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Case-control study to estimate odds of death within 28 days of positive test for SARS-CoV-2 prior to vaccination for residents of long-term care facilities in England, 2020-2021

J Epidemiol Community Health. 2021 Nov 11:jech-2021-218135. doi: 10.1136/jech-2021-218135. Online ahead of print.

ABSTRACT

BACKGROUND: Persons living in long-term care facilities (LTCFs) are presumed to be at higher risk of adverse outcomes from SARS-CoV-2 infection due to increasing age and frailty, but the magnitude of increased risk is not well quantified.

METHODS: After linking demographic and mortality data for cases with confirmed SARS-CoV-2 infection between March 2020 and January 2021 in England, a random sample of 6000 persons who died and 36 000 who did not die within 28 days of a positive test was obtained from the dataset of 3 020 800 patients. Based on an address-matching process, the residence type of each case was categorised into one of private home and residential or nursing LTCF. Univariable and multivariable logistic regression analysis was conducted.

RESULTS: Multivariable analysis showed that an interaction effect between age and residence type determined the outcome. Compared with a 60-year-old person not living in LTCF, the adjusted OR (aOR) for same-aged persons living in residential and nursing LTCFs was 1.77 (95% CI 1.21 to 2.6, p=0.0017) and 3.95 (95% CI 2.77 to 5.64, p<0.0001), respectively. At 90 years of age, aORs were 0.87 (95% CI 0.72 to 1.06, p=0.21) and 0.74 (95% CI 0.61 to 0.9, p=0.001), respectively. The model had an overall accuracy of 94.2% (94.2%) when applied to the full dataset of 2 978 800 patients.

CONCLUSION: This study found that residents of LTCFs in England had higher odds of death up to 80 years of age. Beyond 80 years, there was no difference in the odds of death for LTCF residents compared with those in the wider community.

PMID:34764218 | DOI:10.1136/jech-2021-218135

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Gestational Diabetes Mellitus and the Risks of Overall and Type-Specific Cardiovascular Diseases: A Population- and Sibling-Matched Cohort Study

Diabetes Care. 2021 Nov 11:dc211018. doi: 10.2337/dc21-1018. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate associations between gestational diabetes mellitus (GDM) and various incident cardiovascular disease (CVD) end points, considering the effects of the mediating role of type 2 diabetes and shared environmental/familial factors.

RESEARCH DESIGN AND METHODS: This population-based cohort study included 10,02,486 parous women in Denmark during 1978-2016. We used Cox regression to 1) examine the associations of GDM with overall and type-specific CVDs using full-cohort and sibling-matched analysis, 2) quantify the impact of type 2 diabetes after GDM using mediation analysis, and 3) assess whether these associations were modified by prepregnancy obesity or maternal history of CVD.

RESULTS: Women with a history of GDM had a 40% increased overall CVD risk (hazard ratio [HR] 1.40, 95% CI 1.35-1.45). Sibling-matched analyses yielded similar results (HR, 1.44; 95% CI 1.28-1.62). The proportion of association between GDM and overall CVD explained by subsequent type 2 diabetes was 23.3% (15.4-32.8%). We observed increased risks of specific CVDs, including 65% increased stroke risk and more than twofold risks for myocardial infarction, heart failure, and peripheral artery disease. The elevated overall risks were more pronounced among women with GDM and prepregnancy obesity or maternal history of CVD.

CONCLUSIONS: A history of GDM was associated with increased risks of overall and specific CVDs. Increased risks were partly explained by subsequent type 2 diabetes, and the need to identify other pathways remains important. Continuous monitoring of women with a history of GDM, especially those with prepregnancy obesity or maternal history of CVD, may provide better opportunities to reduce their cardiovascular risk.

PMID:34764208 | DOI:10.2337/dc21-1018

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Adjuvant pembrolizumab versus interferon alfa-2b or ipilimumab in resected high-risk melanoma

Cancer Discov. 2021 Nov 11:candisc.1141.2021. doi: 10.1158/2159-8290.CD-21-1141. Online ahead of print.

