title: Multi-omics identify LRRC15 as a COVID-19 severity predictor and persistent pro-thrombotic signals in convalescence

abstract: Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we performed longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identified transcriptomic and proteomic signatures of COVID-19 severity, and found distinct temporal molecular profiles in patients with severe disease. Supervised learning revealed that the plasma proteome was a superior indicator of clinical severity than the PBMC transcriptome. We showed that both the levels and trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, are the strongest predictors of clinical outcome. Strikingly, we observed that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.

category: infectious diseases


title: Promising efficacy of following a third dose of mRNA SARS-CoV-2 vaccination in patients treated with anti-CD20 antibody who failed 2-dose vaccination

abstract: Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for S1 protein after third vaccination in 22 patients treated with anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving seroconversion rate in patients treated with anti-CD20 antibody who failed standard two-dose vaccination.


title: Characteristics of admissions for Kawasaki Disease from 1997 to 2012: Lessons from a national database

abstract: A majority of large epidemiologic studies on Kawasaki Disease have come from Asia. There is paucity of data assessing Kawasaki Disease on a national level in the U.S., particularly in terms of hospitalization co-morbidities and cost. This study set forth to analyze data from the Kids Inpatient Database from 1997 to 2012. Data were analyzed for age, race, cardiogenic shock, acute kidney injury, liver failure, acute respiratory distress syndrome, arrhythmia, and congenital heart disease. Additionally, multivariate regression analysis was performed to assess the impact of Kawasaki Disease on coronary artery aneurysms, ECMO, length of stay, cost of stay, and mortality. Asian and Pacific Islander children were disproportionally affected by Kawasaki Disease in the U.S (20.8% of Kawasaki Disease admissions vs 3.3% of all other pediatric hospital admissions, p<0.01). Patients hospitalized for Kawasaki Disease had an increased risk of developing coronary artery aneurysms (OR 2,839, 95%CI 2,2985-3,527) and cardiogenic shock (OR 3.42, 95% CI 2.18-5.37). Patients with Kawasaki disease were less likely to have congenital heart disease (OR 0.62, 95%CI 0.55-0.69), arrhythmia (OR 0.31, 95%CI 0.11-0.84), and acute respiratory distress syndrome (OR 0.29, 95%CI 0.19-0.43). Kawasaki disease patients had shorter hospitalization length of stay by 2.59 days (p <0.01) and decreased cost of stay by $5,513 (p <0.01). Kawasaki Disease had lower mortality when compared to all other admissions (OR 0.03, 95%CI 0.01-0.09). No significant differences were found for ECMO, acute kidney injury, or liver failure.

category: cardiovascular medicine


title: Survival analysis of coronary care unit patients from MIMIC IV database: the role of potassium in cardiac patients

abstract: The profile of hospitalizations in coronary care units (CCU) includes patients with different age groups, multiple comorbidities and causes of hospitalization that may or may not be primarily cardiac. This study aimed to estimate survival time and evaluate the association and impact of different factors on this time in a cohort of patients admitted to CCU. A cohort of 7120 adult patients admitted to CCU was analyzed from a subset of data from the MIMIC-IV database (Medical Information Mart for Intensive Care, version 4). A descriptive analysis was performed using Kaplan-Meier survival analysis, with a Log-rank test to establish comparisons between groups. Survival regression was modeled using Coxs proportional risk models for the multiple analysis. The p-value was defined as {inverted exclamation} 0.05 as statistically significant. In patients who died during hospitalization, there was a higher average age, longer hospital stay, and a higher rate of heart and respiratory rate, all with p {inverted exclamation} 0.001. Median overall survival was 28 days (95% CI 26-30 days). The survival probability curve presented a higher inclination in the first weeks, reaching a stable value close to 20% at 10 weeks after hospitalization. When Coxs regression adjusted for age, gender and comorbidities was performed, hyperpotassemia was shown to be an independent risk factor for in-hospital mortality (RR = 1.22, 95% CI: 1.14-1.30) in this group of patients. These results reinforced that the electronic health record may contain, already in the first hours of hospitalization, relevant information to understand the progression of diseases and identify future directions for research. This study is expected to clarify important topics related to the MIMIC-IV database and enable further research using this patient database. Knowledge of the characteristics of the CCU population can allow better management of physical and human hospital resources.


title: Alternative Factor Prescribing after Low-Dose Recombinant Factor VIIa Protocol in Cardiac Surgery

abstract:
BackgroundSafety concerns exist with the off-label use of recombinant factor VIIa (rFVIIa, Novoseven RT(R)) for refractory bleeding in cardiac surgery, including increased risk of thromboembolism. A rFVIIa protocol was implemented in December 2015 to standardize rFVIIa for cardiac surgery related hemorrhage.

MethodsWe performed a retrospective, observational review of rFVIIa in adult cardiac surgery patients pre-protocol (January 2015 to November 2015) vs. post-protocol (December 2015 to March 2016). Study outcomes were rate of rFVIIa administration, rFVIIa dosing characteristics, length of stay, mortality, readmission rate, need for re-exploration, and rate of 4-factor Prothrombin Complex Concentrates (PCC; Kcentra(R)) administration.

ResultsThere was a significant reduction in percentage of cardiac surgery cases receiving rFVIIa pre-vs. post-protocol (14.3 vs. 5.2%, p=0.015). Average total dose per patient decreased between groups (81.4 vs. 56.6 mcg/kg, p=0.059). In-hospital mortality, length of stay, need for re-exploration, readmission rates and 30-day mortality did not differ. Although 4-four-factor PCC significantly increased post-protocol (2.5% vs. 8%, p=0.02), overall use of factor products, rFVIIa or 4-factor PCC, did not change between study periods (16.8% vs. 13%, p=0.416). Mean cost of either rFVIIa or 4-factor PCC pre-protocol was significantly higher than that post-protocol ($8,778 vs. $4,421, p=0.0008).

ConclusionsThe use of rFVIIa decreased after implementation of a rFVIIa protocol targeting 30 mcg/kg/dose without compromising morbidity or mortality outcomes. Four-factor PCC use significantly increased during the study, but the overall cost was reduced. Institutions wanting to implement a rFVIIa protocol should take careful measures to concurrently address off-label use of 4-factor PCC.


title: Effectiveness of ChAdOx1-S COVID-19 Booster Vaccination against the Omicron and Delta variants in England

abstract:
BackgroundDespite the potential widespread global use of the ChAdOx1-S booster, to date there are no published data on the real-world effectiveness. VE studies have found one and two doses of the ChAdOx1-S vaccine to be highly effective, and clinical trial data have demonstrated enhanced immunity following a ChAdOx1-S booster. In England, some individuals received a ChAdOx1-S booster where vaccination with mRNA vaccines was clinically contraindicated.

MethodsThe demographic characteristics of those who received a ChAdOx1-S booster were compared to those who received a BNT162b2 booster. A test-negative case control design was used to estimate vaccine effectiveness of the ChAdOx1-S booster against symptomatic disease and hospitalisation in England.

FindingsThose who received a ChAdOx1-S booster were more likely to be female (adjusted odds ratio (OR) 1.67 (1.64-1.71)), in a clinical risk group (adjusted OR 1.58 (1.54-1.63)), in the CEV group (adjusted OR 1.84 (1.79-1.89)) or severely immunosuppressed (adjusted OR 2.05 (1.96-2.13)).

Protection against symptomatic disease in those aged 65 years and older peaked at 66.1% (16.6 to 86.3%) and 68.5% (65.7 to 71.2%) amongst those who received the ChAdOx1-S and BNT162b2 booster vaccines, respectively. Protection waned to 44.5% (22.4 to 60.2%) and 54.1% (50.5 to 57.5%) after 5-9 weeks. Protection against hospitalisation following Omicron infection peaked at 82.3% (64.2 to 91.3%) after receiving a ChAdOx1-S booster, as compared to 90.9% (88.7 to 92.7%) for those who received a BNT162b2 booster.

InterpretationDifferences in the population boosted with ChAdOx1-S in England renders direct comparison of vaccine effectiveness by manufacturer challenging. Nonetheless, this study supports the use of the ChAdOx1-S booster for protection against severe disease with COVID-19 in settings that have not yet offered booster doses and suggests that those who received ChAdOx1-S as a booster in England do not require re-vaccination ahead of others.

FundingUKHSA

category: epidemiology


title: Forecast Intervals for Infectious Disease Models

abstract: Forecast intervals for infectious disease transmission and mortality have long been overconfident -- i.e., the advertised coverage probabilities of those intervals fell short of their subsequent performances. Further, there was no apparent relation between how good models claimed to be (as measured by their purported forecast uncertainties) and how good the models really were (as measured by their actual forecast errors). The main cause of this problem lies in the misapplication of textbook methods for uncertainty quantification. A solution lies in the creative use of predictive tail probabilities to obtain valid interval coverages. This approach is compatible with all probabilistic predictive models whose forecast error behavior does not change "too quickly" over time.


title: Human behaviour, NPI and mobility reduction effects on COVID-19 transmission in different countries of the world

abstract:
BackgroundThe outbreak of Coronavirus disease, which originated in Wuhan, China in 2019, has affected the lives of billions of people globally. Throughout 2020, the reproduction number of COVID-19 was widely used by decision-makers to explain their strategies to control the pandemic.

MethodsIn this work, we deduce and analyze both initial and effective reproduction numbers for 12 diverse world regions between February and December of 2020. We consider mobility reductions, mask wearing and compliance with masks, mask efficacy values alongside other non-pharmaceutical interventions (NPIs) in each region to get further insights in how each of the above factored into each regions SARS-COV-2 transmission dynamic.

ResultsWe quantify in each region the following reductions in the observed effective reproduction numbers of the pandemic: i) reduction due to decrease in mobility (as captured in Google mobility reports); ii) reduction due to mask wearing and mask compliance; iii) reduction due to other NPIs, over and above the ones identified in i) and ii).

