The Cardiovascular Safety of Five-Alpha-Reductase Inhibitors Among Men with Benign Prostatic Hyperplasia: A Population-Based Cohort Study.

BACKGROUND: Five-alpha reductase inhibitors (5αRIs) are used to treat benign prostatic hyperplasia (BPH). However, the cardiovascular effects of 5αRIs remain poorly understood. The study objective was to compare the rate of hospitalization for heart failure among men with BPH prescribed 5αRIs to that of men with BPH not prescribed BPH medications. METHODS: Using the Clinical Practice Research Datalink linked with hospitalization and vital statistics data, we conducted a population-based cohort study among patients newly diagnosed with BPH. We defined exposure as the current use of 5αRIs, current use of alpha-blockers, and no current use of BPH medications in a time-varying approach. The primary endpoint was hospitalization for heart failure, and secondary endpoints were myocardial infarction, stroke, and cardiovascular death. We used time-dependent Cox-proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Our cohort included 94,440 men with incident BPH. A total of 3893 hospitalizations for heart failure occurred over 527,660 person-years of follow-up (incidence rate 7.38; 95% CI, 7.15-7.61, per 1000 person-years). Compared with no current use of BPH medications, current use of 5αRIs was not associated with an increased risk of hospitalization for heart failure (HR 0.94; 95% CI, 0.86-1.03), myocardial infarction (HR 0.92; 95% CI, 0.81-1.05), stroke (HR 0.94; 95% CI, 0.85-1.05), or cardiovascular death (HR 0.89; 95% CI, 0.80-0.99). CONCLUSIONS: The use of 5αRIs was not associated with an increased risk of hospitalization for heart failure, myocardial infarction, stroke, or cardiovascular death compared with non-use.

5-α reductase inhibitors and the risk of anaemia among men with benign prostatic hyperplasia: A population-based cohort study.

5-α reductase inhibitors (5αRIs) are effective for the treatment of benign prostatic hyperplasia (BPH). However, 5αRIs could lower levels of haemoglobin, increasing the risk of anaemia. The objective of this study was to compare the rate of anaemia between new users of 5αRIs and α-blockers in the UK. METHODS: We conducted a matched, active comparator, new-user cohort study using the Clinical Practice Research Datalink. The study population consisted of men aged ≥40 years with incident BPH who initiated 5αRIs between 1998 and 2019 and were matched 1:1 on propensity score to new users of α-blockers. Anaemia was defined by a measured haemoglobin <130 g/L. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for anaemia. RESULTS: Our study cohort included 9429 new users of 5αRIs and 9429 matched new users of α-blockers. Their median durations of follow-up were 136 days (interquartile range: 54-336 d) and 77 days (interquartile range: 58-236 d), respectively. A total of 2865 5αRIs users and 2407 α-blocker users developed incident anaemia, representing rates of 37.3 (95% CI: 33.6-41.3) and 42.0 (95% CI: 38.1-46.2) per 100 person-years, respectively. The use of 5αRIs was not associated with an increased risk of anaemia compared to the use of α-blockers (HR: 0.95, 95% CI: 0.90-1.00). Similarly, we did not observe an increased risk of mild, moderate, or severe anaemia. CONCLUSION: The use of 5αRIs was not associated with an increased risk of anaemia compared to the use of α-blockers among men with BPH.

Type 2 diabetes mellitus and risk of community-acquired pneumonia: a systematic review and meta-analysis of observational studies.

BACKGROUND: People with type 2 diabetes are at greater risk for infections than those without type 2 diabetes. Our objective was to examine the association between type 2 diabetes and the risk of community-acquired pneumonia (CAP). METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, CINAHL, ProQuest theses and dissertations, Global Health, the Global Index Medicus of the World Health Organization, and Google Scholar. We included observational studies published in English or French between Jan. 1, 1946 (start of MEDLINE) and July 18, 2020. Two independent reviewers extracted data and assessed quality using the ROBINS-I tool. DerSimonian-Laird random-effects models were used to pool estimates of the association between type 2 diabetes and CAP. RESULTS: Our systematic review included 15 articles, reporting on 13 cohort studies and 4 case-control studies (14 538 968 patients). All studies reported an increased risk of pneumonia among patients with type 2 diabetes, and all were at serious risk of bias. When estimates were pooled across studies, the pooled relative risk was 1.64 (95% confidence interval [CI] 1.55-1.73); although there was a substantial amount of relative heterogeneity (I 2 94.2), the amount of absolute heterogeneity was more modest (T2 0.008). The relative risk was 1.70 (95% CI 1.63-1.77, I 2 85.2%, T2 0.002) among cohort studies (n = 13), and the odds ratio was 1.54 (95% CI 1.14-2.09, I 2 92.7%, T2 0.07) among case-control studies (n = 4). INTERPRETATION: Type 2 diabetes may be associated with an increased risk of CAP; however, the available evidence is from studies at serious risk of bias, and additional, high-quality studies are needed to confirm these findings. PROSPERO REGISTRATION: CRD42018116409.

Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The cardiovascular safety of testosterone replacement therapy (TRT) is controversial. While several studies have investigated the association between TRT and the risk of arterial thrombosis, limited information is available regarding its risk of venous thromboembolism (VTE). We aimed to compare the risk of VTE in men randomized to TRT versus placebo or active-comparator in a systematic review. METHODS: We searched Medline, EMBASE, CINAHL, CENTRAL, and clinical trial registries to identify randomized controlled trials (RCTs) comparing TRT to placebo in men aged ≥18 years. We assessed study quality using the Cochrane Risk of Bias assessment tool and the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Data were pooled across RCTs using random-effects models. RESULTS: A total of 13 RCTs (n = 5050) were included in our meta-analysis. In all, 2636 men were randomized to testosterone, and 2414 men to placebo. Sample sizes ranged from 101 to 790 men, and TRT duration from 3 to 36 months. Five studies had a high risk of bias, largely driven by unclear randomization and outcome assessment. When data were pooled across RCTs, testosterone therapy was not associated with VTE compared with placebo (RR: 1.03, 95% CI: 0.49-2.14; I2: 0%; low-quality evidence). Similar estimates were obtained for deep vein thrombosis and pulmonary embolism outcomes. CONCLUSIONS: Our systematic review suggests that TRT is not associated with an increased risk of VTE. However, estimates were accompanied by a wide 95% CIs, and a clinically important increased risk cannot be ruled out.

Trends in the pharmacological treatment of benign prostatic hyperplasia in the UK from 1998 to 2016: a population-based cohort study.

PURPOSE: To describe trends in the pharmacological treatment of BPH in the United Kingdom (UK) from 1998 to 2016. METHODS: We created a cohort of men with a diagnosis of BPH between 1998 and 2016 using the Clinical Practice Research Datalink. Using Poisson regression, we estimated annual prescription rates of 5αRIs, α-blockers, and combination therapy (5αRIs + α-blockers). Adherence was defined by a proportion of days covered > 80%. RESULTS: Our cohort included 192,640 men with BPH who generated 1,176,264 person-years (PYs) of follow-up. The mean age was 68.0 (standard deviation: 10.7) years. The prescription rate of all BPH medications during the study period was 347.6 per 100 PYs (95% CI 347.2-347.9). α-Blockers had the highest prescription rate (222.9 per 100 PYs, 95% CI 222.7-223.2); prescription rates of 5αRIs and combination therapy were 69.1 per 100 PYs (95% CI 69.0-69.3) and 55.5 per 100 PYs (95% CI 55.4-55.7), respectively. The prescription rate for combination therapy was 19 times greater in 2013-2016 than in 1998-2000 (rate ratio: 19.2, 95% CI 18.6-19.7), while the prescription rates for 5αRIs and α-blockers each doubled during this period (rate ratio: 1.86, 95% CI 1.84-1.88 and rate ratio: 2.02, 95% CI 2.01-2.04, respectively). The proportion of patients who were adherent at 1 year to 5αRIs (32.3%), α-blockers (44.0%), and combination therapy (45.6%) was low. CONCLUSION: The prescription rate of BPH medications increased substantially between 1998 and 2016 in the UK, with the greatest relative increase observed with combination therapy. Adherence to BPH medications was low in this population-based study.

Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Infection with Human Immunodeficiency virus (HIV) is an important risk factor for Tuberculosis (TB). Anti-Retroviral Therapy (ART) has improved the prognosis of HIV and reduced the risk of TB infected patients. Isoniazid Preventive Therapy (IPT) aims to reduce the development of active TB in patients with latent TB. OBJECTIVE: Systematically review and synthesize effect estimates of IPT for TB prevention in adult HIV patients. Secondary objectives were to assess the effect of IPT on HIV disease progression, all-cause mortality and adverse drug reaction (ADR). SEARCH STRATEGY: Electronic databases were searched to identify relevant articles in English available by September 11th 2015. SELECTION CRITERIA: Research articles comparing IPT to placebo or no treatment in HIV infected adults using randomized clinical trials. DATA ANALYSIS: A qualitative review included study-level information on randomization and treatment allocation. Effect estimates were pooled using random-effects models to account for between-study heterogeneity. MAIN RESULTS: This review assessed ten randomized clinical trials that assigned 7619 HIV patients to IPT or placebo. An overall 35% of TB risk reduction (RR = 0.65, 95% CI (0.51, 0.84)) was found in all participants, however, larger benefit of IPT was observed in Tuberculin Skin Test (TST) positive participants, with pooled relative risk reduction of 52% [RR = 0.48; 95% CI (0.29, 0.82)] and with a prediction interval ranging from 0.13 to 1.81. There was no statistically significant effect of IPT on TB occurrence in TST negative or unknown participants. IPT also reduced the risk of HIV disease progression in all participants (RR = 0.69; 95% CI (0.48, 0.99)) despite no benefits observed in TST strata. All-cause mortality was not affected by IPT although participants who had 12 months of IPT tend to have a reduced risk (RR = 0.65; 95% CI(0.47, 0.90)). IPT had an elevated, yet statistically non-significant, risk of adverse drug reaction [RR = 1.20; 95% CI (1.20, 1.71)]. Only a single study assessed the effect of IPT in combination with ART in preventing TB and occurrence of multi-drug resistant tuberculosis. CONCLUSIONS: IPT use substantially contributes in preventing TB in persons with HIV in general and in TST positive individuals in particular. More evidence is needed to explain discrepancies in the protective effect of IPT in these individuals.

