Burden of disease and barriers to comprehensive care for rheumatic heart disease in South Africa: an updated systematic review protocol.

INTRODUCTION: Rheumatic heart disease (RHD) is responsible for a significant burden of cardiovascular morbidity and mortality, and remains the most common cause of acquired heart disease among children and young adults in low-income and middle-income countries. Additionally, the global COVID-19 pandemic has forced the emergency restructuring of many health systems, which has had a broad impact on health in general, including cardiovascular disease. Despite significant cost to the health system and estimates from 2015 indicating both high incidence and prevalence of RHD in South Africa, no cohesive national strategy exists. An updated review of national burden of disease estimates, as well as literature on barriers to care for patients with RHD, will provide crucial information to assist in the development of a national RHD programme. METHODS AND ANALYSIS: Using predefined search terms that capture relevant disease processes from Group A Streptococcal (GAS) infection through to the sequelae of RHD, a search of PubMed, Scopus, ISI Web of Science, Sabinet African Journals, SA Heart and Current and Completed Research databases will be performed. All eligible studies on RHD, acute rheumatic fever and GAS infection published from April 2014 to December 2022 will be included. Vital registration data for the same period from Statistics South Africa will also be collected. A standardised data extraction form will be used to capture results for both quantitative and qualitative analyses. All studies included in burden of disease estimates will undergo quality assessment using standardised tools. Updated estimates on mortality and morbidity as well as a synthesis of work on primary, secondary and tertiary prevention of RHD will be reported. ETHICS AND DISSEMINATION: No ethics clearance is required for this study. Findings will be disseminated in a peer-reviewed journal and submitted to national stakeholders in RHD. PROSPERO REGISTRATION NUMBER: CRD42023392782.

Development of a core outcome set on Traditional Chinese Medicine and Western Medicine for rheumatic heart disease: a study protocol.

INTRODUCTION: Globally, rheumatic heart disease (RHD) is an important cause of acquired heart disease in children and adolescents. Clinical trials on RHD treatment with Traditional Chinese Medicine (TCM) or integrated medicine are gradually increasing in China. However, because the outcomes of clinical trials are subject to heterogeneity and selective reporting, similar studies cannot be merged and compared, complicating assessing the effectiveness and safety of TCM, and diminishing the value of clinical trials. Therefore, there is an urgent need to design a TCM or integrated medicine core outcome set (COS) for RHD. METHODS AND ANALYSIS: The development of this study will take place in four stages under the direction of a multidisciplinary advisory board. (1) Establishing a comprehensive outcomes checklist through a systematic review of previously published research, retrieval of clinical trial registration centres, patient's semistructured interviews, and clinician's questionnaire surveys; (2) Screen stakeholder groups from various fields to participate in the Delphi survey; (3) Two e-Delphi surveys will be conducted to determine the outcomes of various concerned stakeholder groups; (4) Hold a face-to-face consensus meeting to develop the COS-TCM-RHD. ETHICS AND DISSEMINATION: The ethical approval for this study has been obtained from the Tianjin University of Traditional Chinese Medicine Ethics Committee (TJUTCM-EC20210008). The findings will be disseminated in peer-reviewed journals and meetings. TRIAL REGISTRATION NUMBER: This study has been registered at the Core Outcome Measures in Effectiveness Trials (COMET) database (Registration #1743).

"The world is so white": improving cultural safety in healthcare systems for Australian Indigenous people with rheumatic heart disease.

OBJECTIVE: To examine the views of senior health system knowledge holders, including Aboriginal experts, regarding the spaces where elimination strategies for rheumatic heart disease take place: Aboriginal and Torres Strait Islander ways of knowing, being and doing; and biomedical healthcare models. We aimed to support the implementation of the RHD Endgame Strategy by providing some of the 'how'. METHODS: In-depth interviews were undertaken with 23 participants. The design of the interview questions and analysis of the data used strengths-based approaches as directed by Aboriginal researchers. RESULTS: Given the dominance of the biomedical worldview, and the complex trajectory of RHD, there is significant tension in the intersection of worldviews. Tensions that limit productive dialogue are juxtaposed with suggestions on how to reduce tension through reflexivity, power shifting and endorsing Aboriginal leadership and governance. Evidence supported cultural safety for RHD care, prevention and elimination as the key action. CONCLUSIONS: Recommendations include addressing power imbalances between dominant and minority populations throughout the health system; reform that both supports and is supported by Non-Indigenous and Aboriginal and Torres Strait Islander leadership. IMPLICATIONS FOR PUBLIC HEALTH: Increased understanding of and support for Indigenous leadership and cultural safety will enable implementation of the new RHD strategy.

[Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease].

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease / 中国中药杂志

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

A community-based program to reduce acute rheumatic fever and rheumatic heart disease in northern Australia.

BACKGROUND: In Australia's north, Aboriginal peoples live with world-high rates of rheumatic heart disease (RHD) and its precursor, acute rheumatic fever (ARF); driven by social and environmental determinants of health. We undertook a program of work to strengthen RHD primordial and primary prevention using a model addressing six domains: housing and environmental support, community awareness and empowerment, health literacy, health and education service integration, health navigation and health provider education. Our aim is to determine how the model was experienced by study participants. METHODS: This is a two-year, outreach-to-household, pragmatic intervention implemented by Aboriginal Community Workers in three remote communities. The qualitative component was shaped by Participatory Action Research. Yarning sessions and semi-structured interviews were conducted with 14 individuals affected by, or working with, ARF/RHD. 31 project field reports were collated. We conducted a hybrid inductive-deductive thematic analysis guided by critical theory. RESULTS: Aboriginal Community Workers were best placed to support two of the six domains: housing and environmental health support and health navigation. This was due to trusting relationships between ACWs and families and the authority attributed to ACWs through the project. ACWs improved health literacy and supported awareness and empowerment; but this was limited by disease complexities. Consequently, ACWs requested more training to address knowledge gaps and improve knowledge transfer to families. ACWs did not have skills to provide health professionals with education or ensure health and education services participated in ARF/RHD. Where knowledge gain among participant family members was apparent, motivation or structural capability to implement behaviour change was lacking in some domains, even though the model was intended to support structural changes through care navigation and housing fixes. CONCLUSIONS: This is the first multi-site effort in northern Australia to strengthen primordial and primary prevention of RHD. Community-led programs are central to the overarching strategy to eliminate RHD. Future implementation should support culturally safe relationships which build the social capital required to address social determinants of health and enable holistic ways to support sustainable individual and community-level actions. Government and services must collaborate with communities to address systemic, structural issues limiting the capacity of Aboriginal peoples to eliminate RHD.

Current Perspectives on Contemporary Rheumatic Mitral Valve Repair.

The surgical management of rheumatic mitral valve disease remains a challenge for cardiac surgeons. Durability of mitral valve repair (MVr) is likely compromised not simply due to high technical demand, but surgeon reluctance, despite boasting copious advantages over MV replacement. This comprehensive review aims to evoke a deeper understanding of MVr concepts necessary to abate these limitations and shift mindset towards a more holistic approach to repair. Details of commonly utilized techniques in contemporary MVr for rheumatic heart disease will be discussed. Of importance, the reparative procedures will be mapped to an in-depth physiological exploration of the mitral complex-dynamism and rheumatic interplay. This is further emphasized by outlining the current "aggressive" resection strategy in contemporary rheumatic MVr.

Effect of postoperative high load long duration inspiratory muscle training on pulmonary function and functional capacity after mitral valve replacement surgery: A randomized controlled trial with follow-up.

OBJECTIVES: Although, pre-operative inspiratory muscle training has been investigated and reported to be an effective strategy to reduce postoperative pulmonary complications, the efficacy of postoperative inspiratory muscle training as well as the proper load, frequency, and duration necessary to reduce the postoperative pulmonary complications has not been fully investigated. This study was designed to investigate the effect of postoperative high-load long-duration inspiratory muscle training on pulmonary function, inspiratory muscle strength, and functional capacity after mitral valve replacement surgeries. DESIGN: Prospective randomized controlled trial. METHODS: A total of one hundred patients (mean age 38.3±3.29years) underwent mitral valve replacement surgery were randomized into experimental (n = 50) and control (n = 50) groups. The control group received conventional physiotherapy care, while experimental group received conventional care in addition to inspiratory muscle training, with 40% of the baseline maximal inspiratory pressure targeting a load of 80% by the end of the 8 weeks intervention protocol. Inspiratory muscle training started on the patient's first day in the inpatient ward. Lung functions, inspiratory muscle strength, and functional capacity were evaluated using a computer-based spirometry system, maximal inspiratory pressure measurement and 6MWT respectively at 5 time points and a follow-up assessment was performed 6 months after surgery. Repeated measure ANOVA and post-hoc analyses were used (p <0.05). RESULTS: Group-time interactions were detected for all the studied variables (p<0.001). Between-group analysis revealed statistically significant postoperative improvements in all studied variables in the experimental group compared to the control group (p <0.001) with large effect size of η2 ˃0.14. Within-group analysis indicated substantial improvements in lung function, inspiratory pressure and functional capacity in the experimental group (p <0.05) over time, and these improvements were maintained at follow-up. CONCLUSION: High intensity, long-duration postoperative inspiratory muscle training is highly effective in improving lung function, inspiratory muscle strength, and functional capacity after mitral valve replacement surgeries.

