Rationale: COVID-19 convalescent plasma (CCP) has been considered a treatment option in COVID-19. Objectives:: To assess the efficacy of neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment. Methods: Patients (n=105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. Primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21. The trial is registered: clinicaltrials.gov #NCT04433910. Measurements and main results: The primary outcome occurred in 43.4% of patients in the CCP and 32.7% in the control group (p=0.32). The median time to clinical improvement was 26 days (IQR 15-not reached (n.r.)) in the CCP group and 66 days (IQR 13-n.r.) in the control group (p=0.27). Median time to discharge from hospital was 31 days (IQR 16-n.r.) in the CCP and 51 days (IQR 20-n.r.) in the control group (p=0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies the primary outcome occurred in 56.0% (versus 32.1%), with a shorter interval to clinical improvement, shorter time to hospital discharge and better survival compared to the control group. Conclusion: CCP added to standard treatment did not result in a significant difference in the primary and secondary outcomes. A pre-defined subgroup analysis showed a significant benefit for CCP among those who received a larger amount of neutralizing antibodies. Primary Funding Source: Bundesministerium fuer Gesundheit
Guillain-Barre Syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation and pathogenesis. Serum antibodies against various gangliosides can be found in less than half of all patients in the acute phase of GBS but the target antigens remain unknown for the remaining half. Our work describes a comprehensive screening for serum autoantibodies targeting peripheral nerve tissue, cells, and purified antigens in a prospective GBS cohort including 100 patients. Our study confirms that (1) GBS patients display a very heterogeneous repertoire of autoantibodies targeting nerve cells and structures, (2) gangliosides are the most frequent antigens in GBS patients and have prognostic value, (3) a small subset of patients display antibodies targeting the myelin sheath, and (4) further antigen-discovery experiments are needed to elucidate other potential disease-specific autoantibodies in GBS.
ABSTRACT Importance: The incidence and severity of coronavirus disease 19 (COVID-19) is higher in men. Sex hormones potentially offer one explanation for differences by sex. Objective: To determine whether men exposed to androgen deprivation therapy (ADT) have lower incidence and severity of COVID-19. Design: We conducted an observational study of male Veterans treated in the Veterans Health Administration from February 15th to July 15th, 2020. We developed a propensity score model to predict the likelihood to undergo Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. We performed multivariable logistic regression modeling adjusted with inverse probability weighting to examine the relationship between ADT and COVID-19 incidence. We conducted logistic regression analysis among COVID-19 patients to test the association between ADT and COVID-19 severity. Setting: The U.S. Department of Veterans Affairs Participants: The study sample consisted of 6,250,417 male Veterans who were alive as of February 15, 2020. Exposure: Exposure to ADT was defined as having any prescription for a luteinizing hormone releasing hormone analogue or an antiandrogen in the six months prior to the index date. Main Outcomes and Measures: To assess incidence, we used a binary variable indicating any positive reverse transcriptase polymerase chain reaction SARS-CoV-2 test result through July 15, 2020. To measure severity, we constructed a binary variable indicating whether a patient was admitted to the intensive care unit, placed on mechanical ventilation, or dead in the 60 days following a positive test up to July 15, 2020. Results: We identified 246,087 patients who had been tested for SARS-CoV-2, of whom 3,057 were exposed to ADT, and 36,096 patients with cancer and no ADT exposure. Of these, 295 ADT patients and 2,427 other cancer patients had COVID-19 illness. In the primary, propensity-weighted comparison of ADT patients to cancer patients not on ADT, ADT was associated with decreased likelihood of testing positive for SARS-CoV-2 (adjusted OR, 0.88 [95% CI, 0.81-0.95]; p=0.001). ADT was associated with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53-0.96]; p=0.03). Conclusions and Relevance: ADT is associated with reduced incidence and severity of COVID-19 amongst male Veterans. Repurposing of drugs that modulate androgen production and/or action may represent viable potential treatments for COVID-19.
