Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD). METHODS: We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia). RESULTS: A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m2). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion. CONCLUSIONS: Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.

Correlates of cardiorespiratory fitness among overweight or obese individuals with type 2 diabetes.

INTRODUCTION: Mechanistic studies suggest that type 2 diabetes is independently associated with low cardiorespiratory fitness (CRF). Little is known about the CRF profile in type 2 diabetes; we assessed the correlates of low CRF among overweight/obese adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 4215 participants with type 2 diabetes and without cardiovascular disease underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Calorie intake and physical activity were assessed using questionnaires. Body fat composition was assessed using dual-energy X-ray absorptiometry. RESULTS: Waist circumference, systolic blood pressure, glycemic measures, whole body fat, caloric intake, and fat-free mass were inversely associated with fitness across sex (all p<0.001). Comparing with moderate or high CRF groups, the low CRF group was associated with higher adjusted odds of obesity (OR 3.19 (95% CI 1.95 to 5.20) in men, 3.86 (95% CI 2.55 to 5.84)) in women), abdominal obesity (OR 3.99 (95% CI 2.00 to 7.96) in men, 2.28 (95% CI 1.08 to 4.79) in women), hypertension (OR 1.74 (95% CI 1.09 to 2.77) in men, 1.44 (95% CI 1.02 to 2.05) in women), metabolic syndrome (OR 5.52 (95% CI 2.51 to 12.14) in men, 2.25 (95% CI 1.35 to 3.76) in women), use of beta-blocker (1.22 (95% CI 0.86 to 1.73) in men, 1.33 (95% CI 1.03 to 1.73) in women), and ACE inhibitor/angiotensin-receptor blocker (1.86 (95% CI 1.39 to 2.50) in men, 1.07 (95% CI 0.86 to 1.32) in women). Women with low CRF had higher odds of current smoking (2.02 (95% CI 1.25 to 3.28)). CONCLUSIONS: Low CRF was associated with increased odds of cardiometabolic correlates in a large cohort of adults with type 2 diabetes.

Prevalence and progression of rheumatic heart disease: a global systematic review and meta-analysis of population-based echocardiographic studies.

This systematic review and meta-analysis aimed to provide a contemporaneous estimate of the global burden of rheumatic heart disease (RHD) from echocardiographic population-based studies. We searched multiple databases between January 01, 1996 and October 17, 2017. Random-effect meta-analysis was used to pool data. We included 82 studies (1,090,792 participant) reporting data on the prevalence of RHD and 9 studies on the evolution of RHD lesions. The pooled prevalence of RHD was 26.1‰ (95%CI 19.2-33.1) and 11.3‰ (95%CI 7.2-16.2) for studies which used the World Heart Federation (WHF) and World Health Organization (WHO) criteria, respectively. The prevalence of RHD varied inversely with the level of a country's income, was lower with the WHO criteria compared to the WHF criteria, and was lowest in South East Asia. Definite RHD progressed in 7.5% (95% CI 1.5-17.6) of the cases, while 60.7% (95% CI 42.4-77.5) of cases remained stable over the course of follow-up. The proportion of cases borderline RHD who progressed to definite RHD was 11.3% (95% CI 6.9-16.5). The prevalence of RHD across WHO regions remains high. The highest prevalence of RHD was noted among studies which used the WHF diagnostic criteria. Definite RHD tends to progress or remain stable over time.

Active smoking among people with diabetes mellitus or hypertension in Africa: a systematic review and meta-analysis.

The objective was to summarize existing data on the prevalence of active tobacco smoking among patients with hypertension or diabetes mellitus in Africa. We searched PubMed, EMBASE, and AJOL to include studies published from January 01, 2000 to August 23, 2017 reporting on the prevalence of active smoking in individuals aged ≥15 years with hypertension or diabetes mellitus residing inside Africa. We used a random-effects meta-analysis model to pool studies. The pooled prevalence of active smoking among patients with hypertension or diabetes was 12.9% (95%CI: 10.6-15.3; 50 studies; 16,980 patients) and 12.9% (95%CI: 9.6-16.6; 42 studies; 18,564 patients), respectively. For both conditions, the prevalence of active smoking was higher in males than in females (p < 0.001), and in Northern compared to sub-Saharan Africa (p < 0.001). There was no difference between urban and rural settings, and between community-based and hospital-based studies, except for patients with diabetes for whom the prevalence was higher in hospital-based studies (p = 0.032). The prevalence of active smoking is high among patients with hypertension or diabetes mellitus in Africa, with the heaviest burden in Northern Africa. Interventions for smoking prevention or cessation should be implemented in these high risk populations, targeting particularly the males.

The Prognostic Value of Histopathologic Lesions in Native Kidney Biopsy Specimens: Results from the Boston Kidney Biopsy Cohort Study.

