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.

Patient level barriers to accessing TB care services during the COVID-19 pandemic in Uganda, a mixed methods study.

INTRODUCTION: Lockdown measure has been utilized widely to mitigate COVID-19 pandemic transmission and recently during the 2022 Sudan Ebola Virus Disease outbreak in Uganda. These have setback effects on the continuity of essential health services such as tuberculosis (TB) care, reversing progress made in the fight against tuberculosis (TB) over the past decade. We set out to understand patient-reported barriers to accessing TB care services during the COVID-19 pandemic in Uganda. METHODS: Mixed methods study involving review of medical records of TB patients who received TB care from January to September 2020. We used quantitative and qualitative methods including phone questionnaires and in-depth interviews. We carried out descriptive statistics, a chi-square test and conducted a thematic analysis. RESULTS: We carried out phone interviews with 672 participants. The majority (60%) were male and with an average of 35 years (SD:11). A significantly higher proportion of patients reported a barrier to TB care access during the COVID-19 lockdown than pre-lockdown (79.9% vs. 68.1% p = 0.027). We carried out in-depth interviews with 28 participants (54% (15/28): male). Barriers experienced by these participants included lack of a means of transport to reach the health facility, lack of money to pay the transport fares, long distances to the facility, fear of COVID-19 infection, stigma due to overlap between TB and COVID-19 symptoms, and few health care workers available during the lockdown period. CONCLUSION: Lockdown measures instituted to mitigate the transmission of COVID1-19 affected access to TB care services in Uganda. Uganda is at risk of future emerging and re-emerging diseases of epidemic potential. Therefore, there should be measures to ensure the continuity of essential services such as tuberculosis care during the implementation of future epidemic response interventions such as a lockdown.

Risk factors for disruptions in tuberculosis care in Uganda during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, TB mortality increased while diagnoses decreased, likely due to care disruption. In March, 2020, Uganda-a country with high TB burden, implemented a COVID-19 lockdown with associated decrease in TB diagnoses. This study aims to examine patient level risk factors for disruption in TB care during the COVID-19 pandemic in Uganda. This retrospective cross-sectional cohort study included six TB clinics in Uganda. Clustered sampling included phases of TB care and three time-periods: pre-lockdown, lockdown and post-lockdown. Characteristics of patients with TB care disruption (TBCD), defined as those with > 2 months of symptoms prior to diagnosis or who missed a TB clinic, and those without TB care disruption (non-TBCD) were analyzed between time-periods. 1,624 charts were reviewed; 1322 were contacted, 672 consented and completed phone interview; pre-lockdown (n = 213), lockdown (n = 189) and post-lockdown (n = 270). TBCD occurred in 57% (385/672) of patients. There was an increase in the proportion of urban patients in the TBCD and non-TBCD groups during post-lockdown (p <0.001). There was no difference in demographics, HIV co-infection, socioeconomic status, or distance to TB clinic between TBCD and non-TBCD groups or within TBCD by time-period. There were few differences amongst TBCD and all TB patients by time-period. The increase in urban patients' post-lockdown may represent a portion of urban patients who delayed care until post-lockdown. Insignificant trends suggesting more TBCD amongst those who lived further from clinics and those without HIV-coinfection require more investigation.

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.

Developing and Implementing Noninvasive Ventilator Training in Haiti during the COVID-19 Pandemic.

