title: Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia

abstract:
The powerful "graft versus leukemia" effect thought partly responsible for the therapeutic effect of allogeneic hematopoietic cell transplantation in acute myeloid leukemia (AML) provides rationale for investigation of immune-based therapies in this high-risk blood cancer. There is considerable pre-clinical evidence for potential synergy between PD-1 immune checkpoint blockade and the hypomethylating agents already commonly used for this disease. We report here the results of 17-H-0026 (PD-AML, NCT02996474), an investigator sponsored, single-institution, single-arm open-label ten-subject pilot study to test the feasibility of the first-in-human combination of pembrolizumab and decitabine in adult patients with refractory or relapsed AML (R-AML). In this cohort of previously treated patients, this novel combination of anti-PD-1 and hypomethylating therapy was feasible and associated with a best response of stable disease or better in 6 of 10 patients. Considerable immunological changes were identified using TCR{beta} sequencing as well as single-cell immunophenotypic and RNA expression analyses on sorted CD3+ T cells in patients who developed immune-related adverse events (irAEs) during treatment. Clonal T cell expansions occurred at irAE onset; single-cell sequencing demonstrated that these expanded clones were predominately CD8+ effector memory T cells with high cell surface PD-1 expression and transcriptional profiles indicative of activation and cytotoxicity. In contrast, no such distinctive immune changes were detectable in those experiencing a measurable anti-leukemic response during treatment. Addition of pembrolizumab to ten-day decitabine therapy was clinically feasible in patients with R-AML, with immunological changes from PD-1 blockade observed in patients experiencing irAEs.

One Sentence SummaryAML patients receiving a novel combination of a PD-1 immune checkpoint inhibitor with a hypomethylating agent demonstrated clear evidence of induced immunological responses in those developing autoimmune toxicity during treatment but not in those demonstrating an anti-leukemic response.

category: hematology


title: Ongoing HIV transmission following a large outbreak among people with long term injecting drug use in Athens, Greece (2014-2020)

abstract:
Background and AimsThe HIV outbreak among People Who Inject Drugs (PWID) in Athens, Greece in 2011-2013 was the largest recent epidemic in Europe and North America. We aim to assess trends in HIV prevalence, drug use and access to prevention among PWID in Athens, to estimate HIV incidence and identify risk factors and to explore HIV-1 dispersal using molecular methods during 2014-2020.

MethodsTwo community-based HIV/hepatitis C programs on PWID were implemented in 2012-2013 (N=3,320) and 2018-2020 (N=1,635) through consecutive Respondent-Driven Sampling (RDS) rounds. PWID were uniquely identified across rounds/programs. We obtained RDS-weighted HIV prevalence estimates per round for 2018-2020 and compared them to 2012-2013. We assessed changes in HIV status, behaviours, and access to prevention in PWID participating in both periods. We estimated HIV incidence in a cohort of seronegative PWID as the number of HIV seroconversions/100 persons-years during 2014-2020 and used Cox regression to identify associated risk factors. Molecular sequencing and phylogenetic analysis were performed in HIV seroconverters.

ResultsHIV prevalence per round ranged between 12.0%-16.2% in 2012-2013 and 10.7%-11.3% in 2018-2020 with overlapping 95% Confidence Intervals (95% CI). Among PWID participating in both programs, HIV prevalence[95% CI] increased from 14.2%[11.7%-17.1%] in 2012-2013 to 22.0%[19.0%-25.3%] in 2018-2020 (p<0.001). There was a deterioration of socioeconomic characteristics such as homelessness (from 16.2%[95% CI: 13.5%-19.2%] to 25.6%[22.3%-29.0%]), a shift in cocaine use (16.6%[13.9%-19.6%] vs. 28.1%[24.7%-31.7%], reduced access to free syringes (51.8%[48.0%-55.7%] vs. 44.5%[40.7%-48.3%]) and a decrease in daily injecting (36.2%[32.6%-39.9%] vs. 28.5%[25.2%-32.1%]). HIV incidence (95% CI) in 2014-2020 was 1.94 (1.50-2.52) new cases/100 person-years and younger age, lower educational level, larger injection network and daily injecting were risk factors. Almost 9% of HIV seroconversions occurred within a newly expanding phylogenetic cluster.

ConclusionsThe ongoing HIV transmission among PWID in Athens provides empirical evidence that the current levels of prevention and treatment are inadequate to control the epidemic. Re-evaluation of prevention programs is urgently needed.

category: hiv aids


title: GRADING prognostic factors for severe and recurrent Clostridioides difficile infection: expected and unexpected findings. A systematic review.

abstract:
BackgroundClostridioides difficile infection (CDI), its subsequent recurrences (rCDI), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Treatment consists of oral antibiotics. Fidaxomicin, bezlotoxumab and fecal microbiota transplantion (FMT) reduce the number of recurrences compared to vancomycin, but are more costly. Identifying patients diagnosed with initial CDI who are at increased risk of developing sCDI/rCDI could lead to more cost-effective therapeutic choices.

ObjectivesIn this systematic review we aimed to identify clinical prognostic factors associated with an increased risk of developing sCDI or rCDI.

MethodsPubMed, Embase, Emcare, Web of Science and COCHRANE Library databases were searched from database inception through March, 2021. Study selection was performed by two independent reviewers on the basis of predefined selection criteria; conflicts were resolved by consensus. Cohort and case-control studies providing an analysis of clinical or laboratory data to predict sCDI/rCDI in patients [≥]18 years diagnosed with CDI, were included. Risk of bias was assessed with the Quality in Prognostic Research (QUIPS) tool and the quality of evidence by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, modified for prognostic studies. Overview tables of prognostic factors were constructed to assess the number of studies and the respective direction of an association (positive, negative, or no association).

Results and conclusions136 studies were included for final analysis. Higher age and the presence of multiple comorbidities were prognostic factors for sCDI. Identified risk factors for rCDI were higher age, healthcare-associated CDI, prior hospitalization, PPIs started during/after CDI diagnosis and previous rCDI. Some variables that were found as risk factors for sCDI/rCDI in previous reviews were not confirmed in the current review, which can be attributed to differences in methodology. Risk stratification for sCDI/rCDI may contribute to a more personalized and optimal treatment for patients with CDI.

category: infectious diseases


title: Clinical Manifestations and Pregnancy Outcomes of Covid-19 in Indonesian Referral Hospital in Central Pandemic Area

abstract:
ObjectivesThe data on clinical manifestations and pregnancy outcomes of pregnant women with COVID-19 are limited, particularly in developing countries. The aim of this study is to analyze the clinical manifestations and pregnancy outcomes in COVID-19 maternal cases in a large referral hospital in Indonesia

MethodsThe study used a prospective cohort design of all pregnant women with suspected COVID-19. Subjects were divided into COVID-19 and non COVID-19 group based on real-time polymerase chain reaction (RT-PCR) of SARS-CoV-2. The clinical characteristics, laboratory results, and pregnancy outcomes were then compared between both groups.

ResultsFrom 141 suspected maternal cases, 62 COVID-19 cases were confirmed (43.9%), while 79 suspected cases were found to be negative (56.1%). The clinical manifestations and laboratory findings between the two groups were not significantly different (p>0.05). However, the maternal mortality directly caused by COVID-19 was significantly higher compared to the non-COVID-19 group (8.3 vs 1.3%; p=0.044; OR 6.91, 95% CI: 0.79-60.81).

ConclusionsThe clinical manifestation and laboratory of suspected pregnant women with positive and negative RT-PCR COVID-19 result are similiar. However, within the Indonesian setting, COVID-19 strongly increases the risk of maternal death through both direct and indirect factors.


title: Switched forced SEIRDV compartmental models to monitor COVID-19 spread and immunization in Italy

abstract: This paper presents a new hybrid compartmental model for studying the COVID-19 epidemic evolution in Italy since the beginning of the vaccination campaign started on 2020/12/27 and shows forecasts of the epidemic evolution in Italy. The proposed compartmental model subdivides the population into six compartments and extends the SEIRD model proposed in [E.L.Piccolomini and F.Zama, PLOS ONE, 15(8):1-17, 08 2020] by adding the Vaccinated population and framing the global model as a hybrid-switched dynamical system. Aiming to represent the quantities that characterize the epidemic behaviour from an accurate fit to the observed data, we partition the observation time interval into sub-intervals. The model parameters change according to a switching rule depending on the data behaviour and the infection rate continuity condition. In particular, we study the representation of the infection rate both as linear and exponential piecewise continuous functions. We choose the length of sub-intervals balancing the data fit with the model complexity through the Bayesian Information Criterion. The calibration of the model shows an excellent representation of the epidemic behaviour and thirty days forecasts have proven to reproduce the infection spread reliably. Finally, we discuss different possible forecast scenarios obtained by simulating an increased vaccination rate.


title: Adaptable Automated Interpretation of Rapid Diagnostic Tests Using Few-Shot Learning

abstract: Point-of-care lateral-flow assays (LFAs) are becomingly increasingly prevalent for diagnosing individual patient disease status and surveying population disease prevalence in a timely, scalable, and cost-effective manner, but a central challenge is to assure correct assay operation and results interpretation as the assays are manually performed in decentralized settings. A smartphone-based software can automate interpretation of an LFA kit, but such algorithms typically require a very large number of images of assays tested with validated specimens, which is challenging to collect for different assay kits, especially for those released during a pandemic. Here, we present an approach - AutoAdapt LFA - that uses few-shot learning, an approach used in other applications such as computer vision and robotics, for accurate and automated interpretation of LFA kits that requires a small number of validated images for training. The approach consists of three components: extraction of membrane and zone areas from an image of the LFA kit, a self-supervised encoder that employs a feature extractor trained with edge-filtered patterns, and few-shot adaptation that enables generalization to new kits using limited validated images. From a base model pre-trained on a commercial LFA kit, we demonstrated the ability of adapted models to interpret results from five new COVID-19 LFA kits (three detecting antigens for diagnosing active infection, and two detecting antibodies for diagnosing past infection). Specifically, using just 10 to 20 images of each new kit, we achieved accuracies of 99% to 100% for each kit. The server-hosted algorithm has an execution time of approximately 4 seconds, which can potentially enable quality assurance and linkage to care for users operating new LFAs in decentralized settings.


title: Evaluation of the Panbio™ rapid antigen test for COVID-19 diagnosis in symptomatic health care workers.

abstract:
If a health care workers (HCW) experiences COVID-19 associated symptoms, SARS-CoV-2 testing must be performed as soon as possible, to prevent transmission of the virus and to guarantee continuity of care. The gold standard for the detection of SARS-CoV-2, RT-PCR, has a high sensitivity but usually takes 6-8 hours. Lateral flow antigen assays take only 15-30 minutes and do not need any high tech equipment.

