Graphical abstract

People with type 2 diabetes are at increased risk of bladder cancer. Pioglitazone is said to increase it further, although published evidence is mixed. We conducted a meta-analysis to determine if any link between the use of pioglitazone and an increased risk of bladder cancer can be found. A comprehensive literature search was conducted through electronic databases as well as registries for data of clinical trials to identify studies that investigate the effect of pioglitazone on bladder cancer in diabetic patients. We used the risk ratio (RR) and the hazard ratio (HR) provided by the studies to illustrate the risk of occurrence of bladder cancer in the experimental group compared to that in the control group. Fourteen studies using RR and 12 studies using HR were included in the analysis. The overall RR was 1.13 with 95% CI (0.96–1.33) with low heterogeneity among the studies using RR, suggesting that no connection exists between use of pioglitazone and the risk of bladder malignancy. The summary HR was 1.07 (0.96–1.18) allowing us to affirm that there is no link between long-term use of pioglitazone and bladder cancer. Our results support the hypothesis of no difference in the incidence of bladder cancer among the pioglitazone group and the nonuser group. Our conclusion is that the explanation of hypothetically increased risk of bladder malignancy should be attributed to other factors. Funding : Tchaikapharma High Quality Medicines Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0273-4) contains supplementary material, which is available to authorized users.

Objectives The present study aimed to provide normative data for the EQ-5D-5L questionnaire in Bulgaria, based on a nationally representative sample. Methods Random sampling was used. In September 2018, a total of 1005 respondents (aged 18-89 years) completed the self-administered paper-based EQ-5D-5L questionnaire, including a visual analogue scale (EQ VAS). Health state utility index scores were derived using the directly measured Polish value set. Results The study sample was representative of the general Bulgarian population in terms of age, sex, geographical region, educational level, social and professional status. Mean EQ-5D-5L and EQ VAS values decreased from 0.986 and 89.7 (age group 18-24 years) to 0.789 and 53.6 (age group ≥ 75 years), respectively. Perfect health (the "11,111" health state) was reported by half of the population (50.1%), more often by men than women (55.8% vs 44.9%). The most frequently reported complaints characterised pain/discomfort dimension (39.1%), followed by anxiety/depression (34.5%). Although the least commonly reported health limitations concerned the self-care dimension, their frequency (13.6%) was the highest among the seventeen identified EQ-5D-5L population norm studies. The mean severity index score for the whole study sample was 6.96. EQ-5D-5L index was higher in respondents from lower age groups and with a higher average income per household member. Conclusions Bulgarian population norms, which were developed for the descriptive part of the EQ-5D-5L and EQ VAS, can be used as reference values. The availability of such normative data should encourage the use of the EQ-5D-5L questionnaire in health-related quality-of-life studies in Bulgaria.

Introduction: Thiazolidinediones are a group of synthetic medications used in type 2 diabetes treatment. Among available thiazolidinediones, pioglitazone is gaining increased attention due to its lower cardiovascular risk in type 2 diabetes mellitus sufferers and seems a promising future therapy. Accumu-lating evidence suggests that diabetic patients may exert bone fractures due to such treatments. Simulta-neously, the female population is thought to be at greater risk. Still, the safety outcomes of pioglitazone treatment especially in terms of fractures are questionable and need to be clarified.Methods: We searched MEDLINE, Scopus, PsyInfo, eLIBRARY.ru electronic databases and clinical trial registries for studies reporting an association between pioglitazone and bone fractures in type 2 dia-betes mellitus patients published before Feb 15, 2016. Among 1536 sources that were initially identified, six studies including 3172 patients proved relevant for further analysis.Result: Pooled analysis of the included studies demonstrated that after treatment with pioglitazone pa-tients with type 2 diabetes mellitus had no significant increase in fracture risk [odds ratio (OR): 1.18, 95% confidence interval (CI): 0.82 to 1.71, p=0.38] compared to other antidiabetic drugs or placebo. Additionally, no association was found between the risk of fractures and pioglitazone therapy duration. The gender of the patients involved was not relevant to the risk of fractures, too.Conclusion: Pioglitazone treatment in diabetic patients does not increase the incidence of bone fractures. Moreover, there is no significant association between patients’ fractures, their gender and the period of exposure to pioglitazone. Additional longitudinal studies need to be undertaken to obtain more detailed information on bone fragility and pioglitazone therapy

Hypertension is a complex syndrome of multiple hemodynamic, neuroendocrine, and metabolic abnormalities. The goals of treatment in hypertension are to optimally control high blood pressure and to reduce associated cardiovascular morbidity and mortality using the most suitable therapy available. Hydrochlorothiazide (HCTZ) and chlorthalidone (CTLD) are with proven hypertensive effects. The topic of our meta-analysis is to compare the efficacy of HCTZ and CTLD therapy in patient with hypertension. A search of electronic databases PubMed, MEDLINE, Scopus, PsyInfo, eLIBRARY.ru was performed. We chose the random-effects method for the analysis and depicted the results as forest plots. Sensitivity analyses were performed in order to evaluate the degree of significance of each study. Of the 1289 identified sources, only nine trials directly compared HCTZ and CTLD and were included in the meta-analysis. Changes in SBP lead to WMD (95% CI) equal to −3.26 mmHg showing a slight but statistically significant prevalence of CTLD. Results from analyzed studies referring to DBP lead to WMD (95% CI) equal to −2.41 mmHg, which is also statistically significant. During our analysis, we found that there were not enough studies presenting enough data on the effect of CTLD and HCTZ on levels of serum potassium and serum sodium. Our meta-analysis has demonstrated a slight superiority for CTLD regarding blood pressure control. At the same time, the two medications do not show significant differences in their safety profile.

