bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron Variant of Concern
Authors: Mazzaferri Fulvia , Mirandola Massimo , Savoldi Alessia , De Nardo Pasquale , Morra Matteo , Tebon Maela , Armellini Maddalena , De Luca Giulia , Calandrino Lucrezia , Sasset Lolita , D’Elia Denise , Sozio Emanuela , Danese Elisa , Gibellini Davide , Monne Isabella , Scroccaro Giovanna , Magrini Nicola , Cattelan Annamaria , Tascini Carlo ,   MANTICO Working Group, Tacconelli Evelina
Published: May 2022

Background

Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting SARS-CoV-2 varies according to the Variant of Concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC.

Methods

The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with early COVID-19. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was COVID-19 progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions.

Results

Overall, 319 patients were included. Among 141 patients infected with Delta, no disease progression was recorded and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.895). Among 170 patients infected with Omicron (80.6% BA.1, 19.4% BA.1.1), two disease progressions were recorded in the bamlanivimab/etesevimab group and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared to bamlanivimab/etesevimab and casirivimab/imdevimab (HR 0.526 and HR 0.451, 95% CI 0.359 - 0.77 and 95% CI 0.303 - 0.669, p 0.001 and 0.0001, respectively).

Conclusions

These results confirm the in-vitro data of superiority of sotrovimab versus casirivimab/imdevimab and bamlanivimab/etesivamab in reducing the time to recovery in patients infected with Omicron BA.1 and BA.1.1, while no difference was detected in Delta infections. Casirivimab/imdevimab seems to maintain a role in preventing severe COVID-19 in the Omicron population. Adaptive clinical trials comparing mAbs by VOC should be pursued to promptly inform clinical recommendations.

Funding

This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101016167.

Clinical trial number

NCT05205759
HostSeq : A Canadian Whole Genome Sequencing and Clinical Data Resource
Authors: Yoo S , Garg E , Elliott LT , Hung RJ , Halevy AR , Brooks JD , Bull SB , Gagnon F , Greenwood CMT , Lawless JF , Paterson AD , Sun L , Zawati MH , Lerner-Ellis J , Abraham RJS , Birol I , Bourque G , Garant J-M , Gosselin C , Li J , Whitney J , Thiruvahindrapuram B , Herbrick J-A , Lorenti M , Reuter MS , Adeoye NO , Liu S , Allen U , Bernier FP , Biggs CM , Cheung AM , Cowan J , Herridge M , Maslove DM , Modi BP , Mooser V , Morris SK , Ostrowski M , Parekh RS , Pfeffer G , Suchowersky O , Taher J , Upton J , Warren RL , Yeung RSM , Aziz N , Turvey SE , Knoppers BM , Lathrop M , Jones SJM , Scherer SW , Strug LJ
Published: May 2022

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.
Rapid growth in disposable e-cigarette vaping among young adults in Great Britain from 2021 to 2022: a repeat cross-sectional survey
Authors: Tattan-Birch Harry , Jackson Sarah E , Kock Loren , Dockrell Martin , Brown Jamie
Published: May 2022

Aims

To estimate recent trends in the prevalence of disposable e-cigarette vaping in Great Britain, overall and across ages.

Design

The Smoking Toolkit Study, a monthly representative cross-sectional survey. Setting: Great Britain.

Participants

29,976 adults (≥18 years) completed telephone interviews from January 2021 to January 2022.

Measurements

Current e-cigarette vapers were asked which type of device they mainly use. We estimated age-specific time trends in the prevalence of current disposable e-cigarette use among vapers and inhaled nicotine use (vaping/smoking) among adults.

Findings

From January 2021 to January 2022, there was a 14-fold increase in the percentage of vapers that used disposables, rising from 1.2% to 16.7% (prevalence ratio [PR], 14.4; 95%CI, 6.6-49.0). Growth in disposable e-cigarette vaping was most pronounced in younger adults (interaction p-value, .0.007): for example, the percentage of 18-year-old vapers using of disposables rose from 0.89% to 56.7% (PR, 64; 95%CI, 15-5790) while it rose from 1.3% to 6.2% (PR, 4.7; 95%CI, 1.7-144) among 45-year-old vapers. However, the overall percentage people currently using any inhaled nicotine, vaped or smoked, remained stable over time both among all adults (20.1% vs. 20.6%; PR, 1.03; 95%CI, 0.88-1.20) and among 18-year-olds (29.6% vs. 29.6%; PR, 1.00; 95%CI, 0.79-1.26).