In a prospective study of our hospitals HCWs, we evaluated the sensitivity of the Panbio COVID-19 Ag Rapid Test (Abbott) against the molecular test Aptima SARS-CoV-2 Assay (Hologic) which uses Transcription Mediated Amplification (TMA). TMA positive samples were further subjected to a quantitative real-time SARS-CoV-2 PCR to obtain Ct values as an indication of the viral load.

Of 1101 HCWs included in the study between November 2020 and February 2021, 84 (7.6%) were TMA positive, of which 48 (57.1%) were antigen test positive. Most false negative antigen test results occurred if the duration of symptoms had been [≤]1 day or [≥]7 days. Sensitivities for symptom onset of [≤]1, 2 or 3 days were 47.1%, 63.0% and 66.7% respectively.

The Panbio rapid test is fast and easy to perform, but is not a suitable SARS-CoV-2 test to confirm or exclude COVID-19 in HCWs with a very recent onset of symptoms.


title: Analysis of Host Immunological Response of Adenovirus-Based COVID-19 Vaccines

abstract: During the SARS-CoV-2 global pandemic, several vaccines, including mRNA and ade-novirus vector approaches, have received emergency or full approval. However, supply chain logistics have hampered global vaccine delivery, which is impacting mass vaccination strategies. Recent studies have identified different strategies for vaccine dose administration so that supply constraints issues are diminished. These include increasing the time between consecutive doses in a two-dose vaccine regimen and reducing the dosage of the second dose. We consider both of these strategies in a mathematical modeling study of a non-replicating viral vector adenovirus vaccine in this work. We investigate the impact of different prime-boost strategies by quantifying their effects on immunological outcomes based on simple ordinary differential equations. The boost dose is administered either at a standard dose (SD) of 1000 or at a low dose (LD) of 500 or 250 vaccine particles. Simulated Second dose fractionation highlights previously shown dose-dependent features of the immune mechanism. In agreement with clinical characteristics of 175 COVID-19 recovered patients, the model predictions for either SD/SD or SD/LD regimens mainly show that by stretching the prime-boost interval until 18 or 20 weeks, the minimum promoted antibody (Nab) response is comparable with the neutralizing antibody level of COVID-19 recovered patients. The minimum stimulated antibody in SD/SD regimen is identical with the high level of clinical trial data. It is at the same range of the medium-high level of Nab in SD/LD, where the second dose is half or quarter of the standard dose.


title: Differential pre-pandemic IgA reactivity against SARS-CoV-2 and circulating human coronaviruses measured in milk collected in Uganda and the USA

abstract:
ObjectiveUganda, like other African countries, has registered fewer COVID-19 cases and deaths per capita than non-African countries. The lower numbers of cases and deaths in Uganda might be due to pre-existing cross-immunity induced by zoonotic coronaviruses or circulating common cold human coronaviruses (HCoVs) before the COVID-19 pandemic. In order to test this premise, we compared IgA reactivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HCoVs in breast milk of US and rural Ugandan mothers collected in 2018 before the COVID-19 epidemic. Ugandan and US pre-pandemic breast milk samples were run in duplicate on enzyme-linked immunoadsorbent assay (ELISA) to measure specific IgA antibody reactivity to the spike proteins of SARS-CoV-2, human coronaviruses (HCoV) NL63, OC43, HKU1, and 229E. Pooled plasma from US COVID-19 positive and negative cases were employed as positive and negative controls, respectively. One Ugandan pre-pandemic milk sample had remarkably high reactivity against all HCoVs and SARS-CoV-2 spike proteins. There was higher IgA reactivity against the betacoronavirus HCoV-OC43 in Ugandan pre-pandemic milk samples by comparison with US pre-pandemic milk samples (p = 0.018). By contrast, there was significantly higher IgA reactivity against the alphacoronaviruses HCoV-229E and HCoV-NL63 in US pre-pandemic milk samples by comparison with Ugandan pre-pandemic milk samples (p < 0.0001 and 0.035, respectively).

ConclusionSome Ugandan mothers may have robust pre-existing immunity against SARS-CoV-2 due to cross-immunity induced by HCoVs which may be passed on to their infants via breastfeeding. The differential pre-pandemic reactivity of US mothers to HCoV 229E and HCoV NL63 may have contributed to suboptimal antibody responses to SARS-CoV-2.


title: Long term positivity of SARS-CoV-2 total immunoglobulins in convalescent plasma and blood donors

abstract:
BackgroundOne of the most questioned issues about SARS-CoV2 immunity is how long does it last. Whether lasting differences exist between infection and vaccination boosted immunity is yet to be known. The answer to this question will determine key issues such as the reliability of individual and herd immunity or the need of sanitary restrictions or periodical revaccination. The aim of this study was to determine how long total anti SARS-CoV2 antibodies due to past infection persist in peripheral blood and whether sex, age or haematological features can influence their lasting.

Material and MethodsA total of 2432 donations SARS-CoV-2 from 662 repeat donors from April 2020 to February 2021 were analysed. Donors were 69.7% males and their average age was 46. An automated chemilumiscence immunoassay for total antibodies recognizing N protein of SARS-CoV-2 in human serum and plasma was performed.

Results and discussionIn 97.6% donors with follow-up, anti SARS-CoV-2 protein N total antibodies remained positive up to 46 weeks after first positive determination. Blood group was not related to antibody waning. Lower lymphocyte counts and higher neutrophils and as well higher seric IgA would help predict future negativization of antibodies. The vast majority of donors keep their total immunoglobulins anti SARS-CoV-2 positive for longer than 10 months. Ageing might have a protective effect against antibody waning but, given the small number of cases that become negative, more studies, or larger cohorts would be needed to confirm these facts.


title: Use of HFNC in COVID-19 patients in non-ICU setting: Experience from a tertiary referral centre of north India and a systematic review of literature

abstract:
IntroductionThe rapid surge of cases and insufficient numbers of intensive care unit (ICU) beds have forced hospitals to utilise their general wards for administration of non-invasive respiratory support including HFNC(High Flow Nasal Cannula) in severe COVID-19. However, there is a dearth of data on the success of such advanced levels of care outside the ICU setting. Therefore, we conducted an observational study at our centre, and systematically reviewed the literature, to assess the success of HFNC in managing severe COVID-19 cases outside the ICU.

MethodsA retrospective cohort study was conducted in a tertiary referral centre where records of all adult COVID-19 patients ([≥]18 years) requiring HFNC support were between September and December 2020 were analysed. HFNC support was adjusted to target SpO2 [≥]90% and respiratory rate [≤]30 per min. The clinical, demographic, laboratory, and treatment details of these patients were retrieved from the medical records and entered in pre-designed proforma. Outcome parameters included duration of oxygen during hospital stay, duration of HFNC therapy, length of hospital stay and death or discharge. HFNC success was denoted when a patient did not require escalation of therapy to NIV or invasive mechanical ventilation, or shifting to the ICU, and was eventually discharged from the hospital without oxygen therapy; otherwise, the outcome was denoted as HFNC failure. Systematic review was also performed on the available literature on the experience with HFNC in COVID-19 patients outside of ICU settings using the MEDLINE, Web of Science and Embase databases. Statistical analyses were performed with the use of STATA software, version 12, OpenMeta[Analyst], and visualization of the risk of bias plot using robvis.

ResultsThirty-one patients receiving HFNC in the ward setting, had a median age of 62 (50 - 69) years including 24 (77%) males. Twenty-one (68%) patients successfully tolerated HFNC and were subsequently discharged from the wards, while 10 (32%) patients had to be shifted to ICU for non-invasive or invasive ventilation, implying HFNC failure. Patients with HFNC failure had higher median D-dimer values at baseline (2.2 mcg/ml vs 0.6 mcg/ml, p=0.001) and lower initial SpO2 on room air at admission (70% vs 80%, p=0.026) as compared to those in whom HFNC was successful .A cut-off value of 1.7 mg/L carried a high specificity (90.5%) and moderate sensitivity (80%) for the occurrence of HFNC failure. Radiographic severity scoring as per the BRIXIA score was comparable in both the groups(11 vs 10.5 out of 18, p=0.78). After screening 98 articles, total of seven studies were included for synthesis in the systematic review with a total of 820 patients, with mean age of the studies ranging from 44 to 83 years and including 62% males. After excluding 2 studies from the analysis, the pooled rates of HFNC failure were 36.3% (95% CI 31.1% - 41.5%) with no significant heterogeneity (I2 =0%, p=0.55).

ConclusionsOur study demonstrated successful outcomes with use of HFNC in an outside of ICU setting among two-thirds of patients with severe COVID-19 pneumonia. Lower room air SpO2 and higher D-dimer levels at presentation were associated with failure of HFNC therapy leading to ICU transfer for endotracheal intubation or death. Also, the results from the systematic review demonstrated similar rates of successful outcomes concluding that HFNC is a viable option with failure rates similar to those of ICU settings in such patients.


title: Mathematical and Statistical models as tools for the control of mosquito-borne diseases: The experience of Costa Rica

abstract: The modeling of infectious diseases provides valuable input for developing mitigating strategies and implementing public health interventions. This article highlights results and current research conducted in Costa Rica using mathematical, statistical, and computational tools to analyze transmission dynamics and provide quantitative information for developing mosquito-borne disease prevention/control methods and resource allocation planning.


title: Viral detection and identification in 20 minutes by rapid single-particle fluorescence in-situ hybridization of viral RNA

abstract: The increasing risk from viral outbreaks such as the ongoing COVID-19 pandemic exacerbates the need for rapid, affordable and sensitive methods for virus detection, identification and quantification; however, existing methods for detecting virus particles in biological samples usually depend on multistep protocols that take considerable time to yield a result. Here, we introduce a rapid fluorescence in situ hybridization (FISH) protocol capable of detecting influenza virus, avian infectious bronchitis virus and SARS-CoV-2 specifically and quantitatively in approximately 20 minutes, in both virus cultures and combined throat and nasal swabs without previous purification. This fast and facile workflow is applicable to a wide range of enveloped viruses and can be adapted both as a lab technique and a future diagnostic tool.


title: Long-term course of humoral and cellular immune responses in outpatients after SARS-CoV-2 infection

abstract:
Characterisation of the naturally acquired B and T cell immune responses to SARS-CoV-2 is important for the development of public health and vaccination strategies to manage the burden of COVID-19 disease. We conducted a prospective, longitudinal analysis in COVID-19 recovered patients at various time points over a 10-month period in order to determine how circulating antibody levels and interferon-gamma (IFN-{gamma}) release by peripheral blood cells change over time following natural infection.

