Occupational exposure to epoxy components and risk of dermatitis: A registry-based follow-up study of the wind turbine industry.

BACKGROUND: Allergic contact allergy and dermatitis are frequently reported among epoxy-exposed workers. OBJECTIVES: To determine the risk of dermatitis associated with epoxy exposure. METHODS: We followed 825 epoxy-exposed and 1091 non-exposed blue-collar workers, and 493 white-collar workers of a Danish wind turbine blade factory during 2017-2022 with linked data from national health registers on diagnoses, patch testing, or fillings of prescriptions for topical corticosteroids. Incidence rate ratios of dermatitis or a first-time topical corticosteroid prescription were estimated with Poisson regression using non-exposed blue-collar workers as reference. We similarly estimated incidence rate ratios for the duration of epoxy exposure and current epoxy exposure. RESULTS: Epoxy-exposed blue-collar workers showed a dermatitis incidence rate of 2.1 per 100 000 person days, a two-fold increased risk of dermatitis and a 20% increased risk of filling a prescription for topical corticosteroids. Incidence rate ratios were higher during early exposure and declined with further exposure for both outcomes. White-collar workers had generally lower risks. CONCLUSION: We observed an increased risk of dermatitis following epoxy exposure confirming previous case reports and cross-sectional studies emphasizing the need for intensified focus on preventive efforts for this group of workers.

Use of methotrexate and risk of skin cancer: a nationwide case-control study.

BACKGROUND: Methotrexate (MTX) use has been suspected of increasing the risk of skin cancer. The aim of this investigation was to examine the association between the use of MTX and the risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous malignant melanoma (CMM). METHODS: In a nationwide Danish case-control study, we identified incident, histologically verified cases of BCC (n = 131,447), cSCC (n = 18,661) or CMM (26,068) from 2004 to 2018. We matched 10 controls to each case on sex and birth year using risk-set sampling and computed crude and adjusted odds ratios (ORs) using conditional logistic regression for the use of MTX (≥2.5 g) compared with never-use. RESULTS: Use of MTX was associated with increased risk of BCC, cSCC and CMM with adjusted ORs of (95% confidence interval) 1.29 (1.20-1.38), 1.61 (1.37-1.89) and 1.35 (1.13-1.61), respectively. For BCC and cSCC, ORs increased with higher cumulative doses. When restricting the study population to patients with psoriasis, the ORs were 1.43 (1.23-1.67), 1.18 (0.80-1.74) and 1.15 (0.77-1.72), respectively. CONCLUSIONS: We observed an increased risk of BCC and cSCC associated with the use of MTX with evidence of a dose-response pattern; however, the association was not consistent when restricting the study population to patients with psoriasis.

Validation of the Danish Comorbidity Index for Acute Myocardial Infarction for predicting one-year mortality in patients with venous thromboembolism.

INTRODUCTION: The Danish Comorbidity Index for Acute Myocardial Infarction (DANCAMI) was developed to predict one-year mortality after myocardial infarction. We validated DANCAMI in predicting one-year mortality after venous thromboembolism (VTE). MATERIALS AND METHODS: We identified all first-time VTE patients in Denmark during 2000-2015. Using Cox regression, we assessed the performance of DANCAMI to predict one-year all-cause mortality using Nagelkerke's R2, Harrell's C-Statistic, the net reclassification index (NRI), and the integrated discrimination improvement (IDI). We compared the performance of DANCAMI with the Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) and evaluated whether DANCAMI comorbidities not included in the CCI predicted one-year mortality. We stratified the analyses by type (deep vein thrombosis [DVT] and pulmonary embolism [PE]) and presence of provoking risk factors. RESULTS: We identified 108,824 VTE patients of whom 20,649 (19%) died within one year. The R2, C-Statistic, NRI, and IDI for DANCAMI were 0.35, 0.76, 0.63, and 0.098 for VTE overall; 0.43, 0.80, 0.70, and 0.105 for DVT; and 0.24, 0.71, 0.54, and 0.083 for PE. The R2 and C-Statistic for VTE overall were 0.35 and 0.76 for CCI and 0.33 and 0.75 for ECI. After adjusting for age, sex, and all CCI comorbidities, seven DANCAMI comorbidities, not included in the CCI, predicted increased mortality. DANCAMI performed better than the CCI and ECI in predicting mortality after provoked VTE, including provoked DVT and PE. CONCLUSION: DANCAMI performed comparable to existing comorbidity indices in predicting one-year mortality after first-time VTE overall, but better after provoked VTE.

Fever of Unknown Origin and Incidence of Cancer.