ConclusionIn most cases mobility reduction coming from nationwide lockdown measures has helped stave off the initial wave in countries who took these types of measures. Beyond the first waves, mask mandates and compliance, together with social-distancing measures (which we refer to as other NPIs) have allowed some control of subsequent disease spread. The methodology we propose here is novel and can be applied to other respiratory diseases such as influenza or RSV.


title: Vaccine Stockpile Sharing For Selfish Objectives

abstract: The COVAX program aims to provide global equitable access to life-saving vaccines. However, vaccine protectionism by wealthy nations has limited progress towards vaccine sharing goals. For example, as of April 2022 only[~] 20% of the population in Africa has received at least one COVID-19 vaccine dose. Here we use a two-nation coupled epidemic model to evaluate optimal vaccine-sharing policies given a selfish objective: in which countries with vaccine stockpiles aim to minimize fatalities in their own populations. Despite the selfish objective, we find it is often optimal for a donor nation to share a significant fraction of its vaccine stockpile. Mechanistically, sharing a vaccine stockpile reduces the intensity of outbreaks in the recipient nation, in turn reducing travel-associated incidence in the donor nation. This effect is intensified as vaccination rates decrease and epidemic coupling increases. Despite acting selfishly, vaccine sharing by a donor nation significantly reduces transmission and fatalities in the recipient nation. Moreover, we find that there are hybrid sharing policies that have a negligible effect on fatalities in the donor nation compared to the optimal policy while significantly reducing fatalities in the recipient nation. Altogether, these findings provide a rationale for nations with extensive vaccine stockpiles to share with other nations.


title: Health-Related Quality of Life and Coping Strategies adopted by COVID-19 survivors: A nationwide cross-sectional study in Bangladesh

abstract:
This study aims to investigate the health-related quality of life and coping strategies among COVID-19 survivors in Bangladesh.

MethodsThis is a cross-sectional study of 2198 adult, COVID-19 survivors living in Bangladesh. Data were collected from previously diagnosed COVID-19 participants (confirmed by an RT-PCR test) via door-to-door interviews in the eight different divisions in Bangladesh. For data collection, Bengali translated Brief COPE inventory and WHO Brief Quality of Life (WHO-QOLBREF) questionnaires were used. The data collection period was from June 2020 to March 2021.

ResultsMales 72.38% (1591) were more affected by COVID-19 than females 27.62% (607). Age showed significant correlations (p<0.005) with physical, psychological and social relationships; whereas, gender showed only significant correlation with physical health (p<0.001). Marital status, occupation, living area, and co-morbidities showed significant co-relation with all four domains of QoL (p<0.001). Education and affected family members showed significant correlation with physical and social relationship (p<0.001). However, smoking habit showed significant correlations with both social relationship and environment (p<0.001). Age and marital status showed a significant correlation with avoidant coping strategy (p<0.001); whereas gender and co-morbidities showed significant correlation with problem focused coping strategies (p<0.001). Educational qualification, occupation and living area showed significant correlation with all three coping strategies (p<0.001).

ConclusionSurvivors of COVID-19 showed mixed types of coping strategies; however, the predominant coping strategy was avoidant coping, followed by problem focused coping, with emotion focused coping reported as the least prevalent. Marital status, occupation, living area and co-morbidities showed a greater effect on QoL in all participants. This study represents the real scenario of nationwide health associated quality of life and coping strategy during and beyond the Delta pandemic.


title: Pre-morbid use of proton pump inhibitors has no effect on the risk of death or hospitalization in COVID-19 patients: a matched cohort study

abstract:
BackgroundSeveral studies assessed the effect of pre-morbid exposure to proton pump inhibitors (PPIs) on disease course in adult COVID-19 patients with somewhat inconsistent results.

MethodsThis population-based matched cohort study embraced first COVID-19 episodes in adults diagnosed up to August 15 2021 in Croatia. Considering over-the-counter (OTC) availability of PPIs, patients were classified based on exposure to PPIs and burden of PPI-requiring conditions as "non-users" (no issued prescriptions, no recorded treatment-requiring conditions between January 1 2019 and COVID-19 diagnosis), "possible users" (no issued prescriptions, recorded treatment-requiring conditions; OTC use possible) and "users" (different intensity of issued prescriptions over 12 months prior to diagnosis, at least one within 3 months). Subsets were mutually exactly matched in respect to a range of pre-COVID-19 characteristics. The contrast between "users" and "possible users" was considered the most informative for the effect of PPIs that is separate of the effect of PPI-requiring conditions.

ResultsAmong 433609 COVID-19 patients, 332389 were PPI "non-users", 18170 were "possible users", and 55098 were "users". Users and possible users were matched 41195 to 17334 and 33272 to 16434 in the primary and sensitivity analyses. There was no relevant difference between "users" and "possible users" regarding COVID-19-related mortality [RR=0.93 (95%CI 0.85-1.02; RD= -0.34% (-0.73, 0.03) in primary and RR=0.88 (0.78-0.98); RD=-0.45 (- 0.80, -0.11) in sensitivity analysis] or COVID-19-related hospitalizations [RR=1.04 (0.97-1.13); RD=0.29% (-0.16, 0.73) in primary and RR=1.05 (0.97-1.15); RD=0.32% (-0.12, 0.75) in sensitivity analysis].

ConclusionsPre-morbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients.

category: gastroenterology


title: Clinicopathological and Imaging Features of Primary Biliary Cholangitis

abstract:
Abstract/KeywordsO_ST_ABSBackground and AimsC_ST_ABSPrimary biliary cholangitis (PBC) is a chronic inflammatory autoimmune disease of the biliary epithelial cells, causing slow progression of cholestasis and fibrosis. The aim of the study is to summarize the imaging features of PBC and examine the correlation between its clinicopathological and radiologic features, elucidating the specific clinicopathological and radiologic differences between male and female PBC patients, as well as between AMA-positive and AMA-negative PBC patients.

MethodsDemographic, laboratory, radiologic and survival data were collected retrospectively for patients diagnosed and treated for PBC at the Mount Sinai Health System between 2016 and 2020 with at least one ultrasound, CT, or MRI of abdomen available for assessment. Biochemical and radiologic data were compared between male v.s. female groups, and AMA-positive v.s. AMA-negative group.

ResultsA total of 273 patients diagnosed with PBC were included. Non-specific hepatic parenchymal disease, cirrhosis, cholelithiasis, splenomegaly, lymphadenopathy, benign liver masses/cysts were the most common features on abdominal images. 24% of PBC patients had biliary tree abnormalities on MRI. LAD was reported in 38-47% of PBC patients. There was no significant difference in age, race, or ethnicity between the sexes of patients with PBC, however imaging characteristics of portal hypertension were more frequently seen in men. AMA-negative PBC patients had similar distributions of age, race/ethnicity and survival to AMA-positive PBC patients.

ConclusionOur study summarized the clinicopathological and imaging features of PBC and distinct subgroups. This would assist in the diagnosis of PBC and avoid over-testing in real-world practice.


title: Prevalence and Genotypic Characterization of Extended Spectrum Beta-Lactamase Uropathogens Isolated from Refugees with Urinary Tract Infections in Nakivale Refugee Settlement camp, Southwestern Uganda

abstract:
BackgroundWorld Health Organization approximates that one in four individuals have had at least one UTI episode requiring treatment with an antimicrobial agent by the teen age. At Nakivale refugee camp, the overwhelming number of refugees often associated with poor living conditions such as communal bathrooms and toilets and multiple sex partners do predispose the refuges to urinary tract infections.

AimTo determine the prevalence of bacterial community-onset urinary tract infections among refugees in Nakivale refugee settlement and determine the antimicrobial susceptibility patterns of the isolated pathogens.

MethodsThis study was a cross-sectional study, that included 216 outpatients attending Nakivale Health Centre III between July and September 2020.

ResultsPrevalence of UTI was 24.1% (52/216). The majority 86(39.81%) of the refugees were from DR Congo, followed by those from Somalia 58(26.85%). The commonest causative agent was Staphylococcus aureus 22/52 (42.31%) of total isolates, followed by Escherichia coli 21/52(40.38%). Multidrug resistant isolates accounted for 71.15% (37/52) and mono resistance was 26.92% (14/52). Out of the 52 bacterial isolates, 30 (58%) were Extended-Spectrum Beta-Lactamase organisms (ESBLs). Twenty-one (70.0%) isolates were ESBL producers while 9(30%) were non-ESBL producers. Both blaTEM and blaCTX-M were 62.5% each while blaSHV detected was 37.5%.

ConclusionsThe prevalence of UTI among refugees in Nakivale settlement is high with Staphylococcus aureus and Escherichia coli as the commonest causes of UTI. There is a high rate of multidrug resistance to common drugs used to treat UTI. The prevalence of ESBL-producing Enterobacteriaceae is high and the common ESBL genes are blaTEM and blaCTX-

category: pathology


title: Early life attachment in term and preterm infants.

abstract:
1BackgroundPreterm birth is associated with atypical cognitive and socioemotional outcomes in childhood. Secure infant attachment protects against adverse outcomes, but could be modified by alterations in the early caregiving environment inherent to essential neonatal intensive care or co-morbidities of preterm birth. We aimed to test the hypothesis that preterm birth is associated with differences in infant attachment compared with infants born at term, and to investigate clinical, neurodevelopmental and socioeconomic variables that could contribute to variance in infant attachment.

Methods68 preterm and 68 term infants with mean (range) gestational age at birth 29.7 (22.1 - 32.9) and 39.6 (36.4 - 42.1) weeks, respectively, completed the Still-Face Paradigm (SFP) at nine months of corrected age. Attachment dimensions and categories were obtained from infant responses to the SFP using a published coding scheme, and an alternative principal component and clustering strategy. Neurodevelopment was assessed using the Vineland Adaptive Behaviour Scales, and socioeconomic status was operationalized as neighborhood deprivation.

ResultsPreterm and term infants did not differ in attachment dimensions (distress, fretfulness, attentiveness to caregivers, p-values > .07; principal components, p-values > .07), or the distribution of attachment categories (attachment styles, p-value = .79; attachment clusters, p-value > .78). In the whole sample, fretfulness correlated with socioeconomic deprivation (n = 136, rs = -0.23, p-value < .01), and attentiveness correlated with motor development (n = 120, rs = .24, p-value < .01).