From March 2020 till January 2021, we enrolled 412 adults mostly with mild or moderate disease course. At each study visit, subjects donated peripheral blood for testing of anti-SARS-CoV-2 IgG antibodies and IFN-{gamma} release after SARS-CoV-2 S-protein stimulation. Anti-SARS-CoV-2 IgG antibodies were identified in 316/412 (76.7%) of the patients and 215/412 (52.2%) had positive neutralizing antibody levels. Likewise, in 274/412 (66.5 %) positive IFN-{gamma} release and IgG antibodies were detected. With respect to time after infection, both IgG antibody levels and IFN-{gamma} concentrations decreased by about half within three hundred days. Statistically, IgG and IFN-{gamma} production were closely associated, but on an individual basis we observed patients with high antibody titres but low IFN-{gamma} levels and vice versa.

Our data suggest that immunological reaction is acquired in most individuals after infection with SARS-CoV-2 and is sustained in the majority of patients for at least 10 months after infection. Since no robust marker for protection against COVID-19 exists so far, we recommend utilizing both, IgG and IFN-{gamma} release for an individual assessment of immunity status.


title: P. acnes qPCR-based antibiotics resistance assay (ACQUIRE) reveals widespread macrolide resistance in acne patients and can eliminate macrolide misuse in acne treatment

abstract:
BackgroundMacrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence, with serious consequences.

ObjectiveWe developed P. acnes qPCR-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of P. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care.

MethodsA cross-sectional observational study was conducted to probe into the macrolide resistance of P. acnes in acne patients.

ResultsThe high sensitivity of ACQUIRE enabled us to reveal a much higher P. acnes 23S rDNA point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies.

ConclusionMacrolide resistance of P. acnes is much higher than previously reported.

category: dermatology


title: Risk factors for long COVID: analyses of 10 longitudinal studies and electronic health records in the UK

abstract:
BackgroundThe impact of long COVID is considerable, but risk factors are poorly characterised. We analysed symptom duration and risk factor from 10 longitudinal study (LS) samples and electronic healthcare records (EHR).

MethodsSamples: 6907 adults self-reporting COVID-19 infection from 48,901 participants in the UK LS, and 3,327 adults with COVID-19, were assigned a long COVID code from 1,199,812 individuals in primary care EHR. Outcomes for LS included symptom duration lasting 4+ weeks (long COVID) and 12+ weeks. Association with of age, sex, ethnicity, socioeconomic factors, smoking, general and mental health, overweight/obesity, diabetes, hypertension, hypercholesterolaemia, and asthma was assessed.

ResultsIn LS, symptoms impacted normal functioning for 12+ weeks in 1.2% (mean age 20 years) to 4.8% (mean age 63 y) of COVID-19 cases. Between 7.8% (mean age 28 y) and 17% (mean age 58 y) reported any symptoms for 12+ weeks, and greater proportions for 4+ weeks. Age was associated with a linear increased risk in long COVID between 20 and 70 years. Being female (LS: OR=1.49; 95%CI:1.24-1.79; EHR: OR=1.51 [1.41-1.61]), having poor pre-pandemic mental health (LS: OR=1.46 [1.17-1.83]; EHR: OR=1.57 [1.47-1.68]) and poor general health (LS: OR=1.62 [1.25-2.09]; EHR: OR=1.26; [1.18-1.35]) were associated with higher risk of long COVID. Individuals with asthma (LS: OR=1.32 [1.07-1.62]; EHR: OR=1.56 [1.46-1.67]), and overweight or obesity (LS: OR=1.25 [1.01-1.55]; EHR: OR=1.31 [1.21-1.42]) also had higher risk. Non-white ethnic minority groups had lower risk (LS: OR=0.32 [0.22-0.47]), a finding consistent in EHR. . Few participants had been hospitalised (0.8-5.2%).

ConclusionLong COVID is associated with sociodemographic and pre-existing health factors. Further investigations into causality should inform strategies to address long COVID in the population.

category: epidemiology


title: Investigating phenotypes of pulmonary COVID-19 recovery: a longitudinal observational prospective multicenter trial

abstract:
BackgroundCOVID-19 is associated with long-term pulmonary symptoms and may result in chronic pulmonary impairment. The optimal procedures to prevent, identify, monitor, and treat these pulmonary sequelae are elusive.

Research questionTo characterize the kinetics of pulmonary recovery, risk factors and constellations of clinical features linked to persisting radiological lung findings after COVID-19.

Study design and methodsA longitudinal, prospective, multicenter, observational cohort study including COVID-19 patients (n = 108). Longitudinal pulmonary imaging and functional readouts, symptom prevalence, clinical and laboratory parameters were collected during acute COVID-19 and at 60-, 100- and 180-days follow-up visits. Recovery kinetics and risk factors were investigated by logistic regression. Classification of clinical features and study participants was accomplished by k-means clustering, the k-nearest neighbors (kNN), and naive Bayes algorithms.

ResultsAt the six-month follow-up, 51.9% of participants reported persistent symptoms with physical performance impairment (27.8%) and dyspnea (24.1%) being the most frequent. Structural lung abnormalities were still present in 45.4% of the collective, ranging from 12% in the outpatients to 78% in the subjects treated at the ICU during acute infection. The strongest risk factors of persisting lung findings were elevated interleukin-6 (IL6) and C-reactive protein (CRP) during recovery and hospitalization during acute COVID-19. Clustering analysis revealed association of the lung lesions with increased anti-S1/S2 antibody, IL6, CRP, and D-dimer levels at the early follow-up suggesting non-resolving inflammation as a mechanism of the perturbed recovery.

Finally, we demonstrate the robustness of risk class assignment and prediction of individual risk of delayed lung recovery employing clustering and machine learning algorithms.

InterpretationSeverity of acute infection, and systemic inflammation is strongly linked to persistent post-COVID-19 lung abnormality. Automated screening of multi-parameter health record data may assist the identification of patients at risk of delayed pulmonary recovery and optimize COVID-19 follow-up management.

Clinical Trial RegistrationClinicalTrials.gov: NCT04416100


title: Predicting elimination of evolving virus variants

abstract: As the SARS-CoV-2 virus spreads around the world new variants are appearing regularly. Although some countries have achieved very swift and successful vaccination campaigns, on a global scale the vast majority of the population is unvaccinated and new variants are proving more resistant to the current set of vaccines. We present a simple model of disease spread which includes the evolution of new variants and varying vaccine effectiveness to these new strains. We show that rapid vaccine updates to target new strains are more effective than slow updates and containing spread through non-pharmaceutical interventions is vital whilst these vaccines are delivered. Finally when measuring the key model inputs, e.g. the rate at which new mutations and variants of concern emerge, is difficult we show how an observable model output, the number of new variants which have been seen, is strongly correlated with the probability the virus is eliminated.


title: Integrating epidemiological and clinical predictors of SARS-CoV2 infection in students and school staff in the state of Sao Paulo

abstract:
BackgroundThere is a great deal of uncertainty concerning which contexts would be safe for returning to school and about individual criteria that would reduce contact between the infected and susceptible people in the school setting. Therefore, the purpose of this study was to estimate the prevalence of infection by SARS-CoV-2 in students and school staff; and to identify predictors of infection, including both municipal epidemiological indicators and individual variables reported by the participants.

MethodsThis was a virological survey carried out among students (over 14 years old) and school staff in Sao Paulo state, between epidemiological weeks 43 to 49 of the year 2020. A self-administrated questionnaire including sociodemographic and clinical information was applied. Moreover, a nasopharynx swab was performed for virological testing (RT-PCR). We evaluate the relationship of COVID-19 epidemiological indicators of the residence municipality with the odds of SARS-CoV-2 infection. For this, a composite index relating recent mortality and previous incidence (RM/PI) was proposed based on the ratio of deaths recorded in the second and third week counted back to the sum of cases during the previous seven weeks (weeks 4 to 10 counted back). We obtained a multiple model using random-effects logit regression integrating epidemiological indicators and individual variables.

ResultsIn total, 3436 participants were included, residents of 72 municipalities. The overall prevalence of infection was 1.7% (95%CI: 1.3%-2.2%). SARS-CoV-2 infection was independently associated with loss of smell, a history of pulmonary disease, and a recent trip outside the municipality. Moreover, the RM/PI index consistently predicted the SARS-CoV-2 infection (adjusted OR: 1.45; 95%CI 1.02-2.04). Based on these associations, we proposed a classification in four groups with different SARS-Cov-2 infection prevalence (0.54%, 1.27%, 3.8%, and 4.13%).

ConclusionEpidemiological and individual variables allowed classifying groups according to the infection probability in a school population of the state of Sao Paulo. This classification could help guide the return to classes in situations in which epidemiological control is evident, maintaining basic protection measures and increasing vaccination coverage.


title: The burden of COVID-19 and Case Fatality Rate in Pune India: An Analysis of First and Second Wave of the Pandemic

abstract:
BackgroundThe recent second wave in India in April-May 2021 placed an unprecedented burden on the Indian health systems. However, limited data exist on the epidemiology of the COVID-19 pandemic from the first wave through the second wave in India. With detailed epidemiologic data, we aimed to assess trends in incident cases and case fatality, its risk between pandemic waves in Pune, an epicenter of COVID-19 cases in India, a country with the second-largest absolute burden worldwide.

MethodsProgrammatic COVID-19 data from Pune city between the first wave (March 09th 2020-October 31st, 2020), maintenance phase (November 01st 2020-February 14th, 2021), the second wave (February 15th, 2021-May 31st, 2021) were assessed for trends of incident cases, time-to-death, and case fatality rate (CFR). In addition, Poisson regression models adjusted for age and gender were used to determine the independent effect of pandemic waves on mortality.

