title: Efficacy and safety of Ayurveda interventions for Sinusitis: A systematic review and meta-analysis.

abstract:
ObjectivesTo provide a broad evaluation of the efficacy and safety of Ayurveda interventions (procedural and non-procedural) for the management of sinusitis, and also of the relative efficacy and safety of different Ayurveda therapies for Sinusitis.

MethodsFive electronic databases for published research articles, three databases for the unpublished doctoral thesis, clinical trial registries, and hand searches were done till August 2020. All comparative clinical trials recruiting sinusitis patients of any age group, receiving Ayurveda intervention, regardless of forms, dosages, and ingredients, for not less than one week were included. The data extraction and the risk of bias(RoB) assessment were done by two reviewers independently.

ResultsA total of 2824 records were identified, of which 09 randomized parallel arms trials met inclusion criteria. No studies were found comparing Ayurveda versus placebo or non-Ayurveda interventions. Combined Ayurveda therapy (CT) was statistically more beneficial compared with either procedural or non-procedural Ayurveda therapy alone in reducing symptoms nasal discharge (standardized MD -0.71, 95% CI -1.16 to -0.26, I2 58%, 210 participants) and headache (standardized MD -0.44, 95% CI -0.86 to -0.02, I2 56%, 218 participants), however, no significant difference was found in reducing symptoms nasal obstruction and loss of smell. No numerical data related to the safety of Ayurveda intervention was found in included trials. Because, included trials(09) were having  high to  unclear overall bias, sub-standard methodology, and heterogeneity in results, the overall findings need to be interpreted cautiously.

ConclusionsAlthough individual studies appeared to produce positive results, very low certainty of total effect(downgraded twice for RoB, once for inconsistency, indirectness, and imprecision each) hindered to arrive at any conclusion regarding efficacy or safety of Ayurveda interventions for sinusitis. There is a need for well-designed-executed-reported clinical studies on clinically relevant outcomes.

PROSPERO registration numberRD42018103995

ARTICLE SUMMARYO_ST_ABSStrength and limitations of this studyC_ST_ABSO_LIThis is the first systematic review to provide the status of available evidence on the efficacy and safety of Ayurveda interventions for sinusitis.
C_LIO_LIThe search strategy was comprehensive, all the relevant sources were searched for published as well as unpublished research works.
C_LIO_LIThis systematic review has a broad review question, which compromises its eternal validity.
C_LIO_LIThe certainty of the overall effect is  very low due to  unclear to  high overall risk of bias, lack of validated outcome measures, inconsistency in results with wide CIs, small sample sizes, incomplete reporting, etc.
C_LI

category: respiratory medicine


title: A survey of current anticoagulation patient education practices and development

abstract:
IntroductionAnticoagulants are high-risk medications widely used to prevent and treat thrombotic events, resulting in a need for adequate patient education to minimize harm. While anticoagulant patient education interventions can improve knowledge and surrogate outcomes, they may not represent current practice. Our objective was to determine provider perceptions of anticoagulation patient education at their institution.

MethodsA quantitative survey was distributed through a national professional organization and across several health systems. Questions included educational delivery methods, perceived effectiveness, evaluation of patient knowledge, development of patient education, and demographics.

ResultsThe 61 survey respondents were 79.0% female, 86.2% white, and an average age of 43. Most respondents (95%) complete patient education interventions in one session. Providers reviewed educational topics in 37% of daily patient interactions. 59% of respondents reported reasons for not performing patient knowledge checks included no formal process requiring knowledge checks, lack of time, and forgetting. The majority (93.4%) reported their patient education process was somewhat or very effective. The main reason underlying perceived less effective patient education was too much information in one session. Thirty-four respondents had some knowledge of patient education development at their institution. Most of these (82.9%) indicated their educational processs development relied on expert opinion. In comparison, 22.9% indicated utilizing user-based design, and 10 (28.9%) respondents used learning theories.

ConclusionWhile most providers felt patient education was effective, they reported reviewing education with patients daily. The lack of formal knowledge checks and best practices in developing patient education tools are significant gaps to address.

category: medical education


title: COVID-19 and Medical Education in Ghana: Assessing the Impact

abstract: Medical education in Ghana has been affected in many ways by the onslaught of the COVID-19 pandemic. Though the pandemic has affected both preclinical and clinical segments of medical education, the effect has been felt more at the clinical stage. Medical students on vacation who started their clinical training abroad could not return to their destination of study to complete their programme because of COVID-19 linked travel restrictions. This qualitative study examined how COVID-19 impacted on teaching and learning at a public higher education institution offering clinical medical education in Ghana for over 200 medical students. These medical students were from three different higher education institutions with varied curriculum outcomes. Thus, for them to be considered as a single group required innovativeness on the part of administrators. Open-ended interviews were held with administrators and the outcome indicated that salient aspects of the clinical training process had been impacted. These included administration of clinical education, curriculum, student learning, student assessment and code of practice. As a result of the pandemic, student learning shifted from traditional face to face interaction to online learning at the beginning. Some of the administrative challenges that ensued included the need for reduced number of students per tutor and introduction of afternoon sessions with a limited budget. The paper concludes that COVID-19 has been disruptive to traditional medical education in Ghana. However, the novel learning processes may provide opportunities to increase access to medical education using a phased system of learning. The findings from this study should have implications for policy and contribute to the discourse on blended learning in medical education in Ghana while ensuring that quality is maintained in all instances.


title: Obesity Related Glomerulopathy: weighing in the effect of Body Surface Area

abstract:
ImportanceObesity-related glomerulopathy (ORG), part of the cardio-renal spectrum, has an early reversible stage of hyperfiltration. Early identification in the obese adolescent population provides an opportunity to reverse the damage.

ObjectiveAge-appropriate formulae for estimated glomerular filtration rate (eGFR), are standardized to ideal body surface area (BSA) and provide assessment of renal function in mL/min/1.73 m2 units, may underestimate prevalence of early ORG. We investigated whether adjusting eGFR to actual BSA more readily identifies early ORG.

DesignCross sectional cohort study. Data were collected between 2011-2015 and analysis was performed between January-November 2020.

SettingElectronic health records clinical data base from 12 academic health centers and community health centers in the New York metropolitan area.

Participants22,417 women and girls ages 12-21 years for whom data of body measurements and renal function were available.

Main Outcome and measuresThe hypothesis was generated using previously collected health record data. eGFR was calculated in two ways: BSA-standardized eGFR according to KDIGO recommended formula; and Absolute eGFR adjusted to individual BSA. Hyperfiltration was defined above a threshold of 135mL/min/1.73 m2 or 135 mL/min, respectively. The prevalence of hyperfiltration according to each formula was assessed in parallel to 24-hour urine creatinine.

Results22,417 female adolescents mean age 17 with high prevalence of underrepresented populations (32.6% African American, 12.8% Caucasians and 40.4% Hispanic) were evaluated. Serum creatinine values and hyperfiltration rates according to BSA-standardized eGFR were similar,13.4-15.3%, across Body Mass Index (BMI) groups. Prevalence of hyperfiltration determined by Absolute eGFR differed across groups: Underweight - 2.3%; Normal 6.1%; Overweight - 17.4%; Obese - 31.4%. This trend paralleled the rise in 24-hour urine creatinine across BMI groups.

Conclusions and relevanceAbsolute eGFR more readily identifies early ORG compared to currently used formulae, which are adjusted to an archaic value of a BSA, not representative of current population BMI measures. The high proportion of underrepresented populations in this study accounts for the higher-than-expected obesity rates and should raise awareness for missed opportunities for screening, early diagnosis, and intervention particularly in young Black adults.

Key pointsO_ST_ABSQuestionC_ST_ABSDo the currently recommended formulae estimating GFR reliably predict hyperfiltration due to Obesity Related Glomerulopathy (ORG)?

FindingsRenal function in relation to BMI was evaluated in a cohort of 22,417 adolescents from the New York metropolitan. Serum creatinine values and BSA-standardized eGFR (mL/min/1.73m2) were similar across BMI groups, and as a result, hyperfiltration rates were also similar. However, Absolute eGFR (mL/min) adjusted to individual BSA, created a positive trend across BMI groups similar to urine creatinine.

MeaningAbsolute eGFR better reflects the prevalence of hyperfiltration due to Obesity Related Glomerulopathy providing an opportunity for early intervention and damage reversal.

category: nephrology


title: Muscle cells of sporadic ALS patients secrete neurotoxic vesicles

abstract:
BackgroundThe cause of the motor neuron (MN) death that drives terminal pathology in Amyotrophic Lateral Sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards motor neurons, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Since MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle-secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology.

MethodsSporadic ALS patients were confirmed to be ALS according to El Escorial criteria, were genotyped to test for classic gene mutations associated with ALS, and physical function was assessed using the ALSFRS-R score. Muscle biopsies of either mildly affected deltoids of ALS patients (n=27) or deltoids of aged-matched healthy subjects (n=30) were used for extraction of muscle stem cells, to perform immunohistology, or for electron microscopy. Muscle stem cells were characterized by immunostaining, RTqPCR and transcriptomic analysis. Secreted muscle vesicles were characterized by proteomic analysis, Western blot, NanoSight, and electron microscopy. The effects of muscle vesicles isolated from the culture medium of ALS and healthy myotubes were tested on healthy human-derived iPSC motor neurons and on healthy human myotubes, with untreated cells used as controls.

ResultsAn accumulation of multivesicular bodies was observed in muscle biopsies of sporadic ALS patients by immunostaining and electron microscopy. Study of muscle biopsies and biopsy-derived denervation-naive differentiated muscle stem cells (myotubes) revealed a consistent disease signature in ALS myotubes, including intracellular accumulation of exosome-like vesicles and disruption of RNA-processing. Compared to vesicles from healthy control myotubes, when administered to healthy motor neurons the vesicles of ALS myotubes induced shortened, less branched neurites, cell death, and disrupted localization of RNA and RNA-processing proteins. The RNA-processing protein FUS and a majority of its binding partners were present in ALS muscle vesicles, and toxicity was dependent on the expression level of FUS in recipient cells. Toxicity to recipient motor neurons was abolished by anti-CD63 immuno-blocking of vesicle uptake.

