Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

Autoimmune lymphoproliferative syndrome identified through reverse phenotyping.

Autoimmune lymphoproliferative syndrome (ALPS) is a chronic non-malignant lymphoproliferative disorder caused by mutations in the genes involved in programmed cell death. It is inherited as an autosomal dominant pattern with variable penetrance. In this paper we present the first report of a Macedonian family with ALPS, caused by a novel heterozygous variant in the FAS gene. The next generation sequencing (NGS) analysis in a patient with splenomegaly, suspected for hereditary spherocytosis, showed presence of the FAS c.913dupA, p.Thr305AsnfsTer16 variant. The same variant was present in the patient's mother, but not in the mother's parents (proband's grandparents). Thus, the pathogenic FAS variant has arisen as a de novo event in the proband's mother. Later, analysis of the newborn affected sister showed presence of the same FAS variant. Additional clinical and laboratory investigations in the proband and her sister confirmed the presence of specific biomarkers for ALPS. A first-line NGS analysis allows identification of the genetic defect and initiation of appropriate clinical examinations to promptly establish the clinical diagnosis in patients with rare diseases. Reverse phenotyping in our case provided a prompt and accurate diagnosis and early initiation of specific therapy.

Feasibility of a pulmonary rehabilitation programme for patients with symptomatic chronic obstructive pulmonary disease in Georgia: a single-site, randomised controlled trial from the Breathe Well Group.

OBJECTIVES: To assess the feasibility of delivering a culturally tailored pulmonary rehabilitation (PR) programme and conducting a definitive randomised controlled trial (RCT). DESIGN: A two-arm, randomised feasibility trial with a mixed-methods process evaluation. SETTING: Secondary care setting in Georgia, Europe. PARTICIPANTS: People with symptomatic spirometry-confirmed chronic obstructive pulmonary disease recruited from primary and secondary care. INTERVENTIONS: Participants were randomised in a 1:1 ratio to a control group or intervention comprising 16 twice-weekly group PR sessions tailored to the Georgian setting. PRIMARY AND SECONDARY OUTCOME MEASURES: Feasibility of the intervention and RCT were assessed according to: study recruitment, consent and follow-up, intervention fidelity, adherence and acceptability, using questionnaires and measurements at baseline, programme end and 6 months, and through qualitative interviews. RESULTS: The study recruited 60 participants (as planned): 54 (90%) were male, 10 (17%) had a forced expiratory volume in 1 second of ≤50% predicted. The mean MRC Dyspnoea Score was 3.3 (SD 0.5), and mean St George's Respiratory Questionnaire (SGRQ) 50.9 (SD 17.6). The rehabilitation specialists delivered the PR with fidelity. Thirteen (43.0%) participants attended at least 75% of the 16 planned sessions. Participants and rehabilitation specialists in the qualitative interviews reported that the programme was acceptable, but dropout rates were high in participants who lived outside Tbilisi and had to travel large distances. Outcome data were collected on 63.3% participants at 8 weeks and 88.0% participants at 6 months. Mean change in SGRQ total was -24.9 (95% CI -40.3 to -9.6) at programme end and -4.4 (95% CI -12.3 to 3.4) at 6 months follow-up for the intervention group and -0.5 (95% CI -8.1 to 7.0) and -8.1 (95% CI -16.5 to 0.3) for the usual care group at programme end and 6 months, respectively. CONCLUSIONS: It was feasible to deliver the tailored PR intervention. Approaches to improve uptake and adherence warrant further research. TRIAL REGISTRATION NUMBER: ISRCTN16184185.

Forms and Frequency of Sanctions against General Practitioners and Family Medicine Specialists in Macedonia.

OBJECTIVE: The goal of this study is to evaluate the reasons for sanctioning and the types of sanctions used on general medicine primary healthcare practitioners (GM-PHPs) in the Republic of Macedonia. MATERIALS AND METHOD: This is a cross-sectional study for which we used an anonymous survey. This survey was distributed in a printed and electronic form to GM-PHPs in different parts of Macedonia and 438 of them responded. We used the SPSS statistical program to process the quantitative data. RESULTS: The GM-PHPs' sex was not associated with the sanctioning in the univariable analysis, but it was in the multivariable. GM-PHPs with ≥30 years of experience have 8.7 times higher odds to be sanctioned than those with ≤5 years of experience. GM-PHPs that worked in the hospital or ≤19 km from the nearest hospital were significantly more frequently sanctioned. The most common three reasons for sanctioning were: "Financial consumption of prescriptions and referrals above the agreed amount", "Higher rate of sick leaves and/or unjustified sick leaves" and "Unrealized preventative goals or education". "Financial sanction by scale" was the most common type of sanction - 49.8% of participants. GM-PHPs who followed the guidelines, but were exposed to violence by patients or their family/companion were sanctioned significantly more frequently. CONCLUSIONS: In our sample, we can observe that in the univariable analysis age, years of experience, family medicine speciality, the distance of the workplace from the nearest hospital and violence are associated with sanctioning. In the multivariable analysis: sex, years of experience, the distance of the workplace from the nearest hospital and violence are associated with sanctioning. The majority of sanctions were financial sanctions (84.5%).