ResultsOf 465,192 COVID-19 cases, 162,182 (35%) were reported in the first wave, and 4,146 (2.5%) died among them; Maintenance period registered 27,517 (6%) cases with 590 (2.1%) deaths; Second wave reported 275,493 (59%) cases and 3184 (1.1%) deaths (p<0.01). The overall CFR was 1.16 per 1000 person-days (PD), which declined from 1.80 per 1000 PD during the first wave to 0.77 per 1000 PD in the second wave. The risk of death was 1.49 times higher during the first wave (adjusted case fatality rate ratio-aCFRR,1.49; 95% CI: 1.37-1.62) and 35% lower in the second wave (aCFRR, 0.65; 95% CI: 0.59 - 0.70), compared to the maintenance phase.

InterpretationThe absolute burden of COVID-19 cases and deaths were more significant in the second wave in Pune, India; however, the CFR declined as the pandemic progressed. Nevertheless, investigating newer therapies and implementing mass vaccinations against COVID-19 are urgently needed.


title: Data-Driven Prediction of COVID-19 Cases in Germany for Decision Making

abstract:
BackgroundThe COVID-19 pandemic has led to a high interest in mathematical models describing and predicting the diverse aspects and implications of the virus outbreak. Model results represent an important part of the information base for the decision process on different administrative levels. The Robert-Koch-Institute (RKI) initiated a project whose main goal is to predict COVID-19-specific occupation of beds in intensive care units: Steuerungs-Prognose von Intensivmedizinischen COVID-19 Kapazitaten (SPoCK). The incidence of COVID-19 cases is a crucial predictor for this occupation.

MethodsWe developed a model based on ordinary differential equations for the COVID-19 spread with a time-dependent infection rate described by a spline. Furthermore, the model explicitly accounts for weekday-specific reporting and adjusts for reporting delay. The model is calibrated in a purely data-driven manner by a maximum likelihood approach. Uncertainties are evaluated using the profile likelihood method. The uncertainty about the appropriate modeling assumptions can be accounted for by including and merging results of different modelling approaches.

ResultsThe model is calibrated based on incident cases on a daily basis and provides daily predictions of incident COVID-19 cases for the upcoming three weeks including uncertainty estimates for Germany and its subregions. Derived quantities such as cumulative counts and 7-day incidences with corresponding uncertainties can be computed. The estimation of the time-dependent infection rate leads to an estimated reproduction factor that is oscillating around one. Data-driven estimation of the dark figure purely from incident cases is not feasible.

ConclusionsWe successfully implemented a procedure to forecast near future COVID-19 incidences for diverse subregions in Germany which are made available to various decision makers via an interactive web application. Results of the incidence modeling are also used as a predictor for forecasting the need of intensive care units.


title: Socioeconomic position and SARS-CoV-2 infections: seroepidemiological findings from a German nationwide dynamic cohort

abstract:
BackgroundEvidence on the relationship between socioeconomic position (SEP) and infections with the SARS-CoV-2 coronavirus is still limited as most of the available studies are ecological in nature. This is the first German nationwide study to examine differences in the risk of SARS-CoV-2 infections according to SEP at the individual level.

MethodsThe  CORONA-MONITORING bundesweit (RKI-SOEP) study is a seroepidemiological survey among a dynamic cohort of the German adult population (n=15,122; October 2020 - February 2021). Dried blood samples were tested for SARS-CoV-2 antibodies and oral-nasal swabs for viral RNA. SEP was measured by education and income. Robust logistic regression was used to examine adjusted associations of SARS-CoV-2 infections with SEP.

Results288 participants were seropositive, PCR-positive, or self-reported a previous laboratory-confirmed SARS-CoV-2 infection. The adjusted odds of SARS-CoV-2 infection were 1.87-fold (95% confidence interval [CI]=1.06-3.29) higher among low-educated than highly educated adults. Evidence was weaker for income differences in infections (odds ratio=1.65; 95% CI=0.89-3.05). Highly educated adults had lower odds of undetected infection.

ConclusionThe results indicate an increased risk of SARS-CoV-2 infection in low-educated groups. To promote health equity in the pandemic and beyond, social determinants should be addressed more in infection protection and pandemic planning.


title: Using mobile health technology to assess childhood autism in low-resource community settings in India : an innovation to address the detection gap

abstract: Autism Spectrum Disorders, hereafter referred to as autism, emerge early and persist throughout life, contributing significantly to global years lived with disability. Typically, an autism diagnosis depends on clinical assessments by highly trained professionals. This high resource demand poses a challenge in resource-limited areas where skilled personnel are scarce and awareness of neurodevelopmental disorder symptoms is low. We have developed and tested a novel app, START, that can be administered by non-specialists to assess several domains of the autistic phenotype (social, sensory, motor functioning) through direct observation and parent report. N=131 children (2-7 years old; 48 autistic, 43 intellectually disabled, and 40 typically developing) from low-resource settings in the Delhi-NCR region, India were assessed using START in home settings by non-specialist health workers. We observed a consistent pattern of differences between typically and atypically developing children in all three domains assessed. The two groups of children with neurodevelopmental disorders manifested lower social preference, higher sensory sensitivity, and lower fine-motor accuracy compared to their typically developing counterparts. Parent-report further distinguished autistic from non-autistic children. Machine-learning analysis combining all START-derived measures demonstrated 78% classification accuracy for the three groups (ASD, ID, TD). Qualitative analysis of the interviews with health workers and families (N= 15) of the participants suggest high acceptability and feasibility of the app. These results provide proof of principle for START, and demonstrate the potential of a scalable, mobile tool for assessing neurodevelopmental disorders in low-resource settings.

category: psychiatry and clinical psychology


title: COVID-19 Susceptibility, Mortality, and Length of hospitalization based on age-sex composition: Evidence from Davao Region Philippines

abstract: The coronavirus disease is spreading continuously worldwide with an unprecedented amount of impact on every human society. In order to reduce the risks of infections and mortality, several interventions such as mobility restrictions for different age groups and vaccination prioritization programs are implemented in the Philippines. Identifying age-sex composition with greater susceptibility, longer hospitalization, and higher fatality is useful to guide the targeted intervention and establish risk stratification for patients infected with COVID-19 within communities and localities. Furthermore, it is also helpful in the allocation of medical resources and assessment of vaccination priority. We analyzed the COVID-19 data provided by the Davao Center for Health Development of the Department of Health Davao Region in the Philippines. The dataset contains records of COVID-19 cases reported from March 2020 to April 2021. Methods that were used include descriptive statistics, graphical presentations, and nonparametric statistical methods. The study reveals that male children and female senior citizens are the most susceptible age-sex composition while male senior citizen is the subgroup with the highest case fatality and mortality. Furthermore, regardless of sex groups, the senior citizen is the subgroup with the longest hospitalization. Susceptibility due to exposure should be included as a criterion in determining the age-sex compositions for vaccination priority against COVID-19 and other potentially deadly viruses. Further, Proper planning and allocation of medical resources for the elderly should be prioritized in the provincial levels.

category: public and global health


title: Meta-Analytic Evidence of Depression and Anxiety in Eastern Europe during the COVID-19 Pandemic

abstract:
ObjectiveTo perform a systematic and meta-analysis on the prevalence rates of mental health symptoms including anxiety and depression during the COVID-19 pandemic in the general population in Eastern Europe, as well as three select sub-populations: students, general healthcare workers, and frontline healthcare workers.

Data sourcesStudies in PubMed, Embase, Web of Science, Psycinfo, and medRxiv up to February 6, 2021.

Eligibility criteria and data analysisPrevalence rates of mental health symptoms in the general population and key sub-populations during the COVID-19 pandemic in Eastern Europe. Data were pooled using a random-effects meta-analysis to estimate the prevalence rates of anxiety and depression.

ResultsThe meta-analysis identifies and includes 21 studies and 26 independent samples in Eastern Europe. Poland (n=4), Serbia (n=4), Russia (n=3), and Croatia (n=3) had the greatest number of studies. To our knowledge, no studies have been conducted in eleven Eastern European countries including Hungary, Slovakia, and Slovenia. The pooled prevalence of anxiety in 18 studies with 22 samples was 30% (95% CI: 24% - 37%) and pooled prevalence of depression in 18 studies with 23 samples was 27% (95% CI: 21% - 34%).

ImplicationsThe cumulative evidence from the meta-analysis reveals high prevalence rates of clinically significant symptoms during the COVID-19 pandemic in Eastern Europe. The findings suggest evidence of a potential mental health crisis in Eastern Europe during the ongoing COVID-19 pandemic. Our synthesis also reveals a relative lack of studies in certain Eastern European countries as well as high heterogeneities among the existing studies, calling for more effort to achieve evidence-based mental healthcare in Eastern Europe.

HighlightsO_LIThe pooled prevalence of anxiety and depression were 30% and 27% in Eastern Europe, respectively.
C_LI

Trial registrationCRD42020224458


title: Association of lung clearance index with survival in individuals with cystic fibrosis

abstract:
BackgroundLung clearance index (LCI) quantifies global ventilation inhomogeneity, a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease.

ObjectivesWe examined the association of LCI with the risk of death or lung transplantation (LTX) in individuals with CF.

MethodsWe performed a retrospective analysis in a cohort of individuals with CF aged [≥] five years with available LCI and FEV1 measurements between 1980 and 2006. Outcome was time until death or LTX. We applied Cox proportional hazard regressions using the earliest available LCI and FEV1 values and adjusted for demographic and clinical variables. For sensitivity analyses, we used the mean of the first three LCI and FEV1 measurements, stratified the cohort based on age, and investigated individuals with normal FEV1.

ResultsIn total, 237 individuals with CF aged mean (range) 13.9 (5.6-41.0) years were included. This time-to-event analysis accrued 3813 person-years, 94 (40%) individuals died or received LTX. Crude hazard ratios [95% CI] were 1.04 [1.01-1.06] per one z-score increase in LCI and 1.25 [1.11-1.41] per one z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, BMI and the number of hospitalisations, hazard ratios were 1.04 [1.01-1.07] for LCI, and 1.12 [0.95-1.33] for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations.

ConclusionsIncreased ventilation inhomogeneity is associated with greater risk of death or LTX. Our data support LCI as novel surrogate of survival in individuals with CF.

TAKE HOME MESSAGELung clearance index (LCI) is a measure of global ventilation inhomogeneity which increases early during the course of Cystic Fibrosis (CF) lung disease. This study shows that LCI is predictive of death or lung transplantation in individuals with CF.

