title: The effectiveness of acupoint herbal patching for non-specific low back pain: A Protocol for systematic review and meta-analysis

abstract:
BackgroundNon-specific low back pain(NS-LBP) is related to disability and work absence and accounts for high economical costs of global.It is a problem that has a negative impact on physical, mental health of patients and quality of life. At present, acupoint herbal patching(AHP) as an adjuvant therapy is currently undergoing clinical trials in different medical centers. This study aimed to design a systematic review and meta-analysis to explore the effects of AHP on non-specific low back pain(NS-LBP).

MethodsWe will search the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database,the Chinese Scientific Journal Database, the Wan-Fang Database and the China National Knowledge Infrastructure. The primary outcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software. Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the GRADE approach to assess the overall quality of evidence supporting the primary outcomes. We will also use Spass software (Version19.0) for complex network analysis to explore the potential core prescription of acupoint herbal patching for functional constipation.

ResultsThis systematic review protocol will analyze the effectiveness, quality of life, improvement of the symptom and safety of acupoint herbal patching therapy for non-specific low back pain.

ConclusionThe findings of this systematic review will provide evidence to evaluate the effectiveness and safety of acupoint herbal patching for non-specific low back pain.


title: Estimating the Effects of Legalizing Recreational Cannabis on Newly Incident Cannabis Use

abstract: Liberalized state-level recreational cannabis policies in the United States (US) fostered important policy evaluations with a focus on epidemiological parameters such as proportions [e.g., active cannabis use prevalence proportions; cannabis use disorder (CUD) prevalence]. This cannabis policy evaluation project adds novel evidence on a neglected parameter - namely, estimated occurrence of newly incident cannabis use for underage (<21 years) versus older adults. The projects study populations were specified to yield nationally representative samples for all 51 major US jurisdictions, with probability sample totals of 819,543 non-institutionalized US civilian residents between 2008 and 2019. Standardized items to measure cannabis onsets are from audio computer-assisted self-interviews. Policy effect estimates are from event study difference-in-difference (DiD) models that allow for causal inference when policy implementation is staggered. The evidence indicates no policy-associated changes in the occurrence of newly incident cannabis onsets for underage persons. For jurisdictions with liberalized cannabis policies, the evidence indicates an increased occurrence of newly onset cannabis use among older adults (i.e., >21 years). We offer a tentative conclusion of public health importance: Legalized cannabis retail sales might be followed by the increased occurrence of cannabis onsets for older adults, but not for underage persons who cannot buy cannabis products in a retail outlet. Cannabis policy research does not yet qualify as  mature science. DiD modeling of newly incident cannabis use might be more informative than the modeling of prevalence proportions.

category: health policy


title: Projecting the seasonality of endemic COVID-19

abstract: Successive waves of infection by SARS-CoV-2 have left little doubt that this virus will transition to an endemic disease 1,2. Projections of the endemic seasonality of SARS-CoV-2 transmission are crucial to informed public health policy 3. Such projections are not only essential to well-timed interventions and the preparation of healthcare systems for synchronous surges with other respiratory viruses 4, but also to the elimination of seasonality as a confounder in the identification of surges that are occurring due to viral evolution, changes in host immunity, or other non-seasonal factors. However, the less than two-year duration of SARS-CoV-2 circulation, pandemic dynamics, and heterogeneous implementation of interventions have grievously complicated evaluations of its seasonality 5. Here we estimate the impending endemic seasonality of SARS-CoV-2 in global population centers via a novel phylogenetic ancestral and descendent states approach 6 that leverages long-term data on the incidence of circulating coronaviruses. Our results validate a major concern that endemic COVID-19 will typically surge coincident with other high-morbidity and -mortality respiratory virus infections such as influenza and RSV 7. In temperate locales in the Northern Hemisphere, we identify spatiotemporal surges of incidences that range from October through January in New York to January through March in Yamagata, Japan. This knowledge of likely spatiotemporal surges of COVID-19 is fundamental to optimal timing of public health interventions that anticipate the impending endemicity of this disease and mitigate SARS-CoV-2 transmission.

category: infectious diseases


title: Projected health impact of post-discharge malaria chemoprevention among children under the age of five years with severe malarial anaemia in Africa: a modelling analysis

abstract: Children recovering from severe malarial anaemia (SMA) remain at high risk of readmission and death after discharge from hospital. However, a recent trial found that post-discharge malaria chemoprevention (PDMC) reduces this risk. We developed a mathematical model describing the daily incidence of uncomplicated and severe malaria requiring readmission among 0-5 year-old children after hospitalised SMA. We fitted the model to a multicentre clinical PDMC trial using Bayesian methods. We then modelled the potential impact of PDMC across malaria-endemic African countries. In the 19 highest-burden countries, we estimate that only 2-5 children need to be given PDMC to prevent one hospitalised malaria episode, and less than 100 to prevent one death. If all hospitalised SMA cases access PDMC, 37,000 (range 16,000-84,000) malaria-associated readmissions could be prevented annually, depending on access to hospital care. We estimate that recurrent SMA post-discharge constitutes 18-29% of all SMA episodes in higher transmission settings.


title: Projected health impact of post-discharge malaria chemoprevention among children with severe malarial anaemia in Africa


title: Impact of voluntary risk-mitigation behaviour on transmission of the Omicron SARS-CoV-2 variant in England

abstract:
BackgroundThe Omicron variant of SARS-CoV-2 infection poses substantial challenges to public health. In England, "plan B" mitigation measures were introduced in December 2021 including increased home working and face coverings in shops, but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown.

MethodsWe developed a rapid online survey of risk mitigation behaviours during the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/Covid Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we describe the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave.

ResultsOver 95% of survey respondents (NALSPAC=2,686 and NTwins=6,155) reported some risk mitigation behaviours, with vaccination and using home testing kits reported most frequently. Less than half of those respondents reported that their behaviour was due to "plan B". We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 15,000 and 46,000 cumulative deaths, depending on assumptions about vaccine effectiveness. We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%.

ConclusionsWe conclude that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant, but that voluntary measures alone would be unlikely to completely control transmission.


title: Anatomy of Covid outbreak of vaccinated: An observational case-control study of Covid breakthrough infections in medical college students at Rural Medical College, India

abstract:
IntroductionBreakthrough infections about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported worldwide in both partially or completely vaccinated individuals irrespective of the type of vaccine. India, also emerged as the vaccine powerhouse producer, initiating the worlds one of the largest vaccination drives since January 16, 2021, with two vaccines named, BBV-152(COVAXIN) and AZD1222 (COVISHIELD). Breakthrough cases are reported from all over the globe for all kinds of vaccines. This is the investigation report into the outbreak of breakthrough COVID-19 infections at one of the medical colleges in Rural India unraveled in early October 2021. This report underscores the role of COVID-19 appropriate behavior along with vaccination and the role of IgG in evaluating immunity generated through vaccination.

ObjectiveThe study objective was to 1. Clinically characterize the recent breakthrough infection of COVID-19 (SARS-CoV-2) infection among (students) vaccinated in BKL Walawalkar Rural Medical College. 2. To evaluate  COVID-19 appropriate behavior (CAB) in cases and controls. 3. To evaluate COVID-19 anti spike IgG in the cases in comparison with the control

MethodsA total of 74 students studying at BKL Walawalkar Rural Medical College and vaccinated for COVID-19 were included in the study. RT-PCR diagnosis was done from 5 to 10 October 2021. The breakthrough infection in the cases was characterized using self-assessment questionnaires in comparison to the controls. The cases were assessed clinically and also using biochemical parameters. Both cases and controls were also assessed for their adherence to COVID-19 appropriate behavior using a separate semi-quantitative questionnaire and scoring system.

ResultsIn our study, out of the total subjects, 50% of Covaxin recipients had experienced vaccine breakthrough infection and 20% of Covishield recipients experienced breakthrough infection. Also, 6 out of the 35 cases were asymptomatic, and the rest were either having mild symptoms. None of them required any hospitalization or O2 therapy. The CAB score was lower in the cases when compared to controls. All the vaccine recipients show seroconversion. Anti-spike IgG antibodies titers are dynamic over time and across the clinically distinct groups. Irrespective of varying IgG titer, the vaccine protects against severity and possibly mortality.

ConclusionThe need for better awareness of COVID-19 appropriate methods as an alternative to and additive to vaccination is necessary to control the transmission of COVID-19 infection and decrease the disease severity. Vaccines are effective against preventing severe disease and possibly mortality. The use of serum anti-spike COVID-19 IgG is restricted to know the status of SARS-CoV-2 seroconversion.


title: Anatomy of SARS-CoV-2 outbreak of vaccinated: An observational case-control study of COVID-19 breakthrough infections, COVID-19 appropriate behavior and anti-spike-IgG response as a correlate of protection in Medical college students at Rural Medical College, India


title: Humoral immune response of patients infected by earlier lineages of SARS-CoV-2 neutralizes wild types of the most prevalent variants in Brazil

abstract: In the present study, serum samples of 20 hospitalized COVID-19 patients from Brazil who were infected by the earlier SARS-CoV-2 lineages B.1.1.28 and B.1.1.33, and by the variant of concern (VOC) Gamma (P.1) were tested by plaque reduction neutralization test (PRNT90) with wild isolates of a panel of SARS-CoV-2 lineages, including B.1, Zeta, N.10, and the VOCs Gamma, Alpha, and Delta that emerged in different timeframes of the pandemic. The main objectives of the present study were to evaluate if serum of COVID-19 patients infected by earlier lineages of SARS-CoV-2 were capable to neutralize recently emerged VOCs, and if PRNT90 is a reliable serologic method to distinguish infections caused by different SARS-CoV-2 lineages. Overall, sera collected from the day of admittance to the hospital to 21 days after diagnostic of patients infected by the two earlier lineages B.1.1.28 and B.1.1.33 presented neutralizing capacity for all challenged VOCs, including Gamma and Delta, that were the most prevalent VOCs in Brazil. Among all variants tested, Delta and N.10 presented the lowest mean of neutralizing antibody titers, and B.1.1.7, presented the highest titers. Four patients infected with Gamma, that emerged in December 2020, presented neutralizing antibodies for B.1, B.1.1.33 and B.1.1.28, its ancestor lineage. All of them had neutralizing antibodies under the level of detection for the VOC Delta. Interestingly, patients infected by B.1.1.28 presented very similar mean of neutralizing antibody titers for both B.1.1.33 and B.1.1.28. Findings presented here indicate that most patients infected in early stages of COVID-19 pandemic presented neutralizing antibodies up to 21 days after diagnostic capable to neutralize wild types of all recently emerged VOCs in Brazil, and that the PRNT90 it is not a reliable serologic method to distinguish natural infections caused by different SARS-CoV-2 lineages.


title: A Quick Displacement of the SARS-CoV-2 variant Delta with Omicron: Unprecedented Spike in COVID-19 Cases Associated with Fewer Admissions and Comparable Upper Respiratory Viral Loads

abstract:
BackgroundThe increase in SARS-CoV-2 infections in December 2021 in the United States was driven primarily by the Omicron variant which largely displaced the Delta over a three week span. Outcomes from infection with the Omicron remain uncertain. We evaluate whether clinical outcomes and viral loads differ between Delta and Omicron infections during the period when both variants were co-circulating.

