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.
In this prospective study, we assessed biomarkers of inflammation (IL-6 and SAA) from the serum of 120 COVID-19 patients, of whom 70 had chronic kidney disease. All the samples were taken at ...emergency-department (ED) admission. Our goal was to relate the biomarkers to the results of death and acute kidney injury. All the patients underwent chest computer tomography to estimate the severity score (0-5), which was performed at hospital admission. Finally, biomarkers were also evaluated in a healthy control group and in non-COVID-19-CKD patients. IL-6 and SAA were statistically different between the subgroups, i.e., they were significantly increased in patients with COVID-19. Both of the biomarkers (IL-6 and SAA) were independently associated with mortality, AKI and a higher grade of pathological changes in the lung's parenchyma. Both high baseline levels of IL-6 and SAA on hospital admission were highly correlated with a later ventilatory requirement and mortality, independent of hospital stay. Mortality was found to be significantly higher when the chest CT severity score was 3-4, compared with a severity score of 0-2 (
< 0.0001). Conclusions: at the admission stage, IL-6 and SAA are useful markers for COVID-19 patients with CKD.
Type 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.
The 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.
Of 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).
Our results prove that the PPAR γ agonist pioglitazone has the potential to be beneficial to patients with T2DM.
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. Accumulating evidence suggests that diabetic patients may exert bone fractures due to such treatments. Simultaneously, 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.
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 diabetes mellitus patients published before Feb 15, 2016. Among 1536 sources that were initially identified, six studies including 3172 patients proved relevant for further analysis.
Pooled analysis of the included studies demonstrated that after treatment with pioglitazone patients 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.
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.
SARS-CoV-2 vaccination is effective in preventing severe Covid-19, but efficacy in reducing viral load and transmission wanes over time. In addition, the emergence of novel SARS-CoV-2 variants ...increases the threat of uncontrolled dissemination and additional antiviral therapies are urgently needed for effective containment. In previous
studies
demonstrated strong antiviral activity against enveloped viruses, including SARS-CoV-2. In this study, we examined the potential of
in preventing and treating respiratory tract infections (RTIs) and in particular, SARS-CoV-2 infections. 120 healthy volunteers (m,f, 18-75 years) were randomly assigned to
prevention or control group without any intervention. After a run-in week, participants went through 3 prevention cycles of 2, 2 and 1 month with daily 2,400 mg
extract (Echinaforce
, EF). The prevention cycles were interrupted by breaks of 1 week. Acute respiratory symptoms were treated with 4,000 mg EF for up to 10 days, and their severity assessed
a diary. Naso/oropharyngeal swabs and venous blood samples were routinely collected every month and during acute illnesses for detection and identification of respiratory viruses, including SARS-CoV-2
RT-qPCR and serology. Summarized over all phases of prevention, 21 and 29 samples tested positive for any virus in the EF and control group, of which 5 and 14 samples tested SARS-CoV-2 positive (RR = 0.37, Chi-square test,
= 0.03). Overall, 10 and 14 symptomatic episodes occurred, of which 5 and 8 were Covid-19 (RR = 0.70, Chi-square test,
> 0.05). EF treatment when applied during acute episodes significantly reduced the overall virus load by at least 2.12 log
or approx. 99% (
-test,
< 0.05), the time to virus clearance by 8.0 days for all viruses (Wilcoxon test,
= 0.02) and by 4.8 days for SARS-CoV-2 (
> 0.05) in comparison to control. Finally, EF treatment significantly reduced fever days (1 day vs 11 days, Chi-square test,
= 0.003) but not the overall symptom severity. There were fewer Covid-19 related hospitalizations in the EF treatment group (
= 0 vs
= 2). EF exhibited antiviral effects and reduced the risk of viral RTIs, including SARS-CoV-2. By substantially reducing virus loads in infected subjects, EF offers a supportive addition to existing mandated treatments like vaccinations. Future confirmatory studies are warranted.
Regarding COVID-19 infection, Bulgaria has one of the lowest rates of vaccination in Europe, and its COVID-19-related mortality rate has been one of the highest in the European Union. Chronic kidney ...disease (CKD)-COVID-19 patients are at higher risk of developing acute kidney injury (AKI) and death after hospital admission. This single-center prospective cohort study from Bulgaria included 120 in-patient COVID-19 subjects of whom 70 had CKD and 50 normal renal function. Diabetes mellitus, hypertension, obesity, and cardiovascular disease were statistically more prevalent in the CKD group as compared to the non-CKD group. At admission, D-dimer, creatinine, and urea levels were significantly higher in the CKD group, whereas estimated glomerular-filtration rate was significantly lower as compared to the non-CKD patients. During hospitalization, 23 patients (19.1%) died, of which 19 were in the CKD group (p-value = 0.0096); in addition, 38 developed AKI (31.6%), of which 31 were in the CKD group (p-value = 0.0006). Using binary logistic regression, being male, having experienced AKI, and not having been treated with remdesivir were independent risk factors for COVID-19-induced mortality. Regarding risk of AKI, having had COVID-19-related symptoms for more than 6 days before admission, having CKD at baseline, and having not received remdesivir therapy were independent predictive factors for developing AKI after admission.
