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AnteayerBMJ Open

Prospective cohort study of TIMP-1 and myocardial fibrosis in Chagas disease at a reference clinic in Pernambuco, Brazil: PTICH trial protocol

Por: Martins · S. M. · Macedo · C. T. · Meira · C. S. · Paim Santos · L. H. · Larocca · T. F. · Cavalcanti da Silva · F. F. · Leandro Lira · C. N. · da Silva · I. P. M. · De Araujo · L. T. · Soares · M. B. P.
Background

Chagas disease affects millions of individuals across Latin America and imposes a substantial economic burden on healthcare systems, particularly in rural and underserved regions. Chronic Chagasic cardiomyopathy remains one of the leading causes of heart failure-related mortality in endemic countries. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has emerged as a potential biomarker of myocardial fibrosis in cardiomyopathies. This study was designed to investigate the association between TIMP-1 and myocardial fibrosis in chronic Chagas disease and to assess its potential as an early biomarker of fibrotic remodelling.

Methods and analysis

Bottom of form: The PTICH trial is a single-centre, prospective observational cohort study conducted at a government reference clinic in Pernambuco, Brazil. The study aims to enrol 210 adults with Chagas heart disease: 140 without ventricular dysfunction (left ventricular ejection fraction (LVEF) ≥52% in women and ≥54% in men) and 70 with ventricular dysfunction (LVEF

Ethics and dissemination

The Research Ethics Committee (REC) of Chagas disease and heart failure outpatient clinic—PROCAPE approved the PTICH trial (CAAE number: 65746322.8.1001.5192). Written informed consent has been obtained from all participants enrolled to date, and data handling is in compliance with applicable privacy and data protection regulations. Study findings will be disseminated through targeted outreach to civil society, the scientific community, healthcare professionals and Brazilian Unified Health System (SUS) policymakers; school-based science communication activities conducted in collaboration with state education departments (potentially including oral health educational materials); policy briefs and targeted reports for public health managers; technical meetings and institutional presentations; a plain-language summary published on the institutional website; and submissions to peer-reviewed journals and presentations at academic and health policy conferences.

Trial registration number

RBR-3dcrj98.

Mitigating chronic respiratory disease through the lens of multimorbidity: the MARES mixed-methods study protocol

Por: Mendes · R. G. · Leonardi · N. T. · Castello-Simoes · V. · Kawakami · D. M. d. O. · Souza · J. V. R. · Schafauser-Segundo · N. S. · Simoes · R. P. · Pinto · F. G. · Araujo · G. H. G. · da Silva · M. M. C. · Moriguchi · C. S. · Franco · F. J. B. Z. · Pires Di Lorenzo · V. A. · Jor
Introduction

Chronic respiratory diseases (CRDs), such as asthma and chronic obstructive pulmonary disease (COPD), are among the leading non-communicable diseases (NCDs) worldwide. However, diagnosing CRDs in low-income and middle-income countries (LMICs) remains challenging due to limited access to spirometry and trained professionals. Aggravating the burden, CRDs often coexist with other NCDs, increasing healthcare costs, reducing quality of life and elevating mortality. These challenges highlight the need for simple case-finding approaches for CRDs, such as the COPD in Low-Income and Middle-Income Countries Assessment (COLA-6) questionnaire, to support prompt identification and appropriate care within NCD services in LMICs.

Objective

To evaluate the discriminative accuracy, feasibility and implementation of the COLA-6 questionnaire in identifying and managing CRDs in Brazilian Primary Healthcare (PHC) services for NCDs.

Methods and analysis

The Multimorbidity Approach for REspiratory Solutions (MARES) study consists of three work packages to be conducted in PHC services in São Carlos/SP and São Paulo/SP, Brazil.

MARES-1: A cross-sectional observational study enrolling 859 individuals with at least one NCD receiving care in PHC. The COLA-6 questionnaire will be administered by the research team and compared with quality-assured spirometry. The Chronic Airways Assessment Test (CAAT), Asthma Control Questionnaire (ACQ-7) and fractional exhaled nitric oxide (FeNO) will also be assessed. The diagnostic performance of COLA-6 for identifying CRDs—including COPD, asthma, preserved ratio impaired spirometry, restriction and overlaps—will be assessed using area under receiver operating characteristic curves and 95% CIs.