Accuracy and cost-effectiveness of different screening strategies for identifying undiagnosed COPD among primary care patients (≥40 years) in China: a cross-sectional screening test accuracy study: findings from the Breathe Well group.

OBJECTIVES: To examine the accuracy and cost-effectiveness of various chronic obstructive pulmonary disease (COPD) screening tests and combinations within a Chinese primary care population. DESIGN: Screening test accuracy study. SETTING: Urban and rural community health centres in four municipalities of China: Beijing (north), Chengdu (southwest), Guangzhou (south) and Shenyang (northeast). PARTICIPANTS: Community residents aged 40 years and above who attended community health centres for any reason were invited to participate. 2445 participants (mean age 59.8 (SD 9.6) years, 39.1% (n=956) male) completed the study (February-December 2019), 68.9% (n=1684) were never-smokers and 3.6% (n=88) had an existing COPD diagnosis. 13.7% (n=333) of participants had spirometry-confirmed airflow obstruction. INTERVENTIONS: Participants completed six index tests (screening questionnaires (COPD Diagnostic Questionnaire, COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE), Chinese Symptom-Based Questionnaire (C-SBQ), COPD-SQ), microspirometry (COPD-6), peak flow (model of peak flow meters used in the study (USPE)) and the reference test (ndd Easy On-PC). PRIMARY AND SECONDARY OUTCOMES: Cases were defined as those with forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) below the lower limit of normal (LLN-GLI) on the reference test. Performance of individual screening tests and their combinations was evaluated, with cost-effectiveness analyses providing cost per additional true case detected. RESULTS: Airflow measurement devices (sensitivities 64.9% (95% CI 59.5% to 70.0%) and 67.3% (95% CI 61.9% to 72.3%), specificities 89.7% (95% CI 88.4% to 91.0%) and 82.6% (95% CI 80.9% to 84.2%) for microspirometry and peak flow, respectively) generally performed better than questionnaires, the most accurate of which was C-SBQ (sensitivity 63.1% (95% CI 57.6% to 68.3%) specificity 74.2% (95% CI 72.3% to 76.1%)). The combination of C-SBQ and microspirometry used in parallel maximised sensitivity (81.4%) (95% CI 76.8% to 85.4%) and had specificity of 68.0% (95% CI 66.0% to 70.0%), with an incremental cost-effectiveness ratio of £64.20 (CNY385) per additional case detected compared with peak flow. CONCLUSIONS: Simple screening tests to identify undiagnosed COPD within the primary care setting in China is possible, and a combination of C-SBQ and microspirometry is the most sensitive and cost-effective. Further work is required to explore optimal cut-points and effectiveness of programme implementation. TRIAL REGISTRATION NUMBER: ISRCTN13357135.

Dyspnea in Children as a Symptom of Acute Respiratory Tract Infections and Antibiotic Prescribing.

BACKGROUND: Dyspnea is an unpleasant feeling of breathing difficulty, shortness of breath and inability to satisfy the hunger for air. The role of family physicians is to be prepared to recognise dyspnea as a symptom of acute respiratory infections (ARI), to perform triage and managing of children with acute dyspnea and make continuous education of parents. In the treatment of acute dyspnea more important is to treat dyspnea as a symptom than the prescribing of antibiotics (AB). Nowadays, even more often large amount of children, because of the noncompliance in the treatment and the pressure from the parents, unnecessary is hospitalised and frequently used antibiotics: According to the guidelines, a small percentage of children with ARI should be treated with AB. The rate of antibiotic prescription should be around 15-20% and lower. AIM: To assess doctor's AB prescriptions in Primary care practices in Macedonia, for ARI and dyspnea in children we use the data from a National project about antibiotic prescribing for acute respiratory tract infections, which has been run in 2014 November as a part of E - quality program. METHODS: Eighty-six general practitioners from Macedonia have taken participation in it. The group of 3026 children, from 0-5 years of age, with symptoms of dyspnea, was analysed. We have found a rate of 54.6% antibiotic prescriptions (AB). From 3026 children with dyspnea, AB got 1519 children, 852 of which were prescribed by a specialist. RESULTS: The children were mostly diagnosed with upper ARI, in 57.7%. The most used AB is amoxicillin + clavulonic acid. We concluded that there was an increased and inappropriate prescribing of antibiotics in children with ARI, presented with dyspnea in Macedonia. CONCLUSION: Perceptions and the parent's attitudes do not correlate with the severity of clinical picture of the disease in children and lack of use Evidence-based medicine (EBM), insecurity, fear, loss of patients effect on antibiotic prescribing of the doctors.