ConclusionALS muscle vesicles are shown to be toxic to motor neurons, which establishes the skeletal muscle as a potential source of vesicle-mediated toxicity in ALS.

One Sentence SummaryMuscle cells of ALS patients secrete vesicles that are toxic to motor neurons

category: neurology


title: Effect of intravesical chemotherapy on the survival of patients with non-muscle-invasive bladder cancer undergoing transurethral resection: a retrospective cohort study among older adults

abstract:
BackgroundThe average age of diagnosis for bladder cancer is 73 and about 75 percent of all bladder cancers are non-muscle invasive at initial diagnosis. It is recommended that non-muscle invasive bladder cancers (NMIBC) should be treated with transurethral resection of the bladder tumor (TURBT) followed by chemotherapy. However, there is no large-scale study from real-world databases to show the effectiveness of chemotherapy on the survival of older adults with NMIBC that have undergone TURBT. This study aimed to investigate the effects of chemotherapy on survival among older NMIBC patients with TURBT.

MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), we performed analyses of cancer-specific mortality and overall mortality comparing chemotherapy versus no chemotherapy after TURBT. Coarsened exact matching was performed to balance the baseline patient characteristics. Cox proportional hazards and Kaplan-Meir analyses were used to evaluate survival outcomes.

ResultsA total of 3,222 matched patients with 1,611 in each arm (chemotherapy and no chemotherapy) were included in our study. After adjusting for covariates, multivariable Cox regression analyses show chemotherapy was associated with lower cancer-specific mortality (HR 0.63; 95% CI 0.42-0.94; p value 0.024). However, chemotherapy did not have any effect on overall mortality (HR 0.84; 95% CI 0.65-1.07; p value 0.159). The Kaplan-Meier curves show the protective effects of chemotherapy on cancer specific survival (p=0.032), but not on overall survival (p=0.34).

ConclusionChemotherapy improved cancer specific survival among older patients with non-muscle invasive bladder cancer undergoing TURBT surgery, but it had no effect on overall survival. There is a need for more granular level real-world data on chemotherapy regimens and dosage to effectively investigate the effects of chemotherapy on survival of older patients with NMIBC that have undergone TURBT.

category: oncology


title: Automated Production of Research Data Marts from a Canonical Fast Healthcare Interoperability Resource (FHIR) Data Repository: Applications to COVID-19 Research

abstract:
ObjectiveObjective: The COVID-19 pandemic has enhanced the need for timely real-world data (RWD) for research. To meet this need, several large clinical consortia have developed networks for access to RWD from electronic health records (EHR), each with its own common data model (CDM) and custom pipeline for extraction, transformation, and load operations for production and incremental updating. However, the demands of COVID-19 research for timely RWD (e.g., 2-week delay) make this less feasible.

Methods and MaterialsWe describe the use of the Fast Healthcare Interoperability Resource (FHIR) data model as a canonical model for representation of clinical data for automated transformation to the Patient-Centered Outcomes Research Network (PCORnet) and Observational Medical Outcomes Partnership (OMOP) CDMs and the near automated production of linked clinical data repositories (CDRs) for COVID-19 research using the FHIR subscription standard. The approach was applied to healthcare data from a large academic institution and was evaluated using published quality assessment tools.

ResultsSix years of data (1.07M patients, 10.1M encounters, 137M laboratory results), were loaded into the FHIR CDR producing 3 linked real-time linked repositories: FHIR, PCORnet, and OMOP. PCORnet and OMOP databases were refined in subsequent post processing steps into production releases and met published quality standards. The approach greatly reduced CDM production efforts.

ConclusionsFHIR and FHIR CDRs can play an important role in enhancing the availability of RWD from EHR systems. The above approach leverages 21st Century Cures Act mandated standards and could greatly enhance the availability of datasets for research.

category: health informatics


title: A rapid review of COVID-19 vaccine prioritization in the U.S.: alignment between Federal guidance and State practice

abstract:
BackgroundPopulation groups to be prioritized for COVID-19 vaccinations in the U.S. have been determined at the Federal level. Evidence suggests that there is variation in how States have implemented this guidance. This review examines how the position of population groups in vaccine priority lists varies between Federal guidance and State practice.

MethodsAn online search of State vaccination prioritization plans was conducted. Data were extracted on each population group included and their relative position. A standardized ranking method was applied to provide a directional measure of variability in prioritization between State and Federal guidance, for each population group.

ResultsHealthcare workers and those in long-term care facilities were largely prioritized in line with Federal guidance. Aside from early education staff, essential workers were often excluded at State level. Of the 37 States including frontline essential workers, 12 assigned them to a lower priority than recommended. Almost all States included the 65-74 year age group and most assigned them to a higher position than recommended in Federal guidance. Those with underlying medical conditions were similarly highly prioritized, although there was more variability across States. Some socially vulnerable groups (not included in Federal guidance) were highly prioritized by many States.

ConclusionsAcross the U.S, the prioritization of groups for COVID-19 vaccination has been highly variable. Essential workers were the most often excluded or less highly prioritised group compared to Federal guidance. Some socially vulnerable groups were highly prioritized in State plans, whilst others were mentioned in only a few States. Future guidance must be relevant to local needs and values, to minimise any unwarranted heterogeneity in vaccine access across populations.

category: health policy


title: KAP survey of practicing doctors on antimicrobial stewardship based on openWHO course

abstract:
SynopsisO_ST_ABSBackgroundC_ST_ABSThe overwhelming, irrational behaviour of using antimicrobial (AM) has added to the amplification and spread of antimicrobial resistance (AMR) burden. Healthcare professionals can curtail the AMR by practicing antimicrobial stewardship (AMS). Keeping this in view WHO has laid down a global action plan to combat AMR including free online availability of openWHO course. So, our study aimed at accessing the knowledge, attitude, and practice (KAP) of practicing doctors towards AMS based on this course in a tertiary care hospital.

MethodsThe study was conducted among practitioners (faculty, senior residents, junior residents) in different clinical departments. The study was designed as a KAP survey. A validated self-administered questionnaire consisting of 29 questions was designed and shared among 200 participants through the mail and physically. Apart from observing knowledge/attitude/practice gaps, the difference in response to questions was evaluated among various groups (surgeon vs physician, faculty vs senior resident vs junior resident, openWHO course participant vs openWHO course aware non-participant vs openWHO course unaware non-participants.

ResultsResponse rate was 62.5% (n=200). Knowledge on AMS was observed among doctors with >50% near correct responses in each question except for the question asking on IV route of AM administration. A significant knowledge gap was found when a comparison was made between faculty members, senior residents, and junior residents (p <0.001) in the spectrum of activity of AM. Almost all the participants agreed that ASP is a necessity in the hospital and believed that ASP reduces healthcare costs and adverse effects of inappropriate AM prescription. A significant difference between the various groups aspects was also observed.

ConclusionKnowledge gap on ASP is observed among all HCPs but significant differences among faculty, senior residents, and junior residents, among openWHO course vs unaware openWHO course participant. This shows faculty has to take the lead including more and more practice and education in ASP. The openWHO course may help in achieving this.

category: health systems and quality improvement


title: Population Impact and Efficiency of Improvements to HIV PrEP Under Conditions of High ART Coverage among San Francisco Men Who Have Sex with Men

abstract:
BackgroundKey components of Ending the HIV Epidemic (EHE) plan include increasing HIV antiretroviral therapy (ART) and HIV preexposure prophylaxis (PrEP) coverage. One complication to addressing this service delivery challenge is the wide heterogeneity of HIV burden and healthcare access across the U.S. It is unclear how the effectiveness and efficiency of expanded PrEP will depend on different baseline ART coverage.

MethodsWe used a network-based model of HIV transmission for men who have sex with men (MSM) in San Francisco. Model scenarios increased varying levels of PrEP coverage relative under current empirical levels of baseline ART coverage and two counterfactual levels. We assessed the effectiveness of PrEP with the cumulative percent of infections averted (PIA) over the next decade and efficiency with the number needed to treat (NNT) by PrEP required to avert one HIV infection.

ResultsIn our projections, only the highest levels of combined PrEP and ART coverage achieved the EHE goals. Increasing PrEP coverage up to 75% showed that PrEP effectiveness was higher at higher baseline ART coverage with the PIA ranging from 61% in the lowest baseline ART coverage population to 75% in the highest ART coverage. The efficiency declined with increasing ART (NNT range from 41 to 113).

