Swu-Jane Lin’s research while affiliated with University of Illinois Chicago and other places

Purpose Hydrochlorothiazide (HCTZ) exposure has been linked to increased skin cancer in Caucasian (white) populations, especially squamous cell carcinoma (SCC), but not basal cell carcinoma (BCC). This study aimed to evaluate and compare skin cancer risks associated with HCTZ‐ and other antihypertensives use. Methods This retrospective cohort study utilized Taiwan's National Health Insurance Research Database. We identified patients aged 20 years and older, newly receiving antihypertensive medications between 2004 and 2015. We calculated the medication possession ratio (MPR) for the first 2 years of treatment to determine patient eligibility and treatment classification, whereby only patients with MPR above 80% were included. These were subsequently categorized by the type of antihypertensives they received, namely HCTZ, other thiazide diuretics, non‐thiazide diuretics or non‐diuretic antihypertensives. Cox proportional hazards model was used to evaluate skin cancer risks, and these were then classified as SCC or BCC. Results Our study included 41 086, 27 402, 19 613, and 856 782 patients receiving HCTZ, other thiazide diuretics, non‐thiazide diuretics, and non‐diuretic antihypertensives, respectively. We found BCC risks were similar when comparing HCTZ with other thiazides (adjusted hazard ratio: 0.84; 95% CI: 0.54–1.33), non‐thiazide diuretics (0.93; 0.51–1.67), and non‐diuretic antihypertensives (0.91; 0.66–1.26). We observed a higher SCC risk in the HCTZ group, compared to other thiazides (1.24; 0.74–2.08), non‐thiazide diuretics (1.32; 0.70–2.51), and non‐diuretic antihypertensives (1.23; 0.87–1.73), although the confidence intervals (CIs) were wide and crossed the null. Conclusions We concluded that skin cancer need not be of major concern to physicians when prescribing antihypertensives for an Asian population.

Purpose To validate the International Classification of Diseases, 10th Revision (ICD-10) codes for Guillain-Barré syndrome (GBS) in Taiwan’s insurance claims database. Methods We identified adult patients hospitalized at any Chang Gung Memorial Foundation branch hospital between January 1st, 2017, and December 31st, 2022, with ICD-10 code G61.0 in any of the five discharge diagnosis positions, indicating possible Guillain-Barré syndrome. We then validated the possible GBS diagnosis using data from electronic medical records of the identified patients, based on the diagnostic criteria established by the National Institute of Neurological Disorders and Stroke. We determined the positive predictive values (PPV) of various operational definitions, including the position (primary or other) where the code was recorded in the discharge diagnosis, nerve conduction study (NCS) claims, and / or specific GBS treatments. Results The final validation cohort of 484 patients with ICD-10 code for GBS in the discharge diagnosis was found to include 368 true GBS patients. Identifying inpatients using only the ICD-10 code for GBS in any of the five positions for discharge diagnosis yielded a PPV of 76.0%. With more restrictive definitions (primary diagnosis only, or requiring additional claims for NCS and/or treatments), the PPV tended to increase, but with fewer true GBS patients identified. Using ICD-10 GBS code in the primary diagnosis plus NCS and treatment claims yielded the highest PPV (98.3%); however, 140 (38.0%) of the true GBS patients were missed using this definition. In contrast, using the ICD-10 GBS code in any position, plus claims for NCS, achieved a relatively good PPV (85.8%) with minimal loss of true GBS patients (13, ie, 3.5%). Conclusion In Taiwan’s NHI claims data, identifying true GBS patients using only the ICD-10 code yielded a PPV of 76.0%; however, adding claims for diagnostic procedure and GBS treatment increased the PPV to 98.3%.

Purpose Exposure of hydrochlorothiazide (HCTZ) has been linked to the increase of skin cancer in the Caucasian population, especially for the squamous cell carcinoma (SCC) but not for basal cell carcinoma (BCC). This study aimed to evaluate the risks of skin cancer between patients receiving HCTZ and those receiving other antihypertensives. Methods This retrospective cohort study was derived from the National Health Insurance Database in Taiwan. We enrolled patients aged 20 years and older who newly receiving antihypertensive medications between 2004 - 2015. We calculated the medication possession ratio (MPR) of the first two years of treatment for patient enrollment and treatment classification, in which patients with MPR above 80% were enrolled and patients were subsequently categorized into receiving HCTZ, other thiazide diuretics, non-thiazide diuretics, and non-diuretic antihypertensives. The Cox proportional hazards model was used to evaluate the risk of skin cancer, and further divided into SCC, and BCC. Results Our study enrolled 41,086, 27,402, 19,613, and 856,782 patients receiving HCTZ, other thiazide diuretics, non-thiazide diuretics, and non-diuretic antihypertensives, respectively. We found BCC risks were similar when comparing HCTZ with other thiazides (adjusted hazard ratio, 0.84; 95% CI: 0.54-1.33), non-thiazide diuretics (0.93; 0.51-1.67), and non-diuretic antihypertensives (0.91; 0.66-1.26). Higher SCC risk was observed in the HCTZ group, compared to other thiazide (1.24; 0.74-2.08), non-thiazide diuretics (1.32; 0.70- 2.51), and non-diuretic antihypertensives (1.23; 0.87-1.73), although the differences were not statistically significant. Conclusions We conclude that skin cancer need not be of major concern to physicians when prescribing antihypertensives for an Asian population.