ConclusionsThere were no differences in attachment between preterm and term infants at nine months of age, suggesting that caregiver-infant attachment relationships are resilient to the effects of prematurity on the developing infant. The results highlight links between socioeconomic deprivation and infant attachment, and suggest there is a relationship between infant attentiveness and motor function in infancy.

category: pediatrics


title: In schizophrenia, the effects of the IL-6/IL-23/Th17 axis on health-related quality of life and disabilities are partly mediated by generalized cognitive decline and the symptomatome.

abstract: Schizophrenia patients show increased disabilities and lower quality of life (DisQoL). Nevertheless, there are no data whether, in schizophrenia, activation of the interleukin (IL)-6, IL-23, T helper (Th)-17 axis and lowered magnesium and calcium levels impact DisQoL scores. This study recruited 90 patients with schizophrenia (including 40 with deficit schizophrenia) and 40 healthy controls and assessed the World Health Association QoL instrument-Abbreviated version and Sheehan Disability scale, Brief Assessment of Cognition in Schizophrenia (BACS), IL-6, IL-23, IL-17, IL-21, IL-22, tumor necrosis factor (TNF)-, magnesium and calcium. Regression analyses showed that a large part of the first factor extracted from the physical, psychological, social and environmental HR-QoL and interference with school/work, social life, and home responsibilities was predicted by a generalized cognitive deterioration (G-CoDe) index (a latent vector extracted from BACs scores), and the first vector extracted from various symptom domains ("symptomatome"), whereas the biomarkers had no effects. Partial Least Squares analysis showed that the IL6IL23Th17 axis and magnesium/calcium had highly significant total (indirect + direct) effects on HR-QoL/disabilities which were mediated by G-CoDe and the symptomatome (a first factor extracted from negative and positive symptoms). The IL6IL23Th17 axis explained 63.1% of the variance in a single latent trait extracted from G-CoDe, symptomatome, HR-QoL and disability data. The latter features are manifestations of a common core, namely the behavioral-cognitive-psycho-social worsening index, which is caused by the neuroimmunotoxic effects of the IL6IL23Th17 axis in subjects with lowered antioxidant defenses (magnesium and calcium) thereby producing damage to neuronal circuits underpinning deficit schizophrenia.

category: psychiatry and clinical psychology


title: Categorical and dimensional brain network-based models of trauma-related dissociative subtypes

abstract:
BackgroundTrauma-related pathological dissociation is a multidimensional and disabling phenomenon that involves disruptions or discontinuities in psychological functioning. Despite its prevalence, personal and societal burden, dissociation remains underappreciated in clinical practice, and it lacks a synthesized neurobiological model that could place it in context with other common psychiatric symptoms. To identify a nuanced neurobiological model of pathological dissociation, we examined the functional connectivity of three core neurocognitive networks as related to the dimensional dissociation subtypes of depersonalization/derealization and partially-dissociated intrusions, and the diagnostic category of a complex dissociation disorder, dissociative identity disorder (DID).

MethodsParticipants were 91 adult women with and without: a history of childhood trauma, current posttraumatic stress disorder (PTSD) and varied levels of pathological dissociation. Participants provided interview and self-report data about pathological dissociation, PTSD symptoms, childhood maltreatment history, and completed a resting-state functional magnetic resonance imaging scan.

ResultsAfter controlling for age, childhood maltreatment and PTSD symptom severity, we found that pathological dissociation was associated with hyperconnectivity within central executive, default, and salience networks, and decreased connectivity of central executive and salience networks with other areas. Moreover, we isolated unique connectivity markers linked to depersonalization/derealization, to partially-dissociated intrusions, and to DID.

ConclusionsOur work suggests subtypes of pathological dissociation have robust, discernable, and unique functional connectivity signatures. The neural correlates of dissociation may serve as potential targets for treatment engagement to facilitate recovery from PTSD and pathological dissociation. These results underscore dissociation assessment as crucial in clinical and medical care settings.


title: Quantifying the relationship between sub-population wastewater samples and community-wide SARS-CoV-2 seroprevalence

abstract:
BackgroundWastewater-based epidemiology is a promising approach but robust epidemiological models to relate wastewater to community prevalence are lacking. Assessments of SARS-CoV-2 infection rates have relied primarily on convenience sampling, which does not provide reliable estimates of community prevalence because of inherent biases.

MethodsFrom August 2020 to February 2021, we conducted a serial stratified randomized samplings to estimate the prevalence of anti-SARS-CoV-2 antibodies in 3,717 participants, and weekly sampling of community wastewater for SARS-CoV-2 concentrations in Jefferson County, KY. With the use of a Susceptible, Infected, Recovered (SIR)-type model, we obtained longitudinal estimates of prevalence and compared these with wastewater concentration, using regression analysis.

FindingsModel analysis revealed significant temporal differences in epidemic peaks; the average incidence rate based on serological sampling in some areas was up to 50% higher than health department rates based on convenience sampling. The model-estimated average prevalence rates correlated well with wastewater (correlation=0{middle dot}63). In regression analysis, a weekly unit increase in wastewater concentration of SARS-CoV-2 corresponded to an average increase of between 1-1{middle dot}3 cases of SARS-CoV-2 infection per 100K residents.

InterpretationPublicly available health department incidence rates vastly underestimate true community incidence and wastewater has a high potential to provide robust estimates of community spread of infection.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAdministratively reported clinical case rates of coronavirus disease 2019 (COVID-19) infected individuals are biased due to a wide range of factors from testing access to concerns about missing low and non-symptomatic and self-tested individuals. Wastewater estimates offer an alternative to support community monitoring based on fecal shedding of the virus but are difficult to interpret when compared with the available public health data sets of infection rates. We examined all English literature until February 24, 2022, on Web of Science and PubMed with the terms ["seroprevalence" or "antibody"] AND ["COVID-19" or "SARS-CoV-2"] AND ["wastewater"]. We identified six studies. None of these studies considered randomized COVID-19 community anti-SARS-CoV-2 antibody testing paired with wastewater data.

Added value of this studyThe study demonstrates how results from serial stratified randomized serological sampling of the community can be used to build a longitudinal model that can interpolate and extrapolate community levels of infection beyond specific testing dates. Such a model correlates well with wastewater concentrations indicating its utility as a surrogate for infection prevalence. The testing data used in the study were collected before wide availability of COVID-19 vaccines and are therefore unique as they are unlikely to include a significant number of false positive results.

Implications of all the available evidenceThe study demonstrates that convenience sampling obtained data from health department reporting seriously underestimates community-wide prevalence of infection. In contrast, wastewater-based epidemiology may be a faster, cost-effective, and more robust method of estimating the prevalence of viral infections within specific urban areas.

category: public and global health


title: How did the COVID-19 pandemic affect access to condoms, chlamydia and HIV testing, and cervical cancer screening at a population level in Britain? (Natsal-COVID)

abstract:
ObjectivesTo investigate how differential access to key interventions to reduce sexually transmitted infections (STI), HIV, and their sequelae changed during the COVID-19 pandemic.

MethodsBritish participants (18-59y) completed a cross-sectional web survey one year (March to April 2021) after the initial lockdown in Britain. Quota-based sampling and weighting resulted in a quasi-representative population sample. We compared Natsal-COVID data with Natsal-3, a household-based probability sample cross-sectional survey (16-74y) conducted in 2010-12. Reported unmet need for condoms because of the pandemic and uptake of chlamydia testing/HIV testing/cervical cancer screening were analysed among sexually-experienced participants (18-44y) (n=2869, Natsal-COVID; n=8551, Natsal-3). Odds ratios adjusted for age (aOR) and other potential confounders (AOR) describe associations with demographic and behavioural factors.

ResultsIn 2021, 6.9% of women and 16.2% of men reported unmet need for condoms because of the pandemic. This was more likely among participants: aged 18-24 years, of Black or Black British ethnicity, and reporting same-sex sex (past five years) or one or more new relationships (past year). Chlamydia and HIV testing were more commonly reported by younger participants, those reporting condomless sex with new sexual partners, and men reporting same-sex partners; a very similar distribution to 10 years previously (Natsal-3). However, there were differences during the pandemic, including stronger associations with chlamydia testing for men reporting same-sex partners; with HIV testing for women reporting new sexual partners; and with cervical screening among smokers.

ConclusionsOur study suggests differential access to key primary and secondary STI/HIV prevention interventions continued during the first year of the COVID-19 pandemic. However, the available evidence does not suggest substantial changes in inequalities in since 2010-12. While the pandemic might not have exacerbated inequalities in access to primary and secondary prevention, it is clear that large inequalities persisted, typically among those at greatest STI/HIV risk.

Key MessagesO_LIMany MSM, people of Black ethnicity and young people (i.e. groups most impacted by STIs) reported unmet need for condoms because of the pandemic
C_LIO_LIWe compared inequalities in access to key interventions using Natsal-COVID (2021) and Natsal-3 (2010-12).
C_LIO_LIDuring the pandemic (Natsal-COVID), there were stronger associations with chlamydia testing for MSM and with HIV testing for women reporting new sexual partners.
C_LIO_LIThere were stronger associations with cervical screening among smokers during the pandemic compared to 2010-12 (Natsal-3).
C_LIO_LIHowever, we did not find strong evidence that vulnerable groups were at additional risk during the pandemic when compared to 2010-12.
C_LI

category: sexual and reproductive health


title: Genetic Risk Factors for Postoperative Atrial Fibrillation - a Nationwide Genome-Wide Association Study (GWAS)

abstract:
BackgroundAtrial fibrillation (AF) is a major cause of morbidity with a high prevalence among the elderly and has an established genetic disposition. Surgery is a well-known risk factor for AF; however, it is currently not recognized how much common genetic variants influence the postoperative risk. The purpose of this study was to identify Single Nucleotide Polymorphisms associated with postoperative AF.

MethodsThe UK Biobank was utilized to conduct a Genome-Wide Association Study (GWAS) to identify variants associated with AF after surgery. An initial discovery GWAS was performed in patients that had undergone surgery with subsequent replication in a unique non-surgical cohort. In the surgical cohort, cases were defined as newly diagnosed AF within 30 days after surgery. The threshold for significance was set at 5 x 10-8.

ResultsAfter quality control, 144,196 surgical patients with 254,068 SNPs were left for analysis. Two variants (rs17042171 (p = 4.86 x 10-15) and rs17042081 (p = 7.12 x 10-15)) near the PITX2-gene reached statistical significance. These variants were replicated in the non-surgical cohort (1.39 x 10-101 and 1.27 x 10-93, respectively). Several other loci were significantly associated with AF in the non-surgical cohort.

