries. Here, we explored potential drivers of this variation among 46 of the 47 World Health Organization African region member states in a cross-sectional study. We described five indicators of early COVID-19 spread and severity for each country as of 29 November 2020: delay in detection of the first case, length of the early epidemic growth period, cumulative and peak attack rates, and crude case fatality ratio (CFR). We tested the influence of 13 pre-pandemic and pandemic response predictor variables on the country-level variation in the spread and severity indicators using multivariate statistics and regression analysis. We found that wealthier African countries, with larger tourism industries and older populations, had higher peak (p < 0.001) and cumulative (p < 0.001) attack rates, and lower CFRs (p = 0.021). More urbanized countries also had higher attack rates (p < 0.001 for both indicators). Countries applying more stringent early control policies experienced greater delay in detection of the first case (p < 0.001), but the initial propagation of the virus was slower in relatively wealthy, touristic African countries (p = 0.023). Careful and early implementation of strict government policies were likely pivotal to delaying the initial phase of the pandemic, but did not have much impact on other indicators of spread and severity. An over-reliance on disruptive containment measures in more resource-limited contexts is neither effective nor sustainable. We thus urge decision-makers to prioritize the reduction of resource-based health disparities, and surveillance and response capacities in particular, to ensure global resilience against future threats to public health and economic stability.

Summary BoxO_ST_ABSWhat is already known on this topic?C_ST_ABSO_LICOVID-19 trajectories varied widely across the world, and within the African continent.
C_LIO_LIThere is significant heterogeneity in the surveillance and response capacities among WHO African region member states.
C_LI

What are the new findings?O_LICumulative and peak attack rates during the first wave of COVID-19 were higher in WHO African region member states with higher per-capita GDP, larger tourism industries, older and more urbanized populations, and higher pandemic preparedness scores.
C_LIO_LIAlthough better-resourced African countries documented higher attack rates, they succeeded in limiting rapid early spread and mortalities due to COVID-19 infection.
C_LIO_LIAfrican countries that had more stringent early COVID-19 response policies managed to delay the onset of the outbreak at the national level. However, this phenomenon is partially explained by a lack of detection capacity, captured in low pandemic preparedness scores, and subsequent initial epidemic growth rates were slower in relatively well-resourced countries.
C_LI

What do the new findings imply?Careful implementation of strict government policies can aid in delaying an epidemic, but investments in public health infrastructure and pandemic preparedness are needed to better mitigate its impact on the population as a whole.


title: COVID-19 in Scottish care homes: A metapopulation model of spread among residents and staff

abstract: Care homes in the UK were disproportionately affected by the first wave of the COVID-19 pandemic, accounting for almost half of COVID-19 deaths over the course of the period from 6th March - 15th June 2020. Understanding how infectious diseases establish themselves throughout vulnerable communities is crucial for minimising deaths and lowering the total stress on the National Health Service (NHS Scotland). We model the spread of COVID-19 in the health-board of NHS Lothian, Scotland over the course of the first wave of the pandemic with a compartmental Susceptible - Exposed - Infected reported - Infected unreported - Recovered - Dead (SEIARD), metapopulation model. Care home residents, care home workers and the rest of the population are modelled as subpopulations, interacting on a network describing their mixing habits. We explicitly model the outbreaks reproduction rate and care home visitation level over time for each subpopulation, and execute a data fit and sensitivity analysis, focusing on parameters responsible for intra-subpopulation mixing: staff sharing, staff shift patterns and visitation. The results suggest that hospital discharges were not predominantly responsible for the early outbreak in care homes, and that only a few such cases led to infection seeding in care homes by the 6th of March Sensitivity analysis show the main mode of entry into care homes are infections by staff interacting with the general population. Visitation (before cancellation) and staff sharing were less significant in affecting outbreak size. Our model suggests that focusing on the protection and monitoring of staff, followed by reductions in staff sharing and quick cancellations of visitation can significantly reduce future infection attack rates of COVID-19 in care homes.


title: Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar

abstract:
BACKGROUNDWaning of vaccine protection against SARS-CoV-2 infection or COVID-19 disease is a concern. This study investigated persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the Beta and Delta variants have dominated incidence and PCR testing is done at a mass scale.

