Real-world evidence of the effects of sodium-glucose co-transporter 2 inhibitors on the dosing of diuretics in patients with heart failure: a retrospective cohort study.

Background: Heart failure (HF) was estimated to impact approximately 64 million individuals worldwide in 2017 and is predicted to rise in the coming years. Therefore, the aim of our study was to evaluate the effects of sodium-glucose transport protein 2 (SGLT2) inhibitors on the dosing of diuretics among individuals diagnosed with HF. Methods: A retrospective cohort study was conducted at Security Forces Hospital in Riyadh, Saudi Arabia, between January 2018 and August 2022. The study included adult patients who were diagnosed with heart failure and received dapagliflozin and/or diuretic. A descriptive analysis was conducted to identify significant differences between both groups by using the chi-square test for categorical variables and the Student's t-test for continuous variables. A logistic regression model was also run to identify the odds of each event. Statistical significance was indicated by p values less than .05. Results: Overall reduction in diuretics was reported in 68 patients in the SGLT2 inhibitors plus diuretic therapy group, while in the diuretic therapy group 25 patients reported overall reduction in diuretics (OR = 4.81, 95% [2.74-8.45]). The reduction of the loop dose level was reported by 58 patients in the SGLT2 inhibitors plus diuretic group and by 25 patients in the diuretic group (OR = 3.48, 95% [1.98-6.11]). The discontinuation of thiazide was reported by 16 patients in the SGLT2 inhibitors plus diuretic therapy group, but by only two patients in the diuretic group (OR = 9.04, 95% [2.03-40.19]). After 6 months, ejection fraction was increased by 2.74 in the SGLT2 inhibitors plus diuretic group (p = .0019) and decreased by 2.56 in the diuretic group (p = .0485), both of which were statistically significant. The mean dose changes were decreased by 14.52 in the SGLT2 inhibitors plus diuretic group (p < .0001), which was statistically significant. Conclusion: Treatment with SGLT2 inhibitors plus diuretic significantly reduced the patients' diuretic requirements. Therefore, our finding supports the theoretical concept of minimizing the level of diuretic upon the initiation of SGLT2 inhibitors.

Examining the Effects of Dasatinib, Sorafenib, and Nilotinib on Vascular Smooth Muscle Cells: Insights into Proliferation, Migration, and Gene Expression Dynamics.

BACKGROUND: Dasatinib, nilotinib, and sorafenib are clinically proven tyrosine kinase inhibitors (TKIs) used for the treatment of leukemia and hepatocellular carcinoma. However, there is a growing concern regarding cardiotoxicity associated with their use. The impact of these TKIs on vascular smooth muscle cells (VSMCs) remains unexplored. This study aims to investigate the effects of TKIs on VSMC proliferation and migration, as well as to elucidate the underlying mechanisms involving inflammatory and apoptotic pathways. METHODS: VSMCs were extracted from albino rats and cultured in vitro. The cells were divided into four experimental groups: control, dasatinib, sorafenib, and nilotinib. The MTT assay was employed to assess the cytotoxic effects of TKIs on VSMCs. A scratch assay was conducted to evaluate the inhibitory potential of TKIs on VSMC migration. Flow cytometry analysis was used to detect apoptotic cells. Real-Time PCR expression was utilized to determine the differential gene expression of apoptotic and inflammatory markers. RESULTS: Dasatinib, nilotinib, and sorafenib demonstrated significant inhibitory effects on VSMC viability and migration at low concentrations (<1 µmol/L, p < 0.05). Furthermore, gene expression analysis revealed up-regulation of inflammatory biomarkers (TNF-α, IL-6, and IL-1ß) and apoptotic markers (P53, BAX), along with down-regulation of the anti-apoptotic biomarker BCL-2 in response to all TKIs. CONCLUSIONS: This study demonstrates that dasatinib, nilotinib, and sorafenib inhibit VSMC proliferation and migration, suggesting their potential to induce vascular injury and remodeling by activating inflammation and apoptosis pathways. These findings highlight the need for further investigation into the cardiotoxic effects of these TKIs and the development of strategies to mitigate their adverse vascular effects.

Adherence to evidence-based guidelines for the management of pneumonia in a tertiary teaching hospital in Riyadh.

