The modified dose (MD) regimen of pembrolizumab (2 mg/kg or 100 mg every 3 weeks) is an alternative option to reduce the financial burden resulting from the extremely high cost of the standard dose (SD) regimen (200 mg every 3 weeks). However, the clinical effectiveness and prognostic outcomes have not been fully elucidated in real-word clinical practice. Sixty-four consecutive patients in Taiwan receiving pembrolizumab for advanced NSCLC between 2018 and 2020 were recruited in this study. Comparisons of overall survival (OS) and progression-free survival (PFS) were performed using Kaplan–Meier survival curves. Additionally, 12 predictors, including pembrolizumab regimen, dose, neutrophil-to-lymphocyte ratio (NLR), age, sex, histopathology, smoking history, ECOG PS, EGFR mutation, PD-L1 expression, distant metastases and treatment line, were analyzed in multivariable Cox models for predicting OS and PFS. The results showed that the MD group and the SD group had similar OS and PFS, especially in patients beyond first-line treatment or with a pretreatment NLR < 5. The NLR was the only independent factor associated with both OS (adjusted HR = 0.052; p = 0.010) and PFS (adjusted HR = 0.259; p = 0.021). The results of this study assure the clinical effectiveness of MD pembrolizumab and suggest that the pretreatment NLR could highlight patients who may benefit from MD pembrolizumab.

Purpose: This study aimed to investigate the association between the use of sodium–glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing depression in patients with type 2 diabetes mellitus. Patients and Methods: This study used Taiwan’s National Health Insurance Database and an active comparator new-user design to evaluate depression risk among 551,917 patients initiating SGLT2i or DPP4i between 2016 and 2018. The primary outcome was depression incidence, assessed over a three-year follow-up. Stratified Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) between groups. Results: Among new SGLT2i users, 3255 cases of depression occurred (7.18 per 1000 person-years) versus 7190 cases among DPP4i users (10.12 per 1000 person-years). After adjustment for demographic and clinical covariates, SGLT2i use was consistently associated with a lower risk of depression in both the full cohort (adjusted HR = 0.77; 95% CI: 0.73– 0.80) and the propensity score–matched cohort (adjusted HR = 0.77; 95% CI: 0.74– 0.81). The association remained robust in multiple sensitivity analyses and across clinical subgroups. Conclusion: SGLT2i use was associated with a reduced risk of depression among individuals with type 2 diabetes mellitus. These findings suggest potential neuropsychiatric benefits of SGLT2i and support further investigation into their broader therapeutic implications.

Background: Hormone therapy (HT) is widely administered for contraception and menopausal symptom management. However, its impact on psoriasis risk remains unclear, requiring an evaluation across diverse age groups to inform clinical practice and optimize treatment strategies. Objectives: To investigate the association between HT and the risk of psoriasis in reproductive-age and postmenopausal women. Methods: This study utilized both nationwide cohort design and target trial emulation, analysing data from Taiwan’s National Health Insurance Database (2001–2021). Women over 20 years old without a prior history of psoriasis, ovarian cancer or breast cancer were included, and categorized into reproductive-age (≤ 50 years) and postmenopausal (> 50 years) groups. Women who initiated HT were assigned as the exposed group, while women without HT formed the comparison group. The primary outcome was the incidence of psoriasis over a 5-year period. The study applied inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs). Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to enhance the robustness of the findings. Results: In the postmenopausal cohort, comprising 1 482 302 HT users and 1 313 799 nonusers, the IPTW-adjusted HR for psoriasis in the ITT analysis was 1.48 [95% confidence interval (CI) 1.44–1.52]. The PP analysis indicated a more pronounced risk, with an HR of 5.93 (95% CI 5.66–6.22). Among the reproductive-age cohort, which included 3 849 721 HT users and 1 585 461 nonusers, the IPTW-adjusted HR in the ITT analysis was 1.93 (95% CI 1.90–1.99). In the PP analysis, the risk increased, showing an HR of 7.85 (95% CI 7.56–8.15). These findings highlight the significantly elevated psoriasis risk associated with HT, especially in younger women. Conclusions: This study establishes an association between HT and an increased risk of psoriasis in both reproductive-age and postmenopausal women using a nationwide cohort design and target trial emulation. These findings further highlight the potential influence of hormonal factors on psoriasis development. Clinicians should remain attentive to early signs of psoriasis in women receiving HT to ensure timely recognition and management.