METHODSA matched test-negative, case-control study design was used to estimate vaccine effectiveness against SARS-CoV-2 infection and against any severe, critical, or fatal COVID-19 disease, between January 1, 2021 to August 15, 2021.

RESULTSEstimated BNT162b2 effectiveness against any infection, asymptomatic or symptomatic, was negligible for the first two weeks after the first dose, increased to 36.5% (95% CI: 33.1-39.8) in the third week after the first dose, and reached its peak at 72.1% (95% CI: 70.9-73.2) in the first five weeks after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating [≥]15 weeks after the second dose, reaching diminished levels of protection by the 20th week. Effectiveness against symptomatic infection was higher than against asymptomatic infection, but still waned in the same fashion. Effectiveness against any severe, critical, or fatal disease increased rapidly to 67.7% (95% CI: 59.1-74.7) by the third week after the first dose, and reached 95.4% (95% CI: 93.4-96.9) in the first five weeks after the second dose, where it persisted at about this level for six months.

CONCLUSIONSBNT162b2-induced protection against infection appears to wane rapidly after its peak right after the second dose, but it persists at a robust level against hospitalization and death for at least six months following the second dose.


title: Depression Remission and Response Rates and Anxiety Response as a Predictor of Depression Response in a Community ECT Clinic

abstract:
ObjectiveTo assess depression response and remission rates with electroconvulsive therapy (ECT) in a community clinic and to identify factors predicting success in treatment.

MethodsWe identified 35 patients by a retrospective chart review with a diagnosis of major depressive disorder or depressive disorder not otherwise specified (according to the Diagnostic and Statistical Manual of Mental Disorders IV-TR) who were treated with an acute series of ECT at the Pine Rest ECT Clinic from March, 2014 to March, 2015. Clinical variables, demographics, depression response rates (based on Patient Health Questionnaire-9; PHQ-9), and anxiety response rates (based on Generalized Anxiety Disorder 7-item) were analyzed.

ResultsDepression response (defined as [≥] 50% reduction in PHQ-9 score) and remission rates (defined as final PHQ-9 score < 5) were 54.3% and 31.4%, respectively. This was a highly treatment resistant sample, with an average of 5.3 antidepressant failures prior to initiating ECT. Logistic regression analysis found that depression response rates were predicted by an improvement in anxiety symptoms (odds ratio 1.41; 95% confidence interval, 1.11, 1.78). Additionally, patients with initial severe anxiety scores were less likely than other patients to exhibit a response in depression (p = .027).

ConclusionAlmost half of this sample of patients with treatment resistant depression did not respond to ECT in this community-based clinic. Patients who experienced a response in anxiety symptoms were more likely to experience a depression response while those with severe anxiety were less likely to respond.


title: Characterisation of type 2 diabetes subgroups and their association with ethnicity and clinical outcomes: a UK real-world data study using the East London Database

abstract:
BackgroundSubgroups of type 2 diabetes (T2DM) have been well characterised in experimental studies. However, it is unclear whether T2DM subgroups can be identified in UK based real-world populations and if they impact clinical outcomes.

AimTo derive T2DM subgroups using primary care data from a multi-ethnic population, evaluate associations with glycaemic control, treatment initiation and vascular outcomes, and understand how these vary by ethnicity.

Design and settingAn observational cohort study in the East London Primary Care Database from 2008-2018.

MethodLatent class analysis using age, sex, glycated haemoglobin, and body mass index at diagnosis was used to derive T2DM subgroups in White, South Asian, and Black groups. Time to treatment initiation and vascular outcomes was estimated using multivariable Cox-proportional hazards regression.