Evidence Based Practice in Using Antibiotics for Acute Tonsillitis in Primary Care Practice.

The increased use of antibiotics for acute tonsillitis is a public health problem. 80% of the antibiotic prescriptions for acute tonsillitis are done in the Primary Care practice (PCP). The inappropriate use of the antibiotic causes bacterial resistance and treatment failure. Only patients with acute tonsillitis caused by Group A beta-hemolytic streptococcus (GAS) have benefit of the antibiotic treatment, which is a predict cause in 5-20%. In order to assess the antibiotic prescribing for acute tonsillitis by the doctors in the PCP in Macedonia we use the data from the national project about antibiotic prescribing for acute respiratory tract infections which was conducted in November 2014 during a period of 4 weeks as part of the E-quality program sponsored by the IPCRG. 86 general practitioners from Macedonia have participated. The group of 1768 patients, from 4 months to 88 years of age, with diagnosis of acute tonsillitis was analyzed. The antibiotic prescriptions according to the Centor score criteria were compared to the Cochran's guidelines which are translated and recommended as national guidelines. 88.8% of the patients with acute tonsillitis were treated with antibiotics, of which 52.9% with Centor score 0 to 2 were treated inappropriate. The diagnosis is mostly made based on the clinical picture and the symptoms. Only (23.6%) of the patients were treated with antibiotics (Penicillin V and cephalexin) according to the guidelines. We concluded that there is a low adherence to the national guidelines. The clinical assessment is not accurate in determining the etiology. Also, there is a high nonadherence in prescribing the first choice of antibiotics. We emphasize the need to change the general practitioners' prescription behavior according to the guidelines.

Comparative Analysis of Family Medicine Education and Exams at Cathedras of Family Medicine of Universities in Southeastern Europe - "Splitska inicijativa", Sarajevo, 2017.

Education means: learning, teaching or the process of acquiring skills or behavior modification through various exercises. Traditionally, medical education meant the oral, practical and more passive transferring of knowledge and skills from the educators to students and health professionals. Today the importance of focus on educational quality, particularly in the professions operating in the services required by people is agreed by all involved. The higher educational system shoulders some critical responsibilities in the economic, social, cultural and educational development and growth in the communities. In countries that are in transition it is in charge of educating professional human workforce in every field and if the education is optimal in terms of quality, it is capable of carrying out its responsibilities. It is reason why there is the necessity behind discovering some strategies to uplift the quality of education, especially at university level.. By increasing the courses and establishing universities and higher education centers, the countries around the world have generated more opportunities for learning, especially using modern information technologies. Regarding to evaluating different educational services quality, one of the most important measures should be the way to develop programs to promote quality and also due to the shortage of resources, evaluating the services quality enables the management to allocate the limited financial resources for realization whole educational process. Advances in medicine in recent decades are in significant correlation with the advances in the new models and concepts of medical education supported by information technologies. Modern information technologies have enabled faster, more reliable and comprehensive data collection. These technologies have started to create a large number of irrelevant information, which represents a limiting factor and a real growing gap, between the medical knowledge on one hand, and the ability of students and physicians to follow its growth on the other. Furthermore, in our environment, the term technology is generally reserved for its technical component. This terminology essentially means not only the purchase of the computer and related equipment, but also the technological foresight and technological progress, which are defined as specific combination of fundamental scientific, research and development work that gives a concrete result. The quality of the teaching-learning process at the universities in former Yugoslav countries and abroad, depends mainly of infrastructure that includes an optimal teaching space, personnel and equipment, in accordance with existing standards and norms at the cantonal or entity level, which are required to implement adequately the educational curriculum for students from first to sixth year by Bologna studying concept. For all of this it is necessary to ensure adequate funding. Technologies (medical and information, including communications) have a special role and value in ensuring the quality of medical education at universities and their organizational units (faculties). "Splitska inicijativa" project, which started 6 years ago as simple intention to exchange experiences of application new model of education, based on: Bologna studying concept, and other types of under and postgraduate education, was good idea to improve also theory and practice of it within Family medicine as academic and scientific discipline. This year scope of our scientific meeting held in Sarajevo on 24th and 25th March 2017, was quality assessment of theoretical and practical education and, also, evaluation of knowledge by students exams (a-y).