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AnteayerBMJ Open

Subphenotypes of self-reported symptoms and outcomes in long COVID: a prospective cohort study with latent class analysis

Por: Kitsios · G. D. · Blacka · S. · Jacobs · J. J. · Mirza · T. · Naqvi · A. · Gentry · H. · Murray · C. · Wang · X. · Golubykh · K. · Qurashi · H. · Dodia · A. · Risbano · M. · Benigno · M. · Emir · B. · Weinstein · E. · Bramson · C. · Jiang · L. · Dai · F. · Szigethy · E. · Mellors · J. W. · Met
Objective

To characterise subphenotypes of self-reported symptoms and outcomes (SRSOs) in postacute sequelae of COVID-19 (PASC).

Design

Prospective, observational cohort study of subjects with PASC.

Setting

Academic tertiary centre from five clinical referral sources.

Participants

Adults with COVID-19 ≥20 days before enrolment and presence of any new self-reported symptoms following COVID-19.

Exposures

We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardised assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via quantitative PCR.

Outcomes measures

Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA) and relationship with viral load.

Results

We analysed baseline data for 214 individuals with a study visit at a median of 197.5 days after COVID-19 diagnosis. Participants reported ever having a median of 9/16 symptoms (IQR 6–11) after acute COVID-19, with muscle-aches, dyspnoea and headache being the most common. Fatigue, cognitive impairment and dyspnoea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3 (1–6)) than those ever experienced (p

Conclusions

We identified three distinct PASC subphenotypes. We highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.

UK medical students self-reported knowledge and harm assessment of psychedelics and their application in clinical research: a cross-sectional study

Por: Song-Smith · C. · Jacobs · E. · Rucker · J. · Saint · M. · Cooke · J. · Schlosser · M.
Objective

To capture UK medical students’ self-reported knowledge and harm assessment of psychedelics and to explore the factors associated with support for changing the legal status of psychedelics to facilitate further clinical research.

Design

Cross-sectional, anonymous online survey of UK medical students using a non-random sampling method.

Setting

UK medical schools recognised by the General Medical Council.

Participants

132 medical students who had spent an average of 3.8 years (SD=1.4; range: 1–6) in medical school.

Results

Most students (83%) reported that they were aware of psychedelic research and only four participants (3%) said that they were not interested in learning more about this type of research. Although medical students’ harm assessment of psychedelics closely aligned with that of experts, only 17% of students felt well-educated on psychedelic research. Teachings on psychedelics were only rarely encountered in their curriculum (psilocybin: 14.1 (SD=19.9), scale: 0 (never) to 100 (very often)). Time spent at medical schools was not associated with more knowledge about psychedelics (r=0.12, p=0.129). On average, this sample of medical students showed strong support for changing the legal status of psychedelics to facilitate further research into their potential clinical applications (psilocybin: 80.2 (SD=24.8), scale: 0 (strongly oppose) to 100 (strongly support)). Regression modelling indicated that greater knowledge of psychedelics (p

Conclusions

Our findings reveal a significant interest among UK medical students to learn more about psychedelic research and a strong support for further psychedelic research. Future studies are needed to examine how medical education could be refined to adequately prepare medical students for a changing healthcare landscape in which psychedelic-assisted therapy could soon be implemented in clinical practice.

Examining geospatial and temporal distribution of invasive non-typhoidal Salmonella disease occurrence in sub-Saharan Africa: a systematic review and modelling study

Por: Kim · J.-H. · Tack · B. · Fiorino · F. · Pettini · E. · Marchello · C. · Jacobs · J. · Crump · J. · Marks · F. · Vacc-iNTS Consortium
Background

Invasive non-typhoidal Salmonella (iNTS) disease is a significant health concern in sub-Saharan Africa. While our knowledge of a larger-scale variation is growing, understanding of the subnational variation in iNTS disease occurrence is lacking, yet crucial for targeted intervention.

Method

We performed a systematic review of reported occurrences of iNTS disease in sub-Saharan Africa, consulting literature from PubMed, Embase and Web of Science published since 2000. Eligibility for inclusion was not limited by study type but required that studies reported original data on human iNTS diseases based on the culture of a normally sterile site, specifying subnational locations and the year, and were available as full-text articles. We excluded studies that diagnosed iNTS disease based on clinical indications, cultures from non-sterile sites or serological testing. We estimated the probability of occurrence of iNTS disease for sub-Saharan Africa on 20 km x 20 km grids by exploring the association with geospatial covariates such as malaria, HIV, childhood growth failure, access to improved water, and sanitation using a boosted regression tree.