Conclusions

Use of disposable e-cigarettes in Great Britain grew rapidly between 2021 and 2022, especially among younger adults, but the overall prevalence of inhaled nicotine use — smoked or vaped — was stable over time. Most young adult vapers in Great Britain now use disposable products.
Meta-analysis methods for risk difference: a comparison of different models
Authors: Guo Juanru , Xiao Mengli , Chu Haitao , Lin Lifeng
Published: May 2022

Risk difference is a frequently-used effect measure for binary outcomes. In a meta-analysis, commonly-used methods to synthesize risk differences include: 1) the two-step methods that estimate study-specific risk differences first, then followed by the univariate common-effect model, fixed-effects model, or random-effects models; and 2) the one-step methods using bivariate random-effects models to estimate the summary risk difference from study-specific risks. These methods are expected to have similar performance when the number of studies is large and the event rate is not rare. However, studies with zero events are common in meta-analyses, and bias may occur with the conventional two-step methods from excluding zero-event studies or using an artificial continuity correction to zero events. In contrast, zero-event studies can be included and modeled by bivariate random-effects models in a single step. This article compares various methods to estimate risk differences in meta-analyses. Specifically, we present two case studies and three simulation studies to compare the performance of conventional two-step methods and bivariate random-effects models in the presence or absence of zero-event studies. In conclusion, we recommend researchers using bivariate random-effects models to estimate risk differences in meta-analyses, particularly in the presence of zero events.
Neighborhood distribution of availability of newer tobacco products: A four-site study, 2021
Authors: Rose Shyanika W. , Annabathula Arati , Westneat Susan , van de Venne Judy , Hrywna Mary , Ackerman Christopher , Lee Joseph G. L. , Sesay Mahdi , Giovenco Daniel P. , Spillane Torra , Hudson Shawna V. , Delnevo Cristine D.
Published: May 2022

Background

Audits of tobacco retail stores can identify marketing patterns as newer tobacco products are introduced in the US. Our study examined store and neighborhood correlates of availability of nicotine pouches and disposable e-cigarettes in four US sites.

Methods

We conducted standardized store audits of n=242 tobacco retailers in 2021 in different states: New Jersey, Kentucky, North Carolina, and New York. Store audits focused on availability of nicotine pouches and disposable e-cigarettes. We geocoded stores linking them with census tract demographics. We conducted unadjusted and adjusted Poisson regression of availability of each product with correlates of the proportion of Non-Hispanic White residents, households under poverty, proximity to schools, site, and store type.

Results

Nicotine pouches and disposable e-cigarettes were each available in around half the stores, but availability differed across sites. In adjusted analyses, nicotine pouches were less likely to be available in each store type vs. chain convenience and more likely in stores in census tracts with more non-Hispanic White residents. In contrast, disposable e-cigarettes were more likely to be available in tobacco store/vape shops than convenience stores and less likely in non-specialty store types like groceries.

Conclusions

The availability of newer tobacco products like nicotine pouches and disposable e-cigarettes were widely available in stores across sites, but retail marketing patterns appear to differ. As these product types become subject to increased regulation as they go through the FDA pre-market authorization process, understanding changes in their retail environment is critical to inform potential policies regulating their sale and marketing.
Socio-economic determinants of SARS-CoV-2 infection: results from a population-based serosurvey in Geneva, Switzerland
Authors: Santa-Ramírez Hugo-Alejandro , Wisniak Ania , Pullen Nick , Zaballa María-Eugenia , Pennacchio Francesco , Lorthe Elsa , Dumont Roxane , Baysson Hélène , Guessous Idris , Stringhini Silvia
Published: May 2022

Background

SARS-CoV-2 infection and its health consequences have disproportionally affected disadvantaged socio-economic groups globally. This study aimed to analyze the association between socio-economic conditions and having developed anti-SARS-CoV-2 antibodies in a population-based sample in the canton of Geneva, Switzerland.

Methods

Data was obtained from a population-based serosurvey of adults in Geneva and their household members, between November and December, 2020, towards the end of the second pandemic wave in the canton. Participants were tested for anti-SARS-CoV-2 antibodies. Socio-economic conditions representing different dimensions were self-reported. Mixed effects logistic regressions were conducted for each predictor to test its association with seropositive status as the main outcome.

Results

2,889 adults completed the study questionnaire and were included in the final analysis. Retired participants and those living in suburban areas had lower odds of a seropositive result when compared to employed participants (OR 0.42, 95% CI - 0.20 – 0.87) and those living in urban areas (OR 0.67, 95% CI - 0.46 – 0.97), respectively. People facing financial hardship for less than a year had higher odds of a seropositive result compared to those who had never faced them (OR 2.23, 95% CI - 1.01 – 4.95). Educational level, occupational position and household income were not associated with being seropositive, nor were ethnicity or country of birth.

Discussion

While traditional measures of socio-economic position did not seem to be related to the risk of being infected in this sample, this study sheds lights on the importance of examining the broader social determinants of health when evaluating the differential impact of the pandemic within the population.
COVID-19 Vaccine Acceptance and Uptake Among Healthcare Workers in Trinidad & Tobago
Authors: Gopaul Chavin D. , Ventour Dale , Thomas Davlin
Published: May 2022

Background

COVID-19 vaccine acceptance is important in ensuring the widespread vaccination of the population to achieve herd immunity. Establishing the acceptance of vaccines among healthcare workers, who play a vital role immunization program success, is important. The aim of this study was to assess the influence of social trust and demographic factors on COVID-19 vaccine acceptance among healthcare workers.