ConclusionsImproving both PrEP and ART coverage would have a synergistic impact on HIV prevention even in a high baseline coverage city like San Francisco. Efforts should focus on narrowing the implementation gaps to achieve higher levels of PrEP retention and ART sustained viral suppression.

category: hiv aids


title: Immunodominant B cell epitope in SARS-CoV-2 RBD comprises a B.1.351 and P.1 mutation hotspot: implications for viral spread and antibody escape

abstract: Recent SARS-CoV-2 variants pose important concerns due to their higher transmissibility (1) and escape (2) from previous infections or vaccine-induced neutralizing antibodies (nAb). The receptor binding domain (RBD) of the Spike protein is a major nAb target (3), but data on its B cell epitopes are still lacking. Using a peptide microarray, we identified an immunodominant epitope (S415-429) recognized by 68% of sera from 71 convalescent Brazilians infected with the ancestral variant. In contrast with previous studies, we have identified a linear IgG and IgA antibody binding epitope within the RBD. IgG and IgA antibody levels for this epitope positively correlated with nAb titers, suggesting a potential target of antibody neutralizing activity. Interestingly, this immunodominant RBD region harbors the mutation hotspot site K417 present in P.1 (K417T) and B.1.351 (K417N) variants. In silico simulation analyses indicate impaired RBD binding to nAb in both variants and that a glycosylation in the B.1.351 417N could further hinder antibody binding as compared to the K417T mutation in P.1. This is in line with published data showing that nAb from either convalescents or anti-CoV-2 vaccinees are less effective towards B.1.351 than for P.1. Our data support the occurrence of immune pressure and selection involving this immunodominant epitope that may have critically contributed to the recent COVID-19 marked rise in Brazil and South Africa, and pinpoint a potential additional immune escape mechanism for SARS-CoV-2.

category: infectious diseases


title: Natural spring water gargle and direct RT-PCR for the diagnosis of COVID-19 (COVID-SPRING study)

abstract: We prospectively compared natural spring water gargle to combined oro-nasopharyngeal swab (ONPS) for the diagnosis of coronavirus disease 2019 (COVID-19) in paired clinical specimens (1005 ONPS and 1005 gargles) collected from 987 unique early symptomatic as well as asymptomatic individuals from the community. Using a direct RT-PCR method with the Allplex 2019-nCoV Assay (Seegene), the clinical sensitivity of the gargle was 95.3% (95% confidence interval [CI], 90.2 to 98.3%) and was similar to the sensitivity of the ONPS (93.8%; 95% CI, 88.2 to 97.3%), despite significantly lower viral RNA concentration in gargles, as reflected by higher cycle threshold values. No single specimen type detected all COVID-19 cases. SARS-CoV-2 RNA was stable in gargles at room temperature for at least 7 days. The simplicity of this sampling method coupled with the accessibility of spring water are clear advantages in a pandemic situation where testing frequency, turnaround time and shortage of consumables and trained staff are critical elements.


title: Using translational in vitro-in vivo modeling to improve drug repurposing outcomes for inhaled COVID-19 therapeutics

abstract: The ongoing COVID-19 pandemic has created an urgent need for antiviral treatments that can be deployed rapidly. Drug repurposing represents a promising means of achieving this objective, but repurposing efforts are often unsuccessful. A common hurdle to effective drug repurposing is a failure to achieve a sufficient therapeutic window in the new indication. A clear example is the use of ivermectin in COVID-19, where the approved dose (administered orally) fails to achieve therapeutic concentrations in the lungs. Our proposed solution to the problem of ineffective drug repurposing for COVID-19 antivirals is two-fold: to broaden the therapeutic window by reformulating therapeutics for the pulmonary route, and to select drug repurposing candidates based on their model-predicted therapeutic index for inhalation. In this article, we propose a two-stage model-driven screening and validation process for selecting inhaled antiviral drug repurposing candidates. While we have applied this approach in the specific context of COVID-19, this in vitro-in vivo translational methodology is also broadly applicable to repurposing drugs for diseases of the lower respiratory tract.


title: SARS-CoV-2 specific immune-signature in direct contacts of COVID-19 cases protect them from contracting disease: A Retrospective Study

abstract:
The response to SARS-CoV-2 is largely impacted by the level of exposure and the status of immunity. The nature of protection shown by direct contacts of COVID-19 positive patients is quite intriguing to note. We aimed to study the immune differences reinforcing contact individuals in circumventing the disease. Our observation showed direct contacts of PCR positive patients developed elevated neutralizing antibody titres and cytokine levels. On the other hand, single cell data revealed differential usage of V(D)J genes and unique BCR clonotypes imparting protective immune signatures.

Topicsserologic tests, immunoglobulin a, immunoglobulin g, immunoglobulin m, antibody titre; cytokine levels; virus neutralization; V(D)J sequencing; BCR clonotypes


title: An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

abstract:
BackgroundNatural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.

MethodsIn a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.

Results13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI <0.01-0.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [0.02-0.38]) and 85% (0.15 [0.08-0.26]) respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [0.21-0.52]) and any PCR-positive result by 64% (0.36 [0.26-0.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7.

ConclusionNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.

SummaryNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provided [≥] 85% protection against symptomatic and asymptomatic SARS-CoV-2 infection in healthcare workers, including against the B.1.1.7 variant. Single dose vaccination reduced symptomatic infection by 67%.


title: Recovered not restored: Long-term health consequences after mild COVID-19 in non-hospitalized patients

abstract:
BackgroundWhile the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalization. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence we focus on mild COVID-19 in non-hospitalized patients.

MethodsWe included 958 patients with confirmed SARS-CoV-2 infection in this study. Patients were observed for seven months from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarized presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model.

FindingsWe observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8.6% (38/442) of patients presented with shortness of breath, 12.4% (55/442) with anosmia, 11.1% (49/442) with ageusia and 9.7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27.8% (123/442) and 34.8% (123/353) at month 4 and 7 post-infection, respectively. This corresponds to 12.8% patients with long-lasting symptoms relative to the initial total cohort (123/958). A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhea during acute COVID-19 were associated with higher risk to develop long-term symptoms.

InterpretationThe on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalized patients was observed at four and seven months post-infection and summarized as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19.

FundingCOVIM:"NaFoUniMedCovid19"(FKZ: 01KX2021)

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSData about long-term health consequences after SARS-CoV-2 infection and COVID-19 is scarce and most available data describe health consequences in hospitalized patients during acute COVID-19. However, these studies do not take into account the vast majority of patients with a milder course of infection (WHO score1-3).

Added value of this studyOur cohort consists of mostly mild COVID-19 cases that have been prospectively followed for a median time of 6.8 months. At least one trained physician critically reviewed the patients reported symptoms at each visit. We assessed SARS-CoV-2 IgG at each visit to correlate reported symptoms with serological data. At 4 months after SARS-CoV-2 infection, shortness of breath occurred in 8.6% (38/442), anosmia in 12.4% (55/442), ageusia in 11.1% (49/442), and fatigue in 9.7% (43/442) of patients. At least one characteristic symptom was present in 27.8% (123/442) and 34.8% (123/353) at months 4 and 7 post-infection, respectively. Symptoms were summarized as post-COVID syndrome (PCS). Relative to our initial total cohort (123/958), this corresponds to 12.8% patients with long-lasting symptoms. Lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhea during acute COVID-19 were associated with higher risk of developing long-term symptoms.

Implications of all available evidenceWe believe that our findings have important implications for the fields of infectious diseases and public health, because we show long-term health consequences may occur even after very mild COVID-19 in the outpatient setting. As up to 81% of all SARS-CoV-2 infected patients present with mild disease, it can be expected that PCS will affect a larger number of individuals than initially assumed, posing major medical, social and economic challenges.


title: Comparison of SARS-CoV-2 detection in Saliva by real-time RT-PCR and RT-PCR/MALDI-TOF Methods

abstract: The coronavirus disease 2019 (COVID-19) pandemic has accelerated the need for rapid implementation of diagnostic assays for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in respiratory specimens. While multiple molecular methods utilize nasopharyngeal specimens, supply chain constraints and need for easier and safer specimen collection warrant alternative specimen types, particularly saliva. Although saliva has been found to be a comparable clinical matrix for detection of SARS-CoV-2, evaluations of diagnostic and analytic performance across platforms for this specimen type are limited. Here, we compared two methods for SARS-CoV-2 detection in saliva: the Roche cobas(R) 6800/8800 SARS-CoV-2 real-time RT-PCR Test and the Agena Biosciences MassARRAY(R) SARS-CoV-2 Panel/MassARRAY(R) System. Overall, both systems had high agreement with one another, and both demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of each platform and determined the limit of detection of the Roche assay was four times lower than that of Agena for saliva specimens (390.6 v. 1,562.5 copies/mL). Furthermore, across individual target components of each assay, T2 and N2 targets had the lowest limits of detection for each platform, respectively. Together, we demonstrate that saliva represents an appropriate specimen for SARS-CoV-2 detection in two technologies that have high agreement and differ in analytical sensitivities overall and across individual component targets. The addition of saliva as an acceptable specimen and understanding the sensitivity for testing on these platforms can further inform public health measures for screening and detection to combat the COVID-19 pandemic.


title: The Use/Abuse of Oral Contraceptive Pills Among Males: A Mixed-Method Explanatory Sequential Study Over Jordanian Community Pharmacists

abstract:
BackgroundOral contraceptive pills (OCPs) are considered one of the most important birth control methods in the world. However, these pills were designed for female administration rather than males. This study was designed to investigate patterns of OCPs use and abuse among Jordanian males, according to the community pharmacists observations.

MethodA mixed-method explanatory sequential study was conducted using an online self - administered survey and semi-structured in-depth interviews for community pharmacists. The interviews were utilized using a conceptual framework. Inductive thematic analysis and descriptive/regression analyses were completed using Nvivo and SPSS, respectively.

ResultsA total of 158 questionnaire responses and 22 interviews were included in our analysis. Around half (48.4%) of the questionnaire responses confirmed that males could use OCPs for hair growth enhancement, muscle gain and acne treatment 12.7%, 31.7% and 4.4%, respectively. Through the interviews, the majority of the pharmacists highlighted that most of the males use OCPs for bodybuilding purposes, according to recommendations by their coaches at the gym. The most abused OCPs containing estrogen (Ethinyl estradiol) and progestins (Drospirenone or Levonorgestrel).

