The use of potentially interacting supplement-drug pairs in adults with type 2 diabetes: A large population-based cohort study in the UK Biobank.

AIMS: To examine the patterns of use of potentially interacting supplement-drug pairs in adults with type 2 diabetes (T2D) in real-world settings, and to explore the impact of potentially interacting supplement-drug pairs on downstream outcomes. METHODS: Potentially interacting supplement-drug pairs were identified from four tertiary databases. We categorized the potential pharmacodynamic interactions into different clinical types according to their related outcomes and explored their associations with incident outcomes using Cox models. RESULTS: 26,394 participants with T2D in the UK Biobank were included. Half (48.5 %) were supplement users, of whom 85.0 % were taking potentially interacting supplement-drug pairs. The potential pharmacodynamic interactions were related to various clinical outcomes, including reducing the effects of glucose-lowering drugs (50.7 %), hypotension (49.8 %), bleeding (50.4 %) and hepatotoxicity (34.8 %). Exploratory analyses found that the use of potentially interacting supplement-drug pairs was associated with incident hepatic diseases (hazard ratio = 1.26, 95 % confidence interval 1.10-1.44, P < 0.001). CONCLUSIONS: Real-world data suggests that most adults with T2D who concurrently used supplements and drugs were on potentially interacting supplement-drug combinations, with the potential of causing adverse outcomes such as incident hepatic diseases. Clinicians should communicate with patients and assess the potential risk of supplement-drug interactions in clinical settings.

Association between potential supplement-drug interactions and liver diseases in patients with cancer: A large prospective cohort study.

BACKGROUND & AIMS: The concurrent use of herbal and dietary supplements and conventional drugs can lead to interactions in patients with cancer, of which hepatotoxicity is one of the most concerning sequelae. This study examined the potential supplement-drug interactions involving the hepatic system, and their associations with documented liver diseases, among patients with cancer in a large population-based cohort in the UK Biobank. METHODS: Participants diagnosed with cancer and had completed supplement-use assessment after diagnosis were included. Potentially interacting supplement-drug combinations that involved CYP enzymes or increased the risk of hepatotoxicity were identified from four tertiary databases. Liver diseases were identified using ICD-codes K70-77. Log-binomial regression was used to investigate the associations between potentially-interacting supplement-drug combinations and liver diseases documented (1) at any time, and (2) confined to only after the time of supplement-use assessment, adjusting for age, sex and pre-existing comorbidities. RESULTS: This analysis included 30,239 participants (mean age = 60.0 years; 61.9% female). Over half (n = 17,698, 58.5%) reported the use of supplements after cancer diagnoses. Among supplements users, 36.9% (n = 6537/17,698) were on supplement-drug combinations with interacting potential involving the hepatic system. Patients taking supplements and drugs who had hepatic comorbidities were more likely to take potentially interacting pairs (adjusted risk ratio = 1.14, 95% CI = 1.06-1.23, p < 0.001). However, no significant association was observed between the use of these combinations and subsequent liver diseases (all p > 0.05). CONCLUSION: Approximately one-third of the participants who had cancer and were supplement users had a risk of potential supplement-drug interactions that contribute to adverse liver effect. Healthcare professionals should communicate with patients with cancer, especially those with pre-existing liver diseases, about supplement use and proactively assess the clinical significance of potential interactions.

