Deciphering mortality risk of diabetes medications in heart failure patients with diabetes mellitus under triple guideline-directed medical therapy.

BACKGROUND: Scientific evidence regarding the impact of different combinations of diabetes medications in heart failure patients with diabetes mellitus (HFwDM) remains limited. AIM: We aimed to investigate the effect of monotherapy and combination therapy for DM on all-cause mortality in HFwDM under triple guideline-directed medical therapy (GDMT). METHOD: This nationwide retrospective cohort study included adult HFwDM under triple GDMT between January 1, 2016 and December 31, 2022.We collected the data from the National Electronic Database of the Turkish Ministry of Health.We created various combination including different diabetes medications based on the current guidelines for DM.The primary endpoint was all-cause mortality. RESULTS: A total of 321,525 HFwDM under triple GDMT (female:49%, median age:68[61-75] years) were included. The highest rate of prescribed combination therapy was metformin and sulfonylureas (n = 55,266). In Cox regression analysis, insülin monotherapy had the highest risk for all-cause mortality (HR:2.25, 95CI%:2.06 - 2.45), whereas combination therapy including metformin, SGLT2i, and sulfonylureas provided the most beneficial effect on survival (HR:0.29, 95CI%:0.22-0.39) when compared to patients not receiving diabetes medication. Among patients taking diabetes medications, the inclusion of SGLT2i demonstrated a survival benefit (p < 0.05), despite concurrent use of volume-retaining medications such as insulin and thiazolidinediones. Conversely, combinations of diabetes medications without SGLT2i did not demonstrate any survival benefit compared to patients not taking diabetes medication (p > 0.05). CONCLUSION: This study underscored the use of SGLT2i as monotherapy or as a part of combination diabetes medications to improve survival among HFwDM, while also highlighting that combinations lacking SGLT2i did not confer any survival benefit.

Navigating Heart Failure: Unveiling Sex Disparities in Guideline-Directed Medical Therapy Combinations.

Major heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the under-representation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from the Turkish Ministry of Health's National Electronic Database between January 1, 2016, and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, ß blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and ß blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on all-cause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations.

Trends in heart failure between 2016 and 2022 in Türkiye (TRends-HF): a nationwide retrospective cohort study of 85 million individuals across entire population of all ages.

Background: Data on the burden of heart failure (HF) outside western countries are limited, but available data suggest it may present differently in other countries. The aim of this study was to examine the incidence, prevalence, and survival rates of HF in Türkiye, with a specific focus on how these rates vary according to age, sex, comorbidities, and socioeconomic status (SES). Methods: We harnessed the extensive National Electronic Database of the Turkish Ministry of Health, covering Turkey's entire population from January 1, 2016, to December 31, 2022, to identify 2,722,151 cases of HF and their associated comorbidities using ICD-10 codes. Analyzing the primary endpoint of all-cause mortality, our study utilized anonymized data to examine patient demographics, comorbidities, socioeconomic status, and survival patterns, employing statistical techniques to delve into relationships and trends. The data were segmented by gender, socioeconomic status, and age, involving cross-tabulations and statistical metrics to explore connections, odds ratios, and survival rates. Findings: The estimated prevalence of HF was 2.114% in Türkiye at the end of 2022, with an annual incidence ranging between 3.00 and 6.06 per 1000 person years. Females were older than males (69.8 ± 13.9 years vs. 66.8 ± 13.9 years, respectively). The most common comorbidities were congenital heart diseases and anemia under the age of 20, and hypertension and atherosclerotic cardiovascular disease in the adult population. Only 23.6% (643,159/2,722,151) of patients were treated with any triple guideline-directed medical therapy (GDMT) and 3.6% (96,751/2,722,151) of patients were on quadruple GDMT. The survival rates for patients with HF at 1, 5, and 7 years were 83.3% (95% CI: 83.2-83.3), 61.5% (95% CI: 61.4-61.6), and 57.7% (95% CI: 57.6-57.8) among females, and 82.1% (95% CI: 82.0-82.2), 58.2% (95% CI: 58.1-58.3), and 54.2% (95% CI: 54.0-54.3) among males. Despite a tendency for an increase from the highest to the lowest SES, the prevalence of HF and mortality were paradoxically lowest in the lowest SES region. Interpretation: The prevalence, incidence, and survival rates of HF in Türkiye were comparable to western countries, despite the notable difference of HF onset occurring 8-10 years earlier in the Turkish population. Drug usage statistics indicate there is a need for effective strategies to improve treatment with GDMT. Funding: None.