MethodsRemnant clinical specimens from patients that tested positive for SARS-CoV-2 after standard of care testing between the last week of November and the end of December 2021were used for whole viral genome sequencing. Cycle threshold values (Ct) for viral RNA, the presence of infectious virus, and levels of respiratory IgG were measured, and clinical outcomes were obtained. Differences in each measure were compared between variants stratified by vaccination status.

ResultsThe Omicron variant displaced the Delta during the study period and constituted 95% of the circulating lineages by the end of December 2021. Patients with Omicron infections (N= 1121) were more likely to be vaccinated compared to patients with Delta (N = 910), but were less likely to be admitted, require ICU level care, or succumb to infection regardless of vaccination status. There was no significant difference in Ct values based on the lineage regardless of the vaccination status. Recovery of infectious virus in cell culture was reduced in boosted patients compared to fully vaccinated without a booster and unvaccinated when infected with the Delta lineage. However, in patients with Omicron infections, recovery of infectious virus was not affected by vaccination.

ConclusionsOmicron infections of vaccinated individuals are expected, yet admissions are less frequent. Admitted patients might develop severe disease comparable to Delta. Efforts for reducing the Omicron transmission are required as even though the admission risk is lower, the numbers of infections continue to be high.

Research in context Evidence before this studyThe unprecedented increase in COVID-19 cases in the month of December 2021, associated with the displacement of the Delta variant with the Omicron, triggered a lot of concerns. An understanding of the disease severity associated with infections with Omicron is essential as well as the virological determinants that contributed to its widespread predominance. We searched PubMed for articles published up to January 23, 2022, using the search terms ("Omicron") AND ("Disease severity") as well as ("Omicron") AND ("Viral load") And/ or ("Cell culture"). Our search yielded 3 main studies that directly assessed the omicrons clinical severity in South Africa, its infectious viral load compared to Delta, and the dynamics of viral RNA shedding. In South Africa, compared to Delta, Omicron infected patients showed a significant reduction in severe disease. In this study, Omicron and non-Omicron variants were characterized based on S gene target failure using the TaqPath COVID-19 PCR (Thermo Fisher Scientific). In the study from Switzerland that assessed the infectious viral load in Omicron versus Delta, the authors analyzed only 18 Omicron samples that were all from vaccinated individuals to show that compared to Delta, Omicron had equivalent infectious viral titers. The third study that assessed the Omicron viral dynamics showed that the peak viral RNA in Omicron infections is lower than Delta. No published studies assessed the clinical discrepancies of Omicron and Delta infected patients from the US, nor comprehensively assessed, by viral load and cell culture studies, the characteristics of both variants stratified by vaccination status.

Added value of this studyTo the best of our knowledge, this is the only study to date to compare the clinical characteristics and outcomes after infection with the Omicron variant compared to Delta in the US using variants characterized by whole genome sequencing and a selective time frame when both variant co-circulated. It is also the first study to stratify the analysis based on the vaccination status and to compare fully vaccinated patients who didnt receive a booster vaccination to patients who received a booster vaccination. In addition, we provide a unique viral RNA and infectious virus load analyses to compare Delta and Omicron samples from unvaccinated, fully vaccinated, and patients with booster vaccination.

Implications of all the available evidenceOmicron associated with a significant increase in infections in fully and booster vaccinated individuals but with less admissions and ICU level care. Admitted patients showed similar requirements for supplemental oxygen and ICU level care when compared to Delta admitted patients. Viral loads were similar in samples from Omicron and Delta infected patients regardless of the vaccination status. The recovery of infectious virus on cell culture was reduced in samples from patients infected with Delta who received a booster dose, but this was not the case with Omicron. The recovery of infectious virus was equivalent in Omicron infected unvaccinated, fully vaccinated, and samples from patients who received booster vaccination.

FundingNIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department of health, Centers for Disease Control and Prevention contract 75D30121C11061.


title: Immunogenicity of COVID-19 mRNA Vaccines in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

abstract: Immunocompromised patients are particularly susceptible to serious complications from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Two mRNA vaccines, BNT162b2 and mRNA-1273, have been shown to have excellent clinical efficacy in immunocompetent adults, but diminished activity in immunocompromised patients. In this study, we measured anti-spike SARS-CoV-2 antibody response, avidity, and surrogate neutralizing antibody activity in Coronavirus Disease 2019 (COVID-19) vaccinated patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Anti-spike SARS-CoV-2 antibody was present in 89% of AML and 88% of MDS patients, but median antibody levels for were lower than in healthy controls (p=0.001 and p=0.04, respectively). SARS-CoV-2 antibody avidity and neutralizing antibody activity from AML patients were significantly lower than controls (p=0.028 and p=0.002, respectively). There was a trend toward higher anti-spike SARS-CoV-2 antibody levels after mRNA-1273 vaccination. Antibody avidity was greater in patients after mRNA-1273 versus BNT162b2 (p=0.01) and there was a trend toward greater neutralizing antibody activity after mRNA-1273 versus BNT162b2 vaccination.


title: EPIDEMIOLOGICAL CHARACTERISTICS AND SEVERITY OF OMICRON VARIANT CASES IN THE APHP CRITICAL CARE UNITS; THE APHP REALITY RESEARCH GROUP

abstract:
ImportanceInformation about the severity of Omicron is scarce.

ObjectiveTo report the respective risk of ICU admission in patients hospitalized with Delta and Omicron variants and to compare the characteristics and disease severity of critically ill patients infected with both variants according to vaccination status.

DesignAnalysis from the APHP database, called Reality, prospectively recording the following information in consecutive patients admitted in the ICU for COVID-19: age, sex, immunosuppression, vaccination, pneumonia, need for invasive mechanical ventilation, time between symptom onset and ICU admission, and in-ICU mortality. Retrospective analysis on an administrative database, "Systeme dInformation pour le Suivi des Victimes" (SI-VIC), which lists hospitalized COVID-19 patients.

Setting39 hospitals in the Paris area from APHP group.

ParticipantsPatients hospitalized from December 1, 2021 to January 18, 2022 for COVID-19.

Main outcomes and measuresRisk of ICU admission was evaluated in 3761 patients and Omicron cases were compared to Delta cases in the ICU in 888 consecutive patients.

ResultsOn January 18, 45% of patients in the ICU and 63.8% of patients in conventional hospital units were infected with the Omicron variant (p < 0.001). The risk of ICU admission with Omicron was reduced by 64% than with Delta (9.3% versus 25.8% of cases, respectively, p < 0.001). In critically ill patients, 400 had the Delta variant, 229 the Omicron variant, 98 had an uninformative variant screening test and 161 did not have information on variant screening test. 747 patients (84.1%) were admitted for pneumonia. Compared to patients infected with Delta, Omicron patients were more vaccinated (p<0.001), even with 3 doses, more immunocompromised (p<0.001), less admitted for pneumonia (p<0.001), especially when vaccinated (62.1% in vaccinated versus 80.7% in unvaccinated, p<0.001), and less invasively ventilated (p=0.02). Similar results were found in the subgroup of pneumonia but Omicron cases were older. Unadjusted in-ICU mortality did not differ between Omicron and Delta cases, neither in the overall population (20.0% versus 27.9%, p = 0.08), nor in patients with pneumonia (31.6% versus 29.7%, respectively) where adjusted in-ICU mortality did not differ according to the variant (HR 1.43 95%CI [0.89;2.29], p=0.14).

Conclusion and relevanceCompared to the Delta variant, the Omicron variant is less likely to result in ICU admission and less likely to be associated with pneumonia. However, when patients with the Omicron variant are admitted for pneumonia, the severity seems similar to that of patients with the Delta variant, with more immunocompromised and vaccinated patients and no difference in adjusted in-ICU mortality. Further studies are needed to confirm our results.

category: intensive care and critical care medicine


title: Open science policies of medical and health sciences journals before and during the COVID-19 pandemic: a repeat cross-sectional study

abstract: Cross-disciplinary openness and transparency of research plays an important role in scientific progress. We evaluated open-science related policies of 19 high ranking health and medical journals before (February 2020) and during (May 2021) the COVID-19 pandemic. The Transparency and Openness Promotion (TOP) guideline and the International Committee of Medical Journal Editors (ICMJE) requirements for disclosing conflicts of interest (COIs) were used to audit journal policies. TOP scores slightly improved during the COVID-19 pandemic, from a median of 5 (IQR: 2-12.5) out of a possible 24 points in February 2020 to 7 (IQR: 4-12) in May 2021. Most journals fulfilled all ICMJE provisions for reporting COIs before (84%; n=16) and during (95%; n=18) the COVID-19 pandemic. The COVID-19 pandemic has highlighted the importance of practising open science, however adherence to open science standards in audited policies was low overall, which may reduce progress in health and medical research.

category: epidemiology


title: Appropriate management of steroids and discharge planning during and after hospital admission for moderate-severe ulcerative colitis

abstract:
BackgroundLimited guidance exists for the post-discharge care of ulcerative colitis (UC) patients hospitalized for moderate-severe flares.

