When using data from both the ICD-9-CM and ICD-10-CM eras, or when using results from ICD-10-CM data to compare to results from ICD-9-CM data, researchers should test multiple ICD-10-CM outcome definitions as part of sensitivity analysis. Ongoing assessment of the impact of ICD-10-CM transition on identification of health outcomes in US electronic health care databases should occur as more data accrue.

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Background European studies reported an increased risk of non-melanoma skin cancer associated with hydrochlorothiazide (HCTZ)-containing products. We examined the risks of basal cell (BCC) and squamous cell carcinoma (SCC) associated with HCTZ compared to angiotensin-converting enzyme inhibitors (ACEIs) in a US population. Methods We conducted a retrospective cohort study in the US Food and Drug Administration’s Sentinel System. From the date of HCTZ or ACEI dispensing, patients were followed until a SCC or BCC diagnosis requiring excision or topical chemotherapy treatment on or within 30 days after the diagnosis date; or a censoring event. Using Cox proportional hazards regression models, we estimated the hazard ratios (HRs), overall and separately by age, sex, and race. We also examined site- and age-adjusted incidence rate ratios (IRRs) by cumulative HCTZ dose within the matched cohort. Results Among 5.2 million propensity-score matched HCTZ and ACEI users, the incidence rate (per 1,000 person-years) of BCC was 2.78 and 2.82 respectively, and 1.66 and 1.60 for SCC. Overall, there was no difference in risk between HCTZ and ACEIs for BCC (HR = 0.99, 95% CI = 0.97–1.00), but an increased risk for SCC (HR = 1.04, 95% CI = 1.02–1.06). HCTZ use was associated with higher risks of BCC (HR = 1.09, 95% CI = 1.07–1.11) and SCC (HR = 1.15, 95% CI = 1.12–1.17) among Caucasians. Cumulative HCTZ dose ≥50,000mg was associated with an increased risk of SCC in the overall population (IRR =1.19, 95% CI = 1.05–1.35) and among Caucasians (IRR = 1.27, 95% CI = 1.10–1.47). Conclusions Among Caucasians, we identified small increased risks of BCC and SCC with HCTZ compared to ACEI. Appropriate risk mitigation strategies should be taken while using HCTZ.