Methods

A cross-sectional survey utilizing an electronic questionnaire inquiring about COVID-19 vaccine uptake, preferences, and concerns was distributed via email to 1,351 North Central Regional Health Authority (NCRHA) healthcare workers of the following categories: medical practitioners, nursing personnel, veterinary surgeons, medical interns, dental interns, paramedics, and pharmacists. These professions were selected as they were granted power to administer COVID-19 vaccines during this period of public emergency by the President of Trinidad and Tobago and were therefore likely to be NCRHA healthcare workers directly involved in vaccine administration services. 584 participants returned a completed questionnaire. Bivariate analysis using Chi-square analysis of association was used to determine the association between the respondents’ characteristics and the acceptance of the vaccine and the association between vaccine acceptance among healthcare workers and trust. The association between the acceptance of the COVID-19 vaccines and healthcare workers’ characteristics and trust was established using multinomial logistic regression.

Results

A total of 584 healthcare workers took part in the study and 1.4% showed unwillingness to receive COVID-19 vaccine. The study indicates that age, profession, and the trust in international organizations and other healthcare providers predict the uptake of COVID-19 vaccines among healthcare workers. However, gender of the healthcare workers does not predict vaccine acceptance.

Conclusions and Relevance

Efforts towards enhanced vaccine acceptance among healthcare workers should take into consideration age, profession, and the trust in international organizations and other healthcare providers. Sensitization programs should be age-specific as well as occupation-based.
Time series modeling to estimate unrecorded burden of 12 symptomatic medical conditions among United States Medicare beneficiaries during the COVID-19 pandemic
Authors: Melgar Michael , Leung Jessica , Colombe Jeffrey , Dooling Kathleen
Published: May 2022

Objective

U.S. healthcare utilization declined during the COVID-19 pandemic, potentially leading to spurious drops in disease incidence recorded in administrative healthcare datasets used for public health surveillance. We used time series modeling to characterize the magnitude and duration of the COVID-19 pandemic’s impact on claims-based monthly incidence of 12 symptomatic conditions among Medicare beneficiaries aged ≥65 years.

Methods

Time series of observed monthly incidence of each condition were generated using Medicare claims data from January 2016–May 2021. Incidence time series were decomposed through seasonal and trend decomposition using Loess, resulting in seasonal, trend, and remainder components. We fit a non-linear mixed effects model to remainder time series components and used it to estimate underlying incidence and number of unrecorded cases of each condition during the pandemic period.

Results

Observed incidence of all 12 conditions declined steeply in March 2020 with nadirs in April 2020, generally followed by return to pre-pandemic trends. The relative magnitude of the decrease varied by condition, but month of onset and duration did not. Estimated unrecorded cases during March 2020–May 2021 ranged from 9,543 (95% confidence interval [CI]: 854–15,703) for herpes zoster to 236,244 (95% CI: 188,583–292,369) for cataracts.

Conclusions

Due to reduced healthcare utilization during the COVID-19 pandemic, claims-based data underestimate incidence of non-COVID-19 conditions. Time series modeling can be used to quantify this underestimation, facilitating longitudinal analyses of disease incidence pre- and post-pandemic.
Artificial Intelligence Model for Analyzing Colonic Endoscopy Images to Detect Changes Associated with Irritable Bowel Syndrome
Authors: Tabata Kazuhisa , Mihara Hiroshi , Nanjo Sohachi , Motoo Iori , Ando Takayuki , Teramoto Akira , Fujinami Haruka , Yasuda Ichiro
Published: May 2022

Background/Aims

IBS is not an organic disease, and the patients typically show no abnormalities in lower gastrointestinal endoscopy. Recently, biofilm formation has been visualized by endoscopy, and the ability of endoscopy to detect microscopic changes due to dysbiosis and microinflammation has been reported. In this study, we investigated whether an Artificial Intelligence (AI) colon image model can detect IBS without biofilsm.

Methods

Study subjects were identified based on electronic medical records and categorized as IBS (group I; n=11), IBS with predominant constipation (IBS-C; group C; n=12), and IBS with predominant diarrhea (IBS-D; group D; n=12). Colonoscopy images from IBS patients and from asymptomatic healthy subjects (group N; n=88) were obtained. Google Cloud Platform AutoML Vision (single-label classification) was used to construct AI image models to calculate sensitivity, specificity, predictive value, and AUC. A total of 2479, 382, 538, and 484 images were randomly selected for groups N, IBS, IBC-C and IBS-D groups, respectively.

