This systematic review and meta-analysis aimed to determine the association between the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and dementia onset as well as cognitive function in patients with diabetes mellitus. We comprehensively searched the MEDLINE, Embase, and CENTRAL databases to select relevant studies published up to August 2023. The use of SGLT-2 inhibitors significantly lowers dementia risk compared to SGLT-2i non-users (Hazard ratio: 0.68, 95 % CI: 0.50-0.92). Furthermore, our findings indicated a positive effect of SGLT-2 inhibitor use on cognitive function score improvement, as demonstrated by the standardized mean difference of 0.88 (95 % CI: 0.32-1.44), particularly among populations with mild cognitive impairment or dementia. This systematic review and meta-analysis indicate a potential role of SGLT-2 inhibitors in reducing the risk of dementia in patients with diabetes mellitus. These findings underscore the need for well-controlled large clinical trials and future research in this field.

Background: The use of opioid–gabapentinoid combinations has increased, raising several safety concerns. However, meta-analysis studies focusing on this issue are limited.Objective: To evaluate the risk of central nervous system (CNS) depression, gastrointestinal (GI) adverse events, and mortality of combination therapy compared with those of opioid therapy and to explore the differences in the results according to study design and indications.Methods: Relevant studies were selected (published before 30 January 2022) by searching the MEDLINE, Embase, and CENTRAL databases. The pooled odds ratios (OR) with 95% confidence intervals (CI) of the outcomes were estimated using the Mantel–Haenszel method. Subgroup and meta-regression analyses were performed according to study characteristics. Quality assessment was conducted using the Risk of Bias 2 tool for randomized controlled trials (RCTs) and Cochrane Collaboration’s Risk of Bias in non-RCTs tool for non-randomized trials.Results: Adverse events were reported in 26 RCTs and 7 non-RCTs, and mortality was reported in 10 non-RCTs. Compared to opioid therapy, dizziness, cognitive dysfunction, and respiratory depression in combination therapy significantly increased in non-RCTs (OR 3.26, 95% CI 1.82–5.85; OR 3.13, 95% CI 1.51–6.50; OR 1.71, 95% CI 1.31–2.24, respectively), and a similar trend for dizziness and cognitive dysfunction was also identified in the RCT analysis, although the difference was not significant. Combination therapy for cancer pain was associated with the highest risk of sedation in subgroup analysis. Combination therapy significantly decreased the risk of GI adverse events, including nausea, vomiting, and constipation. The mortality risk associated with combination therapy was higher than that associated with opioid therapy (OR 2.76, 95% CI 1.26–6.05).Conclusion: Opioid-gabapentinoid combination therapy could be associated with an increased risk of CNS depression and mortality, despite tolerable GI adverse events. These data suggest that combination therapy requires close monitoring of CNS depression, especially in cancer patients. Caution is needed in interpreting the clinical meanings owing to the lack of risk difference in respiratory depression in the RCT-only analysis and the absence of RCT or prospective studies investigating mortality.

Background: Immunosuppressive therapies are vital for solid organ transplant (SOT) recipients to ensure graft survival, but long-term use can lead to complications. This study aimed to comprehensively evaluate the complications associated with immunosuppressive agents across different types of major SOTs. Methods: In a retrospective cohort study using a national claims database, we analyzed adult SOT recipients who began immunosuppressive therapy from 2007 to 2018. We identified complications such as infections, acute kidney injury, hypertensive emergencies, chronic kidney disease, hypertension, diabetes, dyslipidemia, and osteoporosis. These outcomes were determined through diagnostic codes, medication usage data, and hospital or emergency department visits. Results: Among 30,997 transplants with three-year follow up, complication rates varied by transplant type. Pancreatic transplant recipients had the lowest complication rate (225.9 per 1000 patient-years), while lung transplant recipients experienced the highest rate (823.9 per 1000 patient-years). Serious infections and chronic kidney disease were most common 2 to 6 months post transplant. Other complications, like acute kidney injury, hypertensive emergencies, hypertension, diabetes, dyslipidemia, and osteoporosis, were predominantly observed in the first month. Opportunistic infections peaked between 7 months and 1 year after transplantation. Conclusions: This study emphasizes the varied complications related to immunosuppressive therapy among different SOT recipients, delineating specific timeframes for each complication and maintenance regimen.

Hyperbilirubinemia may accompany harmful effects such as jaundice, brain dysfunction, and pharmacokinetic alterations of drugs. Clinical drugs are the important causes of hyperbilirubinemia, especially for patients with certain pathologic conditions or with genetic variations. This article reviews hyperbilirubinemic pathophysiology with respect to the effects of clinical drugs. In addition, this review introduces a new formula that may be utilized to estimate the annual occurrences of drug-induced hyperbilirubinemia in a hospital. Variations in the genes of UDP-glucuronosyltransferases, organic anion-transporting polypeptides and multidrug resistance proteins are the predisposing factors for drug-induced hyperbilirubinemia; therefore, their genetic and ethnic polymorphisms are discussed.

Ah YM, et al. J Korean Med Sci. 2015 Dec;30(12):1800-1806. https://doi.org/10.3346/jkms.2015.30.12.1800

Background: In older adults, depression is associated with several other clinical problems such as cognitive impairment and low quality of life. Several studies have evaluated the relationship between vitamin D and depression in older adults; however, the results have been controversial thus far.Objective: This study aimed to investigate the effects of vitamin D supplementation on depressive symptom improvement among individuals aged ≥60 years with or without a diagnosis of depression or depressive symptoms based on a meta-analysis of randomized controlled trials (RCTs).Methods: RCTs were identified to analyze the relationship between vitamin D supplementation and depressive symptoms. MEDLINE, CENTRAL, Embase, and PsycINFO were systematically searched for relevant articles published from inception to November 2022. RCTs that evaluated the effect of vitamin D supplementation in participants aged ≥60 years compared to placebo were included. A random effects model was used in this meta-analysis because of the differences between the included RCTs. The quality of the RCTs was assessed using Risk of Bias 2.Results: Seven trials were included in the analyses. The primary outcome of pre-post score changes included five trials with a total of 752 participants. The secondary outcome of post-intervention score included all seven trials with a total of 4,385 participants. No significant improvement in depressive symptoms in either pre-post score changes [standardized mean difference (SMD) = −0.49; 95% confidence interval (CI) −1.07–0.09; p = 0.10] or post-intervention score (SMD = −0.10; 95% CI −0.28–0.07; p = 0.25) was found.Conclusion: Vitamin D supplementation in older adults was not associated with an improvement in depressive symptoms. More studies in older adults are needed to evaluate the association between vitamin D supplementation and depression.