Hypomagnesaemia causing functional hypoparathyroidism in rheumatic mitral stenosis leading to sudden cardiac arrest in a young woman.

A 23-year-old young woman with a known history of valvular heart disease of rheumatic origin, post balloon mitral valvotomy 5 years ago, presented with fever, palpitations and breathlessness. ECG showed atrial fibrillation with fast ventricular rate. A 2D transthoracic echocardiography showed severe restenosis of mitral valve and moderate left ventricular dysfunction. She was admitted for evaluation of fever and control of the ventricular rate. She sustained cardiac arrest due to unknown cause and was resuscitated. When the patient sustained another cardiac arrest, torsades de pointes was detected on the monitor. Blood parameters showed hypomagnesaemia, hypocalcaemia and hypokalaemia, causing functional hypoparathyroidism which was treated with intravenous magnesium, oral calcium and vitamin D supplements. Timely detection of a tachyarrhythmia due to a ventricular origin was life saving, which is rarely seen in patients with rheumatic heart disease and mitral stenosis.

Activation of activin/Smad2 and 3 signaling pathway and the potential involvement of endothelial­mesenchymal transition in the valvular damage due to rheumatic heart disease.

Rheumatic heart disease (RHD) is an autoimmune disease caused by rheumatic fever following group A hemolytic streptococcal infection and primarily affects the mitral valve. RHD is currently a major global health problem. However, the exact pathological mechanisms associated with RHD­induced cardiac valve damage remain to be elucidated. The endothelial­mesenchymal transition (EndMT) serves a key role in a number of diseases with an important role in cardiac fibrosis and the activin/Smad2 and 3 signaling pathway is involved in regulating the EndMT. Nevertheless, there are no studies to date, to the best of the authors' knowledge, investigating the association between RHD and EndMT. Thus, the aim of the current study was to investigate the potential role of EndMT in cardiac valve damage and assess whether activin/Smad2 and 3 signaling was activated during RHD­induced valvular injury in a rat model of RHD induced by inactivated Group A streptococci and complete Freund's adjuvant. Inflammation and fibrosis were assessed by hematoxylin and eosin and Sirius red staining. Serum cytokine and rheumatoid factor levels were measured using ELISA kits. Expression levels of activin/Smad2 and 3 signaling pathway­related factors [activin A, Smad2, Smad3, phosphorylated (p­)Smad2 and p­Smad3], EndMT­related factors [lymphoid enhancer factor­1 (LEF­1), Snail1, TWIST, zinc finger E­box­binding homeobox (ZEB)1, ZEB2, α smooth muscle actin (α­SMA) and type I collagen α 1 (COL1A1)], apoptosis­related markers (BAX and cleaved caspase­3) and valvular inflammation markers (NF­κB and p­NF­κB) were detected using reverse transcription­quantitative PCR and western blot analyses. Compared with the control group, the degree of valvular inflammation and fibrosis, serum levels of IL­6, IL­17, TNF­α and expression of apoptosis­related markers (BAX and cleaved caspase­3) and valvular inflammation marker (p­NF­κB), activin/Smad2 and 3 signaling pathway­related factors (activin A, p­Smad2 and p­Smad3), EndMT­related factors (LEF­1, Snail1, TWIST, ZEB 1, ZEB2, α­SMA and COL1A1) were significantly increased in the RHD group. These results suggested that the activin/Smad2 and 3 signaling pathway was activated during the development of valvular damage caused by RHD and that the EndMT is involved in RHD­induced cardiac valve damage.