Results

The AUC of the model discriminating between group N and group I was 0.95. Sensitivity, specificity, positive predictive value, and negative predictive value of group I detection were 30.8%, 97.6%, 66.7%, and 90.2%, respectively. The overall AUC of the model discriminating between groups N, C, and D was 0.83; sensitivity, specificity, and positive predictive value of group N were 87.5%, 46.2%, and 79.9%, respectively.

Conclusions

Using the image AI model, colonoscopy images of IBS could be discriminated from healthy subjects at AUC 0.95. Prospective studies are needed to further validate whether this externally validated model has similar diagnostic capabilities at other facilities and whether it can be used to determine treatment efficacy.
A study protocol for a retrospective cohort study and interrupted time series analysis to assess the effect of the COVID-19 pandemic on major trauma presentations and patient outcomes in English hospitals
Authors: Marincowitz Carl , Bouamra Omar , Coates Tim , Kumar Dhushy , Lockey David , Mason Lyndon , Newcombe Virginia , Thompson Julian , Yates David , Lecky Fiona
Published: May 2022

A protocol for a retrospective cohort study and interrupted time series analysis to investigate the effect of successive COVID related “lockdown” restrictions on major trauma presentations and patient outcomes in English hospitals. The study specifically aims to assess: 1) The impact of successive “lockdowns” on the volume, demographics, injury mechanism, severity, treatment and outcomes of major trauma in England. 2) If the implementation of “lockdowns” affected major trauma related mortality.

A patient cohort will be derived from the Trauma and Audit Research Network (TARN) database, for all trauma receiving hospitals in England, between 1stof January 2017 to 1stof September 2021. This period encompasses two national “lockdown” periods (23rdMarch 2020 to 29thJune 2020 and 2ndNov 2020 to 16thMay 2021) in England. A time series will be used to illustrate changes in the volume and mechanism of injury associated with successive “lockdowns”. Demographic characteristics and features of the clinical care pathways will be compared during the “lockdown” and equivalent pre-COVID periods. To specifically assess if there were any changes in risk adjusted mortality associated with the “lockdowns” interrupted time series analysis will be conducted.
Tracking changes in SARS-CoV-2 transmission with a novel outpatient sentinel surveillance system in Chicago, USA
Authors: Richardson Reese , Jorgensen Emile , Arevalo Philip , Holden Tobias M. , Gostic Katelyn M. , Pacilli Massimo , Ghinai Isaac , Lightner Shannon , Cobey Sarah , Gerardin Jaline
Published: May 2022

Public health indicators typically used for COVID-19 surveillance can be biased or lag changing community transmission patterns. The United States city of Chicago opportunistically investigated whether sentinel surveillance of recently symptomatic individuals receiving outpatient diagnostic testing for SARS-CoV-2 could accurately assess the instantaneous reproductive number R(t) and provide early warning of changes in transmission. Patients tested at community-based diagnostic testing sites between September 2020 and June 2021, and reporting symptom onset within four days preceding their test, formed the sentinel population. R(t) calculated from sentinel cases agreed well with R(t) from other indicators. Retrospectively, trends in sentinel cases did not precede trends in COVID-19 hospital admissions by any identifiable lead time. In deployment, sentinel surveillance held an operational recency advantage of nine days over hospital admissions. The promising performance of opportunistic sentinel surveillance suggests that deliberately designed outpatient sentinel surveillance would provide robust early warning of increasing transmission.
A Discovery and Verification Approach for Pharmacovigilance using Electronic Health Care Data
Authors: Dijkstra LJ , Schink T , Linder R , Schwaninger M , Pigeot I , Wright MN , Foraita R
Published: May 2022

Introduction

Pharmacovigilance shifted its focus from spontaneous reporting systems to electronic health care (EHC) data. Usually, a single statistical method is used to detect signals, i.e., potential adverse drug reactions (ADRs).

Objective and Method

We present a novel approach to detect ADRs in EHC databases. It aggregates the results of multiple statistical signal detection methods applying Borda count ranking, a preference voting system, which results are used by an expert committee to select plausible signals. The obtained signals are afterwards investigated in tailored pharmacoepidemiological studies to provide support of plausibility or spuriousness of the signal.

We showcase the approach using data from the German Pharmacoepidemiological Research Database on drug reactions of the direct oral anticoagulant rivaroxaban. Results of four statistical methods are aggregated into Borda count rankings: longitudinal Gamma Poisson shrinker, Bayesian confidence propagation neural network, random forests and LASSO. A verification study designed as nested active comparator case-control study was conducted. We included patients diagnosed with atrial fibrillation who initiated anticoagulant treatment with rivaroxaban or with phenprocoumon as active comparator between 2011 and 2017.

Results

The case study highlights that our Borda ranking approach (https://borda.bips.eu) is fast, able to retrieve known ADRs and find other interesting signals. Hasty false conclusions are avoided by a verification study, which is, however, time-consuming.