MethodsRAND methodology was used to establish appropriateness of inpatient and post-discharge steroid dosing, discharge criteria, follow-up, and post-discharge biologic or small molecule initiation. A literature review informed the panels voting, which occurred anonymously during two rounds before and after a moderated virtual session.

ResultsMethylprednisolone 40-60mg IV every 24 hours or hydrocortisone 300mg IV three times daily are appropriate for inpatient management, with methylprednisolone 40mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo sub score 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo sub score 0-1). It is appropriate to discharge patients on 40mg of prednisone after observing patients for 24 hours in-hospital to ensure stability prior to discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start anti-TNF therapy after discharge for anti-TNF naive patients. For anti-TNF exposed patients it is appropriate to start vedolizumab or ustekinumab for all patients, and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks, and with lower endoscopy within 4-6 months after discharge.

ConclusionWe provide guidance on the inpatient and post-discharge management of UC patients hospitalized for moderate-severe flares.

STUDY HIGHLIGHTSO_ST_ABSWHAT IS KNOWNC_ST_ABSO_LIUlcerative colitis patients hospitalized for disease flares are a high-risk population
C_LIO_LIGuidance on evaluation and initial management during flares is provided, however, limited guidance exists on standardization of steroid management and post-discharge care
C_LI

WHAT IS NEW HEREO_LIThrough a RAND Appropriateness Panel we provide guidance on the inpatient and post-discharge management of steroids, discharge criteria, post-discharge monitoring and management of biologics or small molecule therapies
C_LIO_LIThese recommendations will help to bring uniformity to care for this high-risk population, and optimize outcomes in clinical practice
C_LI

category: gastroenterology


title: Contributions of age and clinical depression to metacognitive performance

abstract:
BackgroundPivotal for adaptive behaviour is the ability to judge whether our performance is correct or not, even in the absence of external feedback. This metacognitive ability can be measured using confidence ratings. Past research suggests that overall confidence (confidence bias) is lower in Major Depressive Disorder (MDD). Less is known about the ability of MDD patients to discriminate correct from incorrect performance (metacognitive efficiency).

MethodsThe perceptual metacognitive performance of 17 aged MDD patients (62-89 years) was tested and compared to an age matched as well as a young control group (21-28 years). The younger control group was included to disentangle the effects of age and MDD on metacognitive performance. Indeed, earlier studies found an increased confidence bias but a decreased metacognitive efficiency with age.

ResultsOur results showed no difference in confidence bias nor in metacognitive efficiency between MDD patients and age-matched control participants. Importantly, aged participants, including both aged controls and MDD patients, demonstrated lower metacognitive efficiency compared to young participants. This metacognitive deficit found in aged participants was specifically driven by an overconfidence on incorrect trials.

ConclusionsThe relation between MDD and confidence bias may not be as robust as previously claimed. Furthermore, our results point to the importance of age rather than MDD for metacognitive efficiency. This could have important clinical implications as the observation of lower metacognitive abilities in patients is not necessarily caused by the depression.

LimitationsSample size was relatively small. Some clinical variables such as anxiety, or medication were not controlled.

category: psychiatry and clinical psychology


title: COVID-19 vaccine attitude and its predictors among people living with chronic health conditions in Ibadan, Nigeria

abstract:
AbstractsO_ST_ABSBackgroundC_ST_ABSGlobally COVID-19 has caused death among millions of people and new cases continue to be reported daily, including in Nigeria. With the efforts of the Nigerian government to ensure everyone gets vaccinated, the vaccination attitude and its predictors among persons with chronic health conditions remains unclear. The study was therefore conducted to assess vaccination attitude and determine its associated factors among people living with chronic health conditions.

MethodsA descriptive cross-sectional study was conducted among 423 patients attending the medical outpatient clinic of University College Hospital, Ibadan, Oyo State, Nigeria; before COVID-19 vaccination commencement. Data were collected on socio-demographic and COVID-19 related characteristics, via Open Data Kit (ODK) software. The Vaccine Attitude Examination (Vax) Scale including its four subscales was adopted to assess attitude towards COVID-19 vaccine uptake. The main outcome was vaccine attitude status defined as positive if a VAX sum score was above the median value; otherwise, non-positive. Data were analysed using Chi-square and multivariate logistic regression analyses at 5% significance level.

ResultsHypertension (27.4%), diabetes mellitus (22.0%) and heart conditions/diseases (19.6%) were the top three conditions being managed by the participants. The overall proportion of patients with a positive attitude towards the uptake of COVID-19 vaccination was 46.6%; while 29.6% trusted the vaccine benefit, 46.6% were not worried about the aftermath effect of the vaccine and 11.1% were not concerned about the vaccine commercial profiteering. Factors associated with overall vaccine attitude were level of education, income, knowledge of COVID-19, living room arrangement, and confidence in government (p<0.05). The main influential factor on general vaccine positive attitude and the four subscales was confidence in the government.

ConclusionLess than half of people living with a chronic medical condition had a positive attitude towards the COVID vaccine. The attitudes are mediated strongly by confidence in the government and several sociodemographic and COVID related characteristics. A lot still needs to be done to achieve the prescribed herd immunity.

category: public and global health


title: Cardiovascular, respiratory and functional effects of tele-supervised home-based exercise training in individuals recovering from COVID-19 hospitalization: A randomized clinical trial

abstract: Our aim was to test the hypothesis that tele-supervised home-based exercise training (exercise) is an effective strategy for improving cardiovascular, respiratory, and functional capacity parameters in individuals that were hospitalized due to coronavirus disease 2019 (COVID-19). Thirty-two individuals (52 {+/-} 10 years; 17F) randomly assigned to exercise (N = 12) and control groups (N = 20), had their anthropometric (weight, body mass index), hemodynamic (brachial and central blood pressure), vascular (arterial stiffness), ventilatory (pulmonary function and respiratory muscle strength), and functional parameters (handgrip strength, five-time sit to stand [FTSTS], timed up and go test [TUG] and six-minute walking test [6MWT]) assessed at baseline (30 to 45 days of hospital discharged) and after 12 weeks of follow-up. Both groups similarly increased (P < 0.001) forced vital capacity (absolute and % of predicted), forced expiratory volume in the first second (absolute and % of predicted), and handgrip strength during follow-up. However, only exercise group reduced carotid-femoral pulse wave velocity (-2.0 {+/-} 0.6 m/s, P = 0.048), and increased (P < 0.05) resting oxygen saturation (1.9 {+/-} 0.6 %), mean inspiratory pressure (24.7 {+/-} 7.1 cmH2O), mean expiratory pressure (20.3 {+/-} 5.8 cmH2O) and % of predicted mean expiratory pressure (14 {+/-} 22 %) during follow-up. No significant changes were found in any other variable during follow-up. Present findings suggest that tele-supervised home-based exercise training can a potential adjunct therapeutic to rehabilitate individuals that were hospitalized due to COVID-19.

category: rehabilitation medicine and physical therapy


title: Supportive Mobility Across the Lifespan in Cerebral Palsy: A Modified Delphi Study to Establish Stakeholder Research Priorities

abstract:
AimThe overarching aim of this research was to 1) Understand the mobility experiences, supported mobility device (SMD) use, and desired participation outcomes of people with cerebral palsy (CP) across the lifespan; and 2) Describe how perspectives of rehabilitation care and professional resources may influence mobility decision-making processes and outcomes. The aim of this study was to co-develop research priorities and identify meaningful research questions with a diverse group of stakeholders representing the CP community for implementation in subsequent research activities.

MethodsA modified, three-round Delphi consensus study was conducted with a stakeholder advisory panel consisting of three adults with CP, two parents of children with CP, and four SMD providers.

ResultsThe advisory panel identified 13 unique topical categories focused on SMD selection and use, stratified by age group and stakeholder role. Questions or statements within each category were ranked, and top consensus and concordance statements were retained, reviewed, and refined for use in a co-developed focus group guide.

InterpretationA modified Delphi process was a useful tool for stakeholders in co-developing research priorities related to SMD use across the lifespan. Drawing on the lived expertise of stakeholders is important in facilitating improved research translation in the CP community.

What this Paper AddsO_LINine stakeholders from the CP community participated as Stakeholder Advisory Panelists and co-developers of research tools
C_LIO_LIStakeholders identified 175 unique responses across 12 SMD related categories
C_LIO_LIStakeholders prioritized 38 mobility technology research priorities during consensus-building
C_LIO_LIResults from consensus-building will be directly implemented into a qualitative focus group protocol
C_LI


title: A machine learning approach to identifying important features for achieving step thresholds in individuals with chronic stroke

abstract:
BackgroundWhile many factors are associated with stepping activity after stroke, there is significant variability across studies. One potential reason for this variability is that there are some characteristics necessary to achieve greater stepping activity that differ from others that may need to be targeted to improve stepping activity.

ObjectiveUsing two step thresholds (2500 steps/day, corresponding to home vs. community ambulation and 5500 steps/day, corresponding to achieving physical activity guidelines through walking), we applied 3 different algorithms to determine which predictors are most important to achieve these thresholds.

MethodsWe analyzed data from 268 participants with stroke that included 25 demographic, performance-based and self-report variables. Step 1 of our analysis involved dimensionality reduction using lasso regularization. Step 2 applied drop column feature importance to compute the mean importance of each variable. We then assessed which predictors were important to all 3 mathematically unique algorithms.

ResultsThe number of relevant predictors was reduced from 25 to 7 for home vs. community and from 25 to 16 for aerobic thresholds. Drop column feature importance revealed that 6 Minute Walk Test and speed modulation were the only variables found to be important to all 3 algorithms (primary characteristics) for each respective threshold. Other variables related to readiness to change activity behavior and physical health, among others, were found to be important to one or two algorithms (ancillary characteristics).