MARES-2: A cross-sectional observational study enrolling 20 healthcare professionals (physicians, physiotherapists, community health agents and nurses) from five PHC services. These professionals will apply the COLA-6 during routine NCD care to a total sample of 1000 patients. Qualitative interviews will be conducted to explore barriers and facilitators to the implementation of COLA-6, using deductive thematic analysis.

MARES-3: A longitudinal, prospective observational study in which patients from MARES-1 and MARES-2 will be reassessed at 6-month follow-up. A total sample of 473 participants with abnormal spirometry, a diagnosis of CRD or high risk for CRDs is expected. Participants will undergo spirometry, and a subset will be interviewed to explore their healthcare experiences through qualitative thematic analysis. Access to diagnostic and treatment services in Brazil will be assessed. Changes in spirometry values, FeNO, CAAT and ACQ-7 scores from baseline to 6 months in patients from MARES-1 will be analysed.

Ethics and dissemination

This study has been approved by the Ethics Committees of Federal University of São Carlos and University of Santo Amaro (UNISA). Ethical approval was also granted by the University College London. Results will be disseminated through peer-reviewed medical journals and presentations at international conferences. Results will improve identification of CRDs, addressing a significant gap in current PHC settings.

Trial registration number

NCT07050823/NCT07093021/NCT07134855.

Telerehabilitation for people with Parkinsons disease: protocol of a randomised clinical trial of mixed methods

Por: Taveira · R. S. · Vasconcellos · L. S. d. · Bezerra · C. F. · Aires · D. N. · Dias de Oliveira · A. K. · da Silva · K. d. O. C. · Melo · L. P. d. · Ribeiro · T. S.
Introduction

Telerehabilitation (TR) programmes are increasingly recognised for their feasibility and potential benefits, such as eliminating travel time, reducing costs and providing a more comfortable rehabilitation experience at home. However, the comparative efficacy of remote physiotherapy compared with traditional in-person sessions for individuals with Parkinson’s disease (PD) remains uncertain. This study aims to evaluate the effects of TR compared with in-person physiotherapy in individuals with PD, focusing on both motor and non-motor outcomes.

Methods and analysis

This is a randomised, single-blind clinical trial with a mixed-methods approach. A total of 22 individuals diagnosed with PD will be randomly assigned to one of two groups. The experimental group will receive TR, consisting of remote physiotherapy sessions conducted once a week for 1 hour over a 4-month period. The control group will receive the same interventions in person. Interventions will include global muscle strengthening exercises, balance training, gait and motor coordination exercises, and cognitive training. The primary outcome will be motor function, measured using part III of the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale. Secondary outcomes will include cognition (Montreal Cognitive Assessment), gait (Functional Gait Assessment), mobility (Timed Up and Go Test) and quality of life (Parkinson’s Disease Questionnaire). Data will be analysed using repeated measures analysis of variance to compare outcomes between groups across four assessment points (baseline, midpoint, postintervention and 2 months follow-up). Additionally, a qualitative phase will explore participants’ perceptions and experiences regarding TR and in-person interventions, with assessments carried out 2 months after the completion of the 24-week interventions, through semistructured interviews that will be analysed using Bardin’s Content Analysis technique.

Ethics and dissemination

This protocol was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte (approval number: 5.553.701). All participants will provide written informed consent before inclusion. Results will be disseminated through peer-reviewed publications, scientific conferences and communication with participants and healthcare professionals.

Trial registration number

RBR-6h5knrj.

Association between hospitalisations for ambulatory care-sensitive conditions and primary healthcare physician specialisation: a longitudinal ecological study in Belo Horizonte, Brazil

Por: Rodrigues · G. V. · Afonso · M. P. D. · de Mendonca · L. G. · Pedro · S. · da Silva · H. P. · Macieira · C. · de Oliveira · V. B.
Objectives

Ambulatory care sensitive conditions (ACSCs) are conditions for which the provision of timely and skilled primary care can reduce risks of hospitalisation when preventing, treating or controlling a disease. For this reason, hospitalisations for ACSC have been commonly employed by health systems as an indicator of effectiveness for the primary level of care. This study aims to evaluate whether the provision of primary care services by physicians with residency training in family medicine is associated with rates of general hospitalisations for ACSCs in the Brazilian Unified Health System network in the city of Belo Horizonte, Brazil.

