Capecitabine-induced-coronary-vasospasm leading to polymorphic ventricular tachycardia and cardiac arrest.

Capecitabine, a pro-drug of 5-fluorouracil, is commonly used in the treatment of breast and colorectal cancer. Its side effects, including nausea, vomiting, diarrhea, fatigue, loss of appetite, and bone marrow suppression, are well recognized. However, coronary vasospasm represents a less commonly recognized but significant complication of fluoropyrimidine-based therapies such as capecitabine. Proposed mechanisms for this adverse effect complication include direct endothelium-independent vasoconstriction, activation of protein kinase C, and activation of the cyclooxygenase pathway. In this report, we present a case of capecitabine-induced coronary vasospasm leading to progressive, focal ST-elevations, myocardial ischemia, and subsequently polymorphic ventricular tachycardia. These events were captured on telemetry, in a male in his early 40s, diagnosed with stage IIIB sigmoid colon cancer. Notably, the patient had no pre-existing coronary artery disease or other cardiovascular risk factors. Upon diagnosis, the patient was initiated on a calcium channel blocker, verapamil, to mitigate further coronary vasospasm events. After thorough discussions that prioritized the patient's input and values, an implantable cardioverter-defibrillator was placed subcutaneously. Following discharge, the patient restarted capecitabine therapy along with verapamil prophylaxis and did not experience any subsequent shocks from his ICD as assessed during his outpatient follow-up visits. This case emphasizes the need to involve patients in decision-making processes, especially when managing unexpected and serious complications, to ensure treatments align with their quality of life and personal preferences.

Development and validation of an interstitial lung disease exposure questionnaire for sub-Saharan Africa.

Background: American Thoracic Society/European Respiratory Society guidelines recommend context-specific exposure assessments to diagnose interstitial lung disease (ILD). In sub-Saharan Africa, ILD diagnoses are rare, and locally validated ILD exposure questionnaires are not used. Methods: A physician-administered ILD exposure questionnaire was developed using a four-step mixed-methods modified Delphi approach. First, ILD questionnaires from high-income countries and data from Pneumotox were reviewed, compiled and face-validated. Second, a local pilot group of ILD experts ranked item relevance using a Likert scale and suggested additions. Third, the questionnaire format and pilot rankings were addressed in a focus group discussion that was analysed using grounded theory. Finally, following focus group discussion modifications, the resulting items (with three duplicate item groups for evaluation of internal consistency) were ranked for importance by members of the Pan-African Thoracic Society (PATS). Results: Face validation resulted in 82 items in four categories: "Smoking and Drugs", "Environmental Exposures", "Occupations" and "Medications". Pilot group (n=10) ranking revealed 27 outliers and 30 novel suggestions. Focus group (n=12) discussion resulted in 10 item deletions, 14 additions and 22 re-wordings; themes included desire for extensive questionnaires and stigma sensitivity. Final validation involved 58 PATS members (mean±sd age 46±10.6  years, 76% male, from 17 countries) ranking 84 items derived from previous steps and three duplicate question groups. The questionnaire was internally consistent (Cronbach's α >0.80) and ultimately included 73 items. Conclusion: This mixed-methods study included experts from 17 countries in sub-Saharan Africa and successfully developed a 73-item ILD exposure questionnaire for sub-Saharan Africa. African pulmonary experts valued region-specific additions and ranked several items from existing ILD questionnaires as unimportant.

Effectiveness of low-dose theophylline for the management of biomass-associated COPD (LODOT-BCOPD): study protocol for a randomized controlled trial.

BACKGROUND: COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HICs), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting. METHODS: LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in Central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years, (2) full-time resident of the study area, (3) daily biomass exposure, (4) post-bronchodilator FEV1/FVC below the 5th percentile of the Global Lung Initiative mixed ethnic reference population, and (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George's Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every 6 months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP), and theophylline levels at baseline, 1 month, and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D. TRIAL REGISTRATION: ClinicalTrials.gov  NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD).