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Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)

Por: Somayaji · R. · Luke · D. R. · Lau · A. · Guner · R. · Tabak · O. F. · Hepokoski · M. · Gardetto · N. · Conrad · S. A. · Kumar · S. D. · Ghosh · K. · Robbins · S. M. · Senger · D. L. · Sun · D. · Lim · R. K. S. · Liu · J. · Eser · F. · Karaali · R. · Tremblay · A. · Muruve · D.
Objective

Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.

Design

Phase 2a randomised, placebo-controlled, double-blinded, trial.

Setting

Hospitals in Canada, Turkey and the USA.

Participants

A total of 61 subjects with moderate-to-severe COVID-19.

Interventions

Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.

Primary and secondary outcome measures

The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.

Results

At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.

Conclusion

In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.

Trial registration number

NCT04402957.

Impact of human papillomavirus age-related prevalence and vaccination levels on interpretation of cervical screening modalities: a modelling study

Por: Grimes · D. R.
Objective

Cervical screening is a life-saving intervention, which reduces the incidence of and mortality from cervical cancer in the population. Human papillomavirus (HPV) based screening modalities hold unique promise in improving screening accuracy. HPV prevalence varies markedly by age, as does resultant cervical intraepithelial neoplasia (CIN), with higher rates recorded in younger women. With the advent of effective vaccination for HPV drastically reducing prevalence of both HPV and CIN, it is critical to model how the accuracy of different screening approaches varies with age cohort and vaccination status. This work establishes a model for the age-specific prevalence of HPV factoring in vaccine coverage and predicts how the accuracy of common screening modalities is affected by age profile and vaccine uptake.

Design

Modelling study of HPV infection rates by age, ascertained from European cohorts prior to the introduction of vaccination. Reductions in HPV due to vaccination were estimated from the bounds predicted from multiple modelling studies, yielding a model for age-varying HPV and CIN grades 2 and above (CIN2+) prevalence.

Setting

Performance of both conventional liquid-based cytology (LBC) screening and HPV screening with LBC reflex (HPV reflex) was estimated under different simulated age cohorts and vaccination levels.

Participants

Simulated populations of varying age and vaccination status.

Results

HPV-reflex modalities consistently result in much lower incidence of false positives than LBC testing, with an accuracy that improves even as HPV and CIN2+ rates decline.

Conclusions

HPV-reflex tests outperform LBC tests across all age profiles, resulting in greater test accuracy. This improvement is especially pronounced as HPV infection rates fall and suggests HPV-reflex modalities are robust to future changes in the epidemiology of HPV.

Cohort profile: evaluation of immune response and household transmission of SARS-CoV-2 in Costa Rica: the RESPIRA study

Por: Loria · V. · Aparicio · A. · Hildesheim · A. · Cortes · B. · Barrientos · G. · Retana · D. · Sun · K. · Ocampo · R. · Prevots · D. R. · Zuniga · M. · Waterboer · T. · Wong-McClure · R. · Morera · M. · Butt · J. · Binder · M. · Abdelnour · A. · Calderon · A. · Gail · M. H. · Pfeiffer · R. M.
Purpose

The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19.

Participants

From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence.

Findings to date

Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up.

Future plans

RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024.

Trial registration number

NCT04537338.

Vocal tasks for acoustic and/or auditory perceptual analysis for discriminating individuals with and without voice disorders: a systematic review protocol

Por: Gunjawate · D. R. · Chacon · A. M. · Nguyen · D. D. · Madill · C.
Objective

The primary objective of the present systematic review is to: (1) identify the current vocal tasks being used for acoustic and/or auditory perceptual analysis to differentiate between individuals with and without voice disorders. The secondary objectives are to: (2) evaluate the evidence of the sensitivity, specificity and accuracy of those vocal tasks for acoustic and/or auditory perceptual analysis in discriminating the individuals with voice disorders from those without; and (3) compare the values between the vocal tasks in discriminating individuals with voice disorders from those without.

Method and analysis

We search the following electronic databases: MEDLINE, EMBASE, CINAHL, Scopus, Web of Science Core Collection, PubMed Central and Google Scholar. Grey literature searches will include ProQuest Dissertations and Theses, ClinicalTrials.gov and the Cochrane Register of Controlled Trials. Websites of professional organisations and textbooks will be hand searched for relevant information related to the research question. Study screening, selection and data extraction will be conducted independently by two reviewers. Any disagreements will be resolved by discussion or by involving a third reviewer.

The methodological quality of the included studies will be appraised using the relevant Critical Appraisal Tools by JBI. The clinical guidelines and recommendations for voice assessment by professional bodies will be appraised using the Reporting Items for practice Guidelines in HealThcare (RIGHT) checklist. The findings will be presented in the form of an information matrix with the tasks identified tabulated against the nature of the task, dimensions being tested, and their accuracy, sensitivity, and specificity in identifying individuals with voice problems.

Ethics and dissemination

Formal ethics approval is not required. The findings will be presented at national and international conferences and published in a peer-reviewed journal.

PROSPERO registration number

CRD42023431634.

Understanding the patterns and health impact of indoor air pollutant exposures in Bradford, UK: a study protocol

Por: Ikeda · E. · Hamilton · J. · Wood · C. · Chatzidiakou · L. · Warburton · T. · Ruangkanit · A. · Shao · Y. · Genes · D. · Waiblinger · D. · Yang · T. C. · Giorio · C. · McFiggans · G. · O'Meara · S. P. · Edwards · P. · Bates · E. · Shaw · D. R. · Jones · R. L. · Carslaw · N. · McEachan · R.
Introduction

Relative to outdoor air pollution, there is little evidence examining the composition and concentrations of indoor air pollution and its associated health impacts. The INGENIOUS project aims to provide the comprehensive understanding of indoor air pollution in UK homes.