ConclusionThis study provided insight into unexpected uses of OCPs by males in Jordan. Community pharmacists have a crucial role in the management of OCPs use and abuse, However, restricted regulations and monitoring must be released and implemented on the community to limit such practices.

category: addiction medicine


title: Use of digital technology tools to examine patient adherence to a prescription omega-3 polyunsaturated acids therapy intended to mitigate cardiovascular risk: protocol and preliminary demographic data from the DIAPAsOn prospective observational study

abstract:
Sustained adherence and persistence with prescription medications is considered essential to achieve maximal treatment benefit for patients with major chronic non-communicable diseases such as hyperlipidemia and lipid-associated cardiovascular disease. It is widely documented, however, that a large percentage of patients with these conditions have poor longer-term compliance with their treatments. The population of Russia is affected by poor compliance in the same ways as populations elsewhere and continues to have high rates of cardiovascular disease.

Hypertriglyceridemia is suspected of contributing to residual cardiovascular risk in patients whose low-density lipoprotein cholesterol (LDL-C) is well controlled. A preparation of highly purified omega-3 polyunsaturated fatty acids (EPA/DHA=1.2/1-90%, marketed as OMACOR), is indicated for the control of high triglyceride levels and also for secondary prevention of myocardial infarction (MI).

DIAPAsON is a prospective observational program designed to evaluate the impact of digital technologies on patient compliance and adherence in a large sample of patients whose treatment scheme includes EPA/DHA=1.2/1-90%. A bespoke electronic data capture system has been developed for this purpose that enables information obtained during clinic visits to be supplemented by remote patient self-reporting. Other objectives of the program include raising patients awareness about their condition via educational materials available in patient personal accounts in the electronic system.

This report outlines the rationale and methodology of DIAPAsOn and the primary demographics of the study population.

category: cardiovascular medicine


title: Leg-heel chest compression as an alternative for medical professionals in times of COVID-19

abstract:
ObjectiveTo evaluate leg-heel chest compression without previous training as an alternative for medical professionals and its effects on distance to potential aerosol spread during chest compression.

Methods20 medical professionals performed standard manual chest compression followed by leg-heel chest compression after a brief instruction on a manikin. We compared percentage of correct chest compression position, percentage of full chest recoil, percentage of correct compression depth, average compression depth, percentage of correct compression rate and average compression rate between both methods. In a second approach, potential aerosol spread during chest compression was visualized.

ResultsThere was no significant difference between manual and leg-heel compression. The distance to potential aerosol spread could have been increased by leg-heel method.

ConclusionUnder special circumstances like COVID-19-pandemic, leg-heel chest compression may be an effective alternative without previous training compared to manual chest compression while markedly increasing the distance to the patient.

category: emergency medicine


title: A target HbA1c between 7 to 7.7% reduces macrovascular events in T2D regardless of duration of diabetes: a meta-analysis of randomized controlled trials

abstract:
IntroductionThe target glycosylated haemoglobin (HbA1c) at which macrovascular benefits may be derived in type 2 diabetes (T2D) has never been clearly outlined. This meta-analysis was conducted on fifteen randomized controlled trials to highlight the association of HbA1c range with macrovascular events.

MethodsThe association of different HbA1c clusters (intention to treat (ITT) and end-of-study [EOS]) range (less or equal than 6.5%, 6.6%-7.0%, 7.1%-7.7%) with macrovascular complications and also the combined effect of duration of T2D (< 10 years or [≥] 10 years) and HbA1c levels was assessed.

ResultsIntensive glucose-lowering strategy resulted in a significant 13% reduction in non-fatal myocardial infarction (NFMI) (P=0.006). Based on HbA1c achieved, a significant 36% reduction in non-fatal stroke (P=0.008) and a 22% reduction in all-cause mortality (P=0.02) were observed in the group with HbA1c between 7.1% - 7.7% irrespective of diabetes duration. In the cohort, with diabetes duration <10 years, reduction of HbA1c in the range7.1% - 7.7% resulted in a significant 36% reduction in non-fatal stroke (NFS) (P<0.001).

ConclusionThis is probably the first meta-analysis highlighting the importance of treating patients with T2D to a target HbA1C of 7 - 7.7%, as this target is associated with reduction in macrovascular events.

category: endocrinology


title: Comparing COVID-19 risk factors in Brazil using machine learning: the importance of socioeconomic, demographic and structural factors

abstract:
BackgroundThe COVID-19 pandemic continues to have a devastating impact on Brazil. Brazils social, health and economic crises are aggravated by strong societal inequities and persisting political disarray. This complex scenario motivates careful study of the clinical, socioeconomic, demographic and structural factors contributing to increased risk of mortality from SARS-CoV-2 in Brazil specifically.

MethodsWe consider the Brazilian SIVEP-Gripe catalog, a very rich respiratory infection dataset which allows us to estimate the importance of several non-laboratorial and socio-geographic factors on COVID-19 mortality. We analyze the catalog using machine learning algorithms to account for likely complex interdependence between metrics.

FindingsThe XGBoost algorithm achieved excellent performance, producing an AUC-ROC of 0.813 (95%CI 0.810-0.817), and outperforming logistic regression. Using our model we found that, in Brazil, socioeconomic, geographical and structural factors are more important than individual comorbidities. Particularly important factors were: The state of residence and its development index; the distance to the hospital (especially for rural and less developed areas); the level of education; hospital funding model and strain. Ethnicity is also confirmed to be more important than comorbidities but less than the aforementioned factors.

InterpretationSocioeconomic and structural factors are as important as biological factors in determining the outcome of COVID-19. This has important consequences for policy making, especially on vaccination/non-pharmacological preventative measures, hospital management and healthcare network organization.

FundingNone.

category: epidemiology


title: Mean Vitamin D levels in 19 European Countries & COVID-19 Mortality over 10 months

abstract:
ObjectivesReports early in the epidemic linking low mean national Vitamin D level with increased COVID-19 death, and until recently little research on the impact of Vitamin D deficiency on severity of COVID-19, led to this update of the initial report studying mortality up to the end of January 2021.

Design and SettingCoronavirus pandemic data for 19 European countries were downloaded from Our World in Data, which was last updated on January 24, 2021. Data from March 21, 2020 to January 22, 2021 were included in the statistical analysis. Vitamin-D (25)-HD mean data were collected by literature review. Poisson mixed-effect model was used to model the data.

ResultsEuropean countries with Vitamin-D (25)-HD mean less than or equal to 50 have higher COVID-19 death rates as compared with European countries with Vitamin-D (25)-HD mean greater than 50, relative risk of 2.155 (95% CI: 1.068 - 4.347, p-value = 0.032). A statistically significant negative moderate Spearman rank correlation was observed between Vitamin-D (25)-HD mean and the number of COVID-19 deaths for each 14-day period during the COVID-19 pandemic time period.

ConclusionsThe observation of the significantly lower COVID-19 mortality rates in countries with lowest annual sun exposure but highest mean Vitamin-D (25)-HD levels provides support for the use of food fortification. The need to consider re-configuring vaccine strategy due to emergence of large number of COVID-19 variants provides an opportunity to undertake such therapeutic randomized control trials.


title: Genetically-proxied therapeutic inhibition of antihypertensive drug targets and risk of common cancers

abstract:
BackgroundEpidemiological studies have reported conflicting findings on the potential adverse effects of long-term antihypertensive medication use on cancer risk. Naturally occurring variation in genes encoding antihypertensive drug targets can be used as proxies for these targets to examine the effect of their long-term therapeutic inhibition on disease outcomes.

MethodsSingle-nucleotide polymorphisms (SNPs) in ACE, ADRB1, and SLC12A3 associated (P < 5.0 x 10-8) with systolic blood pressure in genome-wide association studies (GWAS) were used to proxy inhibition of angiotensin-converting enzyme (ACE), {beta}-1 adrenergic receptor (ADRB1), and sodium-chloride symporter (NCC), respectively. Summary genetic association estimates for these SNPs were obtained from GWAS consortia for the following cancers: breast (122,977 cases, 105,974 controls), colorectal (58,221 cases, 67,694 controls), lung (29,266 cases, 56,450 controls), and prostate (79,148 cases, 61,106 controls). Replication analyses were performed in the FinnGen consortium (1,573 colorectal cancer cases, 120,006 controls). Inverse-variance weighted random- effects models were used to examine associations between genetically-proxied inhibition of these drug targets and risk of cancer. Multivariable Mendelian randomization and colocalisation analyses were employed to examine robustness of findings to violations of Mendelian randomization assumptions.

ResultsGenetically-proxied ACE inhibition equivalent to a 1 mmHg reduction in systolic blood pressure was associated with increased odds of colorectal cancer (OR 1.13, 95% CI 1.06-1.22; P = 3.6 x 10-4). This finding was replicated in the FinnGen consortium (OR 1.40, 95% CI 1.02-1.92; P = 0.035). There was little evidence of association of genetically-proxied ACE inhibition with risk of breast cancer (OR 0.98, 95% CI 0.94-1.02, P = 0.35), lung cancer (OR 1.01, 95% CI 0.92-1.10; P = 0.93), or prostate cancer (OR 1.06, 95% CI 0.99-1.13; P = 0.08). Genetically-proxied inhibition of ADRB1 and NCC were not associated with risk of these cancers.

ConclusionGenetically-proxied long-term ACE inhibition was associated with an increased risk of colorectal cancer, warranting comprehensive evaluation of the safety profiles of ACE inhibitors in clinical trials with adequate follow-up. There was little evidence to support associations across other drug target-cancer risk analyses, consistent with findings from short-term randomised controlled trials for these medications.


title: Quantifying Contact Patterns in Response to COVID-19 Public Health Measures in Canada

abstract:
BackgroundA variety of public health measures have been implemented during the COVID-19 pandemic in Canada to reduce contact between individuals.

ObjectiveThe objective of this study was to construct contact patterns to evaluate the degree to which social contacts rebounded to normal levels, as well as direct public health efforts toward age- and location-specific settings.

DesignFour population-based cross-sectional surveys.

SettingCanada.

ParticipantsMembers of a paid panel representative of Canadian adults by age, gender, official language, and region of residence.