Conclusion

Post-market signal detection in EHC data is useful to identify and validate safety signals, particularly a few years after first admission to the market, when spontaneous reports are less frequent and more EHC data are available.
Biopsychosocial response to the COVID-19 lockdown in people with major depressive disorder and multiple sclerosis
Authors: Siddi S , Giné-Vázquez I , Bailon R , Matcham F , Lamers F , Kontaxis S , Laporta E , Garcia E , Arranz B , Dalla Costa G , Guerrero Pérez A.I , Zabalza A. , Buron M , Comi G , Leocani L. , Annas P , Hotopf M , Penninx BWJH , Magyari M , Sørensen P. S. , Montalban X , Lavelle G , Ivan A , Oetzmann C , White M K , Difrancesco S , Locatelli P , Mohr DC , Aguiló J , Narayan V , Folarin A , Dobson R , Dineley J , Leightley D , Cummins N , Vairavan S , Ranjan Y , Rashid Z , Rintala A , De Girolamo G , Preti A , Simblett S , Wykes T ,   PAB members, Myin-Germeys I , Haro JM
Published: May 2022

Background

Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDD) and Multiple Sclerosis (MS).

Methods

Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse – Central Nervous System) programme. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender.

Results

Participants with MDD (N=255) and MS (N=214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. Lower mean HR and HR variation were observed between pre and during lockdown during the day for MDD and during the night for MS. HR variation during rest periods also decreased between pre-and post-lockdown in both clinical conditions. We observed a reduction of physical activity for MDD and MS upon the introduction of lockdowns. The group with MDD exhibited a net increase in social interaction via social network apps over the three periods.

Conclusions

Behavioral response to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDD and MS.
Hospital at home: a systematic review of how medication management is conceptualised, described and implemented in practice – a study protocol
Authors: McGlen Sophie , Lasserson Daniel , Crowley Clare , Qamariat Zahra AL , Lim Rosemary H
Published: May 2022

Introduction

Hospital at Home (H@H) is a method of healthcare delivery, where hospital level interventions are conducted in the patient’s usual place of residence, offering an alternative to hospital admission. This often includes the ability to perform point of care diagnostics and treat conditions using a range of treatments traditionally associated with hospital admission, including intravenous medicines and oxygen. H@H services have been established worldwide but there is a wide variation in definition and delivery models and currently no documented evidence supporting the delivery of medicines and medicines management within the H@H model. Therefore, this study aims to 1) describe how medication management in H@H is conceptulised, 2) describe and identify key components of medication management in H@H and 3) describe and identify variability in the implementation of medication management services within H@H models

Methods and Analysis

We will search a range of databases (PubMed, Medline, Embase, CINAHL), publicly accessible documents and expert recommendations. Studies, reports and policy documents published between 1st January 2000 and 31st January 2022 will be included. Two independent reviewers will 1) screen and select studies based on a priori inclusion/exclusion, 2) conduct quality assessment using the Mixed Methods Appraisal Tool on included studies and 3) extract data. Inductive thematic analysis (objectives 1 and 2), the SEIPS 2.0 model (objective 2) and the Consolidated Framework for Implementation Research (objective 3) will be used to synthesise data.

Ethics and dissemination

This systematic review will use secondary data sources from published documents, and as such research ethical approval was not required. We will disseminate the findings of this study in a peer-reviewed journal and national/international conference(s).

PROSPERO registration number

CRD42022300691

Strengths and limitations of this study

The search will be performed on a comprehensive range of databases and relevant information sources to capture a global perspective relating to Hospital at Home (H@H).

A wide range of search terms will be used in our search, however due to the changing nature of H@H, some terms may be unintentionally missed.

Only published literature will be synthesized in this systematic review, and it is recognised that in a rapidly changing environment not all practices will be captured in written form.

A combination of thematic synthesis, a work systems model (Systems Engineering Initiative for Patient Safety 2.0) and the Consolidated Framework for Implementation Research will be used to provide a system-level analysis of studies.

The study team consists of four pharmacists from a range of practice and research backgrounds and a H@H consultant, therefore, will benefit from different perspectives on the topic area.
Reconstruction of Full-length scFv Libraries with the Extended Range Targeted Sequencing Method
Authors: Wei Christopher , Criner Sarah , Sridhar Bharat , Shultzaberger Ryan , Looney Timothy , Fabani Martin M , Glezer Eli N
Published: May 2022

Single chain fragment variable (scFv) phage display libraries of randomly paired VH-VL antibody domains are a powerful and widely adopted tool for the discovery of antibodies of a desired specificity. Characterization of full length VH-VL constructs using synthetic long read assemblies of short read next-generation sequencing data has emerged as a powerful approach to identify antibody candidates with greater speed and sensitivity than classical screening methods. Here we introduce a new version of the synthetic long read approach, which we denote the Extended Range Targeted Sequencing method. We apply the method to demonstrate accurate and high throughput analysis of full-length VH-VL constructs from a commercial scFv combinatorial display library.
Radiological Imaging of Viral Pneumonia Cases Identified Before the COVİD-19 Pandemic Period and COVİD-19 Pneumonia Cases Comparison of Characteristics
Authors: Cömert Rana Günöz , Cingöz Eda , Meşe Sevim , Durak Görkem , Tunacı Atadan , Ağaçfidan Ali , Önel Mustafa , Ertürk Şükrü Mehmet
Published: May 2022

Background

Thoracic CT imaging is widely used as a diagnostic method in the diagnosis of COVID-19 pneumonia. Radiological differential diagnosis and isolation of other viral agents causing pneumonia in patients gained importance, especially during the pandemic period.