Study registration numberNCT04016194

category: respiratory medicine


title: Digital contact tracing contributes little to COVID-19 outbreak containment

abstract: Digital contact tracing applications have been introduced in many countries to aid in the containment of COVID-19 outbreaks. Initially, enthusiasm was high regarding their implementation as a non-pharmaceutical intervention (NPI). Yet, no country was able to prevent larger outbreaks without falling back to harsher NPIs, and the total effect of digital contact tracing remains elusive. Based on the results of empirical studies and modeling efforts, we show that digital contact tracing apps might have prevented cases on the order of single-digit percentages up until now, at best. We show that this poor impact can be attributed to a combination of low participation rates, a non-flexible reliance on symptom-based testing, low engagement of participants, and delays between testing and test result upload. We find that contact tracing does not change the epidemic threshold and exclusively prevents more cases during the supercritical phase of an epidemic, making it unfit as a tool to prevent outbreaks. Locally clustered contact structures may increase the interventions efficacy, but only if the number of contacts per individual is homogeneously distributed, a condition usually not found in contact networks. Our results suggest that policy makers cannot rely on digital contact tracing to contain outbreaks of COVID-19 or similar diseases.


title: Predicting age from 100,000 one week-long 100Hz wrist accelerometer records of physical activity

abstract: Physical activity improves quality of life, physical health and mental health, and is also an important protective factor against highly prevalent age-related diseases such as cardiovascular diseases, diabetes, cancer and mental health. With age, physical activity tends to decrease, leading down a vicious cycle that increases vulnerability to disease in the elderly. In the following, we trained neural network architectures to predict age from 115,456 one week-long 100Hz wrist accelerometer recordings from the UK Biobank (R-Squared=63.5{+/-}2.4%; root mean squared error=4.7{+/-}0.1 years). We achieved this performance by preprocessing the raw data as 2,271 scalar features, 113 time series and four images. We also considered the raw signal at different time scales (weekly activity patterns vs. gait). We then defined accelerated aging for a participant as being predicted older than ones actual age and aimed to characterize these participants. We performed a genome wide association on the accelerated aging phenotypes to estimate its heritability (h_g2=12.3{+/-}0.9%) and identified nine single nucleotide polymorphisms in seven genes associated with it (e.g HIST1H4L, involved in chromatin organization). Similarly, we identified biomarkers (e.g blood pressure), clinical phenotypes (e.g chest pain), diseases (e.g hypertension), environmental (e.g smoking) and socioeconomic (e.g income and education) variables associated with accelerated aging. We conclude that physical activity-derived biological age is a complex phenotype with both genetic and non-genetic factors.

category: health informatics


title: SARS-CoV-2 Breakthrough Infections in Fully Vaccinated Individuals

abstract:
ImportanceWhile COVID-19 vaccines are highly effective against disease, breakthrough infections may occur in the context of rising variants of concern.

ObjectiveWe paired random and passive surveillance nucleic acid testing with analysis of viral whole genomic sequences to detect and describe breakthrough infections, focusing in a university community.

DesignAnterior nasal swabs were collected from individuals for a nucleic acid amplification test (NAAT) for detection of SARS-CoV-2. A subset of NAAT positive samples was sequenced to determine variants associated with infections. Included in the testing and sequencing protocol were individuals that were fully vaccinated.

SettingThis study was performed as part of a surveillance program for SARS-CoV-2 on a university campus with 49,700 students and employees.

ParticipantsSurveillance testing was random and included approximately 10% of the population each week. Additionally, individuals self-identified with COVID-19 related symptoms or those that had close contact with SARS-CoV-2 positive individuals were also tested.


title: Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

abstract:
BackgroundHigher body mass index (BMI) is associated with subfertility in women and men. This relationship is further substantiated by a few small randomized-controlled trials of weight reduction and success of assisted reproduction. The aim of the current study was to expand the current evidence-base by investigating the association between BMI and subfertility in men and women using multivariable regression and Mendelian randomization.

Methods and findingsWe studied 34,157 women (average age 30, average BMI 23.1 kg/m2) and 31,496 men (average age 33, average BMI 25.4 kg/m2) who were genotyped and are participating in the Norwegian Mother, Father and Child Cohort Study. Self-reported information was available on time-to-pregnancy and BMI. A total of 10% of couples were subfertile (time-to-pregnancy [≥]12 months). Our findings support a J-shaped association between BMI and subfertility in both sexes using multivariable logistic regression models. Non-linear Mendelian randomization validated this relationship. A 1 kg/m2 greater genetically predicted BMI was linked to 15% greater odds of subfertility (95% confidence interval 4% to 28%) in obese women ([≥]30.0 kg/m2) and 14% lower odds of subfertility (-25% to -3%) in women with BMI <20.0 kg/m2. A 1 kg/m2 higher genetically predicted BMI was linked to 23% greater odds of subfertility (6% to 43%) among obese men and 36% decreased odds (-62% to 7%) among men BMI <20.0 kg/m2. A genetically predicted BMI of 23 and 25 kg/m2 was linked to the lowest subfertility risk in women and men, respectively. The main limitations of our study were that we did not know whether the subfertility was driven by the woman, man, or both; the exclusive consideration of individuals of northern European ancestry; and the limited amount of participants with obesity or BMI values <20.0 kg/m2.

ConclusionsWe observed a J-shaped relationship between BMI and subfertility in both sexes, when using both a standard multivariable regression and Mendelian randomization analysis, further supporting a potential causal role of BMI on subfertility.

AUTHOR SUMMARYO_ST_ABSWHY WAS THIS STUDY DONE?C_ST_ABSO_LIHigher body mass index (BMI) in both women and men is associated with subfertility in in observational studies. A few small randomized-controlled trials of weight reduction have reported an increased success of assisted reproduction in women. In addition, women with BMI <18.5 kg/m2 have lower conception rates with assisted reproduction technologies. A non-linear relationship between BMI and subfertility is suggested.
C_LIO_LIWe aimed to investigate the association between BMI and subfertility using both a standard multivariable regression and a Mendelian randomization approach.
C_LI

WHAT DID THE RESEARCHERS DO AND FIND?O_LIWe examined the relationship between BMI and subfertility (time-to-pregnancy [≥]12 months) among all men and women in the Norwegian Mother, Father and Child Cohort Study with available genotype information and anthropometric data (34,157 women, 31,496 men).
C_LIO_LIWe observed a J-shaped relationship between BMI and subfertility in both sexes, when using both a standard multivariable regression and Mendelian randomization analysis.
C_LI

WHAT DO THESE FINDINGS MEAN?O_LITogether with previous observational and trial evidence, findings support a causal effect of overweight/obesity on subfertility in women and men.
C_LIO_LIOur findings expand the current evidence by also indicating that individuals at the lower end of the BMI distribution (<20 kg/m2) may have an increased risk of subfertility.
C_LIO_LICurrent advice and support for overweight and obese subfertile couples to lose weight should continue. Additionally, clinicians should consider appropriate advice to those with low BMI on whether they should increase weight to obtain a normal BMI.
C_LI


title: Clinical profile and immediate outcome of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Covid-19: a multicentric study

abstract:
STRUCTURED ABSTRACTO_ST_ABSINTRODUCTIONC_ST_ABSFollowing an asymptomatic or mildly symptomatic Corona virus disease (COVID 19), otherwise healthy children, may develop serious manifestations in form of cardiac, neurological, respiratory, gastrointestinal and dermatologic dysfunction. Many such cases were being observed in Odisha, an eastern state of India and reported from different health care facilities. We related these unexplained serious manifestations to Multisystem Inflammatory Syndrome associated with COVID 19 (MIS-C) and planned this study.

METHODSThis retrospective observational study was carried out in three tertiary care centres: Kalinga Institute of Medical Sciences, Bhubaneswar, MKCG Medical college Berhampur and Jagannath Hospital, Bhubaneswar between July to September of year 2020. Study population include all children from 1 month to 15 years admitted to hospital with MIS-C according to WHO Diagnostic Criteria. All the data were analyzed by SPSS.

RESULTSA total of 21 children were included in our study. Maximum number of cases were male (76.2%), predominate age group was 6-10 yrs (47.6%). Predominate symptoms /signs in our observation were fever, pain abdomen, seizure and hypotension. Most of these cases were positive for SARS CoV antibody (80.95%). Response to immunotherapy was dramatic. Mortality (9%) of our study is higher to 1.8-3% from western literature. None of our patient had coronary abnormality while 2 had mild cardiac dysfunction at discharge comparable to other studies.

CONCLUSIONMIS-C following exposure to COVID 19 infection in children is a clinical syndrome which needs early suspicion and appropriate intervention to prevent mortality.

category: pediatrics


title: COVID-19 pandemic dynamics in India and impact of the SARS-CoV-2 Delta (B.1.617.2) variant

abstract:
BackgroundThe COVID-19 Delta pandemic wave in India surged and declined within 3 months; cases then remained low despite the continued spread of Delta elsewhere. Here we aim to estimate key epidemiological characteristics of the Delta variant based on data from India and examine the underpinnings of its dynamics.

MethodsWe utilize multiple datasets and model-inference methods to reconstruct COVID-19 pandemic dynamics in India during March 2020 - June 2021. We further use model estimates to retrospectively predict cases and deaths during July - mid-Oct 2021, under various vaccination and vaccine effectiveness (VE) settings to estimate the impact of vaccination and VE for non-Delta-infection recoverees.

FindingsWe estimate that Delta escaped immunity in 34.6% (95% CI: 0 - 64.2%) of individuals with prior wildtype infection and was 57.0% (95% CI: 37.9 - 75.6%) more infectious than wildtype SARS-CoV-2. Models assuming higher VE among those with prior non-Delta infection, particularly after the 1st dose, generated more accurate predictions than those assuming no such increases (best-performing VE setting: 90/95% vs. 30/67% baseline for the 1st/2nd dose). Counterfactual modeling indicates that high vaccination coverage for 1st vaccine-dose in India ([~]50% by mid-Oct 2021) combined with the boosting of VE among recoverees averted around 60% of infections during July - mid-Oct 2021.