ConclusionsAddressing physical capacity is necessary but not sufficient to achieve important step thresholds, as ancillary characteristics, such as readiness to change activity behavior and physical health may also need to be targeted. This delineation may explain heterogeneity across studies examining predictors of stepping activity in stroke.


title: Genetic risk factors have a substantial impact on healthy life years

abstract:
The impact of genetic variation on overall disease burden has not been comprehensively evaluated. Here we introduce an approach to estimate the effect of different types of genetic risk factors on disease burden quantified through disability-adjusted life years (DALYs, "lost healthy life years"). We use genetic information from 735,748 individuals with registry-based follow-up of up to 48 years. At the individual level, rare variants had higher effects on DALYs than common variants, while common variants were more relevant for population-level disease burden. Among common variants, rs3798220 (LPA) had the strongest effect, with 1.18 DALYs attributable to carrying 1 vs 0 copies of the minor allele. Belonging to top 10% vs bottom 90% of a polygenic score for multisite chronic pain had an effect of 3.63 DALYs. Carrying a deleterious rare variant in LDLR, MYBPC3, or BRCA1/2 had an effect of around 4.1-13.1 DALYs. The population-level disease burden attributable to some common variants is comparable to the burden from modifiable risk factors such as high sodium intake and low physical activity. Genetic risk factors can explain a sizeable number of healthy life years lost both at the individual and population level, highlighting the importance of incorporating genetic information into public health efforts.

Results of the study can be explored at: https://dsge-lab.shinyapps.io/daly_genetics/

category: genetic and genomic medicine


title: Large Registry Based Analysis of Genetic Predisposition to Tuberculosis Identifies Genetic Risk Factors at HLA

abstract: Tuberculosis is a significant public health concern resulting in the death of over 1 million individuals each year worldwide. While treatment options and vaccines exist, a substantial number of infections still remain untreated or are caused by treatment resistant strains. Therefore, it is important to identify mechanisms that contribute to risk and prognosis of tuberculosis as this may provide tools to understand disease mechanisms and provide novel treatment options for those with severe infection. Our goal was to identify genetic risk factors that contribute to the risk of tuberculosis and to understand biological mechanisms and causality behind the risk of tuberculosis. A total of 1,895 individuals in the FinnGen study had ICD-based tuberculosis diagnosis. GWAS analysis identified genetic variants with statistically significant association with tuberculosis at the Human leukocyte antigen (HLA) region (p<5e-8) and at rs560595454 in gene INPP5A. Fine mapping the HLA-association provided evidence for one protective haplotype tagged by HLA DQB1*05:01 (p=1.82E-06, OR = 0.81 [CI 95 % 0.74-0.88]), and predisposing alleles tagged by HLA DRB1*13:02 (p=0.00011, OR = 1.35 [CI 95% 1.16-1.57]). Furthermore, genetic correlation analysis showed association with earlier reported risk factors including smoking (p<0.05). Mendelian randomization supported smoking as a risk factor for tuberculosis (inverse-variance weighted p<0.05, OR = 1.83 [CI 95 % 1.15-2.93]) with no significant evidence of pleiotropy. Our findings indicate that specific HLA alleles and INPP5A associate with the risk of tuberculosis. In addition, lifestyle risk factors such as smoking contribute to the risk of developing tuberculosis.


title: How dangerous is omicron and how effective are vaccinations?

abstract: The sharp increase in the number of new COVID-19 cases in late 2021 and early 2022, which is associated with the spread of a new strain of coronavirus - omicron - is of great concern and makes it necessary to make at least approximate forecasts for the pandemic dynamics of the epidemic. As this rapid growth occurs even in countries with high levels of vaccinations, the question arises as to their effectiveness. The smoothed daily number of new cases and deaths per capita and the ratio of these characteristics were used to reveal the appearance of new coronavirus strains and to estimate the effectiveness of quarantine, testing and vaccination. The third year of the pandemic allowed us to compare the pandemic dynamics in the period from September 2020 to January 2021 with the same period one year later for Ukraine, EU, the UK, USA, India, Brazil, South Africa, Argentina, Australia, and in the whole world. Record numbers of new cases registered in late 2021 and early 2022 once again proved that existing vaccines cannot prevent new infections, and vaccinated people can spread the infection as intensively as non-vaccinated ones. Fortunately, the daily number of new cases already diminishes in EU, the UK, USA, South Africa, and Australia. In late January - early February 2022,the maximum averaged numbers of new cases are expected in Brazil, India, EU, and worldwide. "Omicron" waves can increase the numbers of deaths per capita, but in highly vaccinated countries, the deaths per case ratio significantly decreases.


title: C-reactive protein guided use of procalcitonin in COVID-19

abstract: Low procalcitonin (PCT) concentrations (<0.5ng/mL) can facilitate exclusion of bacterial co-infection in viral infections, including COVID-19. However, costs associated with PCT measurement preclude universal adoption, indicating a need to identify settings where PCT provides clinical information beyond that offered by other inflammatory markers, such as C-reactive protein (CRP) and white cell count (WCC). In an unselected cohort of 299 COVID-19 patients, we tested the hypothesis that PCT<0.5ng/mL was associated with lower levels of CRP and WCC. We demonstrated that CRP values below the geometric mean of the entire patient population had a negative predictive value for PCT<0.5ng/mL of 97.6% and 100% at baseline and 48 hours into admission respectively, and that this relationship was not confounded by intensive care admission or microbiological findings. CRP-guided PCT testing algorithms can reduce costs and support antimicrobial stewardship strategies in COVID-19.


title: ImplemeNting SARS-CoV-2 Rapid antigen testing in the Emergency wArd of a Swiss univErsity hospital: the INCREASE study

abstract:
BackgroundWhile facing a second wave in SARS-CoV-2 pandemic, in November 2020 the Swiss Federal Office of Public Health (FOPH) authorized the use of rapid antigen tests (RATs) in addition to the gold-standard reverse transcription-polymerase chain reaction (RT-PCR).

MethodsWe implemented the use of RAT in the emergency ward of our university hospital for rapid patients triaging and compared performances of four different antigen tests. All results were compared to SARS-CoV-2 specific RT-PCR (reference standard).

ResultsTriaging patients using RAT in association with RT-PCR allowed us to isolate promptly positive patients and to save resources, in a context of rapid RT-PCR reagents shortage. Among 532 patients with valid results, overall sensitivities were 48.3% for One Step Exdia and 41.2% for Standard Q(R), Panbio-and BD Veritor. All four antigen tests exhibited specificity above 99%. Sensitivity increased up to 74.6%, 66.2%, 66.2% and 64.8% for One Step Exdia, Standard Q, Panbio, and BD Veritor respectively, when considering viral loads above 105copies/ml, up to 100%, 97.8%, 96.6% and 95.6% for viral loads above 106 copies/ml and 100% (for all tests) when considering viral loads above 107 copies/ml. Sensitivity was significantly higher for patients presenting with symptoms onset within 4 days (74.3%, 69.2%, 69.2% and 64%, respectively) versus patients with evolution of symptoms for more than 4 days (36.8%, 21.1%, 21.1% and 23.7%, respectively). Sensitivities of all RAT assays were of only 33% among hospitalized patients without COVID-19 symptoms.

ConclusionRAT might represent a useful epidemiological resource in selected clinical settings as a complementary tool to the molecular tests for rapid patients triaging, but the lower sensitivity compared to RT-PCR, especially in late presenters and subjects without COVID-19 symptoms, must be taken into account in order to correctly use RAT for triaging.


title: SARS-CoV-2 re-infection risk in Austria

abstract:
Background: A key question concerning coronavirus disease 2019 (COVID-19) is how effective and long lasting immunity against this disease is in individuals who were previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the risk of SARS-CoV-2 re-infections in the general population in Austria.

Methods This is a retrospective observational study using national SARS-CoV-2 infection data from the Austrian epidemiological reporting system. As the primary outcome, we aim to compare the odds of SARS-CoV-2 re-infections of COVID-19 survivors of the first wave (February to April 30, 2020) versus the odds of first infections in the remainder general population by tracking polymerase chain reaction (PCR)-confirmed infections of both groups during the second wave from September 1 to November 30, 2020. Re-infection counts are tentative, since it cannot be excluded that the positive PCR in the first and/or second wave might have been a false positive.

Results We recorded 40 tentative re-infections in 14,840 COVID-19 survivors of the first wave (0.27%) and 253,581 infections in 8,885,640 individuals of the remaining general population (2.85%) translating into an odds ratio (95% confidence interval) of 0.09 (0.07 to 0.13).

Conclusions We observed a relatively low re-infection rate of SARS-CoV-2 in Austria. Protection against SARS-CoV-2 after natural infection is comparable to the highest available estimates on vaccine efficacies. Further well-designed research on this issue is urgently needed for improving evidence-based decisions on public health measures and vaccination strategies.


title: Anti-SARS-CoV-2 seropositivity among medical students in Copenhagen

abstract:
Background Healthcare workers are at a higher risk of getting infected with SARS-CoV-2 than the general population. However, detailed knowledge about medical students and exposure to SARS-CoV-2 is lacking. Thus, we measured the prevalence of SARS-CoV-2 antibodies in a cohort of Danish medical students.

Methods We invited all medical students at the University of Copenhagen (UCPH) to participate. A venous blood sample was drawn along with completing a self-report questionnaire. Blood samples were analyzed for total antibodies to SARS-CoV-2 and related to symptomatology, social behaviour, and work-life. Seropositive samples were screened for IgM, IgG, and IgA antibodies.

Results Between October 19th and 26th 1,120 students participated in questionnaire, of these 1,096 were included in the study. Of all included 379 (34.58%) of the participants were seropositive. The risk of seropositivity was significantly increased for participants attending two parties at UCPH, on February the 29th and March 6th 2020 (OR 5.96 (95% CI 4.34-8.24, p<0.001). Further, 461 students (42.06%) worked with COVID-19 patients, which was significantly associated with risk of seropositivity (OR 1.38, 95% CI 1.03-1.85, p=0.033). The symptom most substantially associated with seropositivity was loss of smell and/or taste (n=183 of all, 31.35%) with an OR of 24.48 (95% CI 15.49-40.60, p<0.001).