ABSTRACT

We conducted a randomized phase 3 trial to evaluate whether adjuvant pembrolizumab for one year (648 patients) improved recurrence-free survival (RFS) or overall survival (OS) in comparison to high-dose interferon alfa-2b for one year or ipilimumab for up to three years (655 patients), the approved standard-of-care adjuvant immunotherapies at the time of enrollment for patients with high-risk resected melanoma. At a median follow-up of 47.5 months, pembrolizumab was associated with significantly longer RFS than prior standard-of-care adjuvant immunotherapies (hazard ratio [HR] 0.77; 99.62% confidence interval [CI] 0.59-0.99; P=0.002). There was no statistically significant association with OS among all patients (HR, 0.82; 96.3% CI 0.61-1.09; P=0.15). Proportions of treatment-related adverse events of grades 3 to 5 were 19.5% with pembrolizumab, 71.2% with interferon alfa-2b, and 49.2% with ipilimumab. Therefore, adjuvant pembrolizumab significantly improved RFS but not OS compared to the prior standard-of-care immunotherapies for patients with high-risk resected melanoma.

PMID:34764195 | DOI:10.1158/2159-8290.CD-21-1141

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Tuberculosis and COVID-19 co-infection: description of the global cohort

Eur Respir J. 2021 Nov 11:2102538. doi: 10.1183/13993003.02538-2021. Online ahead of print.

ABSTRACT

Information on tuberculosis (TB) and COVID-19 is still limited. The aim of this study is to describe the features of the TB/COVID-19 co-infected individuals from a prospective, anonymised, multi-country register-based cohort with special focus on the determinants of mortality and other outcomes. We enrolled all patients of any age with either active TB or previous TB and COVID-19. 172 centres from 34 countries provided individual data on 767 TB-COVID-19 co-infected patients, (>50% population-based). Of 767 patients, 553/747 (74.0%) had TB before COVID-19 (including 234/747 with previous TB), 71/747 (9.5%) had COVID-19 first and 123/747 (16.5%) had both diseases diagnosed within the same week (35, 4.6% on the same day). 85/767 patients died (11.08%) (41/289 (14.2%) in Europe and 44/478 (9.2%) outside Europe; (p=0.03)): 42 (49.4%) from COVID-19, 31 (36.5%) from COVID-19 and TB, 1/85 (1.2%) from TB and 11 from other causes. In the univariate analysis on mortality the following variables reached statistical significance: age, being male, having >1 comorbidity; diabetes mellitus, cardiovascular disease, chronic respiratory disease, chronic renal disease, presence of key symptoms, invasive ventilation and hospitalisation due to COVID-19. The final multivariable logistic regression model included age, male gender, and invasive ventilation as independent contributors to mortality. The data suggests TB and COVID-19 are a “cursed duet” and need immediate attention. TB should be considered a risk factor for severe COVID disease and patients with TB should be prioritised for COVID-19 preventative efforts, including vaccination.

PMID:34764184 | DOI:10.1183/13993003.02538-2021

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Sensor technology to monitor health, well-being and movement among healthcare personnel at workplace: a systematic scoping review protocol

BMJ Open. 2021 Nov 11;11(11):e054408. doi: 10.1136/bmjopen-2021-054408.

ABSTRACT

INTRODUCTION: The well-being and health of healthcare personnel is becoming increasingly important in the delivery of high-quality healthcare. The recent developments in technology have provided new opportunities for the objective detection of a wide variety of real-world properties and movement. However, technologies that are used to monitor health, well-being and movement among healthcare personnel have not been fully synthesised. The overall aim of this scoping review is to examine what type of sensor technology is available to monitor the health, well-being and movement of healthcare personnel in healthcare settings. More specifically, we want to explore what types of sensor technology applications, for what purposes and how they have been used to monitor health, well-being and movement among healthcare personnel in different workplace settings.

METHODS AND ANALYSIS: This scoping review protocol will follow Arksey and O’Malley’s methodology, complemented by the approach of the Joanna Briggs Institute to scoping reviews and guidance for conducting systematic scoping reviews. Peer-reviewed literature will be identified using a search strategy developed by a librarian, and a wide range of electronic datasets of medical, computer and information systems disciplines will be used. Eligibility of the articles will be determined using a two-stage screening process consisting of (1) a title and abstract scan, and (2) a full-text review. Extracted data will be thematically analysed and validated by an expert of sensor technology and a group of nurses as stakeholders. Descriptive statistics will be calculated when necessary.

ETHICS AND DISSEMINATION: The results obtained from the review will inform what technology has been used, how it has been used in healthcare settings and what types of technology might still be needed for future innovations. Findings of the scoping review will be published in a peer-reviewed journal.

REGISTRATION: This review was submitted in Open Science Framework on 12 December 2020.

PMID:34764179 | DOI:10.1136/bmjopen-2021-054408

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Neoadjuvant therapy or upfront surgery in advanced endometrial cancer: a systematic review protocol

BMJ Open. 2021 Nov 11;11(11):e054004. doi: 10.1136/bmjopen-2021-054004.