Are COL4A1 and COL4A2 gene polymorphisms associated with cerebral palsy?

OBJECTIVES: This study aims to investigate the association of COL4A1 and COL4A2 gene polymorphisms with susceptibility to risk of developing cerebral palsy (CP) and severity of CP. PATIENTS AND METHODS: Between December 2016 and June 2017, a total of 176 patients with CP (101 males, 75 females; mean age 71.8±37.9 months; range, 24 to 184 months) and age-, sex-, and ethnically-matched 178 (90 males, 88 females; mean age 69.3±55.2 months; range, 24 to 214 months) controls were included. Two polymorphisms of COL4A1 (rs1961495) and COL4A2 (rs9521733) genes were typed from genomic deoxyribonucleic acid. Genotype distributions and allelic frequencies were compared between the patient and control groups. Gross Motor Function Classification System, the use of medical drugs, type of involvement, number of affected limbs, accompanying conditions, birth weight, gestational age, and magnetic resonance imaging (MRI) findings were used to evaluate the disease severity and their relationships with the COL4A1 and COL4A2 gene polymorphisms. RESULTS: There was no statistically significant difference between the groups in terms of genotype distribution and allele frequency of COL4A1 and COL4A2 gene polymorphisms (p>0.05). In addition, there was no relationship between severity of CP and two gene polymorphisms (p>0.05). A significant association was detected between the COL4A2 polymorphism and growth retardation in CP. The TT genotype (57.1%) and T allele (76.2%) were higher, compared to CC (4.8%) and CT genotypes (38.1%) and C allele (23.8%) in patients with CP with growth retardation (p=0.03 for genotype and p=0.01 for allele frequency). CONCLUSION: These findings suggest that COL4A1 and COL4A2 gene polymorphisms are not associated with susceptibility to CP in a group of Turkish populations, although COL4A2 gene polymorphism may be associated with growth retardation in patients with CP.

[Effects of abdominal adhesion-preventing 4% icodextrin solution on healing of bowel anastomoses]. / Karin içi adezyon önleyici %4'lük ikodekstrin solüsyonunun gastrointestinal sistem anastomozlari üzerine etkisi.

BACKGROUND: We aimed to introduce the efficiency of 4% icodextrin solution on preventing adhesions and its effect on anastomotic healing, together with biochemical parameters. METHODS: In total, 40 rats were divided into four groups of 10 rats each as Group A (abrasion+icodextrin), Group B (abrasion), Group C (anastomosis+icodextrin), and Group D (anastomosis). Adhesion grade, anastomotic bursting pressure, histopathological analysis, tissue hydroxyproline level, and serum myeloperoxidase (MPO), nitric oxide (NO), and malondialdehyde (MDA) values were examined. RESULTS: Adhesion score was significantly lower in Group A than in Group B and significantly lower in Group C than in Group D (p=0.003577, p=0.001612). No difference in anastomoses healing was determined between Group C and Group D (p=0.816). Hydroxyproline level was significantly higher in Group A than in Group B and significantly higher in Group C than in Group D (p=0.001, p=0.0001). There were no differences in NO and MDA levels between Group A and Group B, but values were significantly lower in Group C than in Group D (p=0.434, p=0.001, p=0.116, p=0.018). MPO level was significantly lower in Group A than in Group B and significantly lower in Group C than in Group D (p=0.0001, p=0.0001). CONCLUSION: Based on our results, 4% icodextrin solution evidently decreased the formation of adhesion without negatively affecting the anastomotic healing. We also reported herein the biochemical and histopathological results and adhesion scores.

Affected States soft independent modeling by class analogy from the relation between independent variables, number of independent variables and sample size.