Methods and analysis

‘Real Home Assessment’ is a cross-sectional, multimethod study within INGENIOUS. This study monitors indoor air pollutants over 2 weeks using low-cost sensors placed in three rooms in 300 Born in Bradford (BiB) households. Building audits are completed by researchers, and participants are asked to complete a home survey and a health and behaviour questionnaire, in addition to recording household activities and health symptoms on at least 1 weekday and 1 weekend day. A subsample of 150 households will receive more intensive measurements of volatile organic compound and particulate matter for 3 days. Qualitative interviews conducted with 30 participants will identify key barriers and enablers of effective ventilation practices. Outdoor air pollution is measured in 14 locations across Bradford to explore relationships between indoor and outdoor air quality. Data will be analysed to explore total concentrations of indoor air pollutants, how these vary with building characteristics, and whether they are related to health symptoms. Interviews will be analysed through content and thematic analysis.

Ethics and dissemination

Ethical approval has been obtained from the NHS Health Research Authority Yorkshire and the Humber (Bradford Leeds) Research Ethics Committee (22/YH/0288). We will disseminate findings using our websites, social media, publications and conferences. Data will be open access through the BiB, the Open Science Framework and the UK Data Service.

Increasing the reach of evidence-based interventions for weight management and diabetes prevention among Medicaid patients: study protocol for a pilot Sequential Multiple Assignment Randomised Trial

Por: Schlechter · C. R. · Del Fiol · G. · Jones · D. R. · Orleans · B. · Gibson · B. · Nahum-Shani · I. · Maxfield · E. · Locke · A. · Cornia · R. · Bradshaw · R. · Wirth · J. · Jaggers · S. J. · Lam · C. Y. · Wetter · D. W.
Introduction

Over 40% of US adults meet criteria for obesity, a major risk factor for chronic disease. Obesity disproportionately impacts populations that have been historically marginalised (eg, low socioeconomic status, rural, some racial/ethnic minority groups). Evidence-based interventions (EBIs) for weight management exist but reach less than 3% of eligible individuals. The aims of this pilot randomised controlled trial are to evaluate feasibility and acceptability of dissemination strategies designed to increase reach of EBIs for weight management.

Methods and analysis

This study is a two-phase, Sequential Multiple Assignment Randomized Trial, conducted with 200 Medicaid patients. In phase 1, patients will be individually randomised to single text message (TM1) or multiple text messages (TM+). Phase 2 is based on treatment response. Patients who enrol in the EBI within 12 weeks of exposure to phase 1 (ie, responders) receive no further interventions. Patients in TM1 who do not enrol in the EBI within 12 weeks of exposure (ie, TM1 non-responders) will be randomised to either TM1-Continued (ie, no further TM) or TM1 & MAPS (ie, no further TM, up to 2 Motivation And Problem Solving (MAPS) navigation calls) over the next 12 weeks. Patients in TM+ who do not enrol in the EBI (ie, TM+ non-responders) will be randomised to either TM+Continued (ie, monthly text messages) or TM+ & MAPS (ie, monthly text messages, plus up to 2 MAPS calls) over the next 12 weeks. Descriptive statistics will be used to characterise feasibility (eg, proportion of patients eligible, contacted and enrolled in the trial) and acceptability (eg, participant opt-out, participant engagement with dissemination strategies, EBI reach (ie, the proportion of participants who enrol in EBI), adherence, effectiveness).

Ethics and dissemination

Study protocol was approved by the University of Utah Institutional Review Board (#00139694). Results will be disseminated through study partners and peer-reviewed publications.

Trial registration number

clinicaltrials.gov; NCT05666323.

Impact of the COVID-19 pandemic on the cost of chronic diseases treatment and care at public hospitals in Wallaga zones, Oromia Regional State, Ethiopia: a hospital-based, cross-sectional study

Por: Terefa · D. R. · Tesfaye · E. · Tolessa · B. E. · Desisa · A. E. · Olani · W. · Fetensa · G. · Chego · M. · Abdisa · E. · Turi · E. · Bekuma · T. T. · Getachew · M. · Tesfaye · L. · Tilahun · T.
Objective

Globally, around one-third of the population has at least one long-term health condition that could be affected by the COVID-19 pandemic. Despite the fact that studies have revealed the direct impact of COVID-19 on healthcare provision and utilisation, the impact of the pandemic on the cost of chronic disease treatment and care from a patient perspective was scanty. So, the study aimed to determine the impact of the COVID-19 pandemic on cost of chronic diseases treatment and care at public hospitals in Wallaga zones, Oromia Regional State, Ethiopia, from 1 August to 31 August 2020.

Methods

An institutional-based cross-sectional study design was used, and the sample size for the study (n=642) was determined using a single population mean formula. Data were collected using interviews and analysed using SPSS V.25. Descriptive statistics were performed, and the cost of follow-up care before and after the pandemic was compared using a related-samples Wilcoxon signed-rank test, declaring the level of significance of the median cost difference at p

Results

A total of 642 patients were included in the study, of whom 605 (94.2%) responded to the interviews. There was a significant median cost difference (n=593, Z=5.05, p=0.001) between the cost of chronic diseases among follow-up patients during the pandemic and the costs incurred by these patients before the pandemic.

Conclusion

The cost of follow-up care among chronic disease patients during the COVID-19 pandemic was significantly higher compared with before the pandemic era. Therefore, healthcare providers should arrange special fee waiver mechanisms for chronic disease healthcare costs during such types of pandemics and provide the services at proximal health facilities.

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