MethodsRespondents provided information about the age and setting for each direct contact made in a 24-hour period. Contact matrices were constructed and contacts for those under the age of 18 years imputed. The next generation matrix approach was used to estimate the reproduction number (Rt) for each survey. Respondents with children estimated the number of contacts their children made in school and extracurricular settings.

ResultsEstimated Rt values were 0.49 (95% CI: 0.29-0.69) for May, 0.48 (95% CI: 0.29-0.68) for July, 1.06 (95% CI: 0.63-1.52) for September, and 0.81 (0.47-1.17) for December. The highest proportion of reported contacts occurred within the home (51.3% in May), in  other locations (49.2% in July) and at work (66.3% and 65.4% in September and December). Respondents with children reported an average of 22.7 (95% CI: 21.1-24.3) (September) and 19.0 (95% CI 17.7-20.4) (December) contacts at school per day per child in attendance.

ConclusionThe skewed distribution of reported contacts toward workplace settings in September and December combined with the number of reported school-related contacts suggest that these settings represent important opportunities for transmission emphasizing the need to ensure infection control procedures in both workplaces and schools.


title: DIP: Natural History Model for Major Depression with Incidence and Prevalence

abstract:
BackgroundMajor depression is a treatable disease, and untreated depression can lead to serious health complications. Therefore, prevention, early identification, and treatment efforts are essential. Natural history models can be utilized to make informed decisions about interventions and treatments of major depression.

MethodsWe propose a natural history model of major depression. We use steady-state analysis to study the discrete-time Markov chain model. For this purpose, we solved differential equations and tested the parameter and transition probabilities empirically.

ResultsWe showed that bias in parameters might collectively cause a significant mismatch in a model. If incidence is correct, then lifetime prevalence is 33.2% for females and 20.5% for males, which is higher than reported values. If prevalence is correct, then incidence is .0008 for females and .00065 for males, which is lower than reported values. The model can achieve feasibility if incidence is at low levels and recall bias of the lifetime prevalence is quantified to be 31.9% for females and 16.3% for males.

LimitationsModel is limited to major depression, and patients who have other types of depression are assumed healthy. We assume that transition probabilities (except incidence rates) are correct.

ConclusionWe constructed a preliminary model for the natural history of major depression. We determine the lifetime prevalence are underestimated. We conclude that the average incidence rates may be underestimated for males. Our findings mathematically prove the arguments around the potential discordance between reported incidence and lifetime prevalence rates.

category: psychiatry and clinical psychology


title: Comprehensive evaluation of the impact of sociodemographic inequalities on adverse outcomes and excess mortality during the COVID-19 pandemic in Mexico City

abstract: The impact of the COVID-19 pandemic in Mexico City has been sharp, as several social inequalities coexist with chronic comorbidities. Here, we conducted an in-depth evaluation of the impact of social, municipal, and individual factors on the COVID-19 pandemic in working-age population living in Mexico City. To this end, we used data from the National Epidemiological Surveillance System; furthermore, we used a multidimensional metric, the social lag index (DISLI), to evaluate its interaction with mean urban population density (MUPD) and its impact on COVID-19 rates. Influence DISLI and MUPD on the effect of vehicular mobility policies on COVID-19 rates were also tested. Finally, we assessed the influence of MUPD and DISLI on discrepancies of COVID-19 and non-COVID-19 excess mortality compared with death certificates from the General Civil Registry. We detected vulnerable groups who belonged to economically active sectors and who experienced increased risk of adverse COVID-19 outcomes. The impact of social inequalities transcends individuals and has significant effects at a municipality level, with and interaction between DISLI and MUPD. Marginalized municipalities with high population density experienced an accentuated risk for adverse COVID-19 outcomes. Additionally, policies to reduce vehicular mobility had differential impacts across marginalized municipalities. Finally, we report an under-registry of COVID-19 deaths and significant excess mortality associated with non-COVID-19 deaths closely related to MUPD/DISLI in an ambulatory setting, which could be a negative externality of hospital reconversion. In conclusion, social, individual, and municipality-wide factors played a significant role in shaping the course of the COVID-19 pandemic in Mexico City.

category: public and global health


title: Counterproductive effects of Daratumumab and checkpoint inhibitor for the treatment of patients with relapsing NK/T lymphoma

abstract: Natural killer/T cell lymphoma (NK/T L) is an aggressive malignancy associated with poor prognosis in relapsed patients. Although L-asparaginase based treatments are recommended as first-line treatment in relapsed patients, advances in immunotherapies such as checkpoint inhibitions have provided new therapeutic alternatives. However, as clinical outcomes for checkpoint inhibitors seemed to vary between NK/T L patients, combination therapies have been suggested to improve treatment efficacy. Here, we compared the effects of Daratumumab (anti-CD38)/anti-PD-1 combination therapy versus anti-PD-1 monotherapy on two relapsed NK/T L patients. Anti-PD-1 triggered an upregulation of CD38 on activated T cells, leading to depletion by Daratumumab. Concomittantly, EBV-specific antibody titer was also reduced alongside with depletion of CD38+ B cells and antibody-producing plasmablasts. Taken together, combining anti-CD38 and anti-PD-1 is likely to be antithetic.


title: BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for BMI

abstract:
BackgroundObesity is a heritable complex phenotype which can increase the risk of age-related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various "epigenetic clocks." Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely relates with mortality.

ObjectivesWe aimed to assess the cross-sectional association of BMI with age acceleration in twins to limit confounding by genetics and shared environment.

Methods and ResultsParticipants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twins, and DNAm was measured using the Illumina 450k array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p-value = 6.1 x 10-12) per 1-unit BMI increase. Additionally, heavier twins in a BMI-discordant MZ twin pair ({Delta}BMI > 3 kg/m2) had an epigenetic age 5.2 months older than their lighter co-twin (p-value = 0.0074). We also found a positive association between log(HOMA-IR) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 0.0025) from adjusted models.

ConclusionWe identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance.

category: genetic and genomic medicine


title: Magnesium Treatment on Methylation Changes of Transmembrane Serine Protease 2 (TMPRSS2)

abstract:
BackgroundThe viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike (S) protein priming.

ObjectivesTo test the hypothesis that Mg treatment leads to DNA methylation changes in TMPRSS2.

MethodsThis study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2x2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized.

ResultsWe found that 12-week of personalized Mg treatment significantly increased 5-mC methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to placebo arm (decreased by 0.1%) in those aged < 65 years old. The difference remained statistically significant after adjusting for age, sex and baseline methylation as well as FDR correction (FDR-adjusted P =0.014). Additionally, Mg treatment significantly reduced 5-hmC level at cg26337277 (close proximity to TSS200 and 5UTR, promoter) by 2.3% compared to increases by 7.1% in the placebo arm after adjusting for covariates in those aged < 65 years old (P=0.003). The effect remained significant at FDR of 0.10 (adjusted P value=0.088).

ConclusionAmong individuals aged younger than 65 years with the Ca:Mg intake ratios equal to or over 2.6, reducing Ca:Mg ratios to around 2.3 increased 5-mC modifications (i.e. cg16371860) and reduced 5-hmC modifications (i.e. cg26337277) in the TMPRSS2 gene. These findings, if confirmed, provide another mechanism for the role of Mg intervention for the prevention of COVID-19 and treatment of early and mild disease by modifying the phenotype of the TMPRSS2 genotype.


title: Dynamic versus Continuous Interventions: Optimizing Lockdown Policies for COVID-19

abstract: In the context of the ongoing COVID-19 pandemic, while millions of people await the administration of a vaccine, social distancing remains the leading approach towards the effect commonly known as "flattening the curve" of infections. Over the last year, governmental administrations throughout the globe have implemented various lockdown policies in hopes of slowing down the transmission of the disease. However, the current lack of consensus on when and how these policies should be implemented reflects the need for further studies regarding these questions. In this paper, we tackle the issue of lockdown policy management, in particular in terms of lockdown placement (how often, when, and how long these periods should be), in order to minimize the peak of infections in a specific population. We introduce a novel combination of classic mathematical disease modelling using the equation-based SEIR model, and Evolutionary Strategies (ES) for optimizing the peak of infections. The method is evaluated using data collected in different countries, and a particular focus is placed on the study of the effect of specific model parameters on lockdown optimization, such as the transmission rate ({beta}), of which 4 alternative modelling functions have been proposed and analyzed. Our results indicate that this transmission rate parameter significantly influences the resulting optimal strategies. In particular, the presence of a gradual decay of the rate of transmission during lockdown leads to longer, more sparsely placed confinement periods while an abrupt, instantaneous drop in the amount of contacts per person favors shorter but more frequent lockdowns. Although these results are limited by the scope of action provided by the simplicity of the SEIR model, they suggest that the influence of the evolution of the rate of transmission along the disease should be assessed in further studies with alternative optimization strategies (agent-based) and models (SEIRSHUD).


title: Analysis of severe outcomes associated with the SARS-CoV-2 Variant of Concern 202012/01 in England using ICNARC Case Mix Programme and QResearch databases.

abstract:
BackgroundA new, more transmissible variant of SARS-CoV-2, variant of concern (VOC) 202012/01 or lineage B.1.1.7, has emerged in the UK. We estimate the risk of critical care admission, mortality in critical ill patients, and overall mortality associated with VOC B.1.1.7 compared with the original variant. We also compare clinical outcomes between these variants   groups.

MethodsWe linked a large primary care (QResearch), the national critical care (ICNARC CMP) and the COVID-19 testing (PHE) database and extracted two cohorts. The first was used to explore the association between VOC B.1.1.7 and critical care admission and 28-day mortality. The second to determine the risk of mortality in critically ill patients with VOC B.1.1.7 compared to those without. We used Royston-Parmar models adjusted for age, sex, region, other socio-demographics and comorbidities (asthma, COPD, type I and II, hypertension). We reported information on types and duration of organ supports for the two variants   groups.