Objective To evaluate the association between recently raised anticholinergic burden and risk of acute cardiovascular events in older adults. Design Case-case-time-control study (ie, incorporating a case crossover design and a control crossover design consisting of future cases). Setting Taiwan’s National Health Insurance Research Database. Participants 317 446 adults aged ≥65 who were admitted to hospital because of an incident acute cardiovascular event between 2011 and 2018. Acute cardiovascular events included myocardial infarction, strokes, arrhythmias, conduction disorders, and cardiovascular death. Main outcome measures The anticholinergic burden was measured for each participant by adding up the anticholinergic scores for individual drugs using the Anticholinergic Cognitive Burden Scale. Scores were classified into three levels (0 points, 1-2 points, and ≥3 points). For each participant, anticholinergic burden levels during hazard periods (day −1 to −30 before the cardiovascular event) were compared with randomly selected 30 day reference periods (ie, periods between days −61 and −180). Conditional logistic regression determined odds ratios with 95% confidence intervals to evaluate the association between acute cardiovascular events and recently raised anticholinergic burden. Results The crossover analyses included 248 579 current cases. Participants’ average age on the index date was 78.4 years (standard deviation 0.01), and 53.4% were men. The most frequently prescribed drugs with anticholinergic activity were antihistamines (68.9%), gastrointestinal antispasmodics (40.9%), and diuretics (33.8%). Among patients with varying levels of anticholinergic burden in different periods, more patients carried higher levels of anticholinergic burden during hazard periods than during reference periods. For example, 17 603 current cases had 1-2 points of anticholinergic burden in the hazard period with 0 points in the reference period, while 8507 current cases had 0 points in the hazard period and 1-2 points in the reference period. In the comparison of 1-2 points versus 0 points of anticholinergic burden, the odds ratio was 1.86 (95% confidence interval 1.83 to 1.90) in the case crossover analysis and 1.35 (1.33 to 1.38) in the control crossover analysis, which yielded a case-case-time-control odds ratio of 1.38 (1.34 to 1.42). Similar results were found in the comparison of ≥3 versus 0 points (2.03, 1.98 to 2.09) and ≥3 versus 1-2 points (1.48, 1.44 to 1.52). The findings remained consistent throughout a series of sensitivity analyses (eg, cut-off points for anticholinergic burden categories were redefined and different scales were used to measure anticholinergic burden). Conclusions An association was found between recently raised anticholinergic burden and increased risk of acute cardiovascular events. Furthermore, a greater increase in anticholinergic burden was associated with a higher risk of acute cardiovascular events.

Background The ChAdOx1 nCoV-19 vaccine is associated with vaccine-induced thrombosis and thrombocytopenia (VITT). Patients with end-stage renal disease (ESRD) under hemodialysis are at elevated risk of heparin-induced thrombocytopenia, which shares similar mechanisms with VITT. We aimed to examine the risk of VITT after the first dose of ChAdOx1 nCoV-19 vaccine using a self-controlled case series analysis (SCCS) in the hemodialyzed ESRD population. Methods Drawing from the largest multi-center electronic medical records database in Taiwan, we identified adult patients, with or without hemodialysis, between 1st December, 2020, and 31st December, 2021, who received a first dose of ChAdOx1 nCoV-19 vaccine and had an outcome of thrombocytopenia, venous thrombosis, or arterial thrombosis. We calculated the incident rate ratios (IRRs) of outcomes in different periods at risk, compared to periods not at risk. Results We identified 59 hemodialysis patients and 41 non-dialysis patients with an outcome. The SCCS analyses showed, for the hemodialysis group, a significantly increased risk of outcomes during the period 31 to 60 days post-exposure to ChAdOx1 nCoV-19 vaccine (IRR: 2.823; 95% CI: 1.423–5.600). However, in non-dialysis patients there was no increase in risks during any of the post-exposure risk periods. Conclusion For ESRD patients under hemodialysis, the first dose of ChAdOx1 nCoV-19 vaccine was associated with a 2.8-fold increase in risk of thrombosis.

Objective To evaluate post-discharge use of antipsychotics in patients with incident hospital-acquired delirium and the associated risk of mortality. Methods We conducted a nested case-control study for patients newly diagnosed with hospital-acquired delirium and subsequently discharged from hospital using Taiwan’s National Health Insurance Database (NHID) from 2011 to 2018. Results The use of antipsychotics after discharge did not increase the risk of mortality (adjusted OR: 1·03; 95% CI: 0·98–1·09). Conclusions The findings suggested that using antipsychotics after discharge in patients with hospital-acquired delirium may not increase the risk of mortality.

Purpose Development and evaluation of a drug-safety signal detection system integrating data-mining tools in longitudinal data is essential. This study aimed to construct a new triage system using longitudinal data for drug-safety signal detection, integrating data-mining tools, and evaluate adaptability of such system. Patients and Methods Based on relevant guidelines and structural frameworks in Taiwan’s pharmacovigilance system, we constructed a triage system integrating sequence symmetry analysis (SSA) and tree-based scan statistics (TreeScan) as data-mining tools for detecting safety signals. We conducted an exploratory analysis utilizing Taiwan’s National Health Insurance Database and selecting two drug classes (sodium-glucose co-transporter-2 inhibitors (SGLT2i) and non-fluorinated quinolones (NFQ)) as chronic and episodic treatment respectively, as examples to test feasibility of the system. Results Under the proposed system, either cohort-based or self-controlled mining with SSA and TreeScan was selected, based on whether the screened drug had an appropriate comparator. All detected alerts were further classified as known adverse drug reactions (ADRs), events related to other causes or potential signals from the triage algorithm, building on existing drug labels and clinical judgement. Exploratory analysis revealed greater numbers of signals for NFQ with a relatively low proportion of known ADRs; most were related to indication, patient characteristics or bias. No safety signals were found. By contrast, most SGLT2i signals were known ADRs or events related to patient characteristics. Four were potential signals warranting further investigation. Conclusion The proposed system facilitated active and systematic screening to detect and classify potential safety signals. Countries with real-world longitudinal data could adopt it to streamline drug-safety surveillance.