Background Few studies have evaluated whether histopathologic lesions on kidney biopsy provide prognostic information beyond clinical and laboratory data.Methods We enrolled 676 individuals undergoing native kidney biopsy at three tertiary care hospitals into a prospective, observational cohort study. Biopsy specimens were adjudicated for semiquantitative scores in 13 categories of histopathology by two experienced renal pathologists. Proportional hazards models tested the association between histopathologic lesions and risk of kidney disease progression (≥40% eGFR decline or RRT).Results Mean baseline eGFR was 57.5±36.0 ml/min per 1.73 m2 During follow-up (median, 34.3 months), 199 individuals suffered kidney disease progression. After adjustment for demographics, clinicopathologic diagnosis, and laboratory values, the following lesions (hazard ratio; 95% confidence interval) were independently associated with progression: inflammation in nonfibrosed interstitium (0.52; 0.32 to 0.83), moderate and severe versus minimal interstitial fibrosis/tubular atrophy (2.14; 1.24 to 3.69 and 3.42; 1.99 to 5.87, respectively), moderate and severe versus minimal global glomerulosclerosis (2.17; 1.36 to 3.45 and 3.31; 2.04 to 5.38, respectively), moderate and severe versus minimal arterial sclerosis (1.78; 1.15 to 2.74 and 1.64; 1.04 to 2.60, respectively), and moderate and severe versus minimal arteriolar sclerosis (1.63; 1.08 to 2.46 and 2.33; 1.42 to 3.83, respectively). An 11-point chronicity score derived from semiquantitative assessments of chronic lesions independently associated with higher risk of kidney disease progression (hazard ratio per one-point increase, 1.19; 95% confidence interval, 1.12 to 1.27).Conclusions Across a diverse group of kidney diseases, histopathologic lesions on kidney biopsy provide prognostic information, even after adjustment for proteinuria and eGFR.

Prevalence and associated factors of active smoking among individuals living with hypertension and/or diabetes in Africa: a systematic review and meta-analysis protocol.

INTRODUCTION: Tobacco use significantly increases cardiovascular complications in people living with hypertension and/or diabetes. We aim to summarise data on the prevalence and factors associated with active smoking in these conditions in Africa. METHOD AND ANALYSIS: We will search PubMed, Embase, Google Scholar and African Journals Online for relevant abstracts of studies on active smoking in individuals living with diabetes and/or hypertension published from 1 January 2000 to 31 December 2016, with no language restriction. Additionally, relevant unpublished papers and conference proceedings will be checked, as well as references of included articles. Two investigators will independently screen, select studies, extract data and assess the risk of bias in each study. Data will be analysed using Stata software (Stata V.14, Texas, USA). The study-specific estimates will be pooled through a random-effects meta-analysis model to obtain an overall summary estimate of the prevalence of smoking across studies. Also, we will assess factors associated to smoking. Heterogeneity of studies will be evaluated by the χ2 test on Cochrane's Q statistic. Funnel plots analysis and Egger's test will be done to detect publication bias. Results will be presented by geographic region (central, eastern, northern, southern and western Africa). A p value less than 0.05 will be considered significant for factors associated to smoking. ETHICS AND DISSEMINATION: This study is based on published data, and therefore ethical approval is not a requirement. This systematic review and meta-analysis is expected to serve as a basis for designing cost-effective interventions to reduce and prevent smoking in patients with diabetes and/or hypertension, and as a guide for future research based on the remaining gaps. The final report of this study in the form of a scientific paper will be published in peer-reviewed journals. Findings will further be presented at conferences and submitted to relevant health authorities.

Patterns and trends in mortality among HIV-infected and HIV-uninfected patients in a major Internal Medicine Unit in Yaoundé, Cameroon: a retrospective cohort study.

OBJECTIVE: To describe the trends in mortality and the spectrum of disease in HIV-infected and -uninfected inpatients in a population in Yaoundé. DESIGN: A retrospective study. SETTING: Internal Medicine Unit, University Hospital Centre, Yaoundé, Cameroon. PARTICIPANTS: All deaths registered between January 2000 and May 2007 in the unit. MAIN OUTCOMES MEASURES: Sociodemographic characteristics, clinical features and results of all investigations done, cause of death. RESULTS: During the study period, 362 deaths were registered, consisting of 281 (77.6%) in HIV-infected patients, 54.4% of which were women. HIV-infected patients were younger (mean age: 40.2 (SD: 11.6) vs. 55.5 (SD: 18.3) years, p < 0.001) and economically active (60.3% vs. 24.4%, p < 0.001). Most HIV-infected patients (77.6%) were classified as WHO stage IV, with the rest being WHO stage III. Most HIV-infected patients (87.8%) had evidence of profound immunosuppression (CD4 < 200 cells/mm(3)). The mortality trend appeared to be declining with appropriate interventions. The most frequent causes of death in HIV-infected patients were pleural/pulmonary tuberculosis (34.2%), undefined meningoencephalitis (20.3%), other pneumonias (18.2%), toxoplasmosis (16.4%), cryptococcal meningitis (14.2%) and Kaposi sarcoma (15.7%). HIV-uninfected patients died mostly as a result of chronic diseases including liver diseases (17.3%), kidney failure (13.6%), congestive heart failure (11.1%) and stroke (9.9%). CONCLUSION: There was a declining mortality due to HIV with appropriate interventions such as subsidised tests for HIV-infected patients, increased availability of HAART and other medications for prevention and treatment of opportunistic infections. The spectrum of HIV disease was wide and preventable.