Results31,931 adults with T2DM were included: 47% south Asian, 25% White, 20% Black. We replicated two previously described subgroups,  Mild Age-Related Diabetes (MARD),  Mild Obesity-related Diabetes (MOD), and characterised a third  Severe Hyperglycaemic Diabetes (SHD). Compared to MARD, SHD had the poorest long term glycaemic control, fastest initiation of antidiabetic treatment (HR 2.02, 1.76-2.32), and highest risk of microvascular complications (HR 1.38, 1.28-1.49). MOD had the highest risk of macrovascular complications (HR 1.50, 1.23-1.83). Subgroup differences in treatment initiation were most pronounced for the White group, and vascular complications for the Black group.

ConclusionsClinically useful T2DM subgroups, identified at diagnosis, can be generated in routine real-world multi-ethnic populations, and may offer a pragmatic means to develop stratified primary care pathways and improve healthcare resource allocation.

How this fits inPrevious studies of predominantly White European populations have identified four T2DM subgroups. In the UK the clinical measures necessary to replicate these subgroups are only available in secondary care data, limiting their usefulness for diabetes management in primary care settings. In this study, we demonstrate how clinically meaningful T2DM subgroups can be pragmatically generated using real-world primary care data. Furthermore, we highlight important differences between T2DM subgroups with respect to vascular outcomes, treatment initiation, and HbA1c control. Diabetes subgroups are a useful heuristic for helping clinician decision-making which, in turn, this can lead to a more personalised design of diabetes care focussed on more intensive management of subgroups most at risk of complications, such as those with severe hyperglycaemia at time of diagnosis.


title: Decreased Immune Response to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases Treated with Anti TNFα

abstract:
BackgroundPatients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF) biologics are at high risk for vaccine preventable infections. Their ability to mount adequate vaccine responses is unclear.

Aimto assess immune responses to mRNA-COVID-19 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared to healthy controls (HC).

MethodsProspective, controlled, multi-center Israeli study. Subjects enrolled received two BNT162b2 (Pfizer/BioNTech) doses. Anti-spike (S) antibodies levels and functional activity, anti-TNF levels and adverse events (AEs) were detected longitudinaly.

ResultsOverall 258 subjects: 185 IBD (67 treated with anti-TNF), and 73 HC. After the first vaccine dose all HC were seropositive, while some patients with IBD, regardless of treatment, remained seronegative. After the second dose all subjects were seropositive, however anti-S levels were significantly lower in anti-TNF treated compared to untreated patients, and HC (p<0.001; p<0.001, respectively). Neutralizing and inhibitory functions were both lower in anti-TNF treated compared to untreated patients, and HC (p<0.03; p<0.0001, respectively). Anti-TNF drug levels and vaccine responses did not affect anti-S levels. Infection rate ([~]2%) and AEs were comparable in all groups. IBD activity did not change in response to BNT162b2.

ConclusionsIn this prospective study in patients with IBD stratified according to treatment all patients mounted an immune response to two doses of BNT162b2. However, its magnitude was significantly lower in patients treated with anti-TNF, regardless of administration timing and drug levels. Vaccine was safe. As vaccine immune response longevity in this group may be limited, vaccine booster dose should be considered.


title: Racial discrimination and covid-19 vaccine uptake: is mistrust of the health service behind vaccine refusal?

abstract:
ObjectiveTo examine whether racial/ethnic discrimination predicts future COVID-19 vaccine refusal, and whether this association is explained by trust in government and the health system.

DesignLongitudinal observational study of racial/ethnic discrimination occurring since the start of the first lockdown (measured in July 2020) and later COVID-19 vaccine status.

SettingUK (England, Scotland, Wales, and Northern Ireland)

Participants633 adults belonging to ethnic minority groups who took part in the UCL COVID-19 Social Study.

Main outcome measureCOVID-19 vaccine refusal (vs accepted/waiting/had at least one dose) between 23 December 2020 and 14 June 2021.