Aims

We aimed to investigate whether there is a difference between the CT imaging findings characteristically defined in COVID-19 pneumonia and the findings detected in pneumonia due to other viral agents, and which finding may be more effective in the diagnosis.

Study Design

The study included 249 adult patients with pneumonia found in thorax CT examination and positive COVID-19 RT-PCR test and 94 patients diagnosed with non-COVID pneumonia (viral PCR positive, no bacterial/fungal agents were detected in other cultures) from the last 5 years before the pandemic. It was retrospectively analyzed using the PACS System. CT findings were evaluated by two radiologists with 5 and 20 years of experience who did not know to which group the patient belonged, and it was decided by consensus.

Methods

Demographic data (age, gender, known chronic disease) and CT imaging findings (percentage of involvement, number of lesions, distribution preference, dominant pattern, ground-glass opacity distribution pattern, nodule, tree in bud sign, interstitial changes, crazy paving sign, reversed halo sign, vacuolar sign, halo sign, vascular enlargement, linear opacities, traction bronchiectasis, peribronchial wall thickness, air trapping, pleural retraction, pleural effusion, pericardial effusion, cavitation, mediastinal/hilar lymphadenopathy, dominant lesion size, consolidation, subpleural curvilinear opacities, air bronchogram, pleural thickening) of the patients were evaluated. CT findings were also evaluated with the RSNA consensus guideline and the CORADS scoring system. Data were divided into two main groups as non-COVID-19 and COVID-19 pneumonia and compared statistically with chi-square tests and multiple regression analysis of independent variables.

Results

Two main groups; RSNA and CORADS classification, percentage of involvement, number of lesions, distribution preference, dominant pattern, nodule, tree in bud, interstitial changes, crazy paving, reverse halo vascular enlargement, peribronchial wall thickness, air trapping, pleural retraction, pleural/pericardial effusion, cavitation and mediastinal/hilar lymphadenopathy were compared, significant differences were found between the groups (p < 0.01). Multiple linear regression analysis of independent variables found a significant effect of reverse halo sign (β = 0.097, p <0.05) and pleural effusion (β = 10.631, p <0.05) on COVID-19 pneumonia.

Conclusion

Presence of reverse halo and absence of pleural effusion was found to be efficient in the diagnosis of COVID-19 pneumonia.
Autoimmune interactions between the HLA-DQβ157polymorphism, T cell receptors, and microbial mimics of insulin in type 1 diabetes
Authors: García Arcadio Rubio , Paterou Athina , Powell Doherty Rebecca D. , Landry Laurie G. , Lee Mercede , Anderson Amanda M. , Scudder Claire L. , Slawinski Hubert , Ferreira Ricardo C. , Trzupek Dominik , Szypowska Agnieszka , Teyton Luc , Ternette Nicola , Nakayama Maki , Wicker Linda S. , Todd John A. , Pekalski Marcin L.
Published: May 2022

Insulin autoimmunity and pancreatic islet β-cell destruction, mediated by T cells, underlie the pathogenesis of type 1 diabetes (T1D). However, the mechanisms by which genetic and environmental risk factors interact to cause T1D remain incompletely understood. Here, we show how variation in the human leukocyte antigen (HLA) class II region, notably DQβ157, the strongest T1D genetic risk factor, induces a positive thymic selection bias that favors amino acid motifs with negatively charged side chains in the peptide-binding CDR3β region of CD4+T cell receptors (TCRs). This bias was enriched in TCRs from T1D patients and predicted the proportion of anti-insulin infiltrates in pancreatic islets. We link host genetics and immunity to the environment by identifying over 100 gut bacterial proteins with significantly similar sequences to a primary epitope in T1D, insulin B9–25peptide. We show that CD4+T cells isolated from the pancreas of a newly diagnosed child with T1D recognised both insulin and a bacterial mimotope peptide, restricted by the most predisposing DQ molecule. Our results point to the evolution of certain microbial antigens towards mimicry in the regulation of immune tolerance to insulin.
Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection
Authors: Yu Qiuning , Xia Namei , Zhao Yanteng , Jin Huifang , Chen Renyin , Ye Fanglei , Chen Liyinghui , Xie Ying , Wan Kangkang , Zhou Jun , Zhou Dihan , Lv Xianping
Published: May 2022

Background

Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease.