In a prospective, observational, non-interventional, single-center study, we assessed various plasma and urinary biomarkers of kidney injury (neutrophil gelatinase-associated Lipocain NGAL, ...kidney-injury molecule-1 KIM-1, and interleukin-18 IL-18); inflammation (IL-6, C-reactive protein CRP); plus angiotensin converting enzyme 2 (ACE2) in 120 COVID-19 patients (of whom 70 had chronic kidney disease (CKD) at emergency-department (ED) admission). Our aim was to correlate the biomarkers with the outcomes (death, acute kidney injury AKI). All patients had received a chest-CT scan at admission to calculate the severity score (0-5). Biomarkers were also assessed in healthy volunteers and non-COVID-19-CKD patients. These biomarkers statistically differed across subgroups, i.e., they were significantly increased in COVID-19 patients, except for urinary (u)KIM1 and uIL-18. Amongst the biomarkers, only IL-6 was independently associated with mortality, along with AKI and not using remdesivir. Regarding the prediction of AKI, only IL-6 and uKIM1 were significantly elevated in patients presenting with AKI. However, AKI could not be predicted. Having high baseline IL-6 levels was associated with subsequent ventilation requirement and death. The mortality rate was almost 90% when the chest CT-scan severity score was 3 or 4 vs. 6.8% when the severity score was 0-2 (
< 0.0001).
Abstract
Background
Hypertension is a disease with significant clinical and socio-economic 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.
Post-acute sequelae of SARS-CoV-2 (PASC) is a significant health concern, particularly for patients with chronic kidney disease (CKD). This study investigates the long-term outcomes of individuals ...with CKD who were infected with COVID-19, focusing on their health status over a three-year period post-infection. Data were collected from both CKD and non-CKD patients who survived SARS-CoV-2 infection and were followed for three years as part of a research study on the impact, prognosis, and consequences of COVID-19 infection in CKD patients. In this prospective cohort study, we analyzed clinical records, laboratory findings, and patient-reported outcomes assessed at intervals during follow-up. The results indicated no permanent changes in renal function in any of the groups analyzed, although patients without CKD exhibited faster recovery over time. Furthermore, we examined the effect of RAAS-blocker therapy over time, finding no influence on PASC symptoms or renal function recovery. Regarding PASC symptoms, most patients recovered within a short period, but some required prolonged follow-up and specialized post-recovery management. Following up with patients in the post-COVID-19 period is crucial, as there is still insufficient information and evidence regarding the long-term effects, particularly in relation to CKD.
ObjectiveData on the incidence, mortality, and causes of death in patients with Cushing's syndrome (CS) are scarce, due to the rarity of CS. The aim of the study was to analyze mortality in a large ...cohort of patients of all etiologies and to determine the cause of death.DesignThis was a retrospective study of patients with CS, treated over a period of 45 years in the main tertiary referral center in Bulgaria.MethodsThree hundred and eighty-six patients with CS of all etiologies were included. The main outcome measures were the standardized mortality ratio (SMR) and the cause of death.ResultsMean (±s.d.) age at diagnosis was 38±13 years; 84% of patients were women; mean follow-up was 85 months (range: 0–494 months). The SMR in the CS cohort was 4.05 (95% CI 2.50–5.80) (P<0.0001). The following subgroups did not have a significantly increased SMR: patients with Cushing's disease SMR – 1.88 (95% CI 0.69–4.08), adrenal adenomas 1.67 (95% CI 0.20–6.02), and ACTH-independent bilateral adrenal hyperplasia 1.14 (95% CI 0.21–6.34). Patients with adrenal carcinomas, ectopic CS, and those with CS of undetermined etiology had significantly increased SMR: 48.00 (95% CI 30.75–71.42), 13.33 (95% CI 0.00–24.59), and 4.00 (95% CI 0.48–14.45) respectively (P<0.0001). The significant predictors for mortality were active disease at death, age, male sex, etiology of the disease, and the overall duration of active disease. The major causes of death were vascular events (40%) – cardiovascular 29%, and cerebrovascular 11% – followed by infections (12%).ConclusionsPatients with CS have increased mortality due to vascular events and infections.
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