Effect of isoniazid preventive therapy on tuberculosis or death in persons with HIV: a retrospective cohort study.

BACKGROUND: Isoniazid preventive therapy (IPT) is a recommended strategy for prevention of tuberculosis (TB) in persons with Human Immunodeficiency Virus (HIV) although the benefits have not been unequivocally demonstrated in routine clinical practice with widespread ART adoption. Therefore, we assessed the effectiveness of IPT in prevention of TB or death in patients treated with antiretroviral therapy (ART) in a chronic care setting. METHODS: Retrospective cohort study of HIV patients enrolled in chronic care from 2007 to 2013. Eligible participants were HIV infected subjects (age > 15 years) with no (history of) TB. The combined effect of IPT and ART on the composite outcome (TB or death) was estimated using time-dependent Cox regression with adjustment for baseline covariates. RESULTS: 1,922 patients were included, 374 (19.4 %) received IPT and 258 (13.4 %) developed TB or deceased. The median follow-up duration of the cohort was 839 days, with a total of 5491 person years. In unadjusted analysis, the combination of IPT and ART lowered the hazard of TB or death by 65 % [HR = 0.35; 95 % CI (0.16, 0.77)] compared to ART alone. Even after adjustment for confounders, the combined effect of ART and IPT resulted in a 60 % hazard reduction of TB or death in comparison to participants who received ART without IPT [HR = 0.40; 95 % CI (0.18, 0.87)]. The IPT-specific benefit in patients not receiving ART could not be reliably estimated due to high rates of ART adoption. CONCLUSION: The combined effect of IPT and ART to prevent TB or death in HIV patients in a non-experimental setting in comparison to ART alone was estimated to be 60 %.

Malnutrition: Prevalence and its associated factors in People living with HIV/AIDS, in Dilla University Referral Hospital.

BACKGROUND: Literatures on prevalence and factors associated with malnutrition among peoples living with HIV/AIDS are limited in Ethiopia and not well documented either. The proper implementation of nutritional support and its integration with the routine highly active antiretroviral therapy package demands a clear picture of the magnitude and associated factors of malnutrition. The objective of this study is, therefore, to assess the prevalence and factors associated with malnutrition among peoples living with HIV/AIDS. METHODS: Institution based cross sectional study was conducted in Dilla University referral Hospital including adult HIV patients who were in highly active anti retroviral therapy. Interview administered questionnaires were used to collect data on socio demographic factors. Besides, HIV related clinical information was extracted from anti retro viral therapy data base and clinical charts. The nutritional status of the patients was determined by Body Mass Index (BMI) where BMI < 18kg/m2 was defined as malnutrition according to World Health Organization (WHO). Binary logistic regression was used to assess association between different risk factors and malnutrition. Confidence interval of 95% was considered to see the precision of the study and the level of significance was taken at α <0.05. RESULTS: A total of 520 patients were included in the analysis. The overall prevalence of malnutrition was 12.3% (95% CI 9.5-15.0). After full control of all variables; unemployment (OR = 3.61, 95% CI: 3.6 - 7.76), WHO clinical stage four (OR = 12.9, 95% CI: 2.49- 15.25), gastrointestinal symptoms (OR = 5.3, 95% CI: 2.56 - 10.78) and previous (one) opportunistic infection (OR = 3.1, 95% CI 2.06 - 5.46), and two & above previous opportunistic infections (OR = 4.5, 95% CI: 3.38 - 10.57) were significantly associated with malnutrition. However, moderately poor economic condition was found to be protective factor for malnutrition (OR = 0.4, 95% CI: 0.14 - 0.95). CONCLUSION: Unemployment, WHO clinical AIDS stage four, one & more number of previous opportunistic infections and gastrointestinal symptoms were found to be important risk factors for malnutrition among People Living with HIV/AIDS. From this study it has been learnt that nutritional programs should be an integral part of HIV/AIDS continuum of care. Furthermore, it needs to improve household income of PLHIV with employment opportunity and to engage them in income generating activities as well.