OBJECTIVE: The aim of study is to introduce method of Soft Independent Modeling of Class Analogy (SIMCA), and to express whether the method is affected from the number of independent variables, the relationship between variables and sample size. STUDY DESIGN: Simulation study. MATERIAL AND METHODS: SIMCA model is performed in two stages. In order to determine whether the method is influenced by the number of independent variables, the relationship between variables and sample size, simulations were done. Conditions in which sample sizes in both groups are equal, and where there are 30, 100 and 1000 samples; where the number of variables is 2, 3, 5, 10, 50 and 100; moreover where the relationship between variables are quite high, in medium level and quite low were mentioned. RESULTS: Average classification accuracy of simulation results which were carried out 1000 times for each possible condition of trial plan were given as tables. CONCLUSION: It is seen that diagnostic accuracy results increase as the number of independent variables increase. SIMCA method is a method in which the relationship between variables are quite high, the number of independent variables are many in number and where there are outlier values in the data that can be used in conditions having outlier values.

Chemopreventive effect of nonsteroidal anti-inflammatory drugs on the development of a new colorectal polyp or adenoma in a high-risk population: a meta-analysis.

BACKGROUND: Although many experimental, epidemiologic, and clinical studies have suggested that aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in reducing and preventing colorectal adenomas, randomized, controlled trials (RCTs) are still being carried out to obtain statistically reliable results. OBJECTIVE: The aim of this meta-analysis was to review long-term, prospective RCTs investigating the effect of NSAIDs on the relative risk (RR) for developing ≥1 new colorectal polyp or adenoma in a high-risk population. METHODS: We conducted a comprehensive search of MEDLINE, PubMed, and other electronic databases (including Inter-Science, Science Direct, Ebsco, Synergy, and Proquest) (key terms: nonsteroidal anti-inflammatory drugs, aspirin, colorectal, and polyps; years: 1974-2004) for English-language articles. Eligible studies were analyzed in terms of demographic data, adverse effects, and effect of NSAIDs on the RRs. RESULTS: Four long-term, prospective RCTs were used in the statistical analysis. A total of 2069 high-risk patients were enrolled; 1880 patients completed the studies, and 1127 were in active-treatment groups (aspirin 81-325 mg/d or sulindac 150-300 mg/d). Our meta-analysis of these studies revealed that the overall RR for developing ≥ 1 new colorectal polyp or adenoma was significantly reduced by using aspirin or other NSAIDs (RR = 0.809; 95% CI, 0.718-0.912). CONCLUSIONS: The results of this meta-analysis suggest that regular use of aspirin 81 to 325 mg/d or sulindac 150 to 300 mg/d for ≥1 year was associated with a decrease in the RR for developing ≥ 1 new colorectal polyp or adenoma to 0.80 (95% CI, 0.718-0.912) in patients at high risk.

Effect of administration mode (patient vs physician) and patient's educational level on the Turkish version of the International Prostate Symptom Score.

OBJECTIVES: To compare the effectiveness of the International Prostate Symptom Score (IPSS) when administered by the physician to when self-administered by the patient. The effect of the patient's educational level on the IPSS was also evaluated. METHODS: One hundred and seven previously untreated patients with symptomatic benign prostatic hyperplasia (BPH) completed the Turkish version of the International Prostate Symptom Score (Turkish I-PSS) and quality of life (QOL) questionnaires during a single office visit, first on their own and then with an interviewing physician. The patients were categorized into three groups according to their educational levels. Paired t-tests were performed to compare the total IPSS (tIPSS) and QOL results between the two testing modes. IPSS and QOL scores resulting from both modes were compared using a kappa test. Differences between the physician-assisted and self-administered scores among the different educational groups were further compared using a one-way anova test and Post Hoc Multiple Comparisons. To compare the objective effectiveness of tIPSS and QOL between the two testing modes, we selected the positive actual state, which was maximum urine flow (Qmax) of 15 mL/s or less and constructed receiver operating characteristics (ROC) curves for all patients. This estimation was constructed for each educational level. RESULTS: There were no statistical differences in IPSS and QOL values obtained by the patients or physicians (P > 0.05). The ROC areas for tIPSS were 0.94 and 0.93, and the ROC areas for QOL scores were 0.97 and 0.91 for information obtained by physicians and patients, respectively. When IPSS answers and QOL scores were evaluated separately, consistency was found across both modes of administration. However, there were lower levels of consistency in answers to IPSS questions 2, 5 and 6 (P = 0.59;0.42; 0.52, respectively). There was no significant difference among the aforementioned data in the educational groups. CONCLUSION: Although the total IPSS and QOL scores were not affected by the different modes of administration, we recommend that the physicians should evaluate answers to questions 2, 5 and 6 carefully. The present study demonstrates that the educational level did not affect the IPSS and QOL when administered either by the physician or the patient.