ABSTRACT

INTRODUCTION: There is no consensus on the optimal treatment strategy for people with advanced endometrial cancer. Neoadjuvant therapies such as chemotherapy and radiotherapy have been employed to try to reduce the morbidity of surgery, improve its feasibility and/or improve functional performance in people considered unfit for primary surgery. The objective of this review is to assess whether neoadjuvant chemotherapy or radiotherapy improves health outcomes in people with advanced endometrial cancer when compared with upfront surgery.

METHODS AND ANALYSIS: This review will consider both randomised and non-randomised studies that compare health outcomes associated with the neoadjuvant therapy and upfront surgery in advanced endometrial cancer. Potential studies for inclusion will be collated from electronic searches of OVID Medline, Embase, international trial registries and conference abstract lists. Data collection and extraction will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodological quality of the studies will be assessed using the Risk of Bias 2 and Risk of Bias in Non-randomised Studies of Interventions tools. If appropriate, we will perform a meta-analysis and provide summary statistics for each outcome.

ETHICS AND DISSEMINATION: Ethics approval was not required for this study. Once complete, we will publish our findings in peer-reviewed publications, via conference presentations and to update relevant practice guidelines.

PMID:34764178 | DOI:10.1136/bmjopen-2021-054004

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Integrating expert knowledge for dementia risk prediction in individuals with mild cognitive impairment (MCI): a study protocol

BMJ Open. 2021 Nov 11;11(11):e051185. doi: 10.1136/bmjopen-2021-051185.

ABSTRACT

INTRODUCTION: To date, there is no broadly accepted dementia risk score for use in individuals with mild cognitive impairment (MCI), partly because there are few large datasets available for model development. When evidence is limited, the knowledge and experience of experts becomes more crucial for risk stratification and providing MCI patients with prognosis. Structured expert elicitation (SEE) includes formal methods to quantify experts’ beliefs and help experts to express their beliefs in a quantitative form, reducing biases in the process. This study proposes to (1) assess experts’ beliefs about important predictors for 3-year dementia risk in persons with MCI through SEE methodology and (2) to integrate expert knowledge and patient data to derive dementia risk scores in persons with MCI using a Bayesian approach.

METHODS AND ANALYSIS: This study will use a combination of SEE methodology, prospectively collected clinical data, and statistical modelling to derive a dementia risk score in persons with MCI . Clinical expert knowledge will be quantified using SEE methodology that involves the selection and training of the experts, administration of questionnaire for eliciting expert knowledge, discussion meetings and results aggregation. Patient data from the Prospective Registry for Persons with Memory Symptoms of the Cognitive Neurosciences Clinic at the University of Calgary; the Alzheimer’s Disease Neuroimaging Initiative; and the National Alzheimer’s Coordinating Center’s Uniform Data Set will be used for model training and validation. Bayesian Cox models will be used to incorporate patient data and elicited data to predict 3-year dementia risk.

DISCUSSION: This study will develop a robust dementia risk score that incorporates clinician expert knowledge with patient data for accurate risk stratification, prognosis and management of dementia.

PMID:34764172 | DOI:10.1136/bmjopen-2021-051185

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Expert consensus on a standardised definition and severity classification for adverse events associated with spinal and peripheral joint manipulation and mobilisation: protocol for an international e-Delphi study

BMJ Open. 2021 Nov 11;11(11):e050219. doi: 10.1136/bmjopen-2021-050219.

ABSTRACT

INTRODUCTION: Spinal and peripheral joint manipulation (SMT) and mobilisation (MOB) are widely used and recommended in the best practice guidelines for managing musculoskeletal conditions. Although adverse events (AEs) have been reported following these interventions, a clear definition and classification system for AEs remains unsettled. With many professionals using SMT and MOB, establishing consensus on a definition and classification system is needed to assist with the assimilation of AEs data across professions and to inform research priorities to optimise safety in clinical practice.

METHODS AND ANALYSIS: This international multidisciplinary electronic Delphi study protocol is informed by a scoping review and in accordance with the ‘Guidance on Conduction and Reporting Delphi Studies’. With oversight from an expert steering committee, the study comprises three rounds using online questionnaires. Experts in manual therapy and patient safety meeting strict eligibility criteria from the following fields will be invited to participate: clinical, medical and legal practice, health records, regulatory bodies, researchers and patients. Round 1 will include open-ended questions on participants’ working definition and/or understanding of AEs following SMT and MOB and their severity classification. In round 2, participants will rate their level of agreement with statements generated from round 1 and our scoping review. In round 3, participants will rerate their agreement with statements achieving consensus in round 2. Statements reaching consensus must meet the a priori criteria, as determined by descriptive analysis. Inferential statistics will be used to evaluate agreement between participants and stability of responses between rounds. Statements achieving consensus in round 3 will provide an expert-derived definition and classification system for AEs following SMT and MOB.