InterpretationNon-pharmaceutical interventions, infection seasonality, and high coverage of 1-dose vaccination likely all contributed to pandemic dynamics in India during 2021. Given the shortage of COVID-19 vaccines globally and boosting of VE, for populations with high prior infection rates, prioritizing the first vaccine-dose may protect more people.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for studies published through Nov 3, 2021 on the Delta (B.1.617.2) SARS-CoV-2 variant that focused on three areas: 1) transmissibility [search terms: ("Delta variant" OR "B.1.617") AND ("transmission rate" OR "growth rate" OR "secondary attack rate" OR "transmissibility")]; 2) immune response ([search terms: ("Delta variant" OR "B.1.617") AND ("immune evas" OR "immune escape")]; and 3) vaccine effectiveness ([search terms: ("Delta variant" OR "B.1.617") AND ("vaccine effectiveness" OR "vaccine efficacy" OR "vaccination")]. Our search returned 256 papers, from which we read the abstracts and identified 54 relevant studies.

Forty-two studies addressed immune evasion and/or vaccine effectiveness. Around half (n=19) of these studies measured the neutralizing ability of convalescent sera and/or vaccine sera against Delta and most reported some reduction (around 2-to 8-fold) compared to ancestral variants. The remainder (n=23) used field observations (often with a test-negative or cohort-design) and reported lower VE against infection but similar VE against hospitalization or death. Together, these laboratory and field observations consistently indicate that Delta can evade preexisting immunity. In addition, five studies reported higher B-cell and/or T-cell vaccine-induced immune response among recovered vaccinees than naive vaccinees, suggesting potential boosting of pre-existing immunity; however, all studies were based on small samples (n = 10 to 198 individuals).

Sixteen studies examined transmissibility, including 1) laboratory experiments (n=6) showing that Delta has higher affinity to the cell receptor, fuses membranes more efficiently, and/or replicates faster than other SARS-CoV-2 variants, providing biological mechanisms for its higher transmissibility; 2) field studies (n=5) showing higher rates of breakthrough infections by Delta and/or higher viral load among Delta infections than other variants; and 3) modeling/mixed studies (n=5) using genomic or case data to estimate the growth rate or reproduction number, reporting a 60-120% increase. Only one study jointly estimated the increase in transmissibility (1.3-1.7-fold, 50% CI) and immune evasion (10-50%, 50% CI); this study also reported a 27.5% (25/91) reinfection rate by Delta.

Added value of this studyWe utilize observed pandemic dynamics and the differential vaccination coverage for two vaccine doses in India, where the Delta variant was first identified, to estimate the epidemiological properties of Delta and examine the impact of prior non-Delta infection on immune boosting at the population level. We estimate that Delta variant can escape immunity from prior wildtype infection roughly one-third of the time and is around 60% more infectious than wildtype SARS-CoV-2. In addition, our analysis suggests the large increase in population receiving their first vaccine dose ([~]50% by end of Oct 2021) combined with the boosting effect of vaccination for non-Delta infection recoverees likely mitigated epidemic intensity in India during July - Oct 2021.

Implications of all the available evidenceOur analysis reconstructs the interplay and effects of non-pharmaceutical interventions, infection seasonality, Delta variant emergence, and vaccination on COVID-19 pandemic dynamics in India. Modeling findings support prioritizing the first vaccine dose in populations with high prior infection rates, given vaccine shortages.


title: COVID-19 pandemic dynamics in India, the SARS-CoV-2 Delta variant, and implications for vaccination


title: Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization

abstract: Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. Here we evaluate aspects of sexual behaviour in relation to the risk of OPC (2,641 cases and 6,585 controls), using genetic variants associated with age at first sex (AFS) and number of sexual partners (NSP) to perform Mendelian randomization (MR) analyses. While univariable MR showed a causal effect of both later AFS and increasing NSP on OPC, results attenuated in the multivariable models (AFS IVW OR 0.7, 95%CI 0.4, 1.2, p= 0.21; NSP IVW OR 0.9, 95%CI 0.5 1.7, p= 0.76). We also found evidence for correlated pleiotropy in the genetic instruments for sexual behaviour, emphasising the need for multivariable approaches when performing MR of complex behavioural traits and the triangulation of evidence.

category: genetic and genomic medicine


title: In vivo delayed clearance of Plasmodium falciparum malaria independent of kelch13 polymorphisms and with escalating malaria in Bangladesh.

abstract: The emergence of resistance to artemisinin drugs threatens global malaria control. Resistance is widely seen in South East Asia (SEA) and Myanmar, but not comprehensively assessed in Bangladesh. This is due to lack of measuring parasite clearance times in response to drug treatment, a gold standard used to track artemisinin resistance (AR), in the Chittagong Hill Tracts (CHT), where >90% of malaria occurs in Bangladesh. Here we report delay in clinical parasite clearance half-lives > 5 h characteristic of AR, in Bandarban, a south-eastern rural, CHT district with escalating malaria and bordering Myanmar. Thirty-one and 68 malaria patients respectively presented in the clinic in 2018 and 2019, and this increase well correlated to the district-level malaria surge and rise in rainfall, humidity and temperature. A total of 27 patients with uncomplicated Plasmodium falciparum malaria mono-infection, after administration of an artemisinin combination therapy (ACT) showed median (range) parasite clearance half-life and time of 5.6 (1.5 - 9.6) and 24 (12-48) hours (h) respectively. The frequency distribution of parasite clearance half-life and time was bimodal, with a slower parasite clearance of 8 h in 20% of the participants. There was however, no detectable parasitemia 72 h after initiating ACT. Half-life clearance of > 5h, respectively seen in 35% and 40% of participants in 2018 and 2019, lacked in correlation to initial parasitemia, blood count parameters or resistance mutations of PfKelch13 (K13, the major parasite marker of AR). Culture adapted strains await assessment of in vitro resistance and new parasite determinants of AR.


title: Resolution limit-free community detection reveals unique patterns of resting-state network connectivity in posttraumatic stress disorder: A PGC-ENIGMA PTSD Consortium investigation

abstract: Posttraumatic stress disorder (PTSD) is a complex psychiatric condition that has generated much attention in the neuroimaging literature. A neurocircuitry model supporting fronto-limbic dysfunction as a major player in facilitating clinical symptoms of PTSD is well-characterized; however, recent literature suggests that network-based approaches may provide additional insight into neural dysfunction in PTSD. Our analysis uses resting-state neuroimaging scans of 1063 adults from the PGC-ENIGMA PTSD Consortium to investigate a network-based model of functional connectivity in PTSD. With a novel, resolution limit-free community detection approach, 16 communities corresponding to functionally meaningful networks were detected with high quality. After group-level community detection, participants were classified into three groups (PTSD, n=418, trauma-exposed controls without PTSD, n=434, and non-trauma exposed healthy controls, n=211). Individual network connectivity metrics were calculated, including whole-brain, default mode network, and central executive network participation coefficient and connectivity strength. Linear mixed effects models revealed group differences in the whole-brain, default mode, and central executive network participation coefficient and connectivity strength such that individuals with PTSD demonstrated overall greater values. We also described sex differences such that males demonstrate greater whole-brain participation coefficient vs. females and females demonstrate greater default mode network connectivity strength vs. males. Our results suggest that PTSD in adults is associated with reduced specialization and enhanced inter-module communication throughout the brain network, which may contribute to inefficient information processing and poor emotional regulation. This study presents a novel use of resolution limit-free community detection in a large PTSD sample, revealing robust differences in resting-state network topology.


title: Unlocking the global antigenic diversity and balancing selection of Plasmodium falciparum

abstract:
Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies on Plasmodium falciparum antigen diversity have focused on well-known vaccine candidates while the diversity of several others has never been studied. Here we provide an overview of the diversity and population structure of leading vaccine candidate antigens of P. falciparum using the MalariaGEN Pf3K (version 5.1) resource, comprising more than 2600 genomes from 15 malaria endemic countries. We developed a stringent variant calling pipeline to extract high quality antigen gene sequences from the global dataset and a new R-package named VaxPack to streamline population genetic analyses. In addition, a newly developed algorithm that enables spatial averaging of selection pressure on 3D protein structures was applied to the dataset. We analysed the genes encoding 23 leading and novel candidate malaria vaccine antigens including csp, trap, eba175, ama1, rh5, and CelTOS. We found that current malaria vaccine formulations are based on rare variants and thus may have limited efficacy. High levels of diversity with evidence of balancing selection was detected for most of the erythrocytic and pre-erythrocytic antigens. Measures of natural selection were then mapped to 3D protein structures to predict targets of functional antibodies. For some antigens, geographical variation in the intensity and distribution of these signals on the 3D structure suggests adaptations to different human host or mosquito vector populations. This study provides an essential framework for the diversity of P. falciparum antigens for inclusion in the design of the next generation of malaria vaccines.

Author SummaryHighly effective malaria vaccines are important for the sustainable elimination of malaria. However, the diversity of parasite antigens targeted by malaria vaccines has been largely overlooked, with most vaccine formulations based only on a single antigen variant. Failure to accommodate this diversity may result in vaccines only being effective against vaccine-like variants, resulting in limited protective efficacy. Investigation of the diversity of genes encoding parasite antigens can help prioritize and validate them as vaccine candidates as well as to identify the most common variants for inclusion in the next generation of malaria vaccines. Here we measure the diversity of 23 vaccine antigens of Plasmodium falciparum, using the publicly available MalariaGEN Pf3K (version 5.1) resource comprising more than 2600 genomes from 15 malaria endemic countries. We found that variants found in current vaccine formulations are rare and thus may target only a small proportion of circulating malaria parasite strains. Variation in intensity of immune selection in parasites from different geographic areas suggests adaptation to different human host or vector populations. This study provides an essential framework for the design of the next generation of malaria vaccines, in addition to providing novel insights into malaria biology.


title: The accuracy of saliva versus nasopharyngeal and/or oropharyngeal samples for the detection of SARS-CoV-2 in children. A rapid systematic review and meta-analysis

abstract:
BackgroundThe comparative performance of saliva and nasopharyngeal samples for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by reverse transcriptase polymerase chain reaction (RT-PCR) in children remains unclear. As schools reopen around the world, there is an interest in the use of saliva samples for the detection of SARS-CoV-2 in children to circumvent barriers with nasopharyngeal sampling. We systematically reviewed the literature to understand the performance of saliva sampling using RT-PCR on naso- and/or oropharyngeal swabs as the reference standard.

MethodsArticles from PubMed/MEDLINE and Living Evidence were accessed until 28th April 2021. A search method without restriction to children population was applied and during the review phase, if a study included patients <18 years old, authors were contacted to provide additional information on the subset of children. Studies were eligible if they reported on matched saliva and naso- and/or oropharyngeal samples, taken from the same patient on the same day. Studies using other respiratory samples such as sputum samples were excluded. Each paired patient sample had to be tested on the same RT-PCR platform.