Results

We identified 130 unique references reporting human iNTS disease in 21 countries published from 2000 through 2020. The estimated probability of iNTS occurrence grids showed significant spatial heterogeneity at all levels (20 km x 20 km grids, subnational, country and subregional levels) and temporal heterogeneity by year. For 2020, the probability of occurrence was higher in Middle Africa (0.34, 95% CI: 0.25 to 0.46), followed by Western Africa (0.33, 95% CI: 0.23 to 0.44), Eastern Africa (0.24, 95% CI: 0.17 to 0.33) and Southern Africa (0.08, 95% CI: 0.03 to 0.11). Temporal heterogeneity indicated that the probability of occurrence increased between 2000 and 2020 in countries such as the Republic of the Congo (0.05 to 0.59) and Democratic Republic of the Congo (0.10 to 0.48) whereas it decreased in countries such as Uganda (0.65 to 0.23) or Zimbabwe (0.61 to 0.37).

Conclusion

The iNTS disease occurrence varied greatly across sub-Saharan Africa, with certain regions being disproportionately affected. Exploring regions at high risk for iNTS disease, despite the limitations in our data, may inform focused resource allocation. This targeted approach may enhance efforts to combat iNTS disease in more affected areas.

Prevalence and population characteristics associated with frailty in a rural low socioeconomic area in Denmark: the Lolland-Falster Health Study

Por: Christensen · M. G. · Jacobsen · K. K. · Nilsson · C. · Jepsen · R. · Thygesen · L. · Suetta · C. · Holm · E. A.
Background

Frailty is a major geriatric syndrome that predicts increased vulnerability to minor stressor events and adverse outcomes such as falls, fractures, disability and death. The prevalence of frailty among individuals above the age of 65 varies widely with an overall weighted prevalence of 10.7%.

Objectives

The purpose of this study was to examine the prevalence of prefrailty and frailty in community-dwelling older adults from the regions of Lolland-Falster, which is one of the most socioeconomically disadvantaged areas of Denmark with lower income and lower life expectancy compared with the general Danish population. Moreover, the objective was to find selected individual characteristics associated with frailty.

Design

An observational, cross-sectional registry-based population study with data from the regions of Lolland-Falster collected between February 2016 and February 2020.

Results

The study included 19 000 individuals. There were 10 154 above the age of 50 included for analysis. Prevalence of frailty in the age group of 50–64 years was 4.7% and 8.7% in the age group of 65 years and above.

The study demonstrates associations between frailty and high age, female gender, low education level, low income, smoking, living alone, frequency of seeing one’s children and getting help when needed. These associations are comparable with findings from other studies.

Conclusion

The syndrome of frailty consists of not only physiological and medical issues but also education, life conditions such as living alone and living in poverty and how you evaluate your own health.

Implementing adaptive e-learning for newborn care in Tanzania: an observational study of provider engagement and knowledge gains

Por: Meaney · P. A. · Hokororo · A. · Ndosi · H. · Dahlen · A. · Jacob · T. · Mwanga · J. R. · Kalabamu · F. S. · Joyce · C. L. · Mediratta · R. · Rozenfeld · B. · Berg · M. · Smith · Z. H. · Chami · N. · Mkopi · N. · Mwanga · C. · Diocles · E. · Agweyu · A.
Introduction

To improve healthcare provider knowledge of Tanzanian newborn care guidelines, we developed adaptive Essential and Sick Newborn Care (aESNC), an adaptive e-learning environment. The objectives of this study were to (1) assess implementation success with use of in-person support and nudging strategy and (2) describe baseline provider knowledge and metacognition.

Methods

6-month observational study at one zonal hospital and three health centres in Mwanza, Tanzania. To assess implementation success, we used the Reach, Efficacy, Adoption, Implementation and Maintenance framework and to describe baseline provider knowledge and metacognition we used Howell’s conscious-competence model. Additionally, we explored provider characteristics associated with initial learning completion or persistent activity.