ETHICS AND DISSEMINATION: This study was approved by the Canadian Memorial Chiropractic College Research Ethics Board and deemed exempt by Parker University’s Institutional Review Board. Results will be disseminated through scientific, professional and educational reports, publications and presentations.

PMID:34764170 | DOI:10.1136/bmjopen-2021-050219

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Relevance of assessment items in community paramedicine home visit programmes: results of a modified Delphi study

BMJ Open. 2021 Nov 11;11(11):e048504. doi: 10.1136/bmjopen-2020-048504.

ABSTRACT

OBJECTIVE: Guidelines for a structured assessment in community paramedicine home visit programmes have not been established and evidence to inform their creation is lacking. We sought to investigate the relevance of assessment items to the practice of community paramedics according to a pre-established clarity-utility matrix.

DESIGN: We designed a modified-Delphi study consisting of predetermined thresholds for achieving consensus, number of rounds of for scoring items, a defined meeting and discussion process, and a sample of participants that was purposefully representative.

SETTING AND PARTICIPANTS: We established a panel of 26 community paramedics representing 20 municipal paramedic services in Ontario, Canada. The sample represented a majority of paramedic services within the province that were operating a community paramedicine home visit programme.

MEASURES: Drawing from a bank of standardised assessment items grouped according to domains aligned with the International Classification on Functioning, Disability, and Health taxonomy, 64 previously pilot-tested assessment items were scored according to their clarity (being free from ambiguity and easy to understand) and utility (being valued in care planning or case management activities). Assessment items covered a broad range of health, social and environmental domains. To conclude scoring rounds, assessment items that did not achieve consensus for relevance to assessment practices were discussed among participants with opportunities to modify assessment items for subsequent rounds of scoring.

RESULTS: Resulting from the first round of scoring, 54 assessment items were identified as being relevant to assessment practices and 3 assessment items were removed from subsequent rounds. The remaining 7 assessment items were modified, with some parts removed from the final items that achieved consensus in the final rounds of scoring.

CONCLUSION: A broadly representative panel of community paramedics identified consensus for 61 assessment items that could be included in a structured, multidomain, assessment instrument for guiding practice in community paramedicine home visit programmes.

TRAIL REGISTRATION NUMBER: ISRCTN58273216.

PMID:34764166 | DOI:10.1136/bmjopen-2020-048504

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Barn Owl’s Auditory Space Map Activity Matching Conditions for a Population Vector Readout to Drive Adaptive Sound Localizing Behavior

J Neurosci. 2021 Nov 10:JN-RM-1061-21. doi: 10.1523/JNEUROSCI.1061-21.2021. Online ahead of print.

ABSTRACT

Space specific neurons in the owl’s midbrain form a neural map of auditory space, which supports sound orienting behavior. Previous work proposed that a population vector (PV) readout of this map, implementing statistical inference, predicts the owl’s sound localization behavior. This model also predicts the frontal localization bias normally observed and how sound localizing behavior changes when the signal to noise ratio varies, based on the spread of activity across the map. However, the actual distribution of population activity and whether this pattern is consistent with premises of the PV readout model on a trial-by-trial bases remains unknown. To answer these questions, we investigated whether the population response profile across the midbrain map in the barn owl’s optic tectum matches these predictions using in vivo multi-electrode array recordings. We found that response profiles of recorded sub-populations are sufficient for estimating the stimulus ITD using responses from single trials. Furthermore, this decoder matches the expected differences in trial-by-trial variability and frontal bias between stimulus conditions of low and high signal-to-noise ratio. These results support the hypothesis that a PV readout of the midbrain map can mediate statistical inference in sound localizing behavior of barn owls.SIGNIFICANCE STATEMENTWhile the tuning of single neurons in the owl’s midbrain map of auditory space has been considered predictive of this species’ highly specialized sound localizing behavior, response properties across the population remain largely unknown. For the first time, this study analyzed the spread of population responses across the map using multi-electrode recordings and how it changes with signal-to-noise ratio. The observed responses support the hypothesis of a population vector readout’s ability to predict biases in orienting behaviors and mediate uncertainty-dependent behavioral commands. The results are of significance for understanding potential mechanisms for the implementation of optimal behavioral commands across species.

PMID:34764158 | DOI:10.1523/JNEUROSCI.1061-21.2021