Background: Adherence to therapeutic guidelines is crucial when treating pneumonia, as it reduces mortality rate, length of hospital stay and duration of antibiotic therapy. However, the high non-adherence rate to treatment guidelines, in general, and to the Infectious Disease Society of America (IDSA) guidelines, are still reported globally. According to our knowledge, no existing data is available regarding the rate of physicians' adherence to the IDSA guidelines for managing pneumonia in Saudi Arabia. Therefore, we aim to assess the adherence rate and the clinical outcomes among patients treated according to the IDSA guidelines, in a tertiary care center in Riyadh. Methods: A single-centered, retrospective, cross-sectional, observational study was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia. All data were extracted from the hospital's electronic information system, known as Esihi. Adult patients (≥18 years old) diagnosed and treated in the hospital for community-acquired pneumonia, hospital-acquired pneumonia, or ventilator-associated pneumonia from Nov 2019 to Nov 2021 were included. Results: A total of 148 patients were included in this study, and the management of 50% of them (74 patients) adhered to the guidelines' recommendations. Even though the patients who received guidelines-adhered management were older (70 ± 16 vs 59 ± 22; p = 0.001), and had a higher CURB-65 score for pneumonia severity (1.86 ± 1.03 vs 1.39 ± 1.26; p = 0.026) and an average calculated Charlson comorbidity index (4.62 ± 2.19 vs 3.28 ± 2.80; p = 0.001) than patients who were treated irrespectively of the guidelines, yet they had a better cure rate (95% vs 84%; adjusted OR, 3.9; 95% CI, 0.82-18.58), lower mortality (5% vs 14%; adjusted OR, 0.38; 95% CI, 0.04-4.05) and shorter length of hospital stay (LOS) (6.5 vs 8 days; p = 0.082); compared to patients who were treated irrespectively of the guidelines. Conclusions: Comparable to previous literature, non-adherence to evidence-based guidelines has been observed in 50% of patients treated for pneumonia. Despite being nonsignificant, higher clinical cure rates, shorter LOS, and lower mortality rates have been observed in patients who were treated based on evidence-based guidelines. Further measures to improve guidelines compliance in pneumonia treatment are needed.

Antidepressants and health-related quality of life (HRQoL) for patients with depression: Analysis of the medical expenditure panel survey from the United States.

BACKGROUND: Despite the empirical literature demonstrating the efficacy of antidepressant medications for treatment of depression disorder, these medications' effect on patients' overall well-being and health-related quality of life (HRQoL) remains controversial. This study investigates the effect of antidepressant medication use on patient-reported HRQoL for patients who have depression. METHODS: A comparative cohort, secondary database analysis was conducted using data from the United States' Medical Expenditures Panel Survey for patients who had depression. HRQoL was measured using the SF-12 and reported as physical and mental component summaries (PCS and MCS). A cohort of patients that used antidepressant medications were compared to a cohort of patients that did not. Univariate and multivariate difference-in-differences (D-I-D) analyses were used to assess the significance of the mean difference of change on the PCS and MCS from baseline to follow-up. RESULTS: On average, 17.5 million adults were diagnosed with depression disorder each year during the period 2005-2016. The majority were female (67.9%), a larger proportion of whom received antidepressant medications (60.5% vs. 51.5% of males). Although use of antidepressants was associated with some improvement on the MCS, D-I-D univariate analysis revealed no significant difference between the two cohorts in PCS (-0.35 vs. -0.34, p = 0.9595) or MCS (1.28 vs. 1.13, p = 0.6405). The multivariate D-I-D analyses ensured the robustness of these results. CONCLUSION: The real-world effect of using antidepressant medications does not continue to improve patients' HRQoL over time. Future studies should not only focus on the short-term effect of pharmacotherapy, it should rather investigate the long-term impact of pharmacological and non-pharmacological interventions on these patients' HRQoL.

Knowledge regarding Zika Virus Infection among Healthcare Providers in an Academic Tertiary Care Center in Riyadh, Saudi Arabia: A Cross-Sectional Survey Study.

BACKGROUND: Zika virus (ZIKV) has become a major concern across the world. It is highly necessary for healthcare providers (HCPs) to have sufficient knowledge about such a disease. The purpose of this study is to assess the knowledge regarding ZIKV among HCPs in Riyadh, Saudi Arabia. Materials and Methods. A cross-sectional survey study was conducted at a tertiary care center in Riyadh, KSA, during a two-month period from September 19, 2016 to November 19, 2016. Descriptive statistics were performed on data collected. For continuous variables, data were expressed as means ± standard deviations (SDs), medians, and ranges. Proportions were used to describe categorical variables. Knowledge scores were evaluated and compared by demographic characteristics including age, designation, years of practice, and gender, using the t-test/Mann-Whitney U test or the Kruskal-Wallis test, as appropriate. RESULTS: A total of 336 HCPs from different specialties (physicians, dentists, nurses, pharmacists, and nutritionists) completed the questionnaire. Significant differences in knowledge about ZIKV were observed by participant's age. Significantly higher knowledge levels were observed among older participants (45 years or more; p=0.011). A substantial difference in the knowledge level was observed by department, with pairwise comparisons showing significant differences in knowledge scores between all departments except for Pharmacy vs. Nutrition and Nursing vs. Internal Medicine. Knowledge scores were not significantly different by years of practice. CONCLUSION: Our study showed inadequate knowledge of HCPs from different specialties about ZIKV infection which needs to be improved in terms of infection prevention and control. Awareness about ZIKV infection should be ensured and maintained among HCPs to face any possible emergence in the region.