ChAdOx1 nCoV-19 is a vaccine against the COVID-19 infection that was granted a conditional marketing authorization by the European Commission in January 2021. However, following a report from the Pharmacovigilance Risk Assessment Committee (PRAC) of European Medicines Agency, which reported an association with thrombo-embolic events (TEE), in particular Disseminated intravascular coagulation (DIC) and Cerebral venous sinus thrombosis (CVST), many European countries either limited to individuals older than 55-60 years or suspended its use. We used publicly available data to carry out a quantitative risk-benefit analysis of the vaccine among people under 60 in Italy. Specifically, we used data from PRAC, Eudravigilance and ECDC to estimate the excess number of deaths for TEE, DIC and CVST expected in vaccine users, stratified by age groups. We then used data from the National Institute of Health to calculate age-specific COVID-19 mortality rates in Italy. Preventable deaths were calculated assuming a 72% vaccine efficacy over an 8-month period. Finally, benefit-risk ratio of ChAdOx1 nCoV-19 vaccination was calculated as the ratio between preventable COVID-19 deaths and vaccine-related deaths, using Monte-Carlo simulations. We found that among subjects aged 20-29 years the benefit-risk [B-R] ratio was not clearly favorable (0.70; 95% Uncertainty Interval [UI]: 0.27-2.11). However, in the other age groups the benefits of vaccination largely exceeded the risks (for age 30-49, B-R ratio: 22.9: 95%UI: 10.1-186.4). For age 50-59, B-R ratio: 1577.1: 95%UI: 1176.9-2121.5). Although many countries have limited the use of the ChAdOx1 nCoV-19 vaccine, the benefits of using this vaccine clearly outweigh the risks in people older than 30 years. The use of this vaccine should be a strategic and fundamental part of the immunization campaign considering its safety and efficacy in preventing COVID-19 and its complications.
What is already known about this topic? Community-level face mask use is encouraged as an important preventive measure against COVID-19 transmission, and evidence suggests that jurisdictions which implement face mask mandates see a subsequent decline in COVID incidence. What is added by this report? In the Greater Boston area when a face mask mandate is in effect, 95% of people observed were wearing some type of face covering. Most of which were wearing fabric/cloth coverings (51%) or single use surgical masks (40%). Of those wearing a face covering, 85% were appropriately fitted. Indoor locations have higher adherence of appropriately worn face masks, compared to outdoor locations. What are the implications for public health practice? Adherence with face mask mandates was very high, but many individuals wore fabric face masks with unknown filtration efficacy. In addition, it was common for individuals to mis-wear, adjust, or remove their masks. Public health policies requiring mask use should include messaging about appropriate type and best practices for use.
Recent studies have identified notable disparities in SARS-CoV-2 infection risk among ethnic minorities. We evaluated SARS-CoV-2 test results from individuals presenting for testing in Los Angeles between June-December, 2020. We calculated prevalence ratios for various employment categories. Among 518,914 test results, of which 295,295 (56.9%) were from individuals reporting Hispanic ethnicity, SARS-CoV-2 positivity was 16.5% among Hispanic individuals compared to 5.0% among non-Hispanic individuals (p-value<0.01). The prevalence ratios comparing Hispanic and non-Hispanic individuals was highest for members of the media (PR=6.7; 95% CI 4.3-10.4), government employees (PR=4.0; 95% CI 3.3-4.9), and agricultural workers (PR=4.0; 95% CI 3.2-5.0). Such heterogeneity warrants further investigation in order to develop targeted public health interventions towards specific drivers of SARS-CoV-2 transmission.
Understanding human behaviour is essential to the adoption practices for new technologies that promote safer care. This requires capturing the detail of clinical workflows to inform the design of new interactions including those with touchless technologies that decipher human-speech, gesture and motion and allow for interactions that are free of contact. Many environments in hospitals are sub-optimally designed, with a poor layout of work surfaces, cumbersome equipment that requires space and effort to manoeuvre, designs that require healthcare staff to reach awkwardly and medical devices that require extensive touch. This suggests there is a need to better understand how they can be designed. Here, we employ a new approach by installing a single 360 degree camera into a clinical environment to analyse touch patterns and human-environment interactions across a clinical team to recommend design considerations for new technologies with potential to reduce avoidable touch.