ResultsTen studies were included, comprising 1486 matched saliva and on naso- and/or oropharyngeal pairs from children aged 0 to 18 years old. The pooled absolute sensitivity and specificity of saliva sampling using RT-PCR on nasopharyngeal samples as the reference standard was 84.5% (95% CI; 78.0%-90.3%) and 99.5% (95% CI; 98.2%-100.0%). Comparable performance of saliva to nasopharyngeal samples was shown in both symptomatic and asymptomatic children. Stratified analyses of various covariates showed no significant differences.

DiscussionOur pooled accuracy estimates of RT-PCR SARS-CoV-2 testing on saliva in children did not seem to be different from meta-analyses of studies that enrolled mainly adults. Saliva could potentially be considered an alternative sampling method for screening in children and to pick up those with high viral load.


title: How does the local area deprivation influence life chances for children in poverty in Wales: A record linkage cohort study

abstract:
BackgroundChildren growing up in poverty are less likely to achieve in school and more likely to experience mental health problems. This study examined factors in the local area that can help a child overcome the negative impact of poverty.

MethodThis retrospective cohort study included 159,131 children who lived in Wales and completed their age 16 exams (Key Stage 4 (KS4)) between 2009 and 2016. Free School Meal (FSM) provision was used an indicator of household level deprivation. Area level deprivation was measured by the Welsh Index of Multiple Deprivation 2011. An encrypted unique Anonymous Linking Field was used to link the children with their health and educational records. The outcome variable of  Overall doing well was comprised of achieved at KS4, no mental health condition, no substance, and alcohol abuse records. Bidirectional logistic regression models were used to investigate the association between local areas deprivation and childs outcome.

Results22% of children on FSM were overall doing well compared to 54.9% of non-FSM children. FSM Children who lived in the least deprived areas are significantly more likely to do well (adjusted odds ratio (aOR) -2.20 (1.93-2.51)) than children lived in the most deprived areas. FSM children, living in areas with higher community safety, higher relative income, higher access to services, are more likely to do well than their peers.

ConclusionThis study highlights that investing in community development (e.g., safety, back to work schemes, connectivity) helps in childs education attainment, mental health and reduce risk-taking behaviours.

What is already known on this subject?O_LIIn Wales, 29.3% of children are living in poverty
C_LIO_LIWelsh Index of Multiple Deprivation (WIMD) 2019 from Welsh Government highlighted the areas in Wales which remained as the topmost deprived areas for more than last 15 years and indicated a lack of social mobility in most of these areas.
C_LIO_LIGrowing up in a disadvantaged area increases the risk of adverse health and social outcomes in childrens life.
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What this study adds?O_LIChildren from disadvantaged households are significantly more likely to do well if they are living in least deprived areas than the children from most deprived areas.
C_LIO_LIThe findings suggest that investing in community development and local area improvements such as promoting community safety, improving the access to public services and return to work schemes, can also help local children to do well in terms of education, mental health and reducing risk-taking behaviours (alcohol/drug use).
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title: Factors influencing focused practice: A qualitative study resident and early-career family physician practice choices

abstract:
BackgroundAlthough focused practice within family medicine may be increasing globally, there is limited research on the factors contributing to decisions to focus practice. We aimed to examine the factors influencing resident and early-career family physician choices of focused practice across three Canadian provinces.

MethodsWe analyzed a subset of qualitative interview data from a study across British Columbia, Ontario, and Nova Scotia. A total of 22 resident family physicians and 38 early-career family physicians in their first 10 years of practice who intend to or currently practice in a focused area were included in our analysis. We compared participant types, provinces, and the degree of focused practice while identifying themes related to factors influencing the pursuit of focused practice.

ResultsWe identified three key themes of factors contributing to choices of focused practice: self-preservation within the current health care system, support from colleagues, and experiences in medical school and/or residency. Minor themes included alignment of practice with skills, personal values, or ability to derive professional satisfaction; personal lived experiences; and having many attractive opportunities for focused practice.

InterpretationBoth groups of participants unanimously viewed focused practice as a way to circumvent the burnout or exhaustion they associated with comprehensive practice in the current structure of the health care. This finding, in addition to other influential factors, was consistent across the three provinces. More research is needed to understand the implications of resident and early-career family physician choices of focused practice within the physician workforce.

category: primary care research


title: HbA1c and FIB-4 as Serologic Markers for the Risk of Progression of Stage A Heart Failure

abstract:
BackgroundThe classic association of glycemic control as represented by glycosylated hemoglobin (Glyco% or HbA1c) with progression of micro and macro vascular clinical complications is well documented. However, use of the advanced glycation end product (AGE) axis as a marker for early diastolic hemodynamic changes leading to clinical heart failure has been suggested but is less well characterized. This study explored the association between elevated Glyco% and Fibrosis 4 (FIB-4, a 4-component marker for liver fibrosis) values and worsening measures of diastolic cardiac function in order to assess their utility as early serologic markers in cardiovascular disease prevention.

Methods and ResultsA Retrospective cohort analysis was conducted in 102 patients presenting to the Parkview Medical Center health system who had received a full resting echo characterized by normal systolic ejection fraction and clinical risk factors associated with stage A heart failure in conjunction with Glyco% and FIB-4 scores all within a 3-month time window. Using regression analysis, measures of diastolic cardiac function were assessed in conjunction with rising Glyco% levels characterized as <6.5 and > 6.5 and FIB-4 scores after controlling for the presence of hypertension, coronary artery disease and valvular heart disease. Glyco% levels > 6.5 were significantly associated with a higher E/e ratio and closely associated with an elevated left atrial volume index both indicative of elevated left atrial pressure as a sensitive marker for diastolic cardiac dysfunction. FIB-4 scores did not appear to be clinically associated with progression of diastolic dysfunction.

ConclusionsGlyco%, long known to be a marker for metabolic glycemic control can also act as an early marker for identifying patients at increased risk for the progression of stage A heart failure. FIB-4 scores cannot.

Registrationhttps://clinicaltrials.gov/ct2/show/NCT04450576?term=duffee&draw=2&rank=3


title: Mental Health Conditions in Lesbian, Gay, Bisexual, Transgender, Queer and Asexual Youth in Brazil: a call for action

abstract: Lesbian, Gay, Bisexual, Transgender, Queer and Asexual (LGBTQA+) youth have a greater odds of experiencing stressful life events like discrimination and violence when compared to their cisgender heterosexual peers, which can lead to mental health problems. We aimed to estimate the prevalence of mental disorders among LGBTQA+ youths from the 3rd wave of the Brazilian High-Risk Cohort for Psychiatric Disorders (n= 1,475). Mental disorders were assessed using the Brazilian version of the Development and Well-Being Behavior Assessment. Sexual orientation, gender identity and biological sex were assessed using specific questions of a self-report confidential questionnaire. Data were analyzed using sampling weights to account for attrition and our oversampling design. The mean age was 18.14 years (SD= 2.00) and 15.18% of the sample described themselves as LGBTQA+ (n=221). The LGBTQA+ group presented higher rates of anxiety disorders (30.14% vs. 13.37%; OR= 3.66; 95%CI: 2.82 - 4.75; p<0.001), depressive disorders (27.75% vs. 15.34%; OR= 2.51; 95%CI: 1.92 - 3.27, p<0.001) and post-traumatic stress disorder (4.98% vs. 2.25%, OR= 4.21, 95%CI: 2.54 - 6.96, p<0.001), if compared with the cisgender heterosexual group. No difference was found for conduct disorders (2.97% vs. 5.21% OR= 0.81; 95%CI: 0.39 - 1.69; p=0.577) or attention deficit hyperactivity disorder (5.92% vs. 3.28%, OR= 1.29; 95%CI: 0.74 - 2.25; p=0.361). Our results elucidate the mental health disparities between LGBTQA+ people and cisgender heterosexuals in Brazil. It highlights the need to promote the inclusion of this population in policy formulation and to support actions to mitigate and prevent the suffering and mental health problems related to sexual orientation and gender identity.


title: Service user perspectives of community mental health services for people with complex emotional needs: a co-produced qualitative interview study

abstract:
BackgroundThere is consensus that services supporting people with complex emotional needs are part of a mental health care system in which change is needed. To date, service users views and co-production exercises have had little impact on the development of treatment and care. This needs to change, and our paper evidences the experiences and perspectives of a diverse range of people on how community services can best address the needs of people with complex emotional needs.

MethodsA co-produced qualitative research study. Lived experience researchers led data collection and analysis. Individual interviews were conducted with 30 people across England who had a diverse range of experiences and perspectives of using community services for complex emotional needs. Participants were asked about their experiences of using community services for their mental health, and views on how community services can best address their needs. Thematic analysis was used to analyse the data.

ResultsParticipants reported some experiences of good practice but also of experiences of severely stigmatising treatment, a lack of effective support and service fragmentation. Relational Practice was identified as the central overarching theme and describes how community services can best support people with complex emotional needs. This approach involves care delivered in a non-stigmatising, individualised, compassionate and trauma-informed manner. It involves care that is planned collaboratively with service users to ensure their multiple needs are addressed in a flexible, holistic and consistent way which accounts for the long-term and fluctuating nature of their needs.

ConclusionsRelational practice approaches have potential to facilitate better community care for people with complex emotional needs. Research and service development are needed to examine how best to implement such approaches across the mental health service system. This work must be co-produced with people with relevant lived experience, their carers and the professionals who support them.


title: Behavioral and psychological symptoms of dementia in different dementia disorders: A large-scale study of 12 000 individuals.

abstract:
BackgroundThe majority of individuals with dementia will suffer from psychological and behavioral symptoms of dementia (BPSD). There is limited number of studies investigating BPSD in different types of dementia.

ObjectivesTo characterize BPSD in Alzheimers disease (AD), vascular dementia (VaD), mixed (Mixed) dementia, Parkinsons disease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and unspecified dementia (UNS) in individuals residing in long-term care facilities.

MethodsWe included 10,405 individuals with dementia living in long-term care facilities from the Swedish registry for cognitive/dementia disorders (SveDem) and the Swedish BPSD registry. BPSD was assessed with the Neuropsychiatric Inventory - Nursing Home Version (NPI-NH). Multivariate logistic regression models were used to evaluate the associations between dementia diagnoses and different BPSDs.