Conclusion Medical students have the highest reported seropositivity in the Danish healthcare system. The risk of SARS-CoV-2 transmission amongst the students appear to be partly related to working with COVID-19 infected patients, but to a greater extent, their social behaviour.

Mainpoints Medical students have the highest reported seropositivity in the Danish healthcare system. The risk of SARS-CoV-2 transmission amongst the students appear to be partly related to working with COVID-19 infected patients, but to a greater extent, their social behaviour.


title: Associations between measures of social distancing and SARS-CoV-2 seropositivity: a nationwide population-based study in the Netherlands

abstract: This large nationwide population-based seroepidemiological study provides evidence on the effectiveness of physical distancing (>1.5m) and indoor group size reductions on SARS-CoV-2 infection. Additionally, young adults seem to play a significant role in viral spread, opposed to children up until the primary school age with whom close contact is permitted.


title: Performance characteristics of five antigen-detecting rapid diagnostic test (Ag-RDT) for SARS-CoV-2 asymptomatic infection: a head-to-head benchmark comparison

abstract:
Background Mass testing for early identification and isolation of infectious COVID-19 individuals, irrespective of concurrent symptoms, is an efficacious strategy to reduce disease transmission. Antigen-detecting rapid diagnostic tests (Ag-RDT) appear as a potentially suitable tool for mass testing on account of their ease-of-use, fast turnaround time, and low cost. However, benchmark comparisons are scarce, particularly in the context of unexposed asymptomatic individuals.

Methods We used nasopharyngeal specimens from unexposed asymptomatic individuals to assess five Ag-RDTs: PanBio™ COVID-19 Ag Rapid test (Abbott), CLINITEST® Rapid COVID-19 Antigen Test (Siemens), SARS-CoV-2 Rapid Antigen Test (Roche Diagnostics), SARS-CoV-2 Antigen Rapid Test Kit (Lepu Medical), and COVID-19 Coronavirus Rapid Antigen Test Cassette (Surescreen). Samples were collected between December 2020-January 2021 during the third wave of the epidemic in Spain.

Findings The analysis included 101 specimens with confirmed positive PCR results and 185 with negative PCR. For the overall sample, the performance parameters of Ag-RDTs were as follows: Abbott assay, sensitivity 38·6% (95% CI 29·1–48·8) and specificity 99·5% (97–100%); Siemens, sensitivity 51·5% (41·3–61·6) and specificity 98·4% (95·3–99·6); Roche, sensitivity 43·6% (33·7–53·8) and specificity 96·2% (92·4–98·5); Lepu, sensitivity 45·5% (35·6–55·8) and specificity 89·2% (83·8–93·3%); Surescreen, sensitivity 28·8% (20·2–38·6) and specificity 97·8% (94·5–99·4%). For specimens with cycle threshold (Ct) <30 in RT-qPCR, all Ag-RDT achieved a sensitivity of at least 70%, with Siemens, Roche, and Lepu assays showing sensitivities higher than 80%. In models according to population prevalence, all Ag-RDTs will have a NPV >99% and a PPV<50% at 1% prevalence.

Interpretation Two commercial, widely available assays can be used for SARS-CoV-2 antigen testing to achieve sensitivity in specimens with a Ct<30 and specificity of at least 80% and 96%, respectively. Estimated negative and positive predictive values suggests the suitability of Ag-RDTs for mass screenings of SARS-CoV-2 infection in the general population.

Funding Blueberry diagnostics, Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, and #YoMeCorono.org crowdfunding campaign.

Evidence before this study In December 2020, we searched on PubMed for articles containing the terms “antigen”, “test” (or Ag-RDT), and “SARS-CoV-2” or “COVID-19” either in the title or the abstract. Our search yielded 79 entries corresponding to articles written in English. Of them, 33 were articles presenting the diagnostic performance of qualitative lateral-flow antigen-detecting rapid diagnostic tests (Ag-RDT). Four of these articles reported the results of head-to-head comparisons of various Ag-RDTs; in all cases, the number of tests was lower than the recommended for retrospective assessments of diagnostic performance (i.e., minimum of 100 PCR positive and 100 PCR negative). Furthermore, all head-to-head comparisons found in the literature included specimens obtained among individuals with varying disease status (none of which asymptomatic), thus limiting the adequacy of the estimates for an asymptomatic screening strategy.

Added value of this study We compared for the first time head-to-head five Ag-RDT using a powered set of fresh respiratory specimens PCR-confirmed positive or negative, collected from unexposed asymptomatic individuals during screening campaigns for early detection of SARS-CoV-2 infection. The sample size was large enough to draw robust conclusions. Our analysis identified four Ag-RDTs (i.e., assays marketed by Abbott, Siemens, Roche, and Surescreen) with specificity higher than 96%. Despite the low sensitivity for the overall sample (range 29% to 51%), the corresponding values for the subset of samples with Ct <30 were higher than 80% for Siemens, Roche, and Lepu assays. The estimated NPV for a screening performed in an area with 1% prevalence would be >99% for all tests, while the PPV would be <50%.

Implications of all the available evidence Current data on the diagnostic performance of Ag-RDTs is heterogeneous and precludes benchmark assessments. Furthermore, the screening of asymptomatic populations is currently not considered among the intended uses of Ag-RDT, mostly because of lack of evidence on test performance in samples from unexposed asymptomatic individuals. Our findings add to the current evidence in two ways: first, we provide benchmarking data on Ag-RDTs, assessed head-to-head in a single set of respiratory specimens; second, we provide data on the diagnostic performance of Ag-RDTs in unexposed asymptomatic individuals. Our findings support the idea that Ag-RDTs can be used for mass screening in low prevalence settings and accurately rule out a highly infectious case in such setting.


title: Effectiveness of a SARS-CoV-2 mRNA vaccine booster dose for prevention of infection, hospitalization or death in two nation-wide nursing home systems

abstract:
BackgroundA SARS-CoV-2 vaccine booster dose has been recommended for all nursing home residents. However, we lack effectiveness data on boosters preventing infection, death and hospitalization in this frail population.

MethodsWe emulated nested target trials in two large nursing home systems in parallel to evaluate the effectiveness of a SARS-CoV-2 mRNA vaccine booster at preventing infection, hospitalization, or death. Residents who completed a 2-dose series of the mRNA vaccine and were eligible for a booster were included in from September 22, 2021 to November 5, 2021. Outcomes were measured through December 18, 2021, including test-confirmed SARS-CoV-2 infection, hospitalization, or death. The vaccine effectiveness at day 42 was estimated with a Kaplan-Meier estimator, both unadjusted and weighted with the inverse probability of treatment.

ResultsThe two NH systems were large and multi-state, System 1 included 200 NH (8,538 control and 5,721 boosted residents) and System 2 included 127 NHs (4,100 control and 2,291 boosted residents). Booster vaccination reduced infections by 50.4% (95% Confidence Interval [CI]: 29.4%, 64.7%) SARS-CoV-2 infections in System 1 and 58.2% (32.3%, 77.8%) in System 2. Boosted residents in System 1 also had a 97.3% (86.9%, 100.0%) reduction in SARS-CoV-2 associated death, but too few events for comparison in System 2.

ConclusionsDuring a Delta predominant period, SARS-CoV-2 booster vaccination significantly reduced infection in two U.S. nursing home systems. In the larger System 1 a 97% reduction in SARS-CoV-2 related death was also observed. These findings strongly support administration of vaccine boosters to nursing home residents.


title: Clinical experience with paliperidone palmitate in a specialty hospital in the Philippines: A short report

abstract:
ObjectiveTo describe the clinical outcomes related to the introduction of paliperidone palmitate in a specialty hospital in the Philippines

DesignCross-sectional study among patients seen at the psychiatry service of a specialty hospital catering to veterans who were initiated on paliperidone palmitate. We reviewed and abstracted baseline patient data from the medical record of eligible patients. Outcome of treatment was collected through a one-time objective assessment of the patient by a third-party psychiatrist using the Structured Clinical Interview for Symptoms of Remission (SCI-SR) tool.

Main ResultA total of 30 patients were recruited for the study from August 2020 and June 2021, the majority of whom were males (80%), residents of the National Capital Region (50%), and single (20%). The median duration from schizophrenia diagnosis to initiation of paliperidone treatment was 19.50 years (IQR: 16.60 - 33.50). In eight patients (22.67%), other antipsychotic drugs were discontinued following initiation of paliperidone treatment; in the remaining 22 participants (73.33%), paliperidone was taken concurrently with other antipsychotic drugs. The median duration from the initiation of paliperidone treatment to follow-up assessment was 27.20 months (IQR: 24.73 - 30.50), with all participants having at least 6 months of treatment. At follow-up assessment, all participants were classified to be in remission.

ConclusionIn this study among patients with schizophrenia seen in a specialty hospital in the Philippines, we found evidence that clinical outcomes with paliperidone palmitate were comparable to those given a combination of oral and long-acting antipsychotics.


title: Frequency of neutropenia over time in patients on clozapine

abstract:
BackgroundClozapine, the only evidence-based drug for treatment-resistant schizophrenia is associated with agranulocytosis. For this reason, all clozapine patients are required to undergo mandatory regular blood monitoring throughout their clozapine treatment. The blood test results are reported using a traffic light system. The clozapine treatment is stopped immediately after a confirmed red result, which is the indication for risk of agranulocytosis. The need for blood tests places a burden on patients and acts as a barrier to clozapine treatment. There is growing evidence that the risk of agranulocytosis falls steeply after the first few months of treatment, raising the possibility that clozapine monitoring could be discontinued after a certain period of treatment.

AimTo investigate the frequency density of the confirmed red results from clozapine monitoring across clozapine treatment.

MethodBy merging electronic health records (EHR) data with clozapine blood monitoring data, we identified the clozapine treatment dates. The EHR data was from South London and Maudsley NHS Foundation Trust (SLAM). The clozapine blood monitoring data was from Zaponex Treatment Access System (ZTAS). ZTAS is one of the mandatory blood monitoring service providers in the United Kingdom. From these data, Kaplan-Meier survival curve was fitted to determine the time to get confirmed red results. At fixed points in the treatment, the future risk of obtaining a red result were calculated.