ConclusionIn this GWAS-analysis of a large national biobank, we identified 2 variants that were significantly associated with postoperative AF. These variants were subsequently replicated in a unique non-surgical cohort. These findings bring new insight in the genetics of postoperative AF and may help identify at-risk patients and guide management.

category: surgery


title: Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients

abstract:
BackgroundSolid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3rd- (V3) and 4th- (V4) doses of heterologous and homologous vaccines in a kidney transplant population.

Methods724 kidney transplant recipients were prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their 1st dose of vaccine.

Results586/724 (80.9%) patients were infection-naive post-V3; 141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001; immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001.

Post-V4, 45/239 (18.8%) infection-naive patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients who were seronegative post-V3. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. Anti-S post-V4 were sequentially greater in those seroconverting post V2- compared with V3-, and V3- compared with V4-, at 1561 (567-5211), 379 (101-851) and 19 (9.7-48) BAU/ml respectively.

T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type.

ConclusionA significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection.

category: transplantation


title: Predicting longitudinal brain atrophy in Parkinson's disease using a Susceptible-Infected-Removed agent-based model

abstract: Parkinsons disease (PD) is a progressive neurodegenerative disorder characterized by accumulation of abnormal isoforms of alpha-synuclein. Alpha-synuclein is proposed to act as a prion in PD: in its misfolded pathologic state it favours the misfolding of normal alpha-synuclein molecules, spreads trans-neuronally, and causes neuronal or synaptic damage as it accumulates. This theory remains controversial. We have previously developed a Susceptible-Infected-Removed (SIR) computational model that simulates the templating, propagation and toxicity of alpha-synuclein molecules in the brain. Here we test this model with longitudinal MRI collected over four years from the Parkinson Progression Markers Initiative (1068 T1 MRI scans, 790 PD, 278 matched controls). We find that brain deformation progresses in subcortical and cortical regions. The SIR model, using structural connectivity from diffusion MRI, recapitulates the spatiotemporal distribution of brain atrophy observed in PD. We show that connectome topology and geometry significantly contribute to model fit. We also show that the spatial expression of two genes implicated in alpha-synuclein synthesis and clearance, SNCA and GBA, also influences the atrophy pattern. We conclude that the progression of atrophy in PD is consistent with the prion-like hypothesis and that the SIR model is a promising tool to investigate multifactorial neurodegenerative diseases over time.

category: neurology


title: Death by Round Numbers and Sharp Thresholds: How to Avoid Dangerous AI EHR Recommendations

abstract: Recommendations for clinical practice consider consistency of application and ease of implementation, resulting in treatment decisions that use round numbers and sharp thresholds even though these choices produce statistically sub-optimal decisions. To characterize the impact of these choices, we examine four datasets and the biases underlying patient mortality risk. We document two types of suboptimalities: (1) discontinuities in which treatment decisions produce step-function changes in risk near clinically-important round-number cutoffs, and (2) counter-causal paradoxes in which anti-correlation between risk factors and aggressive treatment produces risk curves that contradict underlying causal risk. We also show that outcomes have improved over decades of refinement of clinical practice, reducing but not eliminating the strength of these biases. Finally, we provide recommendations for clinical practice and data analysis: interpretable "glass-box" models can transform the challenges of statistical confounding into opportunities to improve medical practice.

category: health informatics


title: A comprehensive accuracy assessment of Samsung smartwatch heart rate and heart rate variability

abstract:
BackgroundPhotoplethysmography (PPG) is a low-cost and easy-to-implement method to measure vital signs, including heart rate (HR) and heart rate variability (HRV). The method is widely used in various wearable devices. For example, Samsung smartwatches are PPG-based open-source wristbands used in remote well-being monitoring and fitness applications. However, PPG is highly susceptible to motion artifacts and environmental noise. A validation study is required to investigate the accuracy of PPG-based wearable devices in free-living conditions.

ObjectiveWe evaluate the accuracy of PPG signals - collected by the Samsung Gear Sport smartwatch in free-living conditions - in terms of HR and time-domain and frequency-domain HRV parameters against a medical-grade chest electrocardiogram (ECG) monitor.

MethodsWe conducted 24-hours monitoring using a Samsung Gear Sport smartwatch and a Shimmer3 ECG device. The monitoring included 28 participants (14 male and 14 female), where they engaged in their daily routines. We evaluated HR and HRV parameters during the sleep and awake time. The parameters extracted from the smartwatch were compared against the ECG reference. For the comparison, we employed the Pearson correlation coefficient, Bland-Altman plot, and linear regression methods.

ResultsWe found a significantly high positive correlation between the smartwatchs and Shimmer ECGs HR, time-domain HRV, LF, and HF and a significant moderate positive correlation between the smartwatchs and shimmer ECGs LF/HF during sleep time. The mean biases of HR, time-domain HRV, and LF/HF were low, while the biases of LF and HF were moderate during sleep. The regression analysis showed low error variances of HR, AVNN, and pNN50, moderate error variances of SDNN, RMSSD, LF, and HF, and high error variances of LF/HF during sleep. During the awake time, there was a significantly high positive correlation of AVNN and a moderate positive correlation of HR, while the other parameters indicated significantly low positive correlations. RMSSD and SDNN showed low mean biases, and the other parameters had moderate mean biases. In addition, AVNN had moderate error variance while the other parameters indicated high error variances.

ConclusionThe Samsung smartwatch provides acceptable HR, time-domain HRV, LF, and HF parameters during sleep time. In contrast, during the awake time, AVNN and HR show satisfactory accuracy, and the other HRV parameters have high errors.


title: An intermediate step in bridging the gap between evidence and practice: developing and applying a methodology for "general good practices"

abstract:
The gap between evidence and clinical practice has been in the focus of researches for decades. Although successful implementation means the new knowledge must work in particular environments, it doesnt mean that the entire process should exclusively be executed by the individual institutes. This is the point where we assumed that an intermediate step, the "general good practice", could help to ensure that translation is done in a more professional way.

The development of the general good practice methodology was based on our infinitE model, which organized the factors of successful translation into an evidence-editing-embedding-effect on practice framework, using tools from the disciplines of Evidence-Based Medicine, Quality Improvement and Change Management.

The methodology organised the editing and embedding part of the development into a process involving three full-day sessions carried out with different health professionals, experts and moderators. After pilot testing, it was finalized and applied to other topics as well.

The methodology presented in detail in this paper, centred on flow chart, process analysis, failure mode identification and Kotters 8-step model. Beside the pilot topic of the institutional process of resuscitation, the methodology has also proved applicable to more than ten other topics, meaning that at least all the core elements of the proposed bundle of general good practice have been produced in the development process.

Compared to the guidelines, general good practices demonstrate the evidence in operation, helping to develop workflows, responsibilities, documentation, trainings, etc. and can also be a starting point for the digitalisation of care processes.

The next step is to examine how healthcare institutions can build on these in their own editing and embedding activities, and what the results will be. Further studies could explore the applicability of the development methodology in different healthcare systems or at different levels of maturity in terms of quality.

category: health systems and quality improvement


title: Healthcare workers' mental health and wellbeing during the COVID-19 pandemic: Longitudinal analysis of interview and social media data

abstract: The COVID-19 pandemic has shed light on the fractures of healthcare systems around the world, particularly in relation to the healthcare workforce. Frontline staff, in particular, have been exposed to unprecedented strain and delivering care during the pandemic has impacted their safety, mental health and wellbeing. The aim of this paper was to explore the experiences of HCWs delivering care in the UK during the COVID-19 pandemic to understand their wellbeing needs, experiences and strategies used to maintain wellbeing (at individual and organizational levels). We analysed 94 telephone interviews with HCWs and 2000 tweets about HCWs mental health taking place during the first year of the COVID-19 pandemic. Results were grouped under six themes: redeployment; wellbeing support and coping strategies; mental health effects; organisational support; social network and public support. These findings demonstrate a need for open conversations, where staffs wellbeing needs and strategies can be shared and encouraged, rather than implementing solely top-down psychological interventions. At the macro level, findings also highlighted the impact on HCWs wellbeing of public and government support, as well as the need for ensuring protection through PPE, testing, and/or vaccines for frontline workers.


title: A methodology to generate epidemic scenarios for emerging infectious diseases based on the use of key calendar events

abstract: This work presents a methodology to recreate the observed dynamics of emerging infectious diseases and to generate short-term forecasts for their evolution based on superspreading events occurring on key calendar dates. The method is illustrated by the COVID-19 pandemic dynamics in Mexico and Peru up to January 31, 2022. We also produce scenarios obtained through the estimation of a time-dependent contact rate, with the main assumption that the dynamic of the disease is determined by the mobility and social activity of the population during holidays and other important calendar dates. First, historical changes in the effective contact rate on predetermined dates are estimated. Then, this information is used to forecast scenarios under the assumption that the trends of the effective contact rate observed in the past will be similar on the same but future key calendar dates. All other conditions are assumed to remain constant in the time scale of the projections. One of the main features of the methodology is that it avoids the necessity of fixing values of the dynamic parameters for the whole prediction period. Results show that considering the key dates as reference information is useful to recreate the different outbreaks, slow or fast-growing, that an epidemic can present and, in most cases, make good short-term predictions.


title: Omicron sub-lineages BA.4/BA.5 escape BA.1 infection elicited neutralizing immunity

abstract: The SARS-CoV-2 Omicron (B.1.1.529) variant first emerged as the BA.1 sub-lineage, with extensive escape from neutralizing immunity elicited by previous infection with other variants, vaccines, or combinations of both1,2. Two new sub-lineages, BA.4 and BA.5, are now emerging in South Africa with changes relative to BA.1, including L452R and F486V mutations in the spike receptor binding domain. We isolated live BA.4 and BA.5 viruses and tested them against neutralizing immunity elicited to BA.1 infection in participants who were Omicron/BA.1 infected but unvaccinated (n=24) and participants vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV.2S with breakthrough Omicron/BA.1 infection (n=15). In unvaccinated individuals, FRNT50, the inverse of the dilution for 50% neutralization, declined from 275 for BA.1 to 36 for BA.4 and 37 for BA.5, a 7.6 and 7.5-fold drop, respectively. In vaccinated BA.1 breakthroughs, FRNT50 declined from 507 for BA.1 to 158 for BA.4 (3.2-fold) and 198 for BA.5 (2.6-fold). Absolute BA.4 and BA.5 neutralization levels were about 5-fold higher in this group versus unvaccinated BA.1 infected participants. The observed escape of BA.4 and BA.5 from BA.1 elicited immunity is more moderate than of BA.1 against previous immunity1,3. However, the low absolute neutralization levels for BA.4 and BA.5, particularly in the unvaccinated group, are unlikely to protect well against symptomatic infection4.This may indicate that, based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave.