Background WHO-recommended prevalence thresholds for deciding schistosomiasis mass drug administration (MDA) are based on anecdotal evidence and unclear. Objectives This systematic review and meta-analysis commissioned by the WHO, as part of its new schistosomiasis evidence-based guideline development, was to generate a single and global prevalence threshold that should be applied in MDA programmes. Methods We searched several databases from 1979 to 31st March 2021 without language restriction. Two reviewers selected studies, extracted data and assessed the risk of bias using relevant risk of bias tools and resolved disagreements through discussion. The review followed the PRISMA guidelines. Data were analysed and presented as prevalence reduction (PR) and relative risk (RR) for dichotomous outcomes or mean difference for continuous outcomes with their 95% confidence intervals (CIs). Meta-regression of observations on prevalence rates and intensity of infection of MDA programmes and sensitivity analyses to assess the robustness of the results to the risk of bias components were performed. Evidence on benefits, harms, values, preferences, compliance, acceptability, equity and feasibility were also assessed. The overall level of evidence was graded using GRADE. Results Out of 1,232 studies retrieved, 38 studies met our inclusion criteria and 34 studies were included in the meta-analysis. No direct relation was observed between prevalence and intensity of infection. Praziquantel reduced prevalence of S. haematobium in school age children (SAC) at 12 months (RR 0.38, 95% CI 0.28 to 0.52; 8 studies, n=37,868); at 24 months (RR 0.30; 95% CI 0.30 to 0.52; 7 studies; n=37107); at 36 months (RR 0.39, 95% CI 0.21 to 0.71; 5 studies, n=28,146). There was no significant reduction in prevalence at 48 months (2 studies, n=10,954). For S. mansoni, there were reductions in prevalence at 12 months (RR 0.56, 95% CI 0.46 to 0.69; 14 studies, n=86,073); 24 months (RR 0.46; 95% CI 0.32 to 0.66; 14 studies; n=83,721);36 months (RR 0.44, 95% CI 0.33 to 0.58; 7 studies, n=70,933) and at 48 months (RR 0.25, 95% CI 0.11 to 0.59; 5 studies; n=27,483). Further analyses were performed from a series of created prevalence thresholds of 5%, 10%, 15%, 20%, 30% and [≥]40% which showed differences in effect of MDA when each of the thresholds was applied. For annual MDA of school age children (SAC), school-based treatment (SBT) appears to perform better than community-wide treatment (CWT) in terms of prevalence reduction. For the different schistosome species, the model suggests, using the same prevalence threshold, it will take shorter time to reach elimination for S. haematobium than S. mansoni; annual MDA using SBT approach for S. haematobium will require about 10 years to achieve elimination whereas it will take over 10 years to around 15 years to achieve elimination for S. mansoni. Conclusion The evidence presented in this systematic review suggests that 10% prevalence should be used as the global prevalence threshold for implementing MDA in endemic countries.
We systematically investigated the transcriptomes of the peripheral immune cells from 6 inactivated vaccine, BBIBP-CorV recipients at 4 pivotal time points using single-cell RNA-seq technique. First, the significant variation of the canonical immune-responsive signals of both humoral and cellular immunity, as well as other possible symptom-driver signals were evaluated in the specific cell types. Second, we described and compared the common and distinct variation trends across COVID-19 vaccination, disease progression, and flu vaccination to achieve in-depth understandings of the manifestation of immune response in peripheral blood under different stimuli. Third, the expanded T cell and B cell clones were correlated to the specific phenotypes which allowed us to characterize the antigen-specific ones much easier in the future. At last, other than the coagulopathy, the immunogenicity of megakaryocytes in vaccination were highlighted in this study. In brief, our study provided a rich data resource and the related methodology to explore the details of the classical immunity scenarios
The SARS-CoV-2 genetic diversification has a potential impact in the virus escape from natural infection- or vaccine-elicited neutralizing antibodies and higher transmissibility. Here we report the emergence of novel B.1.621 variant of interest with the insertion 145N in the N-terminal domain and amino acid change N501Y, E484K, and P681H in the Receptor Binding Domain of the Spike protein. Further studies in vitro biological assays and epidemiologic analysis will allow evaluating the public health impact of B.1.621 variant.
Variants of concern (VOC) in SARS-CoV-2 refer to viral genomes that differ significantly from the ancestor virus and that show the potential for higher transmissibility and/or worse clinical progression. VOC have the potential to disrupt ongoing public health measures and vaccine efforts. Yet, little is known regarding how frequently different viral variants emerge and under what circumstances. We report a longitudinal study to determine the degree of SARS-CoV-2 sequence evolution in 94 COVID-19 cases and to estimate the frequency at which highly diverse variants emerge. 2 cases accumulated 9 single-nucleotide variants (SNVs) over a two-week period and 1 case accumulated 23 SNVs over a three-week period, including three non-synonymous mutations in the Spike protein (D138H, E554D, D614G). We estimate that in 2% of COVID cases, viral variants with multiple mutations, including in the Spike glycoprotein, can become the dominant strains in as little as one month of persistent in patient virus replication. This suggests the continued local emergence of VOC independent of travel patterns. Surveillance by sequencing for (i) viremic COVID-19 patients, (ii) patients suspected of re-infection, and (iii) patients with diminished immune function may offer broad public health benefits.