Ibutilide with magnesium for conversion of atrial fibrillation or flutter in rheumatic heart disease patients: Ibutilide with magnesium for chemical cardioversion of atrial fibrillation or flutter.

BACKGROUND: Data on adjunctive use of magnesium with ibutilide for conversion of persistent rheumatic atrial fibrillation and flutter to sinus rhythm is lacking. AIM: We aimed to study the efficacy of adjunctive supplementation of intravenous magnesium with ibutilide for conversion of persistent rheumatic atrial fibrillation and flutter to sinus rhythm and to define a definite level of serum magnesium which leads to significant increase in rates of such conversion. METHODS AND RESULTS: This was a prospective study including 33 Rheumatic heart disease patients (13 males and 20 females) with mean age of 49.27 ± 11.4 years and persistent AF or AFl. All patients received intravenous magnesium to raise serum magnesium level in range of 4 mg/dl to 4.5 mg/dl prior to administration of Ibutilide. 25 out of 33 (76%) patients converted to sinus rhythm. Upon univariate analysis, presence of background beta blocker therapy, serum potassium and magnesium at time of Ibutilide injection were found to have significant relation with conversion to sinus rhythm. Upon multivariate analysis serum magnesium level at the time of Ibutilide injection was found to have significant contribution on post injection rhythm reversal (p-value = 0.006). The level of magnesium at 3.8 mg/dl was found to have maximum sensitivity of 96% and specificity of 62.5% for conversion to sinus rhythm by ibutilide with magnesium (p-value< 0.05). CONCLUSIONS: Ibutilide is highly effective in cardioversion of persistent rheumatic atrial fibrillation/flutter patients. Raising Serum Magnesium levels above 3.8 mg/dl significantly improves efficacy of ibutilide.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Rheumatic mitral valve repair: a personal perspective and results.

Rheumatic mitral valve disease remains a challenge for cardiac surgeons. Valve repair has several advantages over valve replacement but is technically demanding for good results. To improve rheumatic mitral valve repair, surgeons need to have a deep understand of the mitral valve complex and its dynamics. The goal of repair is to restore normal diastolic and systolic function. The current approach is to perform a holistic repair of the entire mitral complex. Each part of the complex is thoroughly explored to define the problem. Several innovative techniques have been introduced to correct valve dysfunction and provide gratifying results. The details of these techniques will be described, based on an understanding of the relationship of the mitral valve complex and dynamics. With this approach, rheumatic mitral valve repair is becoming more successful, reproducible, and safe. Long-term follow-up is mandatory.

Sunao Tawara : further musings on his tribulations in providing the basis for the modern-day understanding of cardiac electrophysiology.

Sunao Tawara, who was born in 1873 and died in 1952, is considered the father of modern cardiac electrophysiology. He published his monumental monograph describing the atrioventricular conduction axis in 1906. He achieved this task in the face of multiple tribulations as a doctoral student working in a cultural environment that was not his own. Although his letters underscoring the publication of the monograph have been published, little emphasis has been placed on the potential problems he encountered in bringing his task to fruition. For example, it was not until the final 6 months of his studies that he resolved the issue of the connection between the atrioventricular bundle and the so called "Purkinje cardiomyocytes". His exchanges with his mentor, Ludwig Aschoff, emphasized that the difficulties he encountered in making the connection caused him quite some turmoil. We believe that this issue, and others that he identified in his correspondence, are worthy of further attention.

Intracardiac Thrombus Following Rivaroxaban Treatment in a Patient with Atrial Fibrillation Associated with Rheumatic Heart Disease.

We report a case of atrial fibrillation with rheumatic heart disease (RHD) who had intracardiac thrombus and cardiogenic cerebral embolism with rivaroxaban therapy. Intracardiac thrombus disappeared after switching from rivaroxaban to warfarin. Patients of RHD have the possibility of gradual progression of valvular disease even if they are old, so we need to distinguish nonvalvular atrial fibrillation from RHD before starting direct oral anticoagulants.

Could Short-Term Perioperative High-Dose Atorvastatin Offer Antiarrhythmic and Cardio-Protective Effects in Rheumatic Valve Replacement Surgery?