FindingsThe first cohort included 198,420 patients. Of these, 80,494 had VOC B.1.1.7, 712 were critically ill and 630 died by 28 days. The second cohort included 3432 critically ill patients. Of these, 2019 had VOC B.1.1.7 and 822 died at the end of critical care. Using the first cohort, we estimated adjusted hazard ratios for critical care admission and mortality to be 1.99 (95% CI: 1.59, 2.49) and 1.59 (95% CI: 1.25-2.03) for VOC B.1.1.7 compared with the original variant group, respectively. The adjusted hazard ratio for mortality in critical care, estimated using the second cohort, was 0.93 (95% CI 0.76-1.15) for patients with VOC B.1.1.7, compared to those without.

InterpretationVOC B.1.1.7 appears to be more severe. Patients with VOC B.1.1.7 are at increased risk of critical care admission and mortality compared with patients without. For patients receiving critical care, mortality appears independent of virus strain.

RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSA new variant of the SARS-CoV-2 virus, variant of concern (VOC) 202012/01, or lineage B.1.1.7, was detected in England in September 2020. The characteristics and outcomes of patients infected with VOC B.1.1.7 are not yet known. VOC B.1.1.7 has been associated with increased transmissibility. Early analyses have suggested infection with VOC B.1.1.7 may be associated with a higher risk of mortality compared with infection with other virus variants, but these analyses had either limited ability to adjust for key confounding variables or did not consider critical care admission. The effects of VOC B.1.1.7 on severe COVID-19 outcomes remain unclear.

Added value of this studyThis study found a 60% higher risk of 28-day mortality associated with infection with VOC B.1.1.7 in patients tested in the community in comparison with the original variant, when adjusted for key confounding variables. The risk of critical care admission for those with VOC B.1.1.7 is double the risk associated with the original variant. For patients receiving critical care, the infecting variant is not associated with the risk of mortality at the end of critical care.

Implications of all the available evidenceThe higher mortality and rate of critical care admission associated with VOC B.1.1.7, combined with its known increased transmissibility, are likely to put health care systems under further stress. These effects may be mitigated by the ongoing vaccination programme.

category: primary care research


title: The role of connectivity on COVID-19 preventive approaches

abstract:
Preventive and modelling approaches to address the COVID-19 pandemic have been primarily based on the age or occupation, and often disregard the importance of heterogeneity in population contact structure and individual connectivity. To address this gap, we developed models based on Erd[o]s-Renyi and a power law degree distribution that first incorporate the role of heterogeneity and connectivity and then can be expanded to make assumptions about demographic characteristics. Results demonstrate that variations in the number of connections of individuals within a population modify the impact of public health interventions such as lockdown or vaccination approaches. We conclude that the most effective strategy will vary depending on the underlying contact structure of individuals within a population and on timing of the interventions.

Author summaryThe best strategy for public health interventions, such as lockdown or vaccination, depends on the contact structure of the population and the timing of the intervention. In general, for heterogeneous contact structures that mimic the COVID-19 spread, which is characterized by the presence of super spreaders, vaccinating the most connected individuals first was the most effective strategy to prevent infections and deaths, especially when coupled to serological tests. Models considering heterogeneity in human interactions need be used to identify the best potential vaccine prioritization strategies.


title: Relationships Between Parental Involvement and Suicidal Ideation among In-school Adolescents in Vietnam: A Multilevel Analysis of the Global School-Based Student Health Survey 2019

abstract: Youth suicide is a leading cause of death among adolescents, but evidence about the influences of parental involvement on adolescent suicidal behaviors is inconsistent and have not been well studied. We used nationally representative data from the Vietnam Global School-based Student Health Survey (GSHS) 2019 (n = 7796 students aged 13-18 years). Using the 2-level random intercept logistic regressions, we evaluated the relationship between parental involvement (high expectation, monitoring, and understanding) and suicidal ideation and identified related factors of suicidal ideation. The overall prevalence of suicidal ideation was 15.6%. While high level of parental monitoring and understanding were associated with lower odds of suicidal ideation among adolescents (OR: 0.63; 95% CI: 0.52-0.77 and OR: 0.60; 95% CI: 0.49-0.73, respectively), high parental expectation was linked to higher odds of suicidal ideation (OR: 1.42; 95% CI: 1.24-1.63). Other risk factors at the individual- and school-level for suicidal ideation included being girls, living in urban areas, having mental health problems, involving in risk behaviors, suffering from bullying and violence, and poor school quality. Targeted suicide prevention initiatives should take into account comprehensive aspects of parent-child bonding, student, and school factors to mitigate the burden of suicidal behaviors among adolescents.


title: Prediction of severe COVID-19 cases requiring a ventilator in Tokyo, Japan

abstract:
BackgroundTo avoid exhaustion of medical resources by COVID-19, policy-makers must predict care needs, specifically the proportion of severe cases likely to need ventilator care.

ObjectiveThis study was designed to use a statistical model to elucidate dynamics of severe cases in Tokyo and to discuss the timing of effective policy activation.

MethodsThe study extended from April 27 through October 18, 2020 in Japans Tokyo Metropolitan area. Medical exhaustion was defined as use of more than half of the ventilator capacity available before the COVID-19 outbreak. We regressed the number of severe cases on the newly onset patients of more than 14 days prior. As earlier research indicated, the COVID-19 severity changed at the end of May. Therefore, we added dummy variables to reflect changing severity from June and its product with newly onset patients as the explanatory variable. Then we calculated the threshold using R(t): R(t)=0.99 for the number of patients 14 days prior was used as a threshold at which strong countermeasures should be activated to keep to avoid medical exhaustion.

ResultsThe critical number signaling medical exhaustion in Tokyo was defined as 655 cases. We selected 15, 30, 60 and 90 days prior as explanatory variables for explaining the number of severe cases. A coefficient of determination larger than 0.95 was inferred as indicating good fit. The threshold was estimated as more than 4500 cases for R(t)=1.1 and monotonically decreasing by R(t) to be 600 cases for R(t)=2.5.

Discussion and ConclusionResults showed that newly onset patients reported more than 14 days prior can explain the number of severe cases very well. We also confirmed the threshold number of patients 14 days prior by R(t) for which strong countermeasures should be activated to avoid medical exhaustion with R(t)=0.99. This method is expected to be useful for countermeasure activation policies for Tokyo.


title: Sex ratios and missing women among Asian minority and migrant populations in Aotearoa/New Zealand: A retrospective cohort analysis

abstract:
BackgroundRecent research from the UK, USA, Australia, and Canada point to male-favouring Sex Ratios at Birth (SRB) among their Asian minority populations, attributed to son preference and sex-selective abortion within these cultural groups. The present study conducts a similar investigation of SRBs among New Zealands Asian minority and migrant populations, who comprise 15% of the population.

MethodsThe New Zealand historical census series between 1976-2013 was used to examine SRBs between ages 0-5 by ethnicity. A retrospective birth cohort in New Zealand was created using the Stats NZ Integrated Data Infrastructure from 2003-2018. A logistic regression was conducted and adjusted for selected variables of interest including visa group, parity, maternal age and deprivation. Finally, associations between family size, ethnicity and family gender composition were examined in a subset of this cohort (families with 2 or 3 children).

ResultsThere was no evidence of  missing women or gender bias as indicated by a deviation from the biological norm in New Zealands Asian population. However, Indian and Chinese families were significantly more likely to have a third child if their first two children were females compared to two male children.

ConclusionThe analyses did not reveal male-favouring SRBs or any conclusive evidence of sex-selective abortion among Indian and Chinese populations. Based on this data, we conclude that in comparison to other western countries, New Zealands Asian migrant populations presents as an anomaly. The larger family sizes for Indian and Chinese populations where the first two children were girls suggested potentially  soft practices of son preference.

WHAT IS ALREADY KNOWN ON THIS SUBJECT- There are discrepancies in Sex Ratios at Birth (SRB) among the Asian minority migrant populations - particularly Indian and Chinese populations -in countries like Canada, UK, USA. SRBs show a pronounced number of males over female children, suggesting a widespread practice of sex-selective abortions in these communities since the 1970s.
- These trends implicitly reflect social norms of gender bias through son preference, and daughter devaluation.

WHAT IS BEING ADDED- The present study did not find evidence of skewed SRBs that favour boys over girls among Asian ethnicities. The analyses however did find a tendency for Indian and Chinese families to have larger families especially when the first two children were girls.
- Overall, the findings suggest the absence of widespread practices of sex-selective abortion making New Zealand an anomaly relative to other migrant-receiving countries. However, there are still vestiges of son preference that are seen through decisions around family size and gender composition.


title: Predicting the onset of freezing of gait in de novo Parkinson's disease

abstract: Freezing of gait (FoG) is a debilitating symptom of Parkinsons disease (PD) related to higher risks of falls and poor quality of life. In this study, we predicted the onset of FoG in PD patients using a battery of risk factors from patients enrolled in the Parkinsons Progression Markers Initiative (PPMI) cohort. The endpoint was the presence of FoG, which was assessed every year during the five-year follow-up visit. Overall, 212 PD patients were included in analysis. Seventy patients (33.0%) developed FoG during the visit (pre-FoG group). Age, bradykinesia, TD/PIGD classification, fatigue, cognitive impairment, impaired autonomic functions and sleep disorder were found to be significantly different in patients from pre-FoG and non-FoG groups at baseline. The logistic regression model showed that motor factors such as TD/PIGD classification (OR = 2.67, 95% CI = 1.41-5.09), MDS-UPDRS part III score (OR = 1.05, 95% CI = 1.01-1.09) were associated with FoG occurrence. Several indicators representing non-motor symptoms such as SDMT total score (OR = 0.95, 95% CI = 0.91-0.98), HVLT immediate/Total recall (OR = 0.91, 95% CI = 0.86-0.97), MOCA (OR = 0.87, 95% CI = 0.76-0.99), Epworth Sleepiness Scale (OR = 1.13, 95% CI = 1.03-1.24), fatigue(OR = 1.98, 95% CI = 1.32-3.06), SCOPA-AUT gastrointestinal score (OR = 1.27, 95% CI = 1.09-1.49) and SCOPA-AUT urinary score (OR = 1.18, 95% CI = 1.06-1.32) were found to have the predictive value. PD patients that developed FoG showed a significant reduction of DAT uptake in the striatum. However, no difference at baseline was observed in genetic characteristics and CSF biomarkers between the two patient sets. Our model indicated that TD/PIGD classification, MDS-UPDRS total score, and Symbol Digit Modalities score were independent risk factors for the onset of FoG in PD patients. In conclusion, the combination of motor and non-motor features including the akinetic subtype and poor cognitive functions should be considered in identifying PD patients with high risks of FoG onset.