ResultsNearly one in ten (6.7%) who had refused a COVID-19 vaccine had experienced racial/ethnic discrimination in a medical setting since the start of the pandemic and had experienced twice as many incidents of racial/ethnic discrimination than those who had accepted the vaccine. Structural equation modelling results indicated a nearly 4-fold (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 1.4 to 10.9) total effect of racial/ethnic discrimination on refusing the vaccine was which was mediated by low trust in the health system to handle the pandemic (OR = 2.5, 95% CI = 1.1 to 5.4). Analyses adjusted for a range of demographic and COVID-19 related factors.

ConclusionsFindings underscore the importance of addressing racial/ethnic discrimination and the role the National Health Service in regaining trust from ethnic minority groups to increase COVID-19 vaccine uptake amongst ethnic minority adults.

category: public and global health


title: Racial discrimination, low trust in the health system, and COVID-19 vaccine uptake: a longitudinal observational study of 633 UK adults from ethnic minority groups


title: Differentials and determinants of immunization coverage among children aged 12-36 months in India: Analysis of nationally-representative, population-based survey data

abstract:
IntroductionImmunization coverage among children is still a major public health concern in India and other low-middle income countries. Low coverage likely risks the health of children and therefore impacts their overall growth. We therefore examined the immunization coverage rates among children aged 12-36 months in India and its states. We also explored the associated factors affecting immunization coverage among children aged 12-36 in India.

MethodsWe used data from 75th round of the National Sample Survey Organizations (NSSO), collected from July 2017 to June 2018. The analytical sample of children aged 12-36 months information cases was 15887. Immunization coverage rates of India and its states were calculated. We evaluated the immunization coverage rate by background characteristics in India and its states. We performed multinomial logistic regression analysis to estimate the factors associated with the immunization coverage in India.

ResultsAbout 61.95% were fully immunized, 35.62% were partially immunized and the rest 2.43% had not received any vaccine. The children aged 21-28 months (0.50; p<0.01) & 29-36 months (0.35; p<0.01), belonging to North-Eastern regions (0.60; p<0.01) were found to be significantly less likely to receive fully immunization. Likewise, urban children are (1.26; p<0.1) found to be more likely to receive fully immunization. The lowest fully immunization has been seen in Daman and Diu (1.73%) followed by Nagaland (6.93%), NCT Delhi (34.71%), and Tripura (46.33%).

ConclusionsChild immunization is a key public health concern and vital challenge to be addressed. Socio-economic characteristics play a key role in immunization coverage. Therefore necessary policy measures must be taken to address the challenges of poor immunization coverage and its impact on health and wellbeing of children


title: Father absence and trajectories of offspring mental health across adolescence and young adulthood: findings from a UK-birth cohort

abstract:
BackgroundHigh prevalence of parental separation and resulting biological father absence raises important questions regarding its impact on offspring mental health across the life course. However, few studies have examined prospective associations between biological father absence in childhood and risk of offspring depression and depressive symptoms trajectories across adolescence and young adulthood. We specifically examined whether these relationships vary by sex and the timing of exposure to father absence (early or middle childhood).

MethodsThis study is based on up to 8,409 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants provided self-reports of depression (Clinical Interview Schedule-Revised) at age 24 years and depressive symptoms (Short Mood and Feelings Questionnaire) between the ages of 10 and 24 years. Biological father absence in childhood was assessed through maternal questionnaires at regular intervals from birth to 10 years. We used logistic regression to examine the association between biological father absence and depression/depressive symptoms at age 24. We estimated the association between biological father absence and trajectories of depressive symptoms using multilevel growth-curve modelling.

ResultsEarly but not middle childhood father absence was strongly associated with increased odds of offspring depression and greater depressive symptoms at age 24 years. Early childhood father absence was associated with higher trajectories of depressive symptoms during adolescence and early adulthood compared with father presence. Differences in the level of depressive symptoms between middle childhood father absent and father present groups narrowed into early adulthood. Girls whose father was absent in early childhood, compared with present, manifested higher levels of depressive symptoms throughout adolescence, but this difference narrowed by early adulthood. In contrast, boys who experienced father absence in early childhood had similar trajectories of depressive symptoms compared to the father present group but experienced a steep increase in early adulthood. Girls whose fathers were absent in middle childhood manifested higher trajectories across middle adolescence into young adulthood compared to the father present group.