Methods

The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC and multiple cancer types.

Results

We obtained 438,558 DMCs, 15,462 DMRs, and 1,568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC and nine other cancer types. The HOXL-score estimated by HOXC10 and HOXD1 methylation showed good ability in discriminating ESCC from normal samples, while the methylation of GSX1 displayed potential utility for pan-cancer detection.

Conclusions

We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of multiple cancer types.
Prenatal alcohol exposure alters axon formation and Robo/Slit guidance cue expression in the internal capsule at E15.5
Authors: Chi Peter , Dewees Kevyn , Scoville Jennifer , Deak Terrence , Favero Carlita
Published: May 2022

We previously showed the prenatal alcohol exposure (PAE) induced precocious growth of E15.5 internal capsule axons. We set out to further delineate which axon tracts were affected and a potential mechanism for this phenomenon. Pregnant Swiss Webster mice were exposed to saline or 20% ethanol via subcutaneous injection from embryonic days (E) 7.5 until E14.5. E15.5 embryos were captured via C-section and brains were either fixed for immunostaining or flash frozen for tissue punches. To identify internal capsule axons we performed immunohistochemistry using L1 antibody to visualize all internal capsule axons and NetrinG1 antibody to identify thalamocortical axons specifically. mRNA was extracted from tissue punches to visualize Slit1, Robo1, Slit2, and Robo2 gene expression levels via real time RT PCR. We found that L1-expressing axons exhibited increased axon crossing in females with the opposite effect in males and no difference in Netrin-G1-expressing axons. We also found PAE increased Robo1 mRNA. Taken together, our results indicate that PAE elicits specific effects on axon trajectories, potentially via the Slit/Robo guidance family of repellents and receptors. These findings add to the growing body of evidence demonstrating alcohol disruptions of axon growth and guidance during embryonic development that may contribute to connectivity errors that characterize Fetal Alcohol Spectrum Disorders.
Mapping the landscape of anti-phage defense mechanisms in the E. coli pangenome
Authors: Vassallo Christopher , Doering Christopher , Littlehale Megan L. , Teodoro Gabriella , Laub Michael T.
Published: May 2022

The ancient, ongoing coevolutionary battle between bacteria and their viral predators, bacteriophages, has given rise to sophisticated immune systems including restriction-modification and CRISPR-Cas. Dozens of additional anti-phage systems have been identified based on their co-location within so-called defense islands, but whether these computational screens are exhaustive is unclear. Here, we developed an experimental selection scheme agnostic to genomic context to identify defense systems encoded in 71 diverse E. coli strains. Our results unveil 21 new and conserved defense systems, none of which were previously detected as enriched in defense islands. Additionally, our work indicates that intact prophages and mobile genetic elements are primary reservoirs and distributors of defense systems in E. coli, with defense systems typically carried in specific locations, or hotspots. These hotspots in homologous prophages and mobile genetic elements encode dozens of additional, as-yet uncharacterized defense system candidates. Collectively, our findings reveal an extended landscape of antiviral immunity in E. coli and provide a generalizable approach for mapping defense systems in other species.
Comprehensive Analysis of the Expression and Prognosis for PSMBs in Clear Cell Renal Cell Carcinoma
Authors: Jiang Ning , Zhang Yulin , Zhao Zihan , Li Tianhang , Liu Tianyao , Guo Hongqian , Yang Rong
Published: May 2022

Background

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignances with an ever-increasing incidence and high mortality. Although comprehensive therapy has made great progress in recent years, the prognosis of most ccRCC patients is still poor. The proteasome β subunits (PSMBs) are a group of genes composing the ubiquitin–proteasome pathway, which is the principal mechanism of protein catabolism in mammalian cytoplasm and nucleus and is essential for the regulation of almost all cellular processes. Growing evidence show s that the PSMBs play an important role in the occurrence and progression of various cancers. However, the expression and prognostic value of PSMBs in ccRCC have not been evaluated.

Methods

To solve this issue, ONCOMINE, UALCAN, Human Protein Atlas, cBioPortal, Metascape, GeneMANIA, STRING, DAVID 6.8, TIMER were used in this study.

Results

The transcriptional expression levels of PSMB2/4/7/8/9/10 in ccRCC tissues were found to be significantly upregulated, and the mRNA expression levels of PSMB1/2/3/4/8/9/10 were associated with advanced tumor stage and tumor grade. Besides, higher mRNA expression of PSMB1/2/3/4/5/6/7/10 were associated with a shorter overall survival (OS). Furthermore, the protein expression level of PSMB4/7/8/9/10 in ccRCC was higher than normal renal tissues. Significant relationships were also found between the expression of PSMBs and the infiltration of immune-related cells.