ResultsThe most common symptoms were aberrant motor behavior, agitation and irritability. Compared to AD, we found a lower risk of delusions (in FTD, unspecified dementia), hallucinations (in FTD), agitation (VaD, in PDD, unspecified dementia), elation/euphoria (in DLB), anxiety (Mixed, VaD, unspecified dementia), disinhibition (in PDD); irritability (in DLB, FTD, unspecified dementia), aberrant motor behavior (in Mixed, VaD, unspecified dementia), sleep and night-time behavior changes (in unspecified dementia). Higher risk of delusions (in DLB), hallucinations (in DLB, PDD), apathy (VaD, FTD), disinhibition (in FTD) and appetite and eating abnormalities (in FTD) were also found in comparison to AD.

ConclusionsBPSD was common in all types of dementia, with the most common symptoms being aberrant motor behavior, agitation, and irritability. Additionally, presentation of BPSD differ in different dementia types.


title: Behavioral and psychological symptoms of dementia in different dementia disorders: A large-scale study of 10 000 individuals.


title: Family functioning but not social capital is associated with better mental health in adolescents affected by violence and displacement by armed conflict in Colombia

abstract:
BackgroundThe effect of the Colombian armed conflict on the mental health of adolescents is still poorly understood. Given social interventions are most likely to inform policy, we tested whether two potential intervention targets, family functioning and social capital, were associated with mental health in Colombian adolescents, and whether this was moderated by experience of violence and displacement.

MethodsWe examined the cross-sectional association between family functioning, cognitive social capital, structural social capital and 12-month prevalence of Composite International Diagnostic Interview (CIDI) diagnosed psychiatric disorder, using data on 12-17-year-old adolescents (N = 1754) from the 2015 National Mental Health Survey of Colombia, a nationally representative epidemiological study. We tested whether associations survived cumulative adjustment for demographic confounders, experience of non-specific violence and harm, and displacement by armed conflict.

ResultsNeither structural nor cognitive social capital were associated with better mental health. Better family functioning was associated with reduced risk of poor mental health in an unadjusted analysis (OR 0.90 [0.85 - 0.96]), and after cumulative adjustments for demographic confounders (OR 0.91 [0.86 - 0.97]), non-specific violence and harm (OR 0.91 [0.86 - 0.97]) and social capital variables (OR 0.91 [0.85 - 0.97]). In the final model, each additional point on the family APGAR scale was associated with a 9% reduced odds of any CIDI diagnosed disorder in the last 12 months.

ConclusionsBetter family functioning was associated with better mental health outcomes for all adolescents. This effect remained present in those affected by the armed conflict even after accounting for potential confounders.


title: Conditionality of COVID-19 vaccine acceptance in European countries

abstract:
The COVID-19 vaccine rollout in recent months offers a powerful preventive measure that may help control SARS-CoV-2 transmission. Nevertheless, long-standing public hesitation around vaccines has heightened public health concerns that vaccine coverage may not achieve desired public health impacts.This cross-sectional survey was conducted online in December 2020 among 7000 respondents (aged 18 to 65) in Belgium, France, Germany, Italy, Spain, Sweden, and Ukraine. The survey included open text boxes for fuller explanation of responses. Projected COVID-19 vaccine coverage varied and may not be sufficiently high among certain populations to achieve herd immunity. Overall, 56.9% would accept a COVID-19 vaccine, 19.0% would not, and 24.1% did not know or preferred not to say. By country, between 44% (France) and 66% (Italy) of respondents would accept a COVID-19 vaccine. Respondents expressed conditionality in open responses, voicing concerns about vaccine safety and mistrust of authorities. Public health campaigns must tackle these safety concerns.

HighlightsO_LIMixed-method survey studied expected COVID vaccine uptake in 7 European countries.
C_LIO_LIProjected COVID vaccine acceptance by country ranged from 44% to 66%.
C_LIO_LIExplicit COVID vaccine acceptance or rejection was conditional.
C_LIO_LIStudy finds concerns about vaccine safety and authorities competence and honesty.
C_LIO_LIVaccine communications should address safety anxieties and target specific groups.
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title: Disease-modifying therapies for T1 hypointense lesions (Black Holes) volume in patients with multiple sclerosis: Protocol for a systematic review and meta-analysis

abstract:
RationaleA major part of diagnosis and follow-up in patients with multiple sclerosis is based on MRI evaluations. As T1-hypointense lesions represent neural destruction or axonal loss and anticipate irreversible disability in the patients, evaluation of the effects of Disease-modifying therapies (DMTs) on the volume of black holes seems necessary.

ObjectivesTo evaluate the effects of FDA approved disease-modifying therapies (DMTs) on T1 hypointense lesions (Black Holes) volume in patients with multiple sclerosis (MS)

Data sourcesWe will search MEDLINE (through Ovid), Embase, and CENTRAL. We wont consider any timeframe, language, or geographical restrictions.

MethodsWe will include only randomized controlled trials (RCTs) that have evaluated the effects of DMTs on black holes mean volume in adult patients diagnosed with any phenotype of multiple sclerosis (MS) in comparison to the placebo, routine care, or no treatment regimen. We will assess the risk of bias in the primary studies using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2). Data will be synthesized based on the random-effects model and results will be plotted on a forest plot. Heterogeneity will be assessed using I2 statistics. If feasible, we will also perform subgroup analyses for each DMT.

FundingThis study is not funded.

RegistrationPROSPERO submission ID: 262883.

category: neurology


title: Opinion of Health Care Providers on Birth Companions in Obstetrics Department of a Tertiary Care Hospital in North India

abstract:
BackgroundDespite impressive improvements in institutional births and a fall in maternal mortality, satisfaction of women with birthing experience in public health institutions is low (68%). Birth Companion is an important part of the Labour room Quality Improvement (LaQshya) programme introduced by the Government of India in 2017. Despite mandates, implementation of the concept has been unsatisfactory (9%), even though the importance of Birth Companion has increased due to enhanced risk posed by COVID-19. Little is known about awareness among health care providers on Birth Companions, perceived barriers or their suggestions.

MethodsWe canvassed a 15-question instrument using ordinal scales on 151 health care providers comprising consultants, post graduates, residents, and nurses (response rate 69%) in the department of Obstetrics & Gynecology, Lok Nayak Hospital, Delhi, India to gauge their awareness and opinions about Birth Companions.

ResultsMost health care providers across all categories were aware of the concept (93%), World Health Organizations recommendation (83%) and Governments instructions for its hospitals (68%) that every woman should be accompanied by a Birth Companion of her choice during labour. Birth Companions of choice suggested by them were the mother (70%), husband (69%). sister (46%) or nurse (43%). Most health care providers agreed that a Birth Companion should wear clean clothes (95%), be free from any communicable disease (91%), stay with the pregnant woman throughout the process of labour (74%) and should have herself gone though labour (42%). Almost all providers (95%) agreed that the presence of a Birth Companion during labour will be beneficial, as they would provide emotional support (99%), boost the womans confidence (98%), provide comfort measures like massage (95%), early initiation of breastfeeding (93%), reduce post-partum depression (91%), humanize labour (83%), reduce need for analgesia (70%) and increase spontaneous vaginal births (69%). Yet support for its introduction in their hospital was low (59%). Staff nurses had reservations (62%) with only 40% of those who believed Birth Companion to be beneficial approving of its introduction in their hospital. Over-crowding in labour room and privacy concerns for other women were identified as key barriers.

ConclusionEven though most health care providers were aware of and convinced of multiple benefits of Birth Companion during labour, lack of adequate infrastructure in the labour room prevented them from supporting its introduction. Government should provide adequate funding to upgrade labour rooms in a way that provides privacy to the delivering women and frame guidelines and train Birth Companions to perform their role appropriately.

category: obstetrics and gynecology


title: NeoScore integrates characteristics of the neoantigen:MHC class I interaction and expression to accurately prioritize immunogenic neoantigens

abstract: Accurate prioritization of immunogenic neoantigens is key to developing personalized cancer vaccines and distinguishing those patients likely to respond to immune checkpoint inhibition. However, there is no consensus regarding which characteristics best predict neoantigen immunogenicity, and no model to date has both high sensitivity and specificity and a significant association with survival in response to immunotherapy. We address these challenges in the prioritization of immunogenic neoantigens by 1) identifying which neoantigen characteristics best predict immunogenicity, 2) integrating these characteristics into an immunogenicity score, NeoScore, and 3) demonstrating an improved association of the NeoScore with response to immune checkpoint inhibition compared to mutational burden. One thousand random and evenly split combinations of immunogenic and non-immunogenic neoantigens from a validated dataset were analyzed using a regularized regression model for characteristic selection. The selected characteristics, the dissociation constant and binding stability of the neoantigen:MHC class I complex and expression of the mutated gene in the tumor, were integrated into the NeoScore. A web application is provided for calculation of the NeoScore. The NeoScore results in improved, or equivalent, performance in four test datasets as measured by sensitivity, specificity, and area under the receiver operator characteristics curve compared to previous models. Among cutaneous melanoma patients treated with immune checkpoint inhibition, a high NeoScore had a greater association with improved survival compared to mutational burden. Overall, the NeoScore has the potential to improve neoantigen prioritization for the development of personalized vaccines and contribute to the determination of which patients are likely to respond to immunotherapy.

category: oncology


title: Defining the Critical Components of Informed Consent for Genetic Testing: A Delphi Study

abstract:
PurposeInformed consent for genetic testing has historically happened during pre-test genetic counseling, without specific guidance defining which core concepts are required.

MethodsThe Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendations Workgroup (CADRe) used a modified Expert Delphi consensus process to identify the core concepts essential to consent for clinical genetic testing. A literature review identified 77 concepts that are included in informed consent for genetic tests. Twenty five experts (9 medical geneticists, 8 genetic counselors, and 9 bioethicists) completed two rounds of Delphi surveys ranking concepts importance to informed consent.

ResultsThe most highly ranked concepts included: (1) genetic testing is voluntary; (2) why the test is recommended and what does it test for; (3) what results will be returned and to whom; (4) are there other types of potential results; what choices exist; (5) how will prognosis and management be impacted by results; (6) what is the potential family impact; (7) what are the test limitations and next steps; (8) potential risk for genetic discrimination and legal protections.

ConclusionDefining the core concepts necessary for informed consent for genetic testing provides a foundation for quality patient care across a variety of healthcare providers and clinical indications.