title: A machine learning based predictive model for the diagnosis of sepsis

abstract: The early recognition and treatment of sepsis is essential to increase the probability of survival of the patient. Sepsis is a complex and heterogeneous syndrome influenced by the site of infection, causative microorganisms, acute organ dysfunctions and co-morbidities. So, early diagnosis is a challenge in which complex physiologic, metabolic, biochemical markers and clinical signs must be evaluated simultaneously for a reliable and early identification of sepsis. In this paper, a list of relevant variables involved in sepsis diagnosis is provided. Furthermore, to help answering the question of whether a patient is suffering from sepsis when entering the emergency room, a model based on the machine learning gradient boosting algorithm is proposed. Using three histones H2B, H3, H4 and the activated protein C together with other variables a gradient boosting classifier was trained and evaluated with cross validation. Results show that the model can achieve up to a 97% mean per-class accuracy.

category: intensive care and critical care medicine


title: Evidence for Aerosol Transfer of SARS-CoV2-specific Humoral Immunity

abstract: Despite the obvious knowledge that infectious particles can be shared through respiration, whether other constituents of the nasal/oral fluids can be passed between hosts has surprisingly never even been postulated, let alone investigated. The circumstances of the present pandemic facilitated a unique opportunity to fully examine this provocative idea. The data we show provides evidence for a new mechanism by which herd immunity may be manifested, the aerosol transfer of antibodies between immune and non-immune hosts.

category: allergy and immunology


title: Association between Intraoperative End-Tidal Carbon Dioxide and Postoperative Organ Dysfunction in Major Abdominal Surgery: A Retrospective Cohort Study

abstract:
BackgroundData on the effects of intraoperative end-tidal carbon dioxide (EtCO2) levels on postoperative organ dysfunction are limited. Thus, this study was designed to investigate the relationship between the intraoperative EtCO2 level and postoperative organ dysfunction in patients who underwent major abdominal surgery under general anesthesia.

MethodsWe conducted a retrospective cohort study involving patients who underwent major abdominal surgery under general anesthesia at Kyoto University Hospital. We classified those with a mean EtCO2 of less than 35 mmHg as low EtCO2. The time effect was determined as the minutes when the EtCO2 value was below 35 mmHg, whereas the cumulative effect was evaluated by measuring the area below the 35-mmHg threshold. The outcome was postoperative organ dysfunction, defined as a composite of at least one organ dysfunction among acute renal injury, circulatory dysfunction, respiratory dysfunction, coagulation dysfunction, and liver dysfunction within 7 days after surgery.

ResultsOf the 4,171 patients, 1,195 (28%) had low EtCO2, and 1,428 (34%) had postoperative organ dysfunction. An association was found between low EtCO2 and increased postoperative organ dysfunction (adjusted risk ratio, 1.11; 95% confidence interval [CI], 1.03-1.20; p = 0.006). Additionally, long-term exposure to EtCO2 values of less than 35 mmHg ([≥]224 min) was associated with postoperative organ dysfunction (adjusted risk ratio, 1.18; 95% CI, 1.06-1.32; p = 0.003) and low EtCO2 severity (area under the threshold) (adjusted risk ratio, 1.13; 95% CI, 1.02-1.26; p = 0.018).

ConclusionsIntraoperative low EtCO2 of below 35 mmHg was associated with increased postoperative organ dysfunction.

category: anesthesia


title: PREVALENCE OF PRECONCEPTION CARE PROVISION IN KISUMU COUNTY-KENYA

abstract:
Background Preconception care (PCC) is the provision of biomedical, behavioral and social health interventions to women and couples before conception occurs. The PCC, is valuable and key in preventing and controlling non-communicable diseases. There is the need for comprehensive preconception care provision in Kisumu County in order to promote healthy reproduction, improve maternal and neonatal health indicators in this and similar settings. Unfortunately, the current rate of provision for this service has not been documented in Kenya and more specifically in Kisumu County.

MethodsIn a cross-sectional study, data on the provision of various services as per the recommended package for preconception care was collected in health facilities using a checklist. The targeted facilities (n=28) were selected using multistage sampling. The means for all of the services in the package was determined. The significance of the difference in the means was determined by one sample T-test at P-value [≤] 0.05

ResultsLevel of implementation of PCC was quite low at 39%. It was observed to be lower in the primary level facilities (KEPH level 2 and 3) at 34% and higher in referral facilities (level 4 and above) at 45%. The service with the highest implementation level was HIV prevention and management (84%) followed by sexually transmitted diseases (80%) and vaccination services (75%). The service with lowest level of implementation was environmental risk exposure reduction at 13% for level 2 and 3 followed by management of mental health disorders.

ConclusionProvision of PCC was relatively low at 39% and provision was fragmented. Provision differed across service levels and care packages.


title: Effectiveness of the air-filled technique to reduce the dead space in syringes and needles during ChAdox1-n CoV vaccine administration

abstract:
In the current study, we calculated the vaccine volume and amount of dead space in a syringe and needle during ChAdox1-n CoV vaccine administration using the air-filled technique, to reduce dead space in syringe and needle that administer up to 12 doses per vial. The hypothetical situation uses a vial with a similar size as the ChAdox1-n CoV vial. We used distilled water (6.5 ml), to fill the same volume as five vials of ChAdox1-n CoV. When 0.48 ml of distilled water is drawn according to the number on the side of the barrel, an additional 0.10 ml of air can be used in the dead space of the distilled water in the syringe and needle for 60 doses, which can be divided into an average of 0.5 ml dose. ChAdox1-n CoV was administered using a 1-mL syringe and 25G needle to administer ChAdox1-n CoV vaccine into 12 doses using this air-filled technique. The volume of the recipient vaccine will be increase by 20% and save the budget of a low dead space syringe (LDS).

Graphical Abstract

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category: health policy


title: Implementation strategies for telemental health: a systematic review

abstract:
BackgroundThe COVID-19 pandemic resulted in a rapid shift from traditional face-to-face care provision towards delivering mental health care remotely through telecommunications, often referred to as telemental health care. However, the manner and extent of telemental health implementation have varied considerably across settings and areas, and substantial barriers are encountered. There is, therefore, now a need to identify what works best for service users and staff and establish the key mechanisms for efficient integration into routine care.

ObjectiveWe aimed to identify investigations of pre-planned strategies intended to achieve or improve effective and sustained implementation of telemental health approaches, and to evaluate how different strategies influence implementation outcomes.

MethodsA systematic review was conducted, with five databases searched for relevant literature using any methodological approach, published between January 2010 and July 2021. Studies were eligible for inclusion if they took place in secondary or tertiary mental health services and focused on pre-planned strategies for achieving or improving delivery of mental health care through remote communication between mental health professionals or between mental health professionals and service users, family members, unpaid carers, or peer supporters. All included studies were assessed for risk of bias. Data were synthesised using the Expert Recommendations for Implementing Change (ERIC) compilation of implementation strategies and the taxonomy of implementation outcomes.

ResultsA total of 14 studies were identified which met the inclusion criteria. A variety of implementation strategies were identified, the most commonly reported being  Train and educate stakeholders. All studies reported using a combination of several implementation strategies.

ConclusionsUsing a combination of implementation strategies appears to be a helpful method of supporting the implementation of telemental health. Further research is needed to test the impact of specific implementation strategies on implementation outcomes.


title: High-dimensional deconstruction of pancreatic ductal adenocarcinoma identifies tumor microenvironmental communities associated with survival

abstract:
Bulk and single-cell analyses of the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) have revealed a largely immunosuppressive milieu. Thus far, efforts to utilize insights from TME features to facilitate more effective therapeutics have largely failed. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy samples (n=22) and surgical samples (n=6), integrated with 3 public datasets (n=49), resulting in [~]140,000 individual cells from 77 patients. Based on expression markers assessed by Seurat v3 and differentiation status assessed by CytoTRACE, we divided the resulting tumor cellular clusters into 5 molecular subtypes based on expression of previously reported marker genes: Basal, Mixed Basal/Classical, Classical Low, Classical High, and ADEX. We then queried these 5 tumor cell profiles, along with 15 scRNA-seq-derived tumor microenvironmental cellular profiles, in 391 bulk expression samples from 4 published datasets of localized PDAC with associated clinical metadata using CIBERSORTx. Through unsupervised clustering analysis of these 20 cell state fractions representing tumor, leukocyte and stromal cells, we identified 7 unique clustering patterns representing combinations of tumor cellular and microenvironmental cell states present in PDAC tumors. We termed these cell state patterns communities, and found them to correlate with overall survival, tumor ecotypes, and tumor cellular differentiation status. The community associated with worst overall survival contained basal tumor cells, exhausted CD4 and CD8 T cells, and was enriched for fibroblasts. In contrast, the highest overall survival was associated with a community high in immune cell enrichment. The differentiation state of tumor cells (assessed by CytoTRACE) was also correlated with survival in a dose-dependent fashion. Further, we identified a subset of PDAC samples that were significantly enriched for CD8 T and plasma cells that achieved a 2-year overall survival rate of 71%, suggesting we can identify PDAC patients with significantly improved prognoses and, potentially, higher sensitivity to immunotherapy.