Design

Longitudinal ecological study using a Generalised Linear Model for Gamma-distributed variables.

Setting

Primary healthcare centres in Belo Horizonte, Brazil, from January 2017 to December 2021, aggregated at the primary healthcare centres level.

Participants

Data aggregated at the primary healthcare centre level, encompassing socioeconomic, professional and health-related variables.

Primary outcome measures

Incidence rates of hospitalisations for ACSCs, adjusted for age and sex.

Results

After adjusting for age, sex and socioeconomic variables using the Health Vulnerability Index, a higher concentration of family physicians was significantly associated with a lower incidence of hospitalisations for ACSCs. If all physicians in the primary care network were family physicians, compared with a scenario in which none were, an estimated 11.89% reduction in hospitalisations would be expected (95% CI 7.3% to 16.3%, p

Conclusions

The findings suggest that specialisation in family medicine positively impacts health outcomes by reducing hospitalisations for ACSCs. These results can inform the development of evidence-based public policies to enhance primary care effectiveness.

Factors influencing HPV vaccine acceptance in immunosuppressed patient populations: a protocol for a systematic review

Introduction

The development of effective vaccines targeting human papillomavirus (HPV) has significantly contributed to disease prevention, highly relevant in immunosuppressed patients who have higher incidence of HPV-related cancers than their non-immunosuppressed counterparts. However, the acceptance and uptake of the HPV vaccine among immunosuppressed individuals pose unique challenges. Immunocompromised patients’ acceptance of the HPV vaccine is influenced by multifaceted factors, including concerns about safety and effectiveness, interactions with immunosuppressive medications and uncertainties due to their compromised immunity. This systematic review aims to identify the main factors influencing HPV vaccine acceptance among immunosuppressed patients.

Methods and analysis

A comprehensive search strategy will be executed across databases such as MEDLINE/PubMed, Embase, Scopus, Web of Science, ScienceDirect, Latin American and Caribbean Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature and Cochrane Database. The review will encompass the three WHO-endorsed HPV vaccines (quadrivalent, bivalent and nonavalent) and will consider studies related to HPV vaccines and their administration. The scope includes study focusing on immunosuppressed patients who received organ transplants, cancer treatments or are HIV-positive. No temporal restrictions will be applied, and searches will be conducted until December 2025. Observational studies, including retrospective/prospective cohorts, case–control and cross-sectional studies, reporting factors influencing HPV vaccination in immunosuppressed populations will be included. Studies with overlapping patient populations will be excluded. Data extraction will include study details, demographics, vaccine type, risk/protective factors, outcomes and medical history. Validation and cross-verification will ensure data accuracy. Risk of bias will be assessed using ROBINS-I (Risk Of Bias In Non-randomised Studies of Interventions), and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will rate evidence certainty. Meta-analysis, guided by Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, will employ fixed/random-effects models, assessing heterogeneity using I² statistics.

Ethics and dissemination

This research will analyse previously published data, so ethical approval is not required. The results of the systematic review will be submitted for publication in a peer-reviewed journal.

PROSPERO registration number

CRD42023452537.

Characterisation of a clinical trial-like population of high cardiovascular risk patients prior to myocardial infarction or stroke in the real world: design and protocol for a multidatabase retrospective cohort study

Por: Ochs · A. · Chan · Q. · Dhalwani · N. N. · Duxbury · M. · Shannon · E. · OKelly · J. · Paiva da Silva Lima · G. · Avcil · S. · Chan · A. Y. · Chui · C. S. · Lai · E. C.-C. · Cars · T. · Shin · J.-Y. · Heintjes · E. M. · Wong · I. C.
Introduction

Cardiovascular (CV) disease is the leading cause of morbidity and mortality globally. Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor of major adverse cardiovascular events. Patients without prior myocardial infarction (MI) or stroke but with established risk factors and elevated LDL-C may benefit from intensive lipid-lowering therapy (LLT); however, the size and potential healthcare burden of this population globally are not known. The benefits of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in these patients, are currently being studied in the phase 3 Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke (VESALIUS-CV) trial. To characterise the high-risk pre–CV-event (VESALIUS-CV–like) individuals in the real world, an observational study is being conducted across multiple countries.