BACKGROUND: Diagnostic tools for determining causes of fever of unknown origin (FUO) have improved over time. We examined if cancer incidence among these patients changed over a 20-year period. METHODS: Population-based cohort study using nationwide Danish registries. We identified individuals diagnosed with FUO (1998-2017) to quantify their excess risk of cancer compared with the general population. Follow-up for cancer started 1 month after FUO. We computed absolute risks and standardized incidence ratios (SIRs) of cancer, and mortality rate ratios adjusted for age, sex, and cancer stage. RESULTS: Among 6620 patients with FUO (46.9% male; median age: 39 years), 343 were diagnosed with cancer (median follow-up: 6.5 years). The 1- to <12-month risk was 1.2%, and the SIR was 2.3 (95% CI, 1.8-2.9). The increased 1- to <12-month SIR was mainly due to an excess of Hodgkin lymphoma (SIR = 41.7) non-Hodgkin lymphoma (SIR = 16.1), myelodysplastic syndrome/chronic myeloproliferative diseases (SIR = 6.0), lower gastrointestinal cancer (SIR = 3.3), and urinary tract cancer (SIR = 2.9). Beyond 1-year follow-up, malignant melanoma, hepatobiliary tract/pancreatic cancer, and brain/CNS/eye cancer were diagnosed more often than expected. The 1- to <12-month cancer SIR attenuated over time, and for the 2013-2017 period we found no excess risk. Patients diagnosed with cancer ≤1 year after FUO had similar mortality to cancer patients without this diagnosis. CONCLUSIONS: Patients with FUO have a higher 1- <12-month cancer SIR; thereafter, the incidence for most cancers equals that of the general population. Decreasing SIRs over time suggests improvements in the initial diagnostic workup for FUO.

Adverse outcomes after partner bereavement in people with reduced kidney function: Parallel cohort studies in England and Denmark.

OBJECTIVES: To investigate whether partner bereavement is associated with adverse cardiovascular and kidney-related events in people with reduced kidney function. DESIGN: Two parallel matched cohort studies using linked routinely collected health data. SETTING: England (general practices and hospitals using linked Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics) and Denmark (hospitals and community pharmacies using the Danish National Patient, Prescription and Education Registries and the Civil Registration System). PARTICIPANTS: Bereaved people with reduced kidney function (estimated glomerular filtration rate (eGFR) <60mL/min/1.73m2 (England) or hospital-coded chronic kidney disease (Denmark)) and non-bereaved people with reduced kidney function similarly defined, matched on age, sex, general practice (England), and county of residence (Denmark) and followed-up from the bereavement date of the exposed person. MAIN OUTCOME MEASURES: Cardiovascular disease (CVD) or acute kidney injury (AKI) hospitalization, or death. RESULTS: In people with reduced kidney function, we identified 19,820 (England) and 5,408 (Denmark) bereaved individuals and matched them with 134,828 (England) and 35,741 (Denmark) non-bereaved individuals. Among the bereaved, the rates of hospitalizations (per 1000 person-years) with CVD were 31.7 (95%-CI: 30.5-32.9) in England and 78.8 (95%-CI: 74.9-82.9) in Denmark; the rates of hospitalizations with AKI were 13.2 (95%-CI: 12.5-14.0) in England and 11.2 (95%-CI: 9.9-12.7) in Denmark; and the rates of death were 70.2 (95%-CI: 68.5-72.0) in England and 126.4 (95%-CI: 121.8-131.1) in Denmark. After adjusting for confounders, we found increased rates of CVD (England, HR 1.06 [95%-CI: 1.01-1.12]; Denmark, HR 1.10 [95%-CI: 1.04-1.17]), of AKI (England, HR 1.20 [95%-CI: 1.10-1.31]; Denmark HR 1.36 [95%-CI: 1.17-1.58]), and of death (England, HR 1.10 [95%-CI: 1.05-1.14]; Denmark HR 1.20 [95%-CI: 1.15-1.25]) in bereaved compared with non-bereaved people. CONCLUSIONS: Partner bereavement is associated with an increased rate of CVD and AKI hospitalization, and death in people with reduced kidney function. Additional supportive care for this at-risk population may help prevent serious adverse events.

Association Between Atopic Dermatitis and Educational Attainment in Denmark.