In summary, we identified novel tumor microenvironmental communities from high-dimensional analysis of PDAC RNA sequencing data that reveal new connections between tumor microenvironmental composition and patient survival that could lead to better upfront risk stratification and more personalized clinical decision-making.

category: oncology


title: Independent Replication and Drug-specificity of an Antidepressant Response Polygenic Risk Score

abstract: We here examine associations of a recently published polygenic risk score of antidepressant response (PRS-AR) with antidepressant treatment outcomes (remission and depression score change) in an independent clinical trial. We not only replicate the PRS-AR for escitalopram, but also find antidepressant interaction effects, suggesting drug-specificity of PRS-AR. We therefore also tested the utility of this PRS-AR to stratify between antidepressants and demonstrate a 14% increase in remission rate (from 43.6% to 49.7%), relative to the randomized remission rate.

category: genetic and genomic medicine


title: Genetically determining individualized clinical reference ranges for the biomarker tryptase can limit unnecessary procedures and unmask myeloid neoplasms

abstract: Serum tryptase is a biomarker used to aid in the identification of certain myeloid neoplasms, most notably systemic mastocytosis, where baseline (BST) levels >20 ng/mL are a minor criterion for diagnosis. Whereas clonal myeloid neoplasms are rare, the common cause for elevated BST is the genetic trait hereditary alpha-tryptasemia (HT) caused by increased germline TPSAB1 copy number. To date, the precise structural variation and mechanism(s) underlying elevated BST in HT and the general clinical utility of tryptase genotyping, remain undefined. Through cloning, long-read sequencing, and assembling of the human tryptase locus from an individual with HT, and validating our findings in vitro and in silico, we demonstrate that BST elevations arise from over-expression of replicated TPSAB1 loci encoding wild-type -tryptase due to co-inheritance of a linked over-active promoter element. Modeling BST levels based upon TPSAB1 replication number we generate new individualized clinical reference values for the upper limit of  normal. Using this personalized laboratory medicine approach, we demonstrate the clinical utility of tryptase genotyping, finding that in the absence of HT, BST levels >11.4 ng/mL frequently identify indolent clonal mast cell disease. Moreover, substantial BST elevations (e.g., >100 ng/mL) which would ordinarily prompt bone marrow biopsy, can result from TPSAB1 replications alone and thus be within  normal limits for certain individuals with HT.


title: Epidemiological and clinical features of SARS-CoV-2 Infection in children during the outbreak of Omicron Variant in Shanghai, March 7-March 31, 2022

abstract:
ObjectivesTo understand the epidemiological and clinical characteristics of pediatric SARS-CoV-2 infection during the early stage of Omicron variant outbreak in Shanghai.

MethodsThis study included local COVID-19 cases <18 years in Shanghai referred to the exclusively designated hospital by the end of March 2022 since emergence of Omicron epidemic. Clinical data, epidemiological exposure and COVID-19 vaccination status were collected. Relative risks (RR) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease.

ResultsA total of 376 pediatric cases of COVID-19 (median age:6.0{+/-}4.2 years) were referred to the designated hospital during the period of March 7-31, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children;3 years eligible for COVID-19 vaccination, 110 (40.4%) received 2-dose vaccines and 16 (4.0%) received 1-dose vaccine. The median interval between 2-dose vaccination and infection was 3.5 (IQR: 3, 4.5) months (16 days-7 months). Two-dose COVID-19 vaccination reduced the risks of symptomatic infection and febrile disease by 35% (RR 0.65, 95% CI:0.53-0.79) and 33% (RR 0.64, 95% CI: 0.51-0.81). Two hundred and sixteen (83.4%) symptomatic cases had fever (mean duration: 1.7{+/-}1.0.8 days), 104 (40.2%) had cough, 16.4% had transient leukopenia; 307 (81.6%) had an epidemiological exposure in household (69.1%), school (21.8%) and residential area (8.8%).

ConclusionThe surge of pediatric COVID-19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron-infected children. COVID-19 vaccination can offer protection against symptomatic infection and febrile disease.

category: infectious diseases


title: Outcomes of convalescent plasma with defined high- versus lower-neutralizing antibody titers against SARS-CoV-2 among hospitalized patients: CoronaVirus Inactivating Plasma (CoVIP), double-blind phase 2 study.

abstract:
BackgroundCOVID-19 Convalescent Plasma (CCP) was an early and widely adopted putative therapy for severe COVID-19. Results from randomized control trials and observational studies have failed to demonstrate a clear therapeutic role for CCP for severe SARS-CoV-2 infection. Underlying these inconclusive findings is a broad heterogeneity in the concentrations of neutralizing antibodies (nAb) between different CCP donors. The present study was designed to evaluate nAb titer threshold for clinically effective CCP.

MethodsWe conducted a double-blind, phase 2 study to evaluate the safety and effectiveness of nAb titer-defined CCP in adults admitted to an academic referral hospital. Patients positive on a SARS-CoV-2 nucleic acid amplification test and with symptoms for < 10 days were eligible. Participants received either CCP with nAb titers [≥]1:160-1:640 (standard titer group) or >1:640 (high titer group) in addition to standard of care treatments. Adverse events were contrasted by CCP titer. The primary clinical outcome was time to hospital discharge, with mortality and respiratory support evaluated as secondary outcomes.

FindingsBetween August 28 and December 4, 2020, 316 participants were screened, 55 received CCP, with 41 and 14 receiving standard versus high titer CCP, respectively. Participants were a median of 61 years of age (IQR 52-67), 36% women, 25% Black and 33% Hispanic. Severe adverse events (SAE) ([≥] grade 3) occurred in 4 (29%) and 23 (56%) of participants in the high versus standard titer groups, respectively by day 28 (Risk Difference -0.28 [95% CI -0.56, 0.01]). There were no observed treatment-related AEs. By day 55, time to hospital discharge was shorter among participants receiving high versus standard titer, accounting for death as a competing event (hazard ratio 1.94 [95% CI 1.05, 3.58], Grays p=0.02).

InterpretationIn this phase 2 trial in a high-risk population of patients admitted for Covid-19, we found earlier time to hospital discharge and lower occurrences of life-threatening SAEs among participants receiving CCP with nAb titers >1:640 compared with participants receiving CCP with lower nAb titer CCP. Though limited by a small study size these findings support further study of high-nAb titer CCP defined as >1:640 in the treatment of COVID-19.

FundingThis clinical study was supported by the UNC Health Foundation and the North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill with funding from the North Carolina Coronavirus Relief Fund established and appropriated by the North Carolina General Assembly. The laboratory assays for neutralizing antibody titers and SARS-CoV-2 specific antibody-binding assays were partially supported by The NIH NCI/NIAID SeroNet Serocenter of Excellence Award U54 CA260543.

Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSCOVID-19 Convalescent Plasma (CCP) has emergency use authorization from the FDA for early treatment of COVID-19 in either outpatient or inpatient settings. Evidence supporting the use of CCP for severe COVID-19 is mixed and still emerging. One major limitation in interpreting published clinical trials and the clinical role of CCP is incomplete understanding of necessary neutralizing antibody (nAb) titer for clinically effective CCP. Observational studies suggest that higher antibody-content CCP is more effective than lower antibody-content CCP, or that very low antibody-content CCP is harmful. We searched PubMed articles published between February 1, 2020, and April 15, 2022, using the terms "COVID-19", "convalescent plasma", "SARS-CoV-2", and "CCP" alone and in combination. Our search yielded 6,468 results which we filtered to 280 and 162 by selecting  Clinical Trial and  Randomized Controlled Trial article types, respectively. Among these, we identified 25 open-label or blinded efficacy or effectiveness studies in hospitalized patients that were relevant to our study. Preliminary reports show wide variability in the antibody content of CCP used in clinical trials, the assays used to define CCP antibody content, and the estimates of clinical outcomes following CCP therapy for hospitalized patients. Only one study deliberately infused CCP with nAb > 1:640. Post-hoc analyses of potent monoclonal antibody therapy in hospitalized patients in the UK showed survival benefit when monoclonal antibody was infused to patients who had not yet seroconverted by spike antibody ELISA, suggesting that if dosed appropriately, antibody-based therapies may have a role in improving outcomes of severe COVID-19.

Added value of this studyThis phase 2 study showed that CCP with high nAb titer (>1:640) provided more rapid recovery to hospital discharge and fewer COVID-19 attributable AEs than CCP with nAb titer between the FDA-recommended minimum standard and 4-fold higher ([≥]1:160-1:640). The hazard ratio of time to hospital discharge from baseline through day 55, accounting for death as a competing event, contrasting patients receiving high versus standard CCP titer was 1.94 (95% CI 1.05-3.58). Adjusted hazard ratios of high versus standard titer CCP receipt for time to hospital discharge were consistent with the primary unadjusted findings. Mortality through 55 days was lower in the high titer group, but with a wide confidence interval that did not reach statistical significance.

Implications of all available evidenceOur data that CCP with nAb >1:640 expedites recovery of patients admitted with COVID-19 compared with CCP with nAb [≥]1:160-1:640 suggests that a threshhold of nAb [≥]1:160 may be too low to define CCP as  high titer. Analyses in larger CCP trials should consider full reporting of nAb in CCP units administered at individual study participant level, and specifically whether CCP contained nAb >1:640. Further investigation of CCP with nAb >1:640 is warranted given that raising the threshhold of nAb, or a correlative specific anti-spike antibody assay, used to qualify  high titer CCP in clinical trials could inform policy guidance and clinical use of CCP.


title: Immunogenicity and safety of the CoronaVac inactivated SARS-CoV-2 vaccine in people with underlying medical conditions: a retrospective study

abstract:
BackgroundPeople living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national vaccination campaign in China due to uncertainty of safety and effectiveness. However, this special population made up of most severe symptom and death cases among infected patients and should be prioritized in vaccination program. In this retrospective study, we assessed the safety and immunogenicity of the CoronaVac inactivated vaccines in people with underlying medical conditions to address the vaccine hesitation in this special population.

MethodsIn this cohort study, volunteers aged 40 years and older, had received two doses of CoronaVac inactivated vaccines (3-5 weeks interval), been healthy or with at least one of the six diseases: coronary heart disease (CAD), hypertension, diabetes mellitus (DM), chronic respiratory disease (CRD), obesity and cancer, were recruited from 4 study sites in China. The primary safety outcome was the incidence of adverse events within 14 days after each dose of vaccination. The primary immunogenic outcome was geometric mean titer (GMT) of neutralizing antibodies to living SARS-CoV-2 virus at 14-28 days, 3 months, and 6 months after full two-dose vaccination. This study is registered with ChiCTR.org.cn (ChiCTR2200058281) and is active but no longer recruiting.