title: Ancestrally and Temporally Diverse Analysis of Penetrance of Clinical Variants in 72,434 Individuals

abstract: A major goal of genomic medicine is to quantify the disease risk of genetic variants. Here, we report the penetrance of 37,772 clinically relevant variants (including those reported in ClinVar1 and of loss-of-function consequence) for 197 diseases in an analysis of exome sequence data for 72,434 individuals over five ancestries and six decades of ages from two large-scale population-based biobanks (BioMe Biobank and UK Biobank). With a high-quality set of 5,359 clinically impactful variants, we evaluate disease prevalence in carriers and non-carriers to interrogate major determinants and implications of penetrance. First, we associate biomarker levels with penetrance of variants in known disease-predisposition genes and illustrate their clear biological link to disease. We then systematically uncover large numbers of ClinVar pathogenic variants that confer low risk of disease, even among those reviewed by experts, while delineating stark differences in variant penetrance by molecular consequence. Furthermore, we ascertain numerous variants present in non-European ancestries and reveal how increasing carrier age modifies penetrance estimates. Lastly, we examine substantial heterogeneity of penetrance among variants in known disease-predisposition genes for conditions such as familial hypercholesterolemia and breast cancer. These data indicate that existing categorical systems for variant classification do not adequately capture disease risk and warrant consideration of a more quantitative system based on population-based penetrance to evaluate clinical impact.


title: Google Trends as a method to predict new COVID-19 cases

abstract:
In this paper, we develop a method that can detect and predict the emergence of new cases of COVID-19 at an early stage. With this method, we try to lay the empirical basis for the development of the model of digital monitoring and prediction of the occurrence of new cases of COVID-19 in Croatia, relying on the analytical tool Google Trends (GT).

ResultsIn Croatia search activities using GT for terms such as   PCR +Covid", "PCR + test", and symptoms "cough + corona", "pneumonia + corona"; "muscle pain + corona" correlate strongly with officially reported cases of the disease. Google Trends tools are suitable for predicting the emergence of new COVID-19 cases in Croatia, and that the data collected by this method correlate with official data.

The benefit of this method is reliable estimates that can enable public health officials to prepare and better respond to the possible return of a pandemic in certain parts of the country. If a region experiences an early, sharp increase in Covid-19-like-illness Google searches, it may be possible to focus additional resources on that region to identify the etiology of the outbreak, providing extra medical capacity or raising local media awareness as necessary.

Because the relative frequency of certain queries is highly correlated with the percentage of physician visits in which a patient presents with Covid-19 symptoms, this method can serve as an early alarm to predict the emergence of new cases of COVID-19 in the specific area in Croatia.


title: Rationale and design of the Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) Trial and LIGHT-ACD Trial

abstract:
BackgroundComputerized clinical decision support systems (CDSS) are low-cost, scalable tools with the potential to improve guideline-based antihypertensive treatment in primary care, but their effectiveness needs testing in pragmatic trials.

MethodsThe Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) trial is a pragmatic, four-stage, cluster-randomized trial conducted in 94 primary care practices in China. For each city-based stage, practices are randomly assigned to either implementation of the CDSS for hypertension management (which guides physicians treatment recommendations based on measured blood pressure and patient characteristics), or usual care. Patients are enrolled during the first 3 months after site randomization and followed for 9 months. The primary outcome is the proportion of hypertension management visits at which guideline-based treatment is provided.

In a separate sub-study conducted within the CDSS, with the patient as the unit of randomization, the LIGHT-ACD trial, patients are randomized to receive different initial mono- or dual- antihypertensive therapy. The primary outcome of the LIGHT-ACD trial is the change in blood pressure from the first visit after site randomization to 9 months.

DiscussionThe LIGHT trial will provide evidence on the effectiveness of a CDSS for improving guideline adherence for hypertension management in primary care in China. The sub-study, LIGHT-ACD trial, will provide data on the effect of different initial antihypertensive regimens for blood pressure management in this setting.

Trial registrationClinicalTrials.gov, identifier: LIGHT (NCT03636334) and LIGHT-ACD (NCT03587103). Registered on 3 July 2018.


title: Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study

abstract:
BackgroundA considerable proportion of SARS-CoV-2 transmission occurs from asymptomatic and pre-symptomatic cases. Therefore, different polymerase chain reaction (PCR)- or rapid antigen test (RAT)-based approaches are being discussed and applied to identify infectious cases that would have gone undetected (e.g., in nursing homes). In this article, we provide a framework to estimate the time-dependent risk of being infectious after a negative SARS-CoV-2 test and we simulate the number of expected cases over time in populations of individuals who initially tested negative.

MethodsA Monte Carlo approach is used to simulate infections that occurred over a one-week period in populations with 1,000 individuals following a negative SARS-Cov-2 test. Parameters representing the application of PCR tests or RATs are utilized, and SARS-CoV-2 7-day incidences between 25 and 200 per 100,000 people are considered. Simulation results are compared to case numbers predicted via a mathematical equation.

ResultsThe simulations showed a linear increase in cases over time in populations of individuals who initially tested SARS-CoV-2 negative. The different false negative rates of PCR tests and RATs have a strong impact on the number of simulated cases. The simulated and the mathematically predicted case numbers were comparable. However, Monte Carlo simulations highlight that, due to random effects, infectious cases can exceed predicted case numbers even shortly after a test was conducted.

ConclusionsThe analysis demonstrates that the number of infectious cases in a population can be effectively reduced by the screening of asymptomatic individuals. However, the time since the negative test and the underlying SARS-CoV-2 incidence are critical parameters in determining the observed subsequent number of cases in tested populations.


title: A simplified SARS-CoV-2 pseudovirus neutralization assay

abstract: COVID-19 is an ongoing pandemic caused by the highly infectious coronavirus SARS-CoV-2 that is engaging worldwide scientific research to find a timely and effective eradication strategy. Great efforts have been put into anti-COVID-19 vaccine generation in an effort to protect the world population and block SARS-CoV-2 spread. To validate the protective efficacy of the vaccination campaign and effectively control the pandemy, it is necessary to quantify the neutralizing antibodies induction by vaccination, since they have been established to be a correlate of protection. In this work a SARS-CoV-2 pseudovirus neutralization assay, based on a replication incompetent lentivirus expressing an adapted form of CoV-2 S protein and an ACE2/TMPRSS2 stably expressing cell line, have been minimized in term of protocol steps without loss of accuracy. The goal of the present simplified neutralization system is to improve SARS-CoV-2 vaccination campaign by means of an easy and accessible approach to be performed in any medical laboratory, maintaining the sensitivity and quantitative reliability of classical serum neutralization assays. Further this assay can be easily adapted to different coronaviruses variants by simply modifying the pseudotyping vector.


title: Qualification of the UniBw protection concept in different rooms of the Obermenzinger high school

abstract: Current research has shown that SARS-CoV-2 is transmitted via airborne particles. These particles are generated when infected persons exhale and they spread throughout the room, resulting in a high concentration and thus a high risk of infection of non-infected persons. One way to reduce the concentration of particles is to filter them using mobile room air cleaners, which can be easily set up and reduce the concentration of viruses or keep them at a low level. Since many studies are conducted in generic rooms, the question of the cleaning performance of such room air cleaners in real rooms arises. In order to investigate this, measurements of the effectiveness were carried out in a total of 4 different rooms of the "Obermenzinger Gymnasium" (Obermenzinger high school) in Munich. It can be shown that good effects of the room air cleaners are achieved even under realistic conditions. Even Plexiglas screens, which serve as protection against direct infection, have no negative influence.


title: Prevalence of COVID-19 in Iran: Results of the first survey of the Iranian COVID-19 Serological Surveillance program

abstract:
BackgroundThis study aims to estimate the prevalence of COVID-19 in the general population of Iran.

MethodsThe target population was all Iranian people aged six years and older in the country. A stratified random sampling design was used to select 28,314 subjects from among the individuals registered in the electronic health record systems used in primary health care in Iran. Venous blood was taken from each participant and tested for the IgG antibody against COVID-19. The prevalence of COVID-19 was estimated at provincial and national levels after adjusting for the measurement error of the laboratory test, non-response bias, and sampling design.

ResultsOf the 28,314 Iranians selected, 11,256 (39.75%) participated in the study. Of these, 5406 (48.0%) were male, and 6851 (60.9%) lived in urban areas. The mean (standard deviation) participant age was 35.89 (18.61) years. The adjusted prevalence of COVID-19 until August 20, 2020 was estimated as 14.2% (95% uncertainty interval: 13.3%, 15.2%), which was equal to 11,958,346 (95% confidence interval: 11,211,011-12,746,776) individuals. The prevalence of infection was 14.6%, 13.8%, 16.6%, 11.7%, and 19.4% among men, women, urban population, rural population, and individuals [≥]60 years of age, respectively. Ardabil, Golestan, and Khuzestan provinces had the highest prevalence, and Alborz, Hormozgan, and Kerman provinces had the lowest.

