Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis.

BACKGROUND: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

Rationale and design of the Investigation of the Management of Pericarditis (IMPI) trial: a 2 × 2 factorial randomized double-blind multicenter trial of adjunctive prednisolone and Mycobacterium w immunotherapy in tuberculous pericarditis.

BACKGROUND: In spite of antituberculosis chemotherapy, tuberculous (TB) pericarditis causes death or disability in nearly half of those affected. Attenuation of the inflammatory response in TB pericarditis may improve outcome by reducing cardiac tamponade and pericardial constriction, but there is uncertainty as to whether adjunctive immunomodulation with corticosteroids and Mycobacterium w (M. w) can safely reduce mortality and morbidity. OBJECTIVES: The primary objective of the IMPI Trial is to assess the effectiveness and safety of prednisolone and M. w immunotherapy in reducing the composite outcome of death, constriction, or cardiac tamponade requiring pericardial drainage in 1,400 patients with TB pericardial effusion. DESIGN: The IMPI trial is a multicenter international randomized double-blind placebo-controlled 2 × 2 factorial study. Eligible patients are randomly assigned to receive oral prednisolone or placebo for 6 weeks and M. w injection or placebo for 3 months. Patients are followed up at weeks 2, 4, and 6 and months 3 and 6 during the intervention period and 6-monthly thereafter for up to 4 years. The primary outcome is the first occurrence of death, pericardial constriction, or cardiac tamponade requiring pericardiocentesis. The secondary outcome is safety of immunomodulatory treatment measured by effect on opportunistic infections (eg, herpes zoster) and malignancy (eg, Kaposi sarcoma) and impact on measures of immunosuppression and the incidence of immune reconstitution disease. CONCLUSIONS: IMPI is the largest trial yet conducted comparing adjunctive immunotherapy in pericarditis. Its results will define the role of adjunctive corticosteroids and M. w immunotherapy in patients with TB pericardial effusion.

Right ventricular function in treatment-naïve human immunodeficiency virus-infected patients.

BACKGROUND: Right ventricular dysfunction carries a poorer prognosis in human immunodeficiency virus (HIV)-positive patients. The objectives of this study were to ascertain the prevalence of right ventricular systolic and diastolic dysfunction, as well as its predictors, in antiretroviral therapy-naïve HIV-positive patients. METHODS: Participants in this cross-sectional, descriptive study comprised 60 HIV-positive patients and 60 HIV-negative controls. All participants had transthoracic echocardiography done to assess right ventricular systolic and diastolic function. The HIV-positive patients had their CD4 counts measured. RESULTS: The mean age of the study population was 34.63 ± 8.7 years versus that of the controls (34.45 ± 9.40 years) (p = 1.000). Right ventricular systolic dysfunction was found in 11.6% of the HIV-positive patients versus the controls (3.33%, p = 0.166) while right ventricular diastolic dysfunction was found in 15.0% of HIV-positive patients versus the controls (1.7%, p = 0.021). The CD4 count did not contribute to the frequency and degree of right ventricular systolic or diastolic dysfunction. CONCLUSION: Right ventricular systolic and diastolic dysfunction was common in treatment-naïve HIV-infected individuals but the frequency and degree were not associated with the CD4 count or other measured parameters.

The Effect of Nebivolol on Office Blood Pressure of Blacks Residing in Sub-Saharan Africa (A Pilot Study).