Results

aESNC reached 85% (195/231) of providers: 75 medical, 53 nursing and 21 clinical officers; 110 (56%) were at the zonal hospital and 85 (44%) at health centres. Median clinical experience was 4 years (IQR 1–9) and 45 (23%) had previous in-service training for both newborn essential and sick newborn care. Efficacy was 42% (SD ±17%). Providers averaged 78% (SD ±31%) completion of initial learning and 7% (SD ±11%) of refresher assignments. 130 (67%) providers had ≥1 episode of inactivity >30 day, no episodes were due to lack of internet access. Baseline conscious-competence was 53% (IQR: 38%–63%), unconscious-incompetence 32% (IQR: 23%–42%), conscious-incompetence 7% (IQR: 2%–15%), and unconscious-competence 2% (IQR: 0%–3%). Higher baseline conscious-competence (OR 31.6 (95% CI 5.8 to 183.5)) and being a nursing officer (aOR: 5.6 (95% CI 1.8 to 18.1)), compared with medical officer, were associated with initial learning completion or persistent activity.

Conclusion

aESNC reach was high in a population of frontline providers across diverse levels of care in Tanzania. Use of in-person support and nudging increased reach, initial learning and refresher assignment completion, but refresher assignment completion remains low. Providers were often unaware of knowledge gaps, and lower baseline knowledge may decrease initial learning completion or activity. Further study to identify barriers to adaptive e-learning normalisation is needed.

Hidden sodium in effervescent-tablet dietary supplements and over-the-counter drugs: a comparative cross-sectional study

Por: Kunz · M. · Götzinger · F. · Jacobs · C. M. · Lauder · L. · Ukena · C. · Meyer · M. R. · Laufs · U. · Schulz · M. · Böhm · M. · Mahfoud · F.
Objective

Dietary sodium intake represents a risk factor for cardiovascular disease and mortality. The study sought to analyse the sodium content of effervescent dietary supplements and drugs in Germany and the USA.

Design

Comparative cross-sectional study.

Setting and methods

The sodium content of 39 dietary supplement effervescent tablets available in Germany was measured in May and June 2022 using optical emission spectrometry with inductively coupled argon plasma. The sodium content of 33 common pharmacy-only effervescent tablets (over-the-counter (OTC) drugs) in Germany was obtained from the summary of product characteristics. We compared the sodium content of the measured German dietary supplement effervescent tablets to that of 51 dietary supplement effervescent tablets available in the USA (data: National Institutes of Health’s Dietary Supplement Label Database).

Results

The measured sodium content in the German dietary supplements was 283.9±122.6 mg sodium/tablet, equivalent to 14±6% of the maximum recommended daily sodium intake (MRDSI). Vitamin products had the highest (378.3±112.8 mg, 19±6% of MRDSI), and calcium products had the lowest mean sodium content (170.4±113.2 mg, 9±6% of MRDSI). Vitamin products contained significantly more sodium than magnesium (378.3 mg vs 232.7 mg; p=0.004), calcium (378.3 mg vs 170.4 mg; p=0.006) and mineral products (378.3 mg vs 191.6 mg; p=0.048). The sodium content measured in products available in Germany was higher when compared with the declared sodium content on the label of the products sold in the USA (283.9 mg vs 190.0 mg; p

Conclusion

Effervescent tablets of nutritional supplements and OTC drugs contain high amounts of sodium, which often is not disclosed.

Salmonella Vaccine Study in Oxford (SALVO) trial: protocol for an observer-participant blind randomised placebo-controlled trial of the iNTS-GMMA vaccine within a European cohort

Por: Hanumunthadu · B. · Kanji · N. · Owino · N. · Ferreira Da Silva · C. · Robinson · H. · White · R. · Ferruzzi · P. · Nakakana · U. · Canals · R. · Pollard · A. J. · Ramasamy · M. · Vacc-iNTS Consortium · Agyapong · Breghi · Crump · Fiorino · Gordon · Jacobs · Kariuki · Malvolti · Mante
Introduction

Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal Salmonellae serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.

Method and analysis

The Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.

The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.

Ethics and dissemination

Ethical approval for this study has been obtained from the South Central—Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.

Trial registration number

EudraCT Number: 2020-000510-14.

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