Conclusions

The present study implied that PSMB4 and PSMB10 might act as potential therapy targets and prognostic biomarkers in ccRCC, which may contribute to available knowledge, improve the treatment designs, and enhance the accuracy of prognosis for patients with ccRCC.
DOXYCYCLINE TO TREAT LEVODOPA-INDUCED DYSKINESIAS IN PARKINSON’S DISEASE: A PROOF-OF-CONCEPT STUDY
Authors: Santos-Lobato Bruno Lopes , Brito Manuelina Mariana Capellari Macruz , Pimentel Ângela Vieira , Cavalcanti Rômulo Torres Oliveira , Del-Bel Elaine , Tumas Vitor
Published: May 2022

Background

Levodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinson’s disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties.

Objective

Evaluate the efficacy and safety of doxycycline in patients with PD and LID.

Methods

This was an open-label, single-center, phase 2 proof-of-concept study in patients with PD with mild functional impact of dyskinesia, which used levodopa three times daily, in a movement disorders clinic in Brazil. Participants were treated with doxycycline 200 mg/day for 12 weeks, with evaluations in baseline, week 4, and week 12 of treatment. The primary outcome measure was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) total score at week 12, evaluated by two blinded raters. Key secondary outcomes measures were OFF time and ON time with troublesome dyskinesia in the PD home diary.

Results

Eight patients with PD were treated and evaluated. Doxycycline 200 mg/day reduced the UDysRS total score in week 12, compared with baseline (Friedman’s X2= 9.6, p = 0.008). Further, doxycycline reduced the ON time with troublesome dyskinesia (Friedman’s X2= 10.8, p = 0.004) without worsening parkinsonism. There were no severe adverse events, and dyspepsia was the commonest event.

Conclusions

Doxycycline was effective in reducing LID and safe after a 12-week treatment. Further well-designed placebo-controlled clinical trials with a longer duration and a larger number of participants are needed.
Surface changes of clinical target volume and its sublocations in nasopharyngeal cancer with image-guided radiation therapy
Authors: Tan Wenyong , Yang Ming , Hu Desheng
Published: May 2022

PURPOSE

We aimed to quantify the sublocal geometric uncertainties of the neck prophylactic clinical target volume (CTVprophy) during image-guided radiotherapy for nasopharyngeal cancer (NPC).

MATERIALS AND METHODS

Twenty patients with locally advanced NPC underwent one planning computed tomography (CTplan) followed by six weekly CT (CTrepeat) scans during chemotherapy and intensity-modulated radiation therapy. The sternocleidomastoid muscle (SCM) and its anterior, middle, and posterior parts, as well as the body contours at the 1st (C1) and 2nd (C2) cervical vertebrae, hyoid bone (HB), and cricoid cartilage (CC) in transverse CT sections, were manually delineated in the CTplan and each CTrepeat. The residual error and 2D or 3D vector displacements of each sublocation were calculated, and the planning target volume (PTV) margins were estimated using the PTV margin formula.

RESULTS

The left- and right-sided SCM volume decreased by 3.7 ± 9.6% (1.9–5.4%) and 5.1 ± 6.7% (3.9–6.3%), respectively, and the center of mass shifted medially 0.8–0.9 mm. An anisotropic PTV margin of 2–4 and 1–5 mm was needed in the left-right and anterior-posterior directions, respectively. The geometric changes in the upper neck at the C1 and C2 sections were smaller than those in the middle-lower neck at the HB and CC levels. At the same sublocation, the margin needed in the anterior-middle part was smaller than that needed in the posterior part of the neck. The rigid imaging registration-induced anatomical errors in the upper neck were < 1.9%, and those in the middle and lower neck level were 0.6–3.8%.

CONCLUSIONS

The surface geometrical changes of the neck prophylactic CTV in the sublocations are substantial and an anisotropic PTV margin of 1–5 mm is needed in the context of image-guided radiotherapy for NPC.
Reweighting the UK Biobank to reflect its underlying sampling population substantially reduces pervasive selection bias due to volunteering
Authors: van Alten Sjoerd , Domingue Benjamin W. , Galama Titus , Marees Andries T.
Published: May 2022

The UK Biobank (UKB) is a large cohort study of considerable empirical importance to fields such as medicine, epidemiology, statistical genetics, and the social sciences, due to its very large size (∼ 500,000 individuals) and its wide availability of variables. However, the UKB is not representative of its underlying sampling population. Selection bias due to volunteering (volunteer bias) is a known source of confounding. Individuals entering the UKB are more likely to be older, to be female, and of higher socioeconomic status. Using representative microdata from the UK Census as a reference, we document significant bias in estimated associations due to non-random selection into the UKB. For some associations, volunteer bias in the UKB is so severe that estimates have the opposite sign. E.g., older individuals in the UKB tend to be in better health. To aid researchers in correcting for volunteer bias in the UKB, we construct inverse probability weights based on UK census microdata. The use of these weights in weighted regressions reduces 78% of volunteer bias on average. Our inverse probability weights will be made available.