Immune-related adverse events associated with immune checkpoint inhibitors for advanced gastric and gastroesophageal junction cancer: A meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown promising efficacy in treatment and clinical management of advanced gastric and gastroesophageal junction cancer. However, the inhibitors also cause immune-related adverse events (irAEs). The current systematic review and meta-analysis study aimed to investigate the incidence and nature of irAEs caused by ICIs. AIM: To investigate the incidence and nature of irAEs in advanced gastric and gastroesophageal junction cancer. METHODS: This systematic review was registered with PROSPERO (Reg. number: CRD42020152291). Data included in this study were collected from patients diagnosed with advanced gastric cancer or gastroesophageal junction cancer and treated with ICIs. A systematic literature search was conducted using the PubMed, EMBASE, and Cochrane Library databases. Meta-analysis was carried out using the single sample rate method. Synthesis and analysis of the data was conducted using Stata/SE and Review Manager Software. RESULTS: The patients enrolled in the present study included 14 patients from 14 case reports, 326 patients from 6 case series, and 1249 patients from 8 clinical trials. It was found that the overall incidence of irAEs was 16% [95% confidence interval (CI): 11-20] for all grades and 3% (95%CI: 2-4) for the severe grade. It was evident that the incidence of irAEs varied with the type of inhibitor and organs. A comparative study of the anti-programmed cell death receptor-1 (PD-1) and anti-programmed death receptor-ligand 1 (PD-L1) treatments showed that the anti-PD-1 group had a higher overall incidence of irAEs (20%) as compared with that of the anti-PD-L1 group (13%). Results of this study showed that the endocrine system experienced the highest incidence of organ-specific irAEs (7.4%), including hypothyroidism, hyperthyroidism, thyroiditis, diabetes, and adrenal insufficiency, followed by gastroenterology (2.2%), pulmonology (1.8%), neurology (1.4%), dermatology (1.4%), hematology (0.8%), and hepatology (0.7%). In clinical trials, it was found that the incidence of death related to irAEs was 1% (95%CI: 0-2.0), whereby colitis and interstitial lung diseases were the leading causes of death. CONCLUSION: It was evident that the incidence and nature of irAEs are both organ- and inhibitor-specific. The anti-PD-1 group had the highest incidence of all irAEs grades including the severe grades of irAEs. Early identification and management of irAEs allows clinical oncologists to effectively consider the pros and cons and hence enables them to strike a balance.

Altered Intrinsic Regional Spontaneous Brain Activity in Patients With Severe Obesity and Meibomian Gland Dysfunction: A Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: To evaluate potential regional homogeneity (ReHo) cerebrum function lesions in people with severe obesity and meibomian gland dysfunction (SM) and probe the connection between aberrant cerebrum activity and clinical manifestations. Patients and Methods: An aggregation of 12 patients with SM, and 12 healthy controls (HCs) closely matched in age and gender were enrolled. We applied corneal confocal microscopy and fundus angiography to compare imaging distinctions between the two groups. SMs were required to carefully fill out the Hospital Anxiety Depression Scale (HADS) forms, and a correlation analysis was performed. ReHo was also utilized to appraise partial differences in spontaneous cerebrum function. Receiver operating characteristic (ROC) curves were created to partition ReHo values between patients with SM and the HCs. Results: ReHo values for the left cerebellum (LC), right fusiform gyrus (RFG), left inferior temporal gyrus (LITG), left rectus gyrus (LRG), right thalamus (RT), right caudate (RC), left insula (LI), and left thalamus (LT) of subjects with SM were notably higher than those of the HCs (P < 0.05). ReHo values of the right middle frontal gyrus (RMFG) in subjects with SM were decreased notably compared to the HCs (P < 0.05). ReHo values for the RMFG showed a negative correlation with the anxiety scores (ASs; r = -0.961, P < 0.001) and ReHo values for the RFG showed a positive correlation with the depression scores (DSs; r = 0.676, P = 0.016). The areas under the ROC curve were 1.000 (P < 0.001) for the RMFG, LC, LITG, LRG, RC, LI, and LT and 0.993 (P < 0.001) for the RFG and RT. The results from the ROC curve analysis indicated that changes in the ReHo values of some brain regions may help diagnose SM. Conclusion: Our research emphasized that patients with SM had lesions in synchronized neural activity in many encephalic areas. Our discoveries may provide beneficial information for exploring the neuromechanics of SM.

Fetal growth restriction mice are more likely to exhibit depression-like behaviors due to stress-induced loss of dopaminergic neurons in the VTA.

Fetal growth restriction (FGR) is a severe perinatal complication that can increase risk for mental illness. To investigate the mechanism by which FGR mice develop mental illness in adulthood, we established the FGR mouse model and the FGR mice did not display obvious depression-like behaviors, but after environmental stress exposure, FGR mice were more likely to exhibit depression-like behaviors than control mice. Moreover, FGR mice had significantly fewer dopaminergic neurons in the ventral tegmental area but no difference in serotoninergic neurons in the dorsal raphe. RNA-seq analysis showed that the downregulated genes in the midbrain of FGR mice were associated with many mental diseases and were especially involved in the regulation of NMDA-selective glutamate receptor (NMDAR) activity. Furthermore, the NMDAR antagonist memantine can relieve the stress-induced depression-like behaviors of FGR mice. In summary, our findings provide a theoretical basis for future research and treatment of FGR-related depression.