Introduction: There is substantial clinical evidence that monotherapy with beta-blockers are less effective in reducing blood pressure among hypertensive Black patients compared to Whites. The highly selective beta-1 agents like nebivolol and bisoprolol have, however, been reported to be effective in reducing blood pressure in African Americans. However, results in African Americans cannot be extrapolated to native Africans because of genetic admixture and gene-environment interaction. There is, therefore, the need for us to generate data that are applicable to Africans residing in sub-Saharan Africa. We therefore decided to evaluate the efficacy and tolerability of highly selective beta-1 agent nebivolol in hypertensive Black patients residing in sub-Saharan Africa. Materials and Methods: The nebivolol study was a multicenter, prospective, observational program among hypertensive patients with 4- and 8-week follow up which was conducted in 5 cities in Nigeria of Abuja, Calabar, Enugu, Oghara, and Port Harcourt. Dosages of nebivolol used in keeping with local prescribing information were 5 and 10 mg once daily each. The effectiveness of treatment was assessed by change from baseline in mean office systolic and diastolic blood pressures, and the proportion of patients achieving the therapeutic goal of <140/90 mmHg. Safety and tolerability of this medication were also assessed. Results: We report the results of the 140 patients studied. The mean age and body mass index were 46.9 ± 7.3 years and 22.3 ± 5.8 kg/m2, respectively, and 57.1% were female. Nebivolol reduced SBP and DBP by 7.6 and 6.6 mmHg, respectively, in 4 weeks, and by 11.1 and 8.0 mm Hg, respectively, in 8 weeks. Blood pressure control was achieved in 54.8% of the patients in 4 weeks and increased to 60.4% in 8 weeks. There was no change in metabolic profile between randomization and at 8 weeks, and erectile dysfunction occurred in 1.3% of the study population. Conclusions: Nebivolol 5 and 10 mg appear efficacious in Nigerian Africans with no negative metabolic effect and minimal side effect profile. Clinical Trial Registration: www.ClinicalTrials.gov, Study Identification: NCT03598673.

Knowledge of the Nigerian Code of Health Research Ethics Among Biomedical Researchers in Southern Nigeria.

Responsibility for protection of research participants from harm and exploitation rests on Research Ethics Committees and principal investigators. The Nigerian National Code of Health Research Ethics defines responsibilities of stakeholders in research so its knowledge among researchers will likely aid ethical conduct of research. The levels of awareness and knowledge of the Code among biomedical researchers in southern Nigerian research institutions was assessed. Four institutions were selected using a stratified random sampling technique. Research participants were selected by purposive sampling and completed a pre-tested structured questionnaire. A total of 102 biomedical researchers completed the questionnaires. Thirty percent of the participants were aware of the National Code though 64% had attended at least one training seminar in research ethics. Twenty-five percent had a fairly acceptable knowledge (scores 50%-74%) and 10% had excellent knowledge of the code (score ≥75%). Ninety-five percent expressed intentions to learn more about the National Code and agreed that it is highly relevant to the ethical conduct of research. Awareness and knowledge of the Code were found to be very limited among biomedical researchers in southern Nigeria. There is need to improve awareness and knowledge through ethics seminars and training. Use of existing Nigeria-specific online training resources is also encouraged.

Patient outcomes following after-hours and weekend admissions for cardiovascular disease in a tertiary hospital in Calabar, Nigeria.

BACKGROUND: There are various reports of higher mortality rates occurring after admissions over the weekend and during after-hours. This study aimed to determine if there was a difference in mortality rates occurring during the weekend and after-hours among cardiovascular admissions in a tertiary hospital in Nigeria. METHODS: A review of cardiovascular admissions (including stroke) was carried out at the University of Calabar Teaching Hospital in Nigeria from January 2010 to December 2013. All admissions to the medical wards from the emergency department and medical out-patient department clinics during the study period were included. RESULTS: A total of 339 patients were studied and stroke was the commonest type of cardiovascular disease (CVD) admitted (187; 55.2%). Hypertension was the commonest cause of heart failure (70; 48.6%). Presentation to hospital during after-hours and length of stay of more than 14 days were significant predictors of death (OR: 3.37; 0.22). CONCLUSION: An increase in CVD mortality rates occurred during after-hours, most likely a consequence of uneven staffing patterns and poor access to equipment. Healthcare providers in Nigeria need to consider remedies to this with a view to reducing excess mortality rates.