Background Risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in-vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. Methods Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). Results 629 genes were associated with 25-OHD level (P<0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P<1.0E-07; downregulated gene-set P<2.6E-05) and corresponding GO terms (P=2.90E-02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P<0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI:0.66-1.00]), and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI:0.77-0.89]; PPP1CC AUC=0.91 [95%CI:0.86-0.95]). Conclusions Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumor transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.
Background: The COVID-19 pandemic has affected not only the emergency medical system, but also patients' regular ambulatory care. The number of patients visiting outpatient internal medicine clinics decreased during March-April 2020 compared to 2019. Moreover, the ban on telephone re-examination for outpatient clinics in lieu of ambulatory care for chronic diseases has been lifted since March 2020. In this context, we investigate the impact of the COVID-19 pandemic on ambulatory care at Japanese outpatient clinics for patients with chronic neurological diseases during the first half of 2020. Methods: We collected data from the administrative claims database by DeSC Healthcare. Serial changes in the frequency of subsequent outpatient visits to clinics or hospitals (excluding large hospitals with beds >200) for chronic ambulatory care of epilepsy, migraine, Parkinson's disease (PD), and Alzheimer's disease were measured. We also evaluated the utilization rate of telephone re-examination at outpatient clinics. Results: Since April 2020, the monthly count of outpatient clinic visits for epilepsy or PD decreased slightly but significantly. The use of telephone re-examination was facility-dependent, and it was used in less than 5% of all outpatient clinic visits for the examined neurological diseases in May 2020. The utilization rate of telephone re-examination was not associated with age or the neurological diseases of interest. Conclusion: The impact of the COVID-19 pandemic on ambulatory care for several chronic neurological diseases may have been relatively limited, in terms of the frequency or type of outpatient visit, during the first half of 2020 in Japan.
The aim of surgical training across the ten surgical specialties is to produce competent day one consultants. Progression through training is assessed by the Annual Review of Competency Progression (ARCP). Objective This study aimed to examine variation in ARCP outcomes within surgical training and identify differences between specialties. Design A national cohort study using data from United Kingdom Medical Education Database (UKMED) was performed. ARCP outcome was the primary outcome measure. Multi-level ordinal regression analyses were performed, with ARCP outcomes nested within trainees. Participants Higher surgical trainees (ST3-ST8) from 9 UK surgical specialties were included (vascular surgery was excluded due to insufficient data). All surgical trainees across the UK with an ARCP outcome between 2010 to 2017 were included. Results Eight thousand two hundred and twenty trainees with an ARCP outcome awarded between 2010 and 2017 were included, comprising 31,788 ARCP outcomes. There was substantial variation in the proportion of non-standard outcomes recorded across specialties with general surgery trainees having the highest proportion of non-standard outcomes (22.5%) and urology trainees the fewest 12.4%. After adjustment, general surgery trainees were 1.3 times more likely to receive a non-standard ARCP outcome compared to trainees in T&O (OR 1.33 95%CI 1.21-1.45). Urology trainees were 36% less likely to receive a non-standard outcome compared to T&O trainees (OR 0.64 95%CI 0.54-0.75). Female trainees and older age were associated with non-standard outcomes (OR 1.11 95%CI 1.02-1.22; OR 1.04 95%CI 1.03-1.05). Conclusion There is wide variation in the training outcome assessments across surgical specialties. General surgery has higher rates of non-standard outcomes compared to other surgical specialities. Across all specialities, female sex and older age were associated with non-standard outcomes.