Methods and analysis

This retrospective cohort study will use a common protocol and an analytical common data model approach to characterise VESALIUS-CV–like individuals in the real world across different geographical regions and healthcare settings. The study period will be from 2010 to 2022, subject to data availability in study sites. Patients aged 50 years and older at high risk of CV disease but without prior MI or stroke will be included in this study. VESALIUS-CV–like individuals are defined through a combination of the following: (1) one diagnosis of coronary artery disease, cerebrovascular disease, peripheral artery disease or diabetes with microvascular complications or chronic insulin use; (2) an elevated LDL-C measurement and (3) other high-risk factors. The objectives of this study are to estimate the prevalence of VESALIUS-CV–like individuals, describe their characteristics and care pathways and estimate their incidence rates of CV events and healthcare costs. The prevalence of VESALIUS-CV–like individuals will be expressed as annual prevalence; patient characteristics at index date will be presented using summary statistics; care pathways will be summarised as LLT prescription across time; and the incidence of defined CV events will be expressed as events per person-years as well as at certain time periods. Healthcare costs will be presented as CV-related costs in different time periods.

Ethics and dissemination

Approvals of the study protocol were obtained from relevant local ethics and regulatory frameworks for each participating database. The results of the study will be submitted to peer-reviewed scientific publications and presented at scientific conferences.

Right-restricting measures implemented by Public Health Surveillance services during the COVID-19 pandemic: a systematic review protocol

Por: Vivas · M. D. · Correia · T. · Bragagnolo · L. · da Silva · I. A. L. · Tureck · F. · Santos · R. · Kielmann · S. · do Carmo · D. · Avarca · C. · da Silva · F. · Paes · M. · Tofani · L. F. N. · Chioro · A.
Introduction

The COVID-19 pandemic’s unprecedented nature has exposed significant vulnerabilities in most public health systems and highlighted the importance of coordinated responses across various levels of government. A global debate emerged on the types of health measures necessary to curb the rapid spread of contagious and/or lethal diseases. However, some of these measures involved restricting individual rights, raising significant ethical, legal and public health questions. The protocol of this systematic review aims to address a critical gap in the literature by analysing how Public Health Surveillance services worldwide implemented compulsory right-restricting measures during the COVID-19 pandemic, and what impacts these measures had on public health outcomes and individual rights.

Methods and analysis

This protocol focuses on studies about right-restricting measures enacted by Public Health Surveillance services during the COVID-19 pandemic. It will be unrestrictive as to period (starting in 2019, when the outbreak was identified), language or publication status in a preliminary stage. It will include only peer-reviewed publications, discarding opinion articles, editorials, conference papers and non-peer-reviewed publications. Considering the PICo strategy, the research question of this systematic review can be formulated as follows: Problem—right-restricting measures enacted by Public Health Surveillance services; Interest—implementation modalities and impacts on individual rights and public health outcomes; Context—COVID-19 pandemic. This protocol will use the following databases: Pubmed, Cochrane/CENTRAL, Embase, Scopus and Web of Science. Considering the various measures that may have been adopted, the following categories of analysis will be used: (i) Public Health Surveillance as a field, (ii) the various specific areas of Health Surveillance, (iii) law enforcement, (iv) right-restricting measures and consent, (v) interactions between right-restricting measures and routine Public Health Surveillance functions, (vi) differences between countries and (vii) Health Surveillance lessons learnt from the COVID-19 pandemic. These categories are not strictly mutually exclusive; however, each study will be assigned to the category most aligned with its primary focus. To ensure the validity and reliability of findings, each study will have its risk of bias assessed at both the study and outcome levels.

Ethics and dissemination

Patients and the public were not involved in the design, conduct, reporting or dissemination plans of this systematic review. The results will be presented in one or more articles to be submitted to scientific journals and may also be presented at scientific conferences and to public policy makers.

PROSPERO registration number

This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 20 November 2024 (registration number CRD42024613039).

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