ConclusionsWe found evidence that father absence in childhood is persistently associated with offspring depression in adolescence and early adulthood and that this relationship varies by sex and timing of fathers departure. Further research is needed to examine whether this relationship is causal and to identify mechanisms that could inform preventative interventions to reduce the risk of depression in children who experience father absence.


title: An automatic diagnostic system for pediatric genetic disorders developed by linking genotype and phenotype information

abstract:
BackgroundQuantitatively describe the phenotype spectrum of pediatric disorders has remarkable power to assist genetic diagnosis. Here, we developed a matrix which provide this quantitative description of genomic-phenotypic association and constructed an automatic system to assist the diagnose of pediatric genetic disorders.

Results20,580 patients with genetic diagnostic conclusions from the Childrens Hospital of Fudan University during 2015 to 2019 were reviewed. Based on that, a phenotype spectrum matrix -- cGPS (clinical Genes Preferential Synopsis) -- was designed by Naive Bayes model to quantitatively describe genes contribution to clinical phenotype categories. Further, for patients who have both genomic and phenotype data, we designed a ConsistencyScore based on cGPS. ConsistencyScore aimed to figure out genes that were more likely to be the genetic causal of the patients phenotype and to prioritize the causal gene among all candidates. When using the ConsistencyScore in each sample to predict the causal gene for patients, the AUC could reach 0.975 for ROC (95% CI 0.972-0.976 and 0.575 for precision-recall curve (95% CI 0.541-0.604). Further, the performance of ConsistencyScore was evaluated on another cohort with 2,323 patients, which could rank the causal gene of the patient as the first for 75.00% (95% CI 70.95%-79.07%) of the 296 positively genetic diagnosed patients. The causal gene of 97.64% (95% CI 95.95%-99.32%) patients could be ranked within top 10 by ConsistencyScore, which is much higher than existing algorithms (p <0.001).

ConclusionscGPS and ConsistencyScore offer useful tools to prioritize disease-causing genes for pediatric disorders and show great potential in clinical applications.

category: pediatrics


title: Altered resting-state functional connectivity in hiPSC-derived neuronal networks from schizophrenia patients

abstract: Schizophrenia (SZ) is a complex mental disease thought to arise from abnormal neurodevelopment, characterized by an altered reality perception and widely associated with brain connectivity anomalies. Previous work has shown disrupted resting-state brain functional connectivity (FC) in SZ patients. We used Human Induced Pluripotent Stem Cells (hiPSC)-derived neuronal cultures to study SZs neural communicational dynamics during early development. We conducted gene and protein expression profiling, calcium imaging and mathematical modeling to evaluate FC. Along the neurodifferentiation process, SZ networks displayed altered expression of genes related to synaptic function, cell migration and cytoskeleton organization, suggesting alterations in excitatory/inhibitory balance. Resting-state FC in neuronal networks derived from healthy controls (HC) and SZ patients emerged as a dynamic phenomenon exhibiting "hub-states", which are connectivity configurations reoccurring in time. Compared to HC, SZ networks were less thorough in exploring different FC configurations, changed configurations less often, presented a reduced repertoire of hub-states and spent longer uninterrupted time intervals in this less diverse universe of hubs. Our observations at a single cell resolution may reflect intrinsic dynamical principles ruling brain activity at rest and highlight the relevance of identifying multiscale connectivity properties between functional brain units. We propose that FC alterations in SZ patients are a consequence of an abnormal early development of synaptic communication dynamics, compromising networks ability for rapid and efficient reorganization of neuronal activity patterns. Remarkably, these findings mirror resting-state brain FC in SZ patients, laying the groundwork for future studies among such different spatiotemporal domains, as are brains and neurons, in both health and disease.