Background: Graduate Medical Education training programs transitioned to all-virtual recruitment in 2020. Few data have been published regarding the consequences of this transition. We desired to understand (1) infectious diseases (ID) fellowship programs' recruitment efforts and the effect of virtual recruitment on application and interview numbers, and (2) the number of programs to which matched applicants applied and interviewed, and their perspectives on virtual recruitment. Methods: In 2020-21 we surveyed all United States ID fellowship program directors (PDs) and matched applicants. Descriptive data analysis was performed on quantitative survey items. Free-text responses were analyzed through a quantitative content analysis approach. Results: PD response rate was 68/158 (43%); applicant response rate was at least 23% (85/365). PDs reported a 27% increase in mean number of applications received and a 45% increase in mean number of applicants interviewed. Applicants especially valued online program structure information, PD program overview videos, fellow testimonials, didactic and curriculum content, and current fellow profiles. Most applicants preferred interviews lasting no more than 40 minutes and interview days lasting no more than 5 hours. Nearly all (60/64, 94%) PDs adequately learned about candidates; most (48/64, 75%) felt unable to showcase their program as well as when in-person. Most PDs (54/64, 84%) and applicants (56/73, 77%) want at least an option for virtual recruitment moving forward. Conclusions: Virtual recruitment enabled programs to accommodate more applicants and highlighted applicants' preferences for programs' augmented online presences and time-limited interview days. Most programs and applicants want the option for virtual interviews.
Objective: To evaluate the relationship between medications used to treat acute agitation (antipsychotics, mood stabilizers and benzodiazepines) and subsequent assault incidence in the psychiatric emergency room. Methods: Medication orders and assault incident reports were obtained from electronic health records for 17,052 visits to an urban psychiatric emergency room from 2014-2019. Assault risk was modeled longitudinally using Poisson mixed-effect regression. Results: Assaults were reported during 0.5% of visits. Intramuscular medications (IMs) were administered in 23.3% of visits overall, and predominately administered within the first 4-hours of a visit. IM administration was correlated with assault (IRR=24.2 [5.33, 110.0]), often because IM medication was administered immediately subsequent to reported assaults. Interacted with time, IMs were not significantly associated with reduction in future assaults (IRR=0.700 [0.467, 1.04]). Neither benzodiazepines nor mood stabilizers were associated with subsequent changes to the risk of reported assault. By contrast, antipsychotic medications were associated with decreased assault risk across time (IRR=0.583 [0.360, 0.942]). Conclusions: IM order rates are high relative to overall assault incident risk. Of the three major categories of medications administered commonly in the psychiatric emergency setting, only antipsychotic medications were associated with measurable decreases in subsequent assault risk. Careful weighing of the risks and benefits of medications is encouraged; antipsychotic medication can have a significant side effect burden, and other medications (IMs, benzodiazepines, mood stabilizers) were not associated with subsequent reduction in assault risk in this analysis.
Background COVID-19 is suggested to be more prevalent among ethnic minorities and individuals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas . Methods As part of Testing Denmark, a nationwide sero-epidemiological surveillance survey, we conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas in Denmark. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning previous testing (viral throat- and nasopharyngeal swab or antibody test), test results for COVID-19, demographics, household characteristics, employment, risk factors for SARS-CoV-2 infection and history of symptoms associated with COVID-19. Data on seroprevalence from Danish blood donors in same period using a total Ig ELISA assay were used as a proxy for the general Danish population. Findings Of the 13,279 included participants, 2,296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78-3.16, p>0.001). Seropositivity was higher among males than females (RR 1.1, 95% CI 1.05-1.22%, p=0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00-1.06, p=0.031). Close contact with COVID-19-infected individuals was associated with a higher risk of infection, especially among members of the same households (OR 5.0, 95% CI 4.1-6.2 p<0,001). Adjusted for age, gender and region living at least 4 people in a household significantly increased the OR of seropositivity (OR 1.3, 95% CI 1.1-1.6, p=0.02) as did living in a multi-generational household (OR 1.3 per generation, 95% CI 1.1-1.5, p=0.007). Only 1.6% of participants reported not following any of the national COVID-19 recommendations. Anosmia (RR 3.2 95% CI 2.8-3.7, p<0.001) and ageusia (RR 3.3, 95% CI 2.9-3.8, p<0.001) were strongest associated with seropositivity. Interpretation Danish citizens living in SH areas of low socioeconomic status had a three times higher SARS-CoV-2 seroprevalence compared to the general Danish population. The seroprevalence was significantly higher in males and increased with age. Living in multiple generations or more than four persons in a household was an independent risk factor for being seropositive. Results of this study can be used for future consideration of the need for preventive measures in the populations living in SH areas.