Taste and smell dysfunction are suspected to be associated with substance use. However, representative epidemiological studies remain insufficient. This cross-sectional study explored the relationship between drug use (including cannabis or hashish, cocaine, heroin, and methamphetamine) and olfactory/gustatory dysfunction using data from the 2013–2014 National Health and Nutrition Examination Survey. In this study, participants who completed the smell examination with mean age of 59 were classified into four groups: cannabis users (n = 845), participants without cannabis use (n = 794), illicit drug users (n = 450), and participants without illicit drug use (n = 2000). Participants who completed the taste examination with mean age of 58 were also categorised into four groups: cannabis users (n = 810), participants without cannabis use (n = 714), illicit drug users (n = 428), and participants without illicit drug use (n = 1815). Logistic regression models investigated the association between cannabis or illicit drug use and smell or taste dysfunctions among study participants. Odds ratios and 95% confidence intervals were calculated. Finally, we did not find correlations between illicit drug use and dysfunction of taste or smell senses; our findings were consistent in many subgroup analyses. We recommend that further studies explore the mechanism and dose of illicit drug use that could have chemosensory impacts.

Purpose: Benzodiazepine receptor agonists (BZRAs), including benzodiazepines (BZDs) and Z drugs, are widely prescribed for anxiety and sleep. Therefore, issues of tolerance, dependence and adverse effects are of concern. Recent studies suggested a potential link between BZRAs and hearing problems. However, the actual relationship was still unclear. Accordingly, this study aims to investigate the actual association between BZRA use and risk of sudden sensorineural hearing loss (SSNHL) using population data. Patients and Methods: This study used the Taiwan Longitudinal Health Insurance Database. 137,277 BZRA users and 1,328,554 nonusers were identified for relevant analyses. We used cohort design with inverse-probability treatment weighting (IPTW) strategy to balance the baseline differences of demographics and comorbidities between two groups. The 5-year incidence of SSNHL was followed. Cox proportional-hazard regression analyses were used to estimate the hazard ratios (HRs). Results: BZRA users showed an increased 5-year SSNHL risk (adjusted HR: 1.244) after weighting. Subgroup and sensitivity analyses produced consistent results. Notably, SSNHL risk was higher among young BZRA users (adjusted HR: 1.397). BZRA users had the highest SSNHL risk in the first year (adjusted HR: 2.037) after IPTW. Conclusion: BZRA use elevated the risk of SSNHL, particularly in young adults and in the first year. This emphasises the importance for physicians and policymakers should be aware of the potential hearing difficulties among BZRA users and take necessary examinations.

Purpose: Non-benzodiazepine hypnotics, commonly known as Z-drugs, are widely prescribed for conditions such as insomnia, anxiety, and epilepsy. Emerging evidence suggests that these agents may influence auditory function and may be associated with tinnitus, potentially through their modulation of GABAA receptors. However, existing research findings on this association remain inconsistent. The objective of this study was to examine the potential association between the use of Z-drugs and the subsequent risk of incident tinnitus. Patients and Methods: This study was conducted using the Taiwan Longitudinal Health Insurance Database. The exposure cohort was composed of all beneficiaries who were prescribed a Z-drug during the study period. The comparison cohort was selected from beneficiaries without any prescription history for Z-drugs during the same timeframe. The primary outcome was the risk of tinnitus within a 5-year follow-up period. To minimize potential confounding, propensity score matching was applied, followed by Cox proportional hazards regression analyses to calculate hazard ratios (HRs) comparing Z-drug users with nonusers. Results: 16,225 patients were identified as Z-drug users, while 1,370,776 were classified as nonusers. Over the 5-year period, Cox proportional hazards regression analysis revealed that Z-drug users had a higher risk of developing tinnitus compared to nonusers (adjusted HR: 1.501; 95% CI: 1.423– 1.583). After propensity score matching, this association remained significant (adjusted HR: 1.496; 95% CI: 1.377– 1.624). Furthermore, a consistent association between Z-drug use and tinnitus was observed across most subgroups. Conclusion: The study suggests that the use of Z-drugs, the most prescribed psychoactive drugs globally, may be associated with an increased risk of developing tinnitus. Limitations include the potential for residual confounding and misclassification inherent to claims-based data. Clinicians should consider this potential association when prescribing Z-drugs.