OBJECTIVES: To evaluate the role of prophylactic high-dose atorvastatin for prevention of postoperative atrial fibrillation (POAF), inflammatory response attenuation, and myocardial protection after valve replacement cardiac surgery. DESIGN: Randomized controlled trial. SETTING: Assiut University Hospitals. PARTICIPANTS: Sixty-four adult patients undergoing cardiac valve replacement surgery. INTERVENTIONS: The participants were equally divided into 2 groups. Group S received 80 mg of atorvastatin (oral tablets), 12 and 2 hours preoperatively, and on the 2nd, 3rd, 4th, and 5th postoperative days. Control group C received placebo at the same time periods. MEASUREMENTS: The incidence of POAF, postoperative white blood cell count, serum C-reactive protein, interleukin 6, and troponin I. MAIN RESULTS: Group S patients showed a lower incidence of POAF compared with the placebo group (p = 0.031). The white blood cell count showed significant reductions in group S compared with group C on the second, third, fourth, and fifth postoperative days. The C-reactive protein level showed significant reductions on the third, fourth, and fifth postoperative days in group S compared with group C (p = 0.001, 0.001, and 0.001, respectively). The serum level of interleukin 6 showed a significant reduction on the fifth postoperative day in group S compared with group C (p = 0.001). There was no significant difference between the 2 groups regarding the troponin I level and inotropic score. CONCLUSION: Prophylactic use of high dose atorvastatin can decrease the incidence of POAF and attenuate the inflammatory process in adult patients undergoing isolated rheumatic cardiac valve replacement surgery.

Integrating the prevention and control of rheumatic heart disease into country health systems: a systematic review protocol.

INTRODUCTION: Rheumatic heart disease (RHD) is a preventable chronic condition affecting the valves of the heart. RHD prevention and care programmes have historically originated in more developed countries, implemented in a targeted (or vertical) manner and evaluated using non-controlled approaches. Taking a broad view of the integration of RHD activities within the whole system is critical for health planning in low-income regions with a high burden of RHD and less robust health systems. Therefore, we propose to conduct a systematic review to assess RHD programme models in order to gain a better understanding of the extent of integration within relevant health systems. METHODS AND ANALYSIS: A predefined search strategy will be used to search for relevant articles published in English from January 1990 to December 2017. Electronic databases PubMed, Scopus, Web of Science, Africa Wide, CINAHL, Cochrane Central Register of Controlled Trials, Google Scholar and Global Index Medicus will be searched, as well as reference lists of relevant articles published. A standardised data extraction form will be used to obtain information for analysis from the included studies. The quality, reliability and risk of bias of included studies will be assessed using design-specific criteria. Programme integration will be analysed according to stewardship and governance, financing, planning, service delivery, monitoring and evaluation, and demand generation. Programme inputs, outputs and impact will also be described. ETHICS AND DISSEMINATION: No ethical approval is required. Findings will be disseminated in a peer-review journal in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. PROSPERO REGISTRATION NUMBER: CRD42017076307.

Participation in research improves overall patient management: insights from the Global Rheumatic Heart Disease registry (REMEDY).

BACKGROUND: Rheumatic heart disease (RHD) is a major public health problem in low- and middle-income countries (LIMCs), with a paucity of high-quality trial data to improve patient outcomes. Investigators felt that involvement in a recent large, observational RHD study impacted positively on their practice, but this was poorly defined. AIM: The purpose of this study was to document the experience of investigators and research team members from LMICs who participated in a prospective, multi-centre study, the global Rheumatic Heart Disease Registry (REMEDY), conducted in 25 centres in 14 countries from 2010 to 2012. METHOD: We conducted an online survey of site personnel to identify and quantify their experiences. Telephone interviews were conducted with a subset of respondents to gather additional qualitative data. We asked about their experiences, positive and negative, and about any changes in RHD management practices resulting from their participation in REMEDY as a registry site. RESULTS: The majority of respondents in both the survey and telephone interviews indicated that participation as a registry site improved their management of RHD patients. Administrative changes included increased attention to follow-up appointments and details in patient records. Clinical changes included increased use of penicillin prophylaxis, and more frequent INR monitoring and contraceptive counselling. CONCLUSION: Our study demonstrates that participation in clinical research on RHD can have a positive impact on patient management. Furthermore, REMEDY has led to increased patient awareness and improved healthcare workers' knowledge and efficiency in caring for RHD patients.