Background: Noninvasive ventilation (NIV) is an important component of respiratory therapy for a range of cardiopulmonary conditions. The World Health Organization recommends NIV use to decrease the use of intensive care unit resources and improve outcomes among patients with respiratory failure during periods of high patient capacity from coronavirus disease (COVID-19). However, healthcare providers in many low- and middle-income countries, including Haiti, do not have experience with NIV. We conducted NIV training and evaluation in Port-au-Prince, Haiti. Objectives: To design and implement a multimodal NIV training program in Haiti that would improve confidence and knowledge of NIV use for respiratory failure. Methods: In January 2021, we conducted a 3-day multimodal NIV training consisting of didactic sessions, team-based learning, and multistation simulation for 36 Haitian healthcare workers. The course included 5 didactic session and 10 problem-based and simulation sessions. All course material was independently created by the study team on the basis of Accreditation Council for Continuing Medical Education-approved content and review of available evidence. All participants completed pre- and post-training knowledge-based examinations and confidence surveys, which used a 5-point Likert scale. Results: A total of 36 participants were included in the training and analysis, mean age was 39.94 years (standard deviation [SD] = 9.45), and participants had an average of 14.32 years (SD = 1.21) of clinical experience. Most trainees (75%, n = 27) were physicians. Other specialties included nursing (19%, n = 7), nurse anesthesia (3%, n = 1), and respiratory therapy (3%, n = 1). Fifty percent (n = 18) of participants stated they had previous experience with NIV. The majority of trainees (77%) had an increase in confidence survey score; the mean confidence survey score increased significantly after training from 2.75 (SD = 0.77) to 3.70 (SD = 0.85) (P < 0.05). The mean knowledge examination score increased by 39.63% (SD = 15.99%) after training, which was also significant (P < 0.001). Conclusion: This multimodal NIV training, which included didactic, simulation, and team-based learning, was feasible and resulted in significant increases in trainee confidence and knowledge with NIV. This curriculum has the potential to provide NIV training to numerous low- and middle-income countries as they manage the ongoing COVID-19 pandemic and rising burden of noncommunicable disease. Further research is necessary to ensure the sustainability of these improvements and adaptability to other low- and middle-income settings.

Availability, affordability and access to essential medications for asthma and chronic obstructive pulmonary disease in three low- and middle-income country settings.

INTRODUCTION: Despite the rising burden of chronic respiratory disease globally, and although many respiratory medications are included in the World Health Organization Essential Medications List (WHO-EML), there is limited information concerning the availability and affordability of treatment drugs for respiratory conditions in low- and middle-income countries (LMICs). METHODS: All public and private pharmacies in catchment areas of the Global Excellence in COPD outcomes (GECo) study sites in Bhaktapur, Nepal, Lima, Peru, and Nakaseke, Uganda, were approached in 2017-2019 to assess pricing and availability of medications for the management of asthma and COPD. RESULTS: We surveyed all 63 pharmacies in respective study areas in Nepal (95.2% private), 104 pharmacies in Peru (94.2% private) and 53 pharmacies in Uganda (98.1% private). The availability of any medication for respiratory disease was higher in private (93.3%) compared to public (73.3%) pharmacies. Salbutamol (WHO-EML) monotherapy in any formulation was the most commonly available respiratory medication among the three sites (93.7% Nepal, 86.5% Peru and 79.2% Uganda) while beclomethasone (WHO-EML) was only available in Peru (33.7%) and Nepal (22%). LABA-LAMA combination therapy was only available in Nepal (14.3% of pharmacies surveyed). The monthly treatment cost of respiratory medications was lowest in Nepal according to several cost metrics: the overall monthly cost, the median price ratio comparing medication costs to international reference prices at time of survey in dollars, and in terms of days' wages of the lowest-paid government worker. For the treatment of intermittent asthma, defined as 100 mcg Salbutamol/Albuterol inhaler, days' wages ranged from 0.47 days in Nepal and Peru to 3.33 days in Uganda. CONCLUSION: The availability and pricing of respiratory medications varied across LMIC settings, with medications for acute care of respiratory diseases being more widely available than those for long-term management.

Positive effect of home hemodialysis in a pregnant woman with chronic kidney failure during the COVID-19 pandemic: A case report.

This report discusses the case of a 25-year-old pregnant woman from an underserved community, with two previous failed kidney transplants and a previous miscarriage. The patient required a progressive increase to 30 h a week of in-hospital hemodialysis during the COVID-19 pandemic lockdown. She delivered her baby while transitioning to home hemodialysis. Women with end-stage kidney disease who require hemodialysis and wish to become pregnant or who are pregnant have options to allow for a safe and healthy delivery. This can be achieved with vigorous hemodialysis, even at home.

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).