Development and Validity Assessment of a Chronic Obstructive Pulmonary Disease Knowledge Questionnaire in Low- and Middle-Income Countries

Rationale: The majority of the morbidity and mortality related to chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs). Despite the increasing burden of COPD, disease-specific knowledge among healthcare workers (HCWs) and patients in LMICs remains limited. COPD knowledge questionnaires are valid and reliable tools to assess COPD knowledge and can be employed in settings with limited health literacy. Objective: To develop and assess validity and reliability of a COPD knowledge questionnaire among individuals with COPD in three LMIC settings. Methods: Twelve questions were generated by an expert team of sixteen researchers, physicians, and public health professionals to create an LMIC-specific COPD knowledge questionnaire. Content was based on previous instruments, clinical guidelines, focus group discussions, and questionnaire piloting. Participants with COPD completed the questionnaire across three diverse LMIC settings before and three months after delivery of a standardized COPD specific education package by a local community health worker (CHW) trained to deliver the education to an appropriate standard. We utilized paired t-tests to assess improvement in knowledge post-intervention. Results: Questionnaire development initially yielded 52 items. Based on community feedback and expertise, items were eliminated and added yielding a final 12-item questionnaire, with a maximum total score of 12. A total of 196 participants with COPD were included this study in Nepal (n=86), Peru (n=35) and Uganda (n=75). Mean (± SD) baseline score was 8.0 ± 2.5 and 3-months post-education the mean score was 10.2 ± 1.7 among participants. The CHW-led COPD educational intervention improved COPD knowledge among community members by 2.2 points (95% CI 1.8 to 2.6, t=10.9, p<0.001). Internal consistency using Cronbach’s alpha was 0.75. Conclusion: The LMIC COPD-KQ demonstrates face and content validity and acceptable internal consistency through development phases, suggesting a reliable and valid COPD education instrument that can be utilized to assess educational interventions across LMIC settings. Clinical trial registered with ClinicalTrials.gov (NCT03365713

Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study.

Background. The addition of cyclo-oxygenase-2 (COX-2) inhibitors and prolonged constant infusion (PCI) of gemcitabine to treatment for advanced non-small-cell lung cancer (NSCLC) might improve treatment efficacy. We aimed to assess whether the addition of rofecoxib or PCI gemcitabine could improve overall survival compared with first-line treatment with cisplatin plus gemcitabine given by standard infusion. Methods. Patients with stage IV or IIIb (with supraclavicular nodes or pleural effusion) NSCLC who were under 70 years of age and who had performance status 0 or 1 were eligible for this multicentre, prospective, open-label, randomised phase III trial with 2×2 factorial design. Patients were randomly assigned to one of four treatment groups: group A,gemcitabine 1200 mg/m2 in a 30-min intravenous infusion on days 1 and 8 and intravenous cisplatin 80 mg/m2 on day 1, every 21 days for six cycles; group B, the same treatments as group A plus oral rofecoxib 50 mg/day until disease progression; group C, intravenous PCI gemcitabine 1200 mg/m2 in a 120-min infusion on days 1 and 8 and intravenous cisplatin 80 mg/m2 on day 1, every 21 days for six cycles; group D, the same drugs as group C plus oral rofecoxib 50 mg/day until disease progression. The primary endpoint was overall survival; secondary endpoints were progression free survival, response rate, quality of life, and toxicity. Analyses were intention-to-treat. This trial is registered on the clinical trials site of the US National Institutes of Health website http://clinicaltrials.gov/ct/show/NCT00385606. Findings. Between Jan 30, 2003, and May 3, 2005, 400 patients were enrolled. Median age was 60 years (range 29–71). PCI gemcitabine did not improve overall survival (median 47 weeks [95% CI 40–55] vs 44 [36–52], with standard gemcitabine infusion, hazard ratio (HR) of death 0·93 [0·74–1·17], p=0·41), progression-free survival, nor any other secondary endpoint. Vomiting and fatigue were significantly worse with PCI gemcitabine. The two rofecoxib groups were closed early (on Oct 1, 2004) due to withdrawal of the drug because of safety issues. With intention-to-treat statistical analyses limited to 240 patients (ie, those randomised before July 1, 2004) who had at least 3 months of treatment, rofecoxib did not prolong overall survival (median 44 weeks [CI 36–55] vs 44 [40–54] without rofecoxib, and HR of death 1·00 [0·75–1·34], p=0·85), or progression-free survival, but did improve response rate (41% vs 26%, p=0·02), global quality of life, physical, emotional and role functioning, fatigue, and sleeping. Rofecoxib significantly increased the incidence of diarrhoea and decreased constipation, fatigue, fever, weight loss, and pain, and analgesic consumption. Severe cardiac ischaemia was more frequent with rofecoxib than without; however, the diff erence was not statistically signifi cant in the primary analysis (p=0·06) and became significant when patients who were randomised between July 1, 2004, and Sept 30, 2004, were included in the analysis (p=0·03). Interpretation. Neither PCI gemcitabine nor rofecoxib prolonged survival in the patients in this study. Rofecoxib improved response rate and several quality-of-life items, including pain-related items and global quality of life. Further studies with less cardiotoxic COX-2 inhibitors are needed in NSCLC

Unmet Diagnostic and Therapeutic Opportunities for COPD in Low- and Middle-Income Countries

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis, and access to affordable interventions. There are no previous reports describing therapeutic needs in LMIC populations with COPD identified through screening. OBJECTIVE: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. METHODS: We compared interventions recommended by the international 'GOLD' COPD strategy document, with that received, in 1000 people with COPD identified by population screening at three LMIC sites in Nepal, Peru and Uganda. We calculated costs using data on the availability and affordability of medicines. MEASUREMENT AND MAIN RESULTS: The greatest unmet need for non-pharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%) and advice on biomass smoke exposure (26%). 95% of cases were previously undiagnosed and few were receiving therapy (4.5% had short-acting beta-agonists). Only three of 47 people (6%) with a previous COPD diagnosis had access to drugs consistent with recommendations. None of those with more severe COPD were accessing appropriate maintenance inhalers. Even when available, maintenance treatments were unaffordable with 30 days of treatment more than a low-skilled workers' daily average wage. CONCLUSION: We found significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Whilst there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis together with access to affordable interventions could translate to immediate benefit. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)

Effectiveness-implementation of COPD Case Finding and Self-management Action Plans in Low- and Middle-income Countries: Global Excellence in COPD Outcomes (GECo) Study Protocol

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli. More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs). LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management. Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres. Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD. The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings. The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs. This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings. METHODS/DESIGN: We aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2). To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2. We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry. We will report ROC areas, sensitivity and specificity. Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs. The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers. The control group will receive COPD education and standard of care treatment provided by local health providers. Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St. George's Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year. The primary endpoint is SGRQ at 12 months. Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated. We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD. DISCUSSION: This study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings. TRIAL REGISTRATION: NCT03359915 (GECo1). Registered on 2 December 2017 and NCT03365713 (GECo2). Registered on 7 December 2017. Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2)

Chronic Obstructive Pulmonary Disease Self-Management in Three LMICs: A Pilot Randomized Trial

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) disproportionately affects low- and middle-income countries (LMICs). Health systems are ill-prepared to manage the increase in COPD cases. METHODS: We carried out a pilot effectiveness-implementation randomized field trial of a community health worker (CHW)-supported, one-year self-management intervention in individuals with COPD grade B-D. The study took place in low-resource settings of Nepal, Peru, and Uganda. The primary outcome was the St. George's Respiratory Questionnaire (SGRQ) score at one year. We evaluated differences in moderate-to-severe exacerbations, all-cause hospitalizations and the EuroQol score (EQ5D-3L) at 12 months. RESULTS: We randomly assigned 239 participants (119 control, 120 intervention) with grade B-D COPD to a multi-component, CHW-supported intervention or standard of care and COPD education. 25 participants (21%) died or were lost to follow-up in the control arm compared to 11 (9%) in the intervention arm. At 12 months, there was no difference in mean total SGRQ scores between intervention and control arms (34.7 vs. 34.0 points; adjusted mean difference 1.0, 95% CI -4.2 to 6.1; p=0.71). The intervention arm had a higher proportion of hospitalizations (10% vs 5.2%; adjusted odds ratio 2.2, 95% CI 0.8-7.5; p=0.15) at 12 months compared to controls. CONCLUSION: A CHW-based intervention to support self-management of acute exacerbations of COPD in three resource-poor settings did not result in differences in SGRQ scores at one year. Fidelity was high, and intervention engagement was moderate. While results cannot differentiate between a failed intervention or implementation, it nonetheless suggests that we need to revisit our strategy. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03359915

Effectiveness-implementation of COPD case finding and self-management action plans in low- and middle-income countries : global excellence in COPD outcomes (GECo) study protocol

Background: Chronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli. More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs). LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management. Formal diagnosis of COPD requires quality assured spirometry, which is often limited to urban health centres. Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD. The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings. The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs. This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings. Methods/design: We aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a communityhealth-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2). To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2. We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry. We will report ROC areas, sensitivity and specificity. Individuals who are identified as having COPD grades B–D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs. The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers. The control group will receive COPD education and standard of care treatment provided by local health providers. Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ5D) and St. George’s Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year. The primary endpoint is SGRQ at 12 months. Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated. We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD. Discussion: This study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings

Illness representations of chronic obstructive pulmonary disease (COPD) to inform health education strategies and research design-learning from rural Uganda

More than 90% of chronic obstructive pulmonary disease (COPD)-related deaths occur in low- and middle-income countries; however, few studies have examined the illness experiences of individuals living with and providing treatment for COPD in these settings. This study characterizes illness representations for COPD in Nakaseke, Uganda from the perspectives of health care providers, village health teams and community members (CMs) with COPD. We conducted 40 in-depth, semi-structured interviews (16 health care providers, 12 village health teams and 12 CMs, aged 25–80 years). Interviews were analyzed using inductive coding, and the Illness Representations Model guided our analysis. Stakeholder groups showed concordance in identifying causal mechanisms of COPD, but showed disagreement in reasons for care seeking behaviors and treatment preferences. CMs did not use a distinct label to differentiate COPD from other respiratory illnesses, and described both the physical and social consequences of COPD. Local representations can inform development of adapted educational and self-management tools for COPD

Effectiveness-implementation of COPD case finding and self-management action plans in low- and middle-income countries: global excellence in COPD outcomes (GECo) study protocol.

BackgroundChronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli. More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs). LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management. Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres. Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD. The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings. The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs. This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings.Methods/designWe aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2). To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40&nbsp;years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD&nbsp;in to GECo2. We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry. We will report ROC areas, sensitivity and specificity. Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs. The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers. The control group will receive COPD education and&nbsp;standard of care treatment provided by local health providers. Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St. George's Respiratory Questionnaire (SGRQ) every 3&nbsp;months over a period of 1 year. The primary endpoint is SGRQ at 12&nbsp;months. Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated. We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD.DiscussionThis study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings.Trial registrationNCT03359915 (GECo1). Registered on 2 December 2017 and NCT03365713 (GECo2). Registered on 7 December 2017. Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2)