ResultsBy merging over 301,000 data points that came from the blood monitoring results and EHR data of 1,362 patients, we identified 1,891 clozapine treatment periods. Of these, 75 treatments were stopped due to confirmed red results. The Kaplan-Meier survival curve and the incidence rates data showed that 56 (74.7%) confirmed red results occur within the first 6 months of clozapine treatment.

ConclusionWe found a contrast between the relatively high density of the confirmed red results at the beginning of clozapine treatment which significantly reduces after 6 months of treatment which remained low thereafter.


title: Positive attribute framing increases COVID-19 booster vaccine intention for unfamiliar vaccines

abstract: Positive framing has been proposed as a potential intervention to increase COVID-19 vaccination intentions. However, most available research has examined fictitious or unfamiliar treatments. This pre-registered study compared positively and negatively attribute-framed side effect information for real COVID-19 booster vaccines (AstraZeneca, Pfizer, Moderna) and measured booster intentions pre- and post-intervention in 1,222 UK-based participants. As hypothesised, vaccine familiarity significantly modulated the effect of framing. While positive framing was effective for the least familiar vaccine (i.e., Moderna), standard negative framing appeared to increase intentions for familiar vaccines (AstraZeneca/Pfizer), particularly among those with low baseline intentions. These findings provide important new evidence that positive framing could improve vaccine uptake globally when switches or new developments require individuals to receive less familiar vaccines - as is currently the case for millions of booster vaccines across the world. Positive framing of familiar vaccines, however, should be treated with caution.


title: Critical success factors for high routine immunization performance: A case study of Senegal

abstract:
BACKGROUNDThe essential components of a vaccine delivery system are well-documented, but robust evidence is lacking on how policies and implementation strategies are operationalized to drive catalytic improvements in coverage. To address this gap, we identified success factors that supported improvements in routine immunization coverage in Senegal, especially from 2000 to 2019.

METHODSWe identified Senegal as an exemplar in the delivery of childhood vaccines through analysis of DTP1 and DTP3 coverage data. Through interviews and focus group discussions at the national, regional, district, health facility, and community-level, we investigated factors that contributed to high and sustained vaccination coverage. We conducted a thematic analysis through application of implementation science frameworks to determine critical success factors. We triangulated these findings with quantitative analyses using publicly available data.

RESULTSThe following success factors emerged: 1) Strong political will and prioritization of resources for immunization programming supported urgent allocation of funding and supplies; 2) Collaboration between the Ministry of Health and Social Action and external partners fostered innovation, capacity building, and efficiency; 3) Improved surveillance, monitoring, and evaluation allowed for timely and evidence-based decision making; 4) Community ownership of vaccine service delivery supported tailored programming and quick response to local needs; and 5) Community health workers spearheaded vaccine promotion and demand generation for vaccines.

CONCLUSIONThe vaccination program in Senegal was supported by evidence-based decision making at the national-level, alignment of priorities between governmental entities and external partners, and strong community engagement initiatives that fostered local ownership of vaccine delivery and uptake. High routine immunization coverage was likely driven by prioritization of immunization programming, improved surveillance systems, a mature and reliable community health worker program, and tailored strategies for addressing geographical, social, and cultural barriers.


title: A Symbolic Regression Approach to Hepatocellular Carcinoma Diagnosis Using Hypermethylated CpG Islands in Circulating Cell-Free DNA

abstract:
PurposeHepatocellular carcinoma is the most common primary liver cancer, accounting for 90% of cases, and a major cause of death worldwide. Despite this, alpha-fetoprotein tests are the only blood-based diagnostic tools available, and their use is limited by their low sensitivity. DNA methylation changes, which have been implicated in a majority of cancers, offer an alternative method of diagnosis through measuring such changes in circulating cell-free DNA present in blood plasma.

MethodA genetic programming-based symbolic regression approach was applied to gain the benefits of machine learning while avoiding the opacity drawbacks of "black box" models. The data included plasma samples from 36 patients with hepatocellular carcinoma as well as a control group of 55 that contained patients with and without cirrhosis. A 75-25 train-test splitting was done before training.

ResultsThe symbolic regression methodology developed an equation utilizing the methylation levels of three biomarkers, with an accuracy of 91.3%, a sensitivity of 100%, and a specificity of 87.5% on the test data. The performance matches prior research while providing the added benefits of transparency.

ConclusionCirculating cell-free DNA presents opportunities for minimally invasive early diagnosis of hepatocellular carcinoma, and utilizing transparent machine learning approaches like symbolic regression can allow accurate diagnosis by combining biological and mathematical principles. Future validation of the model obtained here on a larger and more diverse dataset can reveal the potential for such approaches in cancer diagnosis and pave the way for further research.

category: oncology


title: Acceptability and preliminary effectiveness of a remote dementia educational training among healthcare professionals

abstract:
BackgroundOptimal care for families living with Alzheimers disease and related disorders (ADRD) has the potential to improve their lives. However, ADRD care remains under-implemented among healthcare professionals, partly due to professionals limited ADRD training and inexperience. Professional training might help, but most training is in person, time-intensive, and does not focus on the potential of early detection, client empowerment, and cultural competency. We aimed to explore the acceptability and preliminary effectiveness of an online ADRD training, The Dementia Update Course, which addressed these issues. We hypothesized that the Dementia Update Course would lead to increased levels of perceived ADRD care competency among healthcare professionals.

MethodsThis was a mixed-methods research design using pre-post training assessments. The training included 59 primary care providers (PCPs) and other healthcare professionals (e.g., medical specialists, nurses, social workers). The Dementia Update Course was a remote 6.5-hour training that included didactic lectures, case discussion techniques, and materials on ADRD detection and care. Outcomes included two 5-point Likert scales on acceptability, eleven on perceived dementia care competency, and the three subscales of the General Practitioners Confidence and Attitude Scale for Dementia. We used paired samples t-tests to assess the mean differences in all preliminary effectiveness outcomes.

ResultsThe training included 18.0% of professionals that self-identified as non-White or Latino and 37.7% of professionals who served in rural areas. Most participants (90.0% and 87.5%) reported a high likelihood to recommend the training and high satisfaction respectively. All preliminary effectiveness outcomes analyzed in the total sample experienced a statistically significant improvement from pre- to post-training averaging 0.7 points in 1-5 scales (p<0.05). Most outcomes improved statistically among PCPs too.

ConclusionsA relatively brief, remote, and inclusive ADRD training led to high levels of acceptability and improved perceived ADRD care competency among PCPs and other healthcare professionals. Future research should include a control group and assess guideline compliance, behavioral outcomes, and health outcomes among people with ADRD and their families.

category: geriatric medicine


title: SARS-CoV-2 seroprevalence in children, parents and school personnel from June 2020 to April 2021: cohort study of 55 schools in Switzerland

abstract: We measured SARS-CoV-2 seroprevalence in cohorts of children, parents and school personnel in 55 randomly selected schools in the canton of Zurich, Switzerland. In June-September 2020, seroprevalence was low (4.4% to 5.8%) in all cohorts. In March-April 2021, seroprevalence in children and parents (18.1% and 20.9%) was slightly higher than in school personnel (16.9%). Childrens seroprevalence was slightly higher in classes with infected main teachers and families with one infected parent, and substantially higher in families with two infected parents.


title: A longitudinal seroconversion panel shows anti-SARS-CoV-2 antibody levels up to 6.5 months after vaccination with mRNA-1273 (Moderna)

abstract:
BackgroundVaccines have emerged as a crucial tool in combatting the COVID-19 pandemic particularly those based on SARS-CoV-2 S-protein mRNA. A crucial aspect of vaccine efficacy is the duration of antibody responses. In this study, a seroconversion panel was created to assess antibody responses to the mRNA-1273 vaccine over time (6.5 months).

MethodsBlood samples collected from 15 healthy adult participants prior to and up to 6.5 months after vaccination with the mRNA-1273 vaccine (Moderna). Serum from these blood samples were analyzed for anti-SARS-CoV-2 antibody activity by chemiluminescent immunoassay.

ResultsThe immunoassay results showed that one participant was positive for anti-SARS-CoV- 2 antibodies prior to vaccination indicating a prior infection. All participants showed a positive antibody response after the first vaccination. Highest antibody responses were seen after the second dose (41-45 days from the first dose). Subsequent samples collected at 69-75 days, 130-135 days and 221-229 days after the first vaccination showed positive responses but declining levels of anti-SARS-CoV-2 antibodies.

ConclusionsDeclining antibody levels in these participants support the use of booster vaccination to increase antibody levels 4-6 months after the initial vaccine series and continued monitoring to assess the durability of COVID-19 vaccine responses. These results are in agreement with other studies showing antibody persistence but declining the antibody levels in the months after immunization with mRNA-based vaccines.


title: Is mandatory vaccination in population over 60 adequate to control the COVID-19 pandemic in E.U.?

abstract: Vaccine hesitancy, which potentially leads to refusal or delayed acceptance of COVID-19 vaccines, is considered a key driver for the increasing death toll from the pandemic in the E.U.. European Commission and several member states governments are either planning or have already directly or indirectly announced mandatory vaccination for individuals aged over 60, the group repeatedly proved to be the most vulnerable. In this paper, an assessment of this strategy benefits is attempted. This is done by examining the reduction of Standard Expected Years of Life Lost (SEYLL) per person of the EU population over 60 as a function of their vaccination percentage. Publicly available data and some first results of the second iteration of the SHARE COVID-19 survey conducted during the summer of 2021 on acceptance of COVID-19 vaccines are used as input.