Prevalence and clinical predictors of drug-resistant tuberculosis in three clinical settings in Calabar, Nigeria.

BACKGROUND AND AIMS: Drug-resistant tuberculosis (TB) poses a serious challenge to global control of TB. This multicentre study was to identify risk factors for drug resistance to the first line anti-TB drugs among TB patients presenting for care in three health facilities in Calabar, Nigeria. MATERIALS AND METHODS: A cohort of 100 consecutive TB patients were recruited. Demographic information such as age, sex, weight, height, occupation, previous TB diagnosis and treatment, smoking, alcohol dependence and substance abuse were obtained. Sputum samples were collected from participants and cultured on Lowenstein - Jensen (LJ) slopes. Drug susceptibility testing was then carried out for the isolates identified as Mycobacterium tuberculosis, using isoniazid, rifampicin, ethambutol and streptomycin. RESULTS: Forty-two of the 100 participants evaluated were found to be resistant to at least one drug. Multi-drug-resistant TB was seen in four persons. Statistically significant differences were found with respect to three variables: younger age, abandonment of TB treatment and presence of cavitary lesions on chest radiograph. The variables sex, alcohol dependence, tobacco use and previous imprisonment were not significantly associated with TB drug resistance. Four variables were significant following the multivariate analysis with the following adjusted odds ratios: abandonment of TB treatment (9.34), cavitary lesions on chest radiograph (5.88), younger age (6.25) and male sex (3.25). CONCLUSION: Thus, risk stratification of TB patients is advocated in clinical settings where diagnostic facilities for drug-resistant TB are scarce using the identified predictors. This group will benefit from close monitoring and early drug susceptibility testing.

Coronary artery disease and the profile of cardiovascular risk factors in South South Nigeria: a clinical and autopsy study.

Introduction. Death from coronary artery disease (CAD) has been until recently considered rare in Nigeria. We present a report of a study of CAD with its predisposing cardiovascular (CVD) risk factors in South South Nigeria. Methods. We examined the autopsy reports of 747 coroner cases and 41 consecutive clinically diagnosed cases of ischemic heart disease seen in South South Nigeria. Results. CAD was diagnosed in 13 (1.6%) of 747 autopsies. They were predominantly males, urban residents, and of high social class with combination of CVD risk factors of hypertension, alcohol use, diabetes mellitus, cigarette smoking, poor physical activities, and obesity. The mean serum cholesterol of the clinical subjects was 4.7 ± 1.57 mmol/L and 5.07 ± 1.94 mmol/L for angina and myocardial infarction, respectively, which was higher than the mean total cholesterol for locality of 3.1 mmol/L. Conclusion. CAD and its risk factors are contributing to mortality and morbidity in South South Nigeria. These risk factors include hypertension, alcohol use, diabetes mellitus, cigarette smoking, poor physical activity, and obesity. Nigerians in this locality with CAD have raised serum lipids.

Drug Resistance among Pulmonary Tuberculosis Patients in Calabar, Nigeria.

Background. This study aimed to determine the pattern of drug susceptibility to first-line drugs among pulmonary TB patients in two hospitals in Calabar, Nigeria. Methods. This was a descriptive cross-sectional study carried out between February 2011 and April 2012. Sputum samples from consecutive TB patients in Calabar were subjected to culture on Lowenstein-Jensen (LJ) slopes followed by drug susceptibility testing (DST). The DST was performed on LJ medium by the proportion method. Results. Forty-two of the 100 Mycobacterium tuberculosis strains were found to be resistant to at least one drug. Resistance to only one drug (monoresistance) was found in 17 patients. No strains with monoresistance to rifampicin were found. Resistance to two drugs was found in 22 patients, while one patient was resistant to both three and four drugs. MDR TB was seen in 4% (4/100). The independent variables of HIV serology and sex were not significantly associated with resistance (P > 0.05). Conclusion. There was a high prevalence of anti-TB drug resistance in Calabar.