FindingsAmong 1,302 volunteers screened between Jul 5 and Dec 30, 2021, 969 were eligible and enrolled in our cohort, including 740 living with underlying medical conditions and 229 as healthy control. All of them formed the safety cohort. The overall incidence of adverse reactions was 150 (20.27%) of 740 in the comorbidities group versus 32 (13.97%) of 229 in the healthy group, with significant difference (P=0.0334). The difference was mainly contributed by fatigue and injection-site pain in some groups. Most adverse reactions were mild (Grade 1). We did not observe any serious adverse events related to vaccination. By day 14-28 post vaccination, the seroconversion rates and GMT of neutralizing antibody showed no significant difference between disease group and healthy group, except CAD group (P=0.03) and CRD group (P=0.04) showed slight reduction. By day 90, the neutralizing antibody GMTs were significantly reduced in each group, with no significant difference between diseases and healthy group. By day 180, the neutralizing antibody continued to decrease in each group, but with slower declination.

InterpretationFor people living with chronic disease especially seniors older than 60 years, the CoronaVac vaccines are as safe as in healthy people. Although the immunogenicity is slightly different in subgroup of some diseases compared with that of the healthy population, the overall trend was consistent. Our findings highlight the evidence to address vaccine hesitancy for seniors and people living with chronic diseases.

FundingYunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), Sinovac Biotech Ltd (PRO-nCOV-4004).


title: Passive surveillance of human-biting ticks correlates with town-level disease rates in Massachusetts

abstract:
We assessed the temporal and spatial distribution of Borrelia burgdorferi, Borrelia miyamotoi, Babesia microti, and Anaplasma phagocytophilum among human-biting Ixodes scapularis ticks in Massachusetts using ticks submitted to the TickReport pathogen passive surveillance program. From January 2015 to December 2017, Ixodes scapularis was the most frequently submitted tick species (n=7462). B. burgdorferi prevalence increased in ticks during the study period in adults and nymphs (37.1-39.1% in adults, 19.0%-23.9% in nymphs). The proportion of B. microti infected ticks increased from 5.7% to 8.1% in adult ticks but remained constant in nymphs (5.4-5.6%). Stable or decreasing annual prevalence of B. miyamotoi (2.2 - 2.2% in adults, 1.0-1.9% in nymphs) and A.phagocytophilum (7.6-7.2% in adults, 5.0-4.0% in nymphs) were detected. Coinfections were observed and included all pathogen combinations.

Ticks were submitted year-round and had stable infection rates. The temporal pattern of B. burgdorferi- positive nymphs aligned with reported cases of Lyme disease, as did positive B. microti nymphs and babesiosis. A similar situation is seen with B. miyamotoi with an insignificant fall peak in cases. Anaplasmosis demonstrated a significant bimodal distribution with reported cases peaking in the spring and fall. This pattern is similar to that of A. phagocytophilum-infected adult ticks.

B. microti infected nymphs were significantly predictive of town-level babesiosis incidence and A. phagocytophilum infected adults were significantly predictive of town-level anaplasmosis incidence in a spatially adjusted negative binomial model. Unlike field collection studies, the high number of ticks submitted provides a high-resolution picture of pathogen prevalence and provides data relevant to human health at the town level. Through temporal and geographic analyses we demonstrate concordance between our passive surveillance tick pathogen data and state reports of tickborne disease.

category: epidemiology


title: Reduced motor planning underlying inhibition of prepotent responses in children with ADHD

abstract:
To flexibly regulate their behavior, childrens ability to inhibit prepotent responses arises from cognitive and motor mechanisms that have an intertwined developmental trajectory. Subtle differences in planning and control can contribute to impulsive behaviors, which are common in Attention Deficit and Hyperactivity Disorder (ADHD) and difficult to be assessed and trained. We adapted a Go/No-Go task and employed a portable, low-cost kinematic sensor to explore the different strategies used by children with ADHD or typical development to provide a prepotent response (dominant condition) or inhibit the prepotent and select an alternative one (non-dominant condition). Although no group difference emerged on accuracy levels, the kinematic analysis of correct responses revealed that, unlike neurotypical children, those with ADHD did not show increased motor planning in non-dominant compared to dominant trials. Despite motor control could have compensated and led to good accuracy in our simple task, this strategy might make inhibition harder in more naturalistic situations that involve complex actions. Combining cognitive and kinematic measures is a potential innovative method for assessment and intervention of subtle differences in executive processes such as inhibition, going deeper than is possible based on behavioral outcomes alone.

Significance StatementThis study proposes an innovative method that integrates kinematic measurement with neuropsychological evaluation, thus providing information on the planning and control mechanisms underlying behavioral outcomes. It is applicable to the study not only of inhibition but more generally of executive functions, which are the basis of the ability of children and adults to achieve goal-directed actions. The use of a wearable motion sensor ensures good applicability in research, clinical evaluation, and intervention.


title: Insecticide Resistance Surveillance of Malaria and Arbovirus Vectors in Papua New Guinea 2017-2022.

abstract:
BackgroundInsecticide resistance monitoring is key for evidence-based control of Anopheles and Aedes disease vectors in particular, since the vast majority of insecticide-based public health adult vector control tools are reliant on pyrethroids. While widespread pyrethroid resistance in Anopheles species and Aedes aegypti has been described in many countries, data for Papua New Guinea are scarce. Available data indicate the local Anopheles populations remain pyrethroid-susceptible, making regular insecticide resistance monitoring even more important. Knowledge on Aedes insecticide resistance in PNG is very limited, however, high levels of Aedes aegypti resistance have been described. Here we present insecticide resistance monitoring data from across PNG generated between 2017 and 2022.

MethodsMosquito larvae were collected in larval habitat surveys and through ovitraps. Mosquitoes were reared to adults and subjected to insecticide treated filter papers in WHO insecticide susceptibility bioassays. Subsets of Aedes mosquitoes were subjected to sequencing of the voltage-sensitive sodium channel (Vssc) region to identify resistance mutations.

ResultsOverall, nearly 20,000 adult female mosquitoes from nine PNG provinces were used in the tests. We show that in general, Anopheline mosquitoes in PNG remain susceptible to pyrethroids but with worrying signs of reduced 24 h mortality in some areas. In addition, some Anopheles populations were indicated to be resistant against DDT. We show that Ae. aegypti in PNG are pyrethroid, DDT and likely bendiocarb resistant with a range of Vssc resistance mutations identified. We demonstrate that Ae. albopictus is DDT resistant and is likely developing pyrethroid resistance based on finding a low frequency of Vssc mutations.

ConclusionThis study represents the largest overview of insecticide resistance in PNG. While Ae. aegypti is highly pyrethroid resistant, the Anopheline and Ae. albopictus populations exhibit low levels of resistance in some areas. It is important to continue to monitor insecticide resistance in PNG and prepare for the widespread emergence of pyrethroid resistance in major disease vectors.


title: Vestibular contribution to path integration deficits in at genetic risk for Alzheimer disease

abstract: Path integration changes may precede a clinical presentation of Alzheimers disease by several years. Studies to date have focused on how grid cell changes affect path integration in preclinical AD. However, vestibular input is also critical for intact path integration. Here, we developed a naturalistic vestibular task that requires individuals to manually point an iPad device in the direction of their starting point following rotational movement, without any visual cues. Vestibular features were derived from the sensor data using feature selection. Completing machine learning models illustrate that the vestibular features accurately classified Apolipoprotein E {varepsilon}3{varepsilon}4 carriers and {varepsilon}3{varepsilon}3 carrier controls (mean age 62.7 years), with 65% to 79% accuracy depending on task trial or algorithm. Our results demonstrate the cross-sectional role of the vestibular system in Alzheimers disease risk carriers and may explain individual phenotypic heterogeneity in path integration within this population


title: Children with Critical Illness Carry Risk Variants Despite Non-Diagnostic Whole Exome Sequencing

abstract: Rapid genetic sequencing is an established and important clinical tool for management of pediatric critical illness. The burden of risk variants in children with critical illness but a non-diagnostic exome has not been explored. This was a retrospective case-control analysis of research whole exome sequencing data that first underwent a diagnostic pipeline to assess the association of rare loss-of-function variants with critical illness in children with diagnostic and non-diagnostic whole exome sequencing including those with virally mediated respiratory failure. Using a gene-based collapsing approach, the odds of a child with critical illness carrying rare loss-of-function variants were compared to controls. A subset of children with virally mediated respiratory failure was also compared to controls. Cases were drawn from the general pediatric ward and pediatric intensive care unit (PICU) at Morgan Stanley Childrens Hospital of NewYork-Presbyterian (MSCH) - Columbia University Irving Medical Center (CUIMC) and from the Office of the Chief Medical Examiner (OCME) of New York City. Of the 285 enrolled patients, 228 (80.0%) did not receive a diagnosis from WES. After quality control filtering and geographic ancestry matching, an analysis of 232 children with critical illness compared to 5,322 healthy and unrelated controls determined cases to harbor more predicted loss-of-function (pLOFs) in genes with a LOEUF score [≤] 0.680 (p-value = 1.0 x 10-5). After quality control and geographic ancestry matching, a subset of 176 children without a genetic diagnosis compared to 5,180 controls harbored pLOFs in genes without a disease association (OR 1.7, CI [1.2 - 2.3], FDR adjusted p-value = 4.4 x 10-3) but not in genes with a disease association (OR 1.2, CI [0.8 - 1.7], FDR adjusted p-value = 0.40). This enrichment primarily existed among ultra-rare variants not found in public data sets. Among a subset of 25 previously healthy children with virally mediated respiratory failure compared to 2,973 controls after quality control and geographic ancestry matching, cases harbored more variants than controls in genes without a disease association at the same LOEUF threshold [≤] 0.680 (OR 2.8, CI [1.2 - 7.2], FDR adjusted p-value = 0.026) but not in genes with a disease association (OR 0.7, CI [0.2 - 2.2], FDR adjusted p-value = 0.84). Finally, children with critical illness for whom whole exome sequencing data from both biological parents were available, we found an enrichment of de novo pLOF variants in genes without a disease association among 114 children without a genetic diagnosis (unadjusted p-value < 0.05) but not among 46 children with a genetic diagnosis. Children with critical illness and non-diagnostic whole exome sequencing may still carry risk variants for their clinical presentation in genes not previously associated with disease.


title: Questioning the association of the STMN2 dinucleotide repeat with ALS

abstract:
Lowered expression of STMN2 is associated with TDP-43 pathology in amyotrophic lateral sclerosis (ALS). Recently, the number of dinucleotide CA repeats in an intron of the STMN2 gene was reported to be associated with increased risk for ALS. Here, we used a case-control cohort of whole genome sequencing (WGS) as well as WGS from populations in the gnomAD cohort to attempt to replicate this proposed association. We find that repeats well above the previously reported pathogenic threshold of 19 are commonly observed in unaffected individuals across different populations. Further, we did not observe an association between longer STMN2 CA repeats and ALS phenotype. In summary, our results do not support a role of STMN2 CA repeats towards ALS risk.

DisclosuresNone to disclose


title: Adherence to the HIV early infant diagnosis testing protocol among HIV exposed infants in a hard-to-reach fishing community in Uganda

abstract:
BackgroundInfants born to HIV-infected mothers are at a high risk of acquiring the infection. The World Health Organization (WHO) recommends early diagnosis of HIV-exposed infants (HEIs) through deoxyribonucleic acid polymerase chain reaction (DNA PCR) and rapid HIV testing. Early detection of paediatric HIV is critical for access to antiretroviral therapy treatment (ART) and child survival. Theres, however, limited evidence of the adherence to early infant diagnosis (EID) of HIV testing protocol among HEIs in fishing communities in Uganda. This study assessed adherence to EID of HIV testing protocol among HIV-exposed infants in a hard-to-reach fishing community in Uganda.

MethodsWe conducted a cross-sectional study employing quantitative data collection methods among HEIs in selected healthcare facilities in Buvuma islands, Buvuma district. We obtained secondary data from mother-infant pair files enrolled on the EID program using a data extraction tool. Data were analysed using STATA Version 14. Modified poisson regression analysis was used to determine the factors associated with non-adherence to the 1st DNA PCR test among HIV-exposed infants enrolled into care.

ResultsNone of the HIV-exposed infants had done all the EID tests prescribed by the HIV testing protocol within the recommended time frame for the period of January 2014-December 2016. Adherence to the 1st and 2nd DNA PCR, and rapid HIV tests was 39.5%, 6.1% and 81.0% respectively. Being under the care of single mothers (PR=1.11, 95% CI: 1.01-1.23, p=0.023) and cessation of breast feeding (PR=0.90, 95% CI: 0.83-0.98, p=0.025) were significantly associated with non-adherence to the 1st DNA PCR.

ConclusionNone of the HIV-exposed infants adhered to all the EID tests of HIV testing protocol. Adherence to the 1st DNA PCR was positively associated with being a single mother and exclusive breast feeding. Therefore, single mothers and those who stop breastfeeding should be supported to ensure timely EID.

category: hiv aids


title: Then and NOW: A Prospective Population-Level Validation of the Abbott ID NOW SARS-CoV-2 Device Implemented in Multiple Settings for Testing Asymptomatic and Symptomatic Individuals

abstract:
IMPORTANCESince December, 2020, the ID NOW was implemented for use in 4 different populations across Alberta: in mobile units as part of community outbreak response, COVID-19 community collection sites, emergency shelters and addiction treatment facilities (ES), and hospitals.

OBJECTIVEDiagnostic evaluation of the ID NOW in various real world settings among symptomatic and asymptomatic individuals

DESIGNDepending on the implemented site, the ID NOW was tested on patients with symptoms suggestive of COVID-19, asymptomatic close contacts or asymptomatic individuals as part of outbreak point prevalence screening. From Jan - April, a select number of sites also switched from using oropharyngeal swabs to combined oropharyngeal + nasal (O+N) swabs. For every individual tested, two swabs were collected: one for ID NOW testing and the other for either reverse-transcriptase polymerase chain reaction (RT-PCR) confirmation of negative ID NOW results or for variant testing of positive ID NOW results.

RESULTSA total of 129,112 paired samples were analyzed (16,061 RT-PCR positive). 81,697 samples were from 42 COVID-19 community collection sites, 16,924 from 69 rural hospitals, 1,927 from 9 ES, 23,802 samples from 6 mobile units that responded to 356 community outbreaks, and 4,762 from 3 community collection sites and 1 ES using O+N swabs for ID NOW testing. ID NOW sensitivity was highest among symptomatic individuals presenting to community collection sites [92.5%, 95% confidence interval (CI) 92.0-93.0%, n=10,633 RT-PCR positive] and lowest for asymptomatic individuals associated with community outbreaks (73.9%, 95% CI 69.8-77.7%, n=494 RT-PCR positive). Specificity was greater than 99% in all populations tested, but positive predictive value (PPV) was lower among asymptomatic populations (82.4-91.3%) compared to symptomatic populations (96.0-96.9%). There was no statistically significant differences in sensitivity with respect to age, gender, NP vs OP swab for RT-PCR confirmation, variants of concern, or with combined oropharyngeal and nasal swabs using COVID-19 ID NOW testing.

CONCLUSIONSSensitivity of ID NOW SARS-CoV-2 testing is highest when used on symptomatic community populations not seeking medical care. Sensitivity and PPV drops by approximately 10% when tested on asymptomatic populations. Using combined oropharyngeal and nasal swabs did not improve ID NOW performance.


title: Effectiveness of Covid-19 vaccines against SARS-CoV-2 Omicron variant (B.1.1.529): A systematic review with meta-analysis and meta-regression

abstract:
BackgroundThere is a need for evaluation regarding vaccine effectiveness (VE) and the urgency of booster vaccination against Covid-19 B.1.1.529 (Omicron) variant.

MethodsSystematic search was conducted on April 6th, 2022, on databases (PubMed, ScienceDirect, CENTRAL, Web of Science, Scopus). VE difference (VED) estimates were assessed using random-effects model and DerSimonian-Laird tau estimators. Two models result, i.e., within 3 months and within 3 months or more, are compared. VE versus time meta-regression analysis was evaluated using mixed-effects model with Restricted-Maximum Likelihood tau estimators and Hartung-Knapp adjustments.

FindingsAd26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 vaccines were included in the analyses. Compared to full dose, booster dose of overall vaccines provided better protection against any (VED=22% (95%CI 15%-29%), p<0.001), severe (VED=20% (95%CI 8%-32%), p=0.001) and symptomatic (VED=22% (95%CI 11%-34%), p<0.001) Omicron infections within 3 months, as well as within 3 months or more (VED=30% (95%CI 24%-37%), p<0.001 for any, VED=18% (95%CI 13%-23%), p<0.001 for severe and VED=37% (95%CI 29%-46%), p<0.001 for symptomatic infections). The meta-regression analysis of overall vaccines revealed that the full dose VE against any and symptomatic Omicron infections were significantly reduced each month by 3.0% (95%CI 0.9%-4.8%, p=0.004) and 5.2% (95%CI 3.3%-7.1%, p=0.006), respectively; whereas booster dose effectiveness against severe and symptomatic Omicron infections were decreased by 3.7% (95%CI 5.1%-12.6%, p=0.030) and 3.9% (95%CI 1.2%-6.5%, p=0.006), respectively.

InterpretationCompared to full dose only, a booster dose addition provides better protection against B.1.1.529 infection. Although the VE estimates of Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 vaccines against B.1.1.529 infection after both full and booster doses are generally moderate, and the booster dose provides excellent protection against severe infection, it is important to note that the VE estimates decline over time, suggesting the need for a regular Covid-19 booster injection after certain period of time to maintain VE.


title: Comparative Analysis Of Bacteriological And Physicochemical Characteristics Of Water Samples From Different Sources Used By Students Of Federal University Dutsinma, Katsina State, Nigeria.

abstract: The aim of this study is to comparatively analyze the bacterial load and physiochemical parameters of water samples from various sources used by the students of Federal University, Dutsinma Katsina State. Samples from tap, well, dam, rain, sachet and boreholes were collected at different locations where students reside. There were 6 sources of water, namely; tap water, dam water, well water, borehole water, sachet water and rain water from which 10 samples were obtained each, making a total of 60 samples for analysis. The physicochemical parameters of each water samples were detected. According the technique adopted by Chessbrough. (2000), the samples were serially diluted, 3 test tubes were sterilized and distilled water of 9ml were Pipette into these test tubes, 1ml of the water sample was pipette into the first test tube and was shaken vigorously to have a homogeneous mixture (stock). Bacterial count of each water sample was carried out and presence of Escherichia coli, P.aeruginosa, S.aureus, S.typhi, K.pneumoniae, B.subtilis, Proteus sp, Shigella sp, and E.aerogenes were identified. Biochemical tests were carried out for accurate characterization of the isolates. The pattern of occurrence the studied physico-chemical parameters (except pH) of borehole water, sachet water, Dam, Rain, well, tap water were within the permissible limit set by World Health Organization. The pH of all samples of sachet water were within the permissible limit set by World Health Organization However, the pH of 7 out of 10 samples of borehole water and 8 out of 10 samples of tap water were within the permissible limit set by World Health Organization. The prevalence of indicator organisms in water samples are as follows; Klebsiella pneumoniae (Dam water=100%, Sachet water=0, Tap water=80%, Borehole=70%, Rain=20%, Well=100%), Escherichia coli (Dam water=100%, Sachet water=0, Tap water=20%, Borehole=10%, Rain=0, Well=100%), Pseudomonas aeruginosa (Dam water=100%, Sachet water=60%, Tap water=100%, Borehole=100%, Rain=100, Well=100%), Staphylococcus aureus (Dam water=100%, Sachet water=40%, Tap water=50%, Borehole=50%, Rain=20%, Well=100%), Salmonella TYPHI (Dam water=100%, Sachet water=0, Tap water=30%, Borehole=10%, Rain=10%, Well=100%), Bacillus subtilis (Dam water=100%, Sachet water=60%, Tap water=70%, Borehole=50%, Rain=30%, Well=100%), Proteus sp (Dam water=100%, Sachet water=0, Tap water=50%, Borehole=30%, Rain=10%, Well=100%), Shigella sp (Dam water=100%, Sachet water=0, Tap water=30%, Borehole=10%, Rain=10%, Well=100%), Enterobacter aerogenes (Dam water=100%, Sachet water=30%, Tap water=60%, Borehole=50%, Rain=30%, Well=100%). The research indicates the polluted condition of water in Dutsin-ma. Only sachet water is fit for consumption without further treatment in Dutsin-ma. Tap and borehole water should be treated before consumption. Dam water and well water should be used for other domestic purposes. However it should be treated by sedimentation followed by boiling. Rain water has less bacterial load but has an acidic pH, therefore it is unfit for consumption.