title: Covaxin (BBV152) Vaccine Neutralizes SARS-CoV-2 Delta and Omicron variants

abstract: The SARS-CoV-2 vaccine BBV152/Covaxin is well-tolerated and was shown to be 77.8% efficacious against symptomatic and 93.4% efficacious against severe symptomatic COVID-19 disease in adults. Previous studies have shown that sera from Covaxin vaccinated individuals have neutralizing activity against B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), B.1.1.28 (Zeta), and B.1.617.1 (Kappa) SARS-CoV-2 variants. The B.1.1.529 variant (Omicron) recently emerged in November 2021 and has spread throughout the world. The Omicron variant has more than 30 mutations within the spike protein that could impact vaccine-mediated immunity. We used a live virus neutralization assay to evaluate the neutralizing activity against the Omicron variant of sera collected from subjects who received a booster dose (6-month after primary series last dose) of Covaxin. We found that sera from Covaxin boosted individuals showed neutralizing activity against D614G (vaccine strain), Delta, and Omicron variants. One hundred percent of boosted subjects showed neutralizing activity against the Delta variant while over 90% of boosted subjects showed neutralizing activity against the Omicron variant. These findings show that a booster dose of Covaxin can generate robust neutralizing antibody responses against the Omicron variant.


title: Foodborne Outbreaks, Product Recalls, and Firm Learning: A Recurrent Event Survival Analysis of U.S. Meat and Poultry Recalls

abstract: Firms in the food industry may experience more than one contamination incident over time. In a food safety context, increasing the time between foodborne outbreaks represents a key objective for the food industry and public health officials. We evaluate factors that influence time to next recall for food firms and, more importantly, identify the extent of firm learning from previous food safety incidents in the context of increased time to next recall. Using a recurrent event survival analysis framework, we examine repeated recall data of meat/poultry products in the United States for the period 1994-2015. Our findings indicate more diversified firms incur a smaller risk of repeat recall as firm size expands compared to firms producing primarily meat/poultry products. The hazard of a recall incident decreases with the quantity of meat/poultry recalled in the past recall. The risk of a future recall is smaller for firms whose previous recall was of Class I, the most severe class of recalls, compared to those whose past recall was of Class II. Some evidence of firm learning is found, but there is no definitive evidence indicating that a firms ability to prevent recalls grows with the number of foodborne outbreaks it has experienced.


title: Exploring human mixing patterns based on time use and social contact data and their implications for infectious disease transmission models

abstract:
BackgroundThe increasing availability of data on social contact patterns and time use provides invaluable information for studying transmission dynamics of infectious diseases. Social contact data provide information on the interaction of people in a population whereas the value of time use data lies in the quantification of exposure patterns. Both have been used as proxies for transmission risks within in a population and the combination of both sources has led to investigate which kind of social encounters are most relevant to describe transmission risk.

MethodsWe used social contact and time use data from 1707 participants from a survey conducted in Flanders, Belgium in 2010-2011. We calculated weighted exposure time and social contact matrices to analyze age- and gender-specific mixing patterns and to quantify behavioral changes by distance from home. We compared the value of both data sources, individually and combined, for explaining seroprevalence and incidence data on parvovirus-B19, Varicella-Zoster virus (VZV) and influenza-like illnesses (ILI), respectively.

ResultsAssortative mixing and inter-generational interaction is more pronounced in the exposure matrix due to the high proportion of time spent at home. This pattern is less pronounced in the social contact matrix, which is more impacted by the reported contacts at school and work. The average number of contacts declined with distance, however on the individual-level, we observed an increase in the number of contacts and the transmission potential by distance when travelling.

We found that both social contact data and time use data provide a good match with the seroprevalence and incidence data at hand. When comparing the use of different combinations of both data sources, we found that the social contact matrix based on close contacts of at least 4 hours appeared to be the best proxy for parvovirus-B19 transmission. Social contacts and exposure time were both on their own able to explain VZV seroprevalence data though combining both scored best. Compared with the contact approach, the time use approach provided the better fit to the ILI incidence data.

ConclusionsOur work emphasises the common and complementary value of time use and social contact data for analysing mixing behavior and infectious disease transmission. We derived spatial, temporal, age-, gender- and distance-specific mixing patterns, which are informative for future modelling studies.


title: Automatic Identification of Tinnitus Malingering Based on Overt and Covert Behavioral Responses During Psychoacoustic Testing

abstract: Tinnitus, or ringing in the ears, is a prevalent condition that imposes a substantial health and financial burden on the patient and to society. The diagnosis of tinnitus, like pain, relies on patient self-report. Subjective self-report measures can complicate the distinction between actual and fraudulent claims and obscure accurate severity assessments. In this study, we combined tablet-based self-directed hearing assessments with neural network classifiers to objectively determine tinnitus severity, and to differentiate participants with tinnitus (N=24) from a malingering cohort, who were instructed to feign an imagined tinnitus percept (N=28). We identified clear differences between the groups, both in their overt rating of tinnitus severity but also covert differences in their fingertip movement trajectories on the tablet surface as they performed the reporting assay. Using only 10 minutes of data, we achieved 81% accuracy classifying patients vs malingerers (ROC AUC=0.88) with leave-one-participant-out cross validation. Objective measurements of tinnitus will improve estimates of tinnitus prevalence and help to prioritize and direct funds for tinnitus compensation.

category: otolaryngology


title: On health effects of resveratrol in wine. A bibliometric view based on papers having achieved a high citation impact within the scientific discourse

abstract: We analyzed 3344 publications that are concerned with the health-related effects of resveratrol that occurs in wine and grapes. We found that the publication activity increased until 2010 and decreased slightly afterwards. The most frequent author keywords were classified into six groups: (1) beverages-related keywords, (2) compounds-related keywords, (3) diseases-related keywords, (4) effects-related keywords, (5) mechanisms-related keywords, and (6) broader keywords. By means of reference publication year spectroscopy, we analyzed and discussed the most frequently cited references (i.e., key papers) within the publication set. A rather large portion of the key papers takes a positive attitude and reports about health effects of resveratrol, although limited data in humans preclude drawing unambiguous conclusions on the health-related benefits of resveratrol. From our analysis, we could not identify specific publications that provide a distinct change of direction of the ongoing scientific discourse. Moderate red wine consumption seems to have the potential of being health promoting, whereas excessive alcohol consumption can induce liver cirrhosis and cancer.

category: pharmacology and therapeutics


title: DNA methylation and general psychopathology in childhood: An epigenome-wide meta-analysis from the PACE consortium

abstract: The general psychopathology factor (GPF) has been proposed as a way to capture variance shared between psychiatric symptoms. Despite a growing body of evidence showing both genetic and environmental influences on GPF, the biological mechanisms underlying these influences remain unclear. In the current study, we conducted epigenome-wide meta-analyses to identify both probe- and region-level associations of DNA methylation (DNAm) with school-age general psychopathology in six cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. DNAm was examined both at birth (cord blood; prospective analysis) and during school-age (peripheral whole blood; cross-sectional analysis) in total samples of N=2,178 and N=2,190, respectively. At school-age, we identified one probe (cg11945228) located in the Bromodomain-containing protein 2 gene (BRD2) that negatively associated with GPF (p=8.58x10-8). We also identified a significant DMR at school-age (p=1.63x10-8), implicating the SHC Adaptor Protein 4 (SHC4) gene that has been previously implicated in multiple types of psychiatric disorders in adulthood, including obsessive compulsive disorder and major depressive disorder. In contrast, no prospective associations were identified with DNAm at birth. Taken together, results of this study revealed some evidence of an association between DNAm at school-age and GPF. Future research with larger samples is needed to further assess DNAm variation associated with GPF.


title: SARS-CoV-2 third vaccine immune response in MS patients treated with ocrelizumab

abstract: The introduction of a third dose vaccination along with new variants of concerns raises questions regarding serology and T-cell responses in patients with MS (pwMS) treated with B-cell depletion who develop attenuated humoral response to vaccines. The aim of this study is to longitudinally evaluate humoral and cellular response to SARS-CoV-2 mRNA vaccine in ocrelizumab-treated pwMS before and following third vaccine dose. Following the third vaccine dose, patients who are low or non-responders following initial vaccination did not increase antibody titers. In HCs and ocrelizumab-treated pwMS, cellular response decreased 6 months following initial vaccination and increased significantly after the third booster.

category: neurology


title: Validation of diagnostic nomograms based on CE-MS urinary biomarkers to distinguish clinically significant prostate cancer

abstract:
BackgroundProstate cancer (PCa) is the most common cancer and one of the leading causes of death worldwide. However, a significant proportion of PCa are low risk PCa which do not require an active treatment due to its low mortality rates. Thus, one major issue in PCa management is to accurately distinguish between indolent and clinically significant (cs) PCa to reduce overdiagnosis and overtreatment. In this study, we aim to validate the performance of diagnostic nomograms (DN) based on previously published urinary biomarkers for discriminating csPCa.

Patients and MethodsCapillary electrophoresis/ mass spectrometry has been employed to validate a published biomarker model based on 19 urinary peptides specific for csPCa. Added value of the 19-biomarker model (19-BM) was assessed in diagnostic nomograms including prostate specific antigen (PSA), PSA density and the risk calculator from The European Randomized Study of Screening for Prostate Cancer (ERSPC). For this purpose, urine samples from 147 PCa patients (including 80 low, 44 intermediate and 17 high risk patients) were collected prior to prostate biopsy. The 19-BM score was calculated via a support vector machine-based software based on the pre-defined cut-off criterion of -0.07. DNs were subsequently developed to assess added value of integrative diagnostics.

ResultsIndependent validation of the 19-BM resulted in 87% sensitivity and 65% specificity, with an AUC of 0.81, outperforming PSA (AUCPSA:0.64), PSA density (AUCPSAD: 0.64) and ERSPC-3/4 risk calculator (0.67). Integration of 19-BM with the other clinical variables into distinct DN, resulted in improved (AUC range: 0.82-0.88) but not significantly better performance compared to 19-BM alone.

Conclusions19-BM alone or combined with clinical variables into DN, demonstrated value for detecting csPCa, and decreasing the number of biopsies.


title: Phenome-wide association study of loci harboring de novo tandem repeat mutations in UK Biobank exomes

abstract:
BackgroundTandem repeats (TRs) are a major source of variation in the human genome under-investigated by large-scale genetic studies. When present in coding regions, TRs may have large effects on protein structure and function contributing to health and disease.