ConclusionsBased on the study results, a large proportion of the Iranian population had not yet been infected by COVID-19. The observance of hygienic principles and social restrictions should therefore continue until the majority of the population has been vaccinated.


title: Sars-CoV-2 attack rate in reception and accommodation centres for asylum seekers: systematic review of outbreak media reports in Germany

abstract:
ObjectivesDespite concerns about the impact of the severe acute respiratory syndrome corona virus (Sars-CoV-2) in refugee camps, data on attack rates and effectiveness of containment measures are lacking. We aimed to (1) quantify the attack rate of Sars-CoV-2 during outbreaks in reception and accommodation centres in Germany, (2) assess differences in the attack rate based on containment measures, and (3) provide an overview of testing strategies, communication, conflicts, and protection measures for refugees with special needs.

MethodsSystematic web-based review of outbreak media reports (until June 2020) on confirmed Sars-CoV-2 cases in reception centers for asylum seekers in Germany using the google search engine. Reports were screened for pre-defined inclusion criteria and complemented by snowball searches. Data on facility name, location, confirmed cases, containment measures, communication, protection strategies, and conflicts was extracted for each outbreak and reporting date. Evidence synthesis: meta-analysis and negative binomial regression.

FindingsWe identified 337 media reports on 101 Sars-CoV-2 outbreaks in 99 reception and accommodation centers in Germany. The pooled Sars-CoV-2 attack rate was 13.1% (95% confidence interval, CI: 9.8-16.7). Outbreak sites implementing mass quarantine (n=76) showed higher rates (15.7; 95% CI: 11.6 - 20.2) compared to sites using conventional strategies (6.6; 95%CI: 3.1 - 11.2), yielding a rate ratio of 0.44 (95%CI: 0.27-0.72) adjusted for testing strategies, type and size of accommodation. Conflicts occurred in at least 11.8% of all outbreaks. Few sites reported specific measures to protect refugees with special needs.

ConclusionMass quarantine is associated with higher attack rates, and appears to be a counter-productive containment measure in overcrowded camps. Although further research with individual-level data is required to rule out residual confounding, reception centers and refugee camps should follow the available guidelines on Covid-19 response and refrain from mass quarantine if physical distancing cannot be guaranteed.


title: Spatial Prevalence and Determinants of Malaria among under-five Children in Ghana

abstract: In Ghana malaria is an endemic disease and the incidence of malaria still accounts for 38.0% of all outpatient attendance with the most vulnerable groups being children under 5 years of age. In order to alleviate this problem, it is essential to design geographically targeted and cost-effective intervention mechanisms guided by up-to-date and reliable data and maps that show the spatial prevalence of the disease. The 2016 Ghana Malaria Indicator Survey data (N = 2,910 under-five children) were analyzed using model-based geostatistical methods with the two objectives to: (1) explore individual-, household-, and community-level determinant variables associated with malaria illness in U5 children, and (2) produce prevalence maps of malaria across the study locations in the country. The overall weighted prevalence of malaria by microscopy blood smear and rapid diagnostic tests were 20.63% (with 95% CI: 18.85% - 22.53%) and 27.82% (with 95% CI: 25.81% - 29.91%), respectively. Across regions of Ghana, the prevalence of malaria ranges from 5% in Greater Accra to 31% in Eastern region. Malaria prevalence was higher in rural areas, increased with child age, and decreased with better household wealth index and higher level of mothers education. Given the high prevalence of childhood malaria observed in Ghana, there is an urgent need for effective and efficient public health interventions in hot spot areas. The determinant variables of malaria infection that have been identified in this study as well as the maps of parasitaemia risk could be used in malaria control program implementation to define priority intervention areas.


title: COVID-19 vaccine hesitancy among undergraduate medical students: results from a nationwide survey in India

abstract: COVID-19 vaccine was launched in India on 16 January 2021, prioritizing health care workers which included medical students. We aimed to assess vaccine hesitancy and factors related to it among undergraduate medical students in India. An online questionnaire was filled by 1068 medical students across 22 states and union territories of India from 2 February - 7 March 2021. Vaccine hesitancy was found among 10.6%. Concern regarding vaccine safety and efficacy, hurried testing of vaccines prior to launch and lack of trust in government agencies predicted COVID-19 vaccine hesitancy. Risk perception regarding contracting COVID-19 vaccine reduced COVID-19 vaccine hesitancy as well as hesitation in participating in COVID-19 vaccine trials. Choosing between the two available vaccines (Covishield and Covaxin) was considered important by medical students both for themselves and their future patients. Covishield was preferred to Covaxin by students. Majority of those willing to take the COVID-19 vaccine felt that it was important for them to resume their clinical posting, face-to-face classes and get their personal life back on track. Around three-fourths medical students viewed that COVID-19 vaccine should be made mandatory for both health care workers and international travellers. Prior adult vaccination didnt have an effect upon COVID-19 vaccine hesitancy. Targeted awareness campaigns, regulatory oversight of vaccine trials and public release of safety and efficacy data and trust building activities could further reduce COVID-19 vaccine hesitancy among medical students.


title: Modelling, prediction and design of national COVID-19 lockdowns by stringency and duration

abstract: The implementation of lockdowns has been a key policy to curb the spread of COVID-19 and to keep under control the number of infections. However, quantitatively predicting in advance the effects of lockdowns based on their stringency and duration is a complex task, in turn making it difficult for governments to design effective strategies to stop the disease. Leveraging a novel mathematical "hybrid" approach, we propose a new epidemic model that is able to predict the future number of active cases and deaths when lockdowns with different stringency levels or durations are enforced. The key observation is that lockdown-induced modifications of social habits may not be captured by traditional mean-field compartmental models because these models assume uniformity of social interactions among the population, which fails during lockdown. Our model is able to capture the abrupt social habit changes caused by lockdowns. The results are validated on the data of Israel and Germany by predicting past lockdowns and providing predictions in alternative lockdown scenarios (different stringency and duration). The findings show that our model can effectively support the design of lockdown strategies by stringency and duration, and quantitatively forecast the course of the epidemic during lockdown.


title: SARS-CoV-2 infection and risk of clinical sequelae during the post-acute phase: a retrospective cohort study

abstract:
ObjectiveClinical sequelae have not been well characterized during the post-acute phase of SARS-CoV-2 among adults 18 to 65 years old, and this study sought to fill that gap by evaluating excess risk and relative hazards for developing incident clinical sequelae during the post-acute phase.

DesignRetrospective cohort study including three propensity-matched groups.

SettingThis study merged three data sources from a large United States health plan: a large national administrative claims database, an outpatient lab testing database, and an inpatient hospital admissions database.

ParticipantsIndividuals 18 to 65 years old with continuous health plan enrollment from January 2019 to date of SARS-CoV-2 diagnosis. Three comparator groups were identified and propensity-score matched to individuals infected with SARS-CoV-2: a 2020 comparator group, a historical 2019 comparator group and a historical comparator group with viral lower respiratory tract illness (vLRTI).

Main outcome measuresOver 50 clinical sequelae during the post-acute phase (index date + 21 days) were ascertained using ICD-10 codes. Excess risk due to SARS-CoV-2 during the 4 months following the acute phase of illness and hazard ratios with 95% Bonferroni-corrected confidence intervals were calculated.

ResultsThis study found 14% of adults [≤]65 years of age who were infected with SARS-CoV-2 (n=193113) had at least one new clinical sequelae that required medical attention during the post-acute phase of illness. When considering risk for specific sequelae attributable to SARS-Cov-2 infection during the post-acute phase, clinical outcomes including chronic respiratory failure, cardiac arrythmia, hypercoagulability, encephalopathy, peripheral neuropathy, amnesia (memory difficulty), diabetes, liver test abnormalities, myocarditis, anxiety and fatigue were significantly elevated compared to the three propensity-matched comparator groups (2020, 2019, vLRTI). Significant risk differences due to SARS-CoV-2 infection ranged from 0.02 to 2.26 per 100 people and hazard ratios ranged from 1.24 to 25.65 when compared to the 2020 comparator group.

ConclusionsOur results confirm excess risk for developing clinical sequelae due to SARS-CoV-2 during the post-acute phase, including specific types of sequelae less commonly seen among other viral illnesses. Although individuals who were older, had pre-existing conditions, and were hospitalized due to COVID-19 were at greatest excess risk, younger adults ([≤]50 years), adults who did not have pre-existing conditions or adults who were not hospitalized due to COVID-19 were still at elevated risk for developing new clinical sequelae. The elevated risk for incident sequelae during the post-acute phase is relevant for healthcare planning.

Summary BoxO_ST_ABSWhat is already known on this topicC_ST_ABSSmall observational studies and case reports of hospitalized patients have shown some COVID-19 survivors suffer from short- and long-term sequelae. Few studies have characterized the excess risk of clinical sequelae attributable to SARS-CoV-2 during the post-acute phase among adults [≤]65 years of age in a large generalizable sample.

What this study addsThis study found 14% of individuals [≤]65 years of age who were infected with SARS-CoV-2 (n=193113) had a diagnosis of at least one new sequelae that required medical attention during the post-acute phase of illness. Elevated risk for specific clinical sequelae during the post-acute phase of illness was noted across a range of organ systems including cardiovascular, neurologic, kidney, respiratory, and mental health complications. The risk for incident sequelae increases with age, pre-existing conditions, and hospitalization for COVID-19; however, even among adults [≤] 50 years of age and individuals without pre-existing conditions or hospitalization due to COVID-19, risk for some clinical sequelae is still elevated. These results indicate where additional diagnostic follow-up, rehabilitation, and symptom management may be warranted among younger adults with milder infection.