BackgroundType 2 diabetes mellitus (T2DM) is one of the most common diseases worldwide and insulin insufficiency and insulin resistance are two main metabolic issues connected with it. The dyslipidemia associated with insulin resistance and T2DM is characterized by higher triglycerides (TGs), higher very-low-density lipoprotein cholesterol and lower apo A1. Pioglitazone, a member of the thiazolidinedione class, with a proven antihyperglycemic effect, is known to positively influence insulin sensitivity and β-cell function and to have the potential to alter the lipid profile.MethodsThe aim of our meta-analysis is to summarize and determine the influence of pioglitazone on the glycemic profile and lipoprotein metabolism as well as on weight and BMI in order to highlight the benefit of pioglitazone therapy in patients with T2DM. A comprehensive literature search was conducted through the electronic databases PubMed, MEDLINE, Scopus, PsyInfo, eLIBRARY.ru (from 2000 until February 2016) to identify studies that investigate the effect of pioglitazone on the glycemic and lipid profile and on the weight and BMI. We chose the random-effects method as the primary analysis. Forest plots depict estimated results from the studies included in the analysis and funnel plots are used to evaluate publication bias. Sensitivity analyses were performed in order to evaluate the degree of influence of the consequent elimination of each individual study on the final result.ResultsOf the 1536 identified sources only 15 randomised trials were included in the meta-analysis. Pioglitazone treatment was associated with improvement in the glycemic profile. It reduced FPG levels by a mean of 1.1–2 mmol/l and HbA1c by a mean of 0.9–1.3%. Our results reaffirmed the hypothesis that pioglitazone has a positive influence on the lipid profile of T2DM patients with increase in TC and HDL, no significant changes in LDL and notable decrease in TGs. Results also showed that pioglitazone therapy led to increase in both weight and BMI (WMD 1.755, 95% CI 0.674 to 2.837 and 1.145, 95% CI 0.389 to 1.901 respectively).ConclusionOur results prove that the PPAR γ agonist pioglitazone has the potential to be beneficial to patients with T2DM.Electronic supplementary materialThe online version of this article (10.1186/s13098-017-0290-5) contains supplementary material, which is available to authorized users.

Background: Hypertension is a disease with significant clinical and socioeconomic consequences. The reduction in cardiovascular mortality and morbidity in patients treated for hypertension is directly related to the magnitude of blood pressure reduction. Diuretics have proven useful for the prevention of cardiovascular complications in addition to a long history of safety and efficacy. The main aim for this meta-analysis is to compare the efficacy of the combination of angiotensin receptor blocker (ARB) and chlorthalidone (CTLD) to the combination of ARB and hydrochlorothiazide (HCTZ) in patients with hypertension. Methods: A comprehensive literature search was conducted through electronic databases PubMed, MEDLINE, Scopus, PsyInfo, Cochrane, eLIBRARY.ru, http://ClinicalTrials.gov and http://www.clinicaltrialsregister.eu in July 2020 to identify studies that investigate the effect of the combination of angiotensin receptor blocker with chlorthalidone or hydrochlorothiazide on the systolic and diastolic blood pressure in patients with hypertension. Changes in systolic and diastolic blood pressure (BP) expressed as a weighted mean difference (WMD) were our primary outcomes. The random-effects method was chosen as the primary analysis and results were presented with a 95% confidence interval (CI). Sensitivity analysis was performed and bias was assessed. Results: Our search returned 2745 titles. Of them, 51 full-text articles remained to be subjected to assessment. Comparisons of ARB/HCTZ versus ARB showed changes in BP of −6.89 (−8.09, −5.69) mmHg for systolic BP and − 3.67 (−4.15, −3.19) mmHg for diastolic BP. For the ARB/CTLD versus ARB/HCTZ comparison changes were − 6.30 (−7.30, −5.29) mmHg for systolic BP and − 3.57 (−4.17, 2.98) mmHg for diastolic BP. Conclusion: Our analysis suggests a small but significant favor for CTLD in blood pressure control when compared to HCTZ. We believe it should be considered as a valuable alternative for HCTZ and an option for fixed dose combinations with an ARB although further research is required.

Hypertension is a chronic condition leading to increased stress on the heart and blood vessels, a critical risk factor for clinically significant events such as myocardial infarction heart failure, stroke and death. Chlorthalidone and hydrochlorothiazide are first-line antihypertensive agents for most patients with hypertension. The aim of our meta-analysis was to compare the efficacy and safety of both therapies in patients with hypertension. Searches of electronic databases PubMed, MEDLINE, Scopus, PsycInfo and eLIBRARY.ru, were performed. We used network meta-analysis to combine direct and indirect evidence. Forest plots and closed loops depict estimated results from studies included in our meta-analysis. Of 1289 identified sources, only 37 were included in our meta-analysis. Our analysis has demonstrated a slight superiority for chlorthalidone regarding SBP and not statistically significant differences regarding DBP. Simultaneously, hydrochlorothiazide seems to be a safer choice of therapy, as evidenced by the levels of serum potassium. The two diuretics can be used interchangeably.