MethodsIn a family-based design of 39 European ancestry trios from the UK Biobank (UKB), the GangSTR and MonSTR methods were used to identify de novo TRs in whole-exome sequences. TRs were annotated for association with gene expression and gene set enrichment. The loci harboring de novo TRs were investigated in a phenome-wide association study in up to 148,607 unrelated UKB participants of European descent. Linear and logistic regression included age, sex, sexxage, age2, sexxage2, and ten within-ancestry principal components as covariates. TR loci were fine-mapped to identify likely causal associations.

ResultsThere were 427 mutated TRs with a trend towards expansions versus contractions ({chi}2=5.46, df=1, P=0.019). These TRs were enriched for targets of the tumor suppressor microRNA-184 (21.1-fold, P=4.30x10-5). There were 123 TR-phenotype associations with posterior probabilities>0.95. These were related to body structure, cognition, and cardiovascular, metabolic, psychiatric, and respiratory outcomes. The most significant was between NCOA6-[GT]N and "ease of skin tanning" (beta=0.069, se=0.003, P=1.51x10-155). There were several loci with large likely causal effects on tissue microstructure, including the association of FAN1-[TG]N with carotid intima-media thickness (mean thickness: beta=5.22, se=1.08, P=1.22x10-6; maximum thickness: beta=6.44, se=1.32, P=1.12x10-6.

ConclusionsCombined with the TR de novo mutational background characterized herein, TR-phenotype associations contribute clear and testable hypotheses of dose-dependent TR implications linking genetic variation and protein structure with health and disease outcomes.


title: A phenome-wide association study identifies effects of copy number variation of VNTRs and multicopy genes on multiple human traits

abstract: The human genome contains tens of thousands of large tandem repeats and hundreds of genes that show common and highly variable copy number changes. Due to their large size and repetitive nature, these Variable Number Tandem Repeats (VNTRs) and multicopy genes are generally recalcitrant to standard genotyping approaches, and as a result this class of variation is poorly characterized. However, several recent studies have demonstrated that copy number variation of VNTRs can modify local gene expression, epigenetics and human traits, indicating that many have a functional role. Here, using read depth from whole genome sequencing to profile copy number, we report results of a phenome-wide association study (PheWAS) of VNTRs and multicopy genes in a discovery cohort of [~]35,000 samples, identifying 32 traits associated with copy number of 38 VNTRs and multicopy genes at 1% FDR. We replicated many of these signals in an independent cohort, and observed that VNTRs showing trait associations were significantly enriched for expression QTLs with nearby genes, providing strong support for our results. Fine-mapping studies indicated that in the majority ([~]90%) of cases, the VNTR and multicopy genes we identified represent the causal variants underlying the observed associations. Furthermore, several lie in regions where prior SNV-based GWAS have failed to identify any significant associations with these traits. Our study indicates that copy number of VNTRs and multicopy genes contributes to diverse human traits, and suggests that complex structural variants potentially explain some of the so-called "missing heritability" of SNV-based GWAS.


title: Fifteen Days in December: Capture and Analysis of Omicron-Related Travel Restrictions

abstract:
Following the identification of the Omicron variant of the SARS-CoV-2 virus in late November 2021, governments worldwide took actions intended to minimize the impact of the new variant within their borders. Despite guidance from the World Health Organization advising a risk-based approach, many rapidly implemented stringent policies focused on travel restrictions. In this paper, we capture 221 national-level travel policies issued during the three weeks following publicization of the Omicron variant. We characterize policies based upon whether they target travelers from specific countries or focus more broadly on enhanced screening, and explore differences in approaches at the regional level. We find that initial reactions almost universally focused on entry bans and flight suspensions from Southern Africa, and that policies continued to target travel from these countries even after community transmission of the Omicron variant was detected elsewhere in the world. While layered testing and quarantine requirements were implemented by some countries later in this three-week period, these enhanced screening policies were rarely the first response. The timing and conditionality of quarantine and testing requirements were not coordinated between countries or regions, creating logistical complications and burdening travelers with costs. Overall, response measures were rarely tied to specific criteria or adapted to match the unique epidemiology of the new variant.

Summary boxO_LIDuring the initial three-week period following the discovery of the SARS-CoV-2 Omicron variant, nations rushed to implement travel restrictions - often at odds with guidance from the World Health Organization.
C_LIO_LIBy sourcing and cataloging initial national-level travel restrictions worldwide, we demonstrate how the distribution of entry bans, flight suspensions, quarantine measures, vaccination requirements, and testing protocols evolved in response to emerging information during a period of uncertainty.
C_LIO_LICountries that issued entry bans almost universally targeted the same Southern African countries and continued to do so even after widespread community transmission of the Omicron variant was reported elsewhere in the world.
C_LIO_LILayers of testing and quarantine requirements were added later during the observation period but were rarely the initial response, with the exception of restrictions issued by countries in Africa, where leading with enhanced screening measures was more common.
C_LIO_LIAnalysis of the disconnect between travel restrictions and transmission patterns that followed emergence of the Omicron variant provides a basis to inform evidence-based control measures for future virus mitigation efforts.
C_LI


title: Escherichia marmotae - a human pathogen easily misidentified as Escherichia coli

abstract: We hereby present the first descriptions of human invasive infections caused by Escherchia marmotae, a recently described species that encompasses the former "Escherichia cryptic clade V". We report four cases, one acute sepsis of unknown origin, one post-operative sepsis after cholecystectomy, one spondylodiscitis and one upper urinary tract infection. Cases were identified through unsystematic queries in a single clinical lab during six months. Through genome sequencing of the causative strains combined with available genomes from elsewhere we demonstrate E. marmotae to be a likely ubiquitous species containing genotypic virulence traits associated with Escherichia pathogenicity. The invasive isolates were scattered among isolates from a range of non-human sources, thus indicating inherent virulence in multiple phylogenetic lineages. Pan genome analyses indicate that E. marmotae has a large accessory genome and is likely to obtain ecologically advantageous traits like genes encoding antimicrobial resistance. Reliable identification might be possible by MALDI-ToF MS, but relevant spectra are missing in commercial databases. E. marmotae can be identified through 16S rRNA sequencing. Escherichia marmotae could represent a relatively common human pathogen and improved diagnostics will provide a better understanding of its clinical importance.


title: Comparison of total and neutralizing SARS-CoV-2 spike antibodies against omicron and other variants in paired samples after two or three doses of mRNA vaccine

abstract: Recognizing that anti-SARS-CoV-2 antibody levels wane over time following the 2-dose SARS-CoV-2 mRNA series, the FDA approved a booster dose for people greater than 12 years old. Limited data exist on whether a booster dose of the mRNA vaccine results in greater antibody protection than the primary series. We examined total and neutralizing antibodies to the spike protein of SARS-CoV-2, and neutralizing antibodies against Washington-1 (WA-1) and variants of concern (VOC) including Beta, Delta and Omicron in a longitudinal cohort. Healthcare workers (HWs) were included in the analysis if serum was collected 1) within 14-44 days post-dose2 of an mRNA SARS-CoV-2 vaccine (Timepoint 1, TP1), or 2) at least 8 months post-dose2 (Timepoint 2, TP2), or 3) within 14-44 days following mRNA booster (Timepoint 3, TP3). HWs with prior covid-positive PCR were excluded. We found that there is little to no neutralizing capability following a 2-dose mRNA vaccine series against the omicron variant, and neutralizing capacity to any variant strain tested has been lost by 8-months post two-dose vaccination series. However, the mRNA booster series eliminates the immune escape observed by the omicron variant with the two-dose series. Neutralizing titers were significantly higher for all variants post-boost compared to the titers post two-dose series. The longitudinal nature of our cohort facilitated the analysis of paired samples pre and post boost, showing a greater than 15-fold increase in neutralization against omicron post-boost in these paired samples. An mRNA booster dose provides greater quantity and quality of antibodies compared to a two-dose regimen and is critical to provide any protection against the omicron variant.


title: mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in patients with antibody deficiency syndromes

abstract: Patients with primary antibody deficiency syndromes (PAD) have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed PAD patients after SARS-CoV-2 vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fc{gamma}R binding, and neutralizing activities. Immunoglobulin replacement products had low anti-spike and receptor binding domain (RBD) titers and neutralizing activity. In COVID-19-naive PAD patients, anti-spike and RBD titers increased after mRNA vaccination but decreased to pre-immunization levels by 90 days. Patients vaccinated after SARS-CoV-2 infection developed higher responses comparable to healthy donors. Most vaccinated PAD patients had serum neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this was improved by boosting. Thus, currently used immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of PAD patients with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.

category: allergy and immunology


title: Investigating childhood maltreatment as a modifier of genetic risk for cardiovascular disease in the UK Biobank

abstract:
Cardiovascular disease (CVD) is influenced by genetic and environmental factors. Childhood maltreatment is associated with CVD and may modify genetic susceptibility to cardiovascular risk factors. We used genetic and phenotypic data from 100,833 White British UK Biobank participants (57% female; mean age = 55.9 years). We regressed nine cardiovascular risk factors/diseases (alcohol consumption, body mass index [BMI], low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes, and stroke) on their respective polygenic scores (PGS) and self-reported exposure to childhood maltreatment. Effect modification was tested on the additive and multiplicative scales by including a product term (PGS*maltreatment) in regression models.

On the additive scale, childhood maltreatment accentuated the effect of genetic susceptibility to higher BMI. Individuals not exposed to childhood maltreatment had an increase in BMI of 0.12 SD (95% CI: 0.11, 0.13) per SD increase in BMI PGS, compared to 0.17 SD (95% CI: 0.14, 0.19) in those exposed to all types of childhood maltreatment. On the multiplicative scale, similar results were obtained for BMI though these did not withstand to Bonferroni correction. There was little evidence of effect modification by childhood maltreatment in relation to other outcomes, or of sex-specific effect modification.

Our study suggests the effects of genetic susceptibility to a higher BMI may be moderately accentuated in individuals exposed to childhood maltreatment. However, gene*environment interactions are likely not a major contributor to the excess CVD burden experienced by childhood maltreatment victims.

category: cardiovascular medicine