IMPORTANCE: Atopic dermatitis (AD) may affect academic performance through multiple pathways, including poor concentration associated with itching, sleep deprivation, or adverse effects of medications. Because educational attainment is associated with health and well-being, any association with a prevalent condition such as AD is of major importance. OBJECTIVE: To examine whether a childhood diagnosis of AD is associated with lower educational attainment. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used linked routine health care data from January 1, 1977, to June 30, 2017 (end of registry follow-up), in Denmark. The study population included all children born in Denmark on June 30, 1987, or earlier with an inpatient or outpatient hospital clinic diagnosis of AD recorded before their 13th birthday (baseline) and a comparison cohort of children from the general population matched by birth year and sex. A secondary analysis included exposure-discordant full siblings as a comparison cohort to account for familial factors. Data were analyzed from September 11, 2019, to January 21, 2021. EXPOSURES: Hospital-diagnosed AD. MAIN OUTCOMES AND MEASURES: Estimated probability or risk of not attaining specific educational levels (lower secondary, upper secondary, and higher) by 30 years of age among children with AD compared with children in the matched general population cohort. Corresponding risk ratios (RRs) were computed using Poisson regression that was conditioned on matched sets and adjusted for age. The sibling analysis was conditioned on family and adjusted for sex and age. RESULTS: The study included a total of 61 153 children, 5927 in the AD cohort (3341 male [56.4%]) and 55 226 from the general population (31 182 male [56.5%]). Compared with matched children from the general population, children with AD were at increased risk of not attaining lower secondary education (150 of 5927 [2.5%] vs 924 of 55 226 [1.7%]; adjusted RR, 1.50; 95% CI, 1.26-1.78) and upper secondary education (1141 of 5777 [19.8%] vs 8690 of 52 899 [16.4%]; RR, 1.16; 95% CI, 1.09-1.24), but not higher education (2406 of 4636 [51.9%] vs 18 785 of 35 408 [53.1%]; RR, 0.95; 95% CI, 0.91-1.00). The absolute differences in probability were less than 3.5%. The comparison of 3259 children with AD and 4046 of their full siblings yielded estimates that were less pronounced than those in the main analysis (adjusted RR for lower secondary education, 1.29 [95% CI, 0.92-1.82]; adjusted RR for upper secondary education, 1.05 [95% CI, 0.93-1.18]; adjusted RR for higher education, 0.94 [95% CI, 0.87-1.02]). CONCLUSIONS AND RELEVANCE: This population-based cohort study found that hospital-diagnosed AD was associated with reduced educational attainment, but the clinical importance was uncertain owing to small absolute differences and possible confounding by familial factors in this study. Future studies should examine for replicability in other populations and variation by AD phenotype.

The DANish Comorbidity Index for Acute Myocardial Infarction (DANCAMI): Development, Validation and Comparison with Existing Comorbidity Indices.

OBJECTIVE: To develop and validate the DANish Comorbidity index for Acute Myocardial Infarction (DANCAMI) for adjustment of comorbidity burden in studies of myocardial infarction prognosis. METHODS: Using medical registries, we identified patients with first-time myocardial infarction in Denmark during 2000-2013 (n=36,685). We developed comorbidity indices predicting 1-year all-cause mortality from all comorbidities (DANCAMI) and restricted to non-cardiovascular comorbidities (rDANCAMI). For variable selection, we eliminated comorbidities stepwise using hazard ratios from multivariable Cox models. We compared DANCAMI/rDANCAMI with Charlson and Elixhauser comorbidity indices using standard performance measures (Nagelkerke's R2, Harrell's C-statistic, the Integrated Discrimination Improvement, and the continuous Net Reclassification Index). We assessed the significance of the novel DANCAMI variables not included in the Charlson Comorbidity Index. External validation was performed in patients with myocardial infarction in New Zealand during 2007-2016 (n=75,069). RESULTS: The DANCAMI included 24 comorbidities. The rDANCAMI included 17 non-cardiovascular comorbidities. In the Danish cohort, the DANCAMI indices outperformed both the Charlson and the Elixhauser comorbidity indices on all performance measures. The DANCAMI indices included multiple variables that were significant predictors of 1-year mortality even after controlling for all variables in the Charlson Comorbidity Index. These novel variables included valvular heart disease (hazard ratio for 1-year mortality=1.25, 95% CI: 1.14-1.35), coagulopathy (1.13, 95% CI: 1.05-1.22), alcohol and drug abuse (1.35, 95% CI: 1.15-1.58), schizophrenia (1.60, 95% CI: 1.46-1.76), affective disorder (1.29, 95% CI: 1.22-1.36), epilepsy (1.26, 95% CI: 1.05-1.50), neurodegenerative disorder (1.30, 95% CI: 1.10-1.54) and chronic pancreatitis (1.71, 95% CI: 1.14-2.56). The results were supported by the external validation in New Zealand. CONCLUSION: DANCAMI assessed comorbidity burden of patients with first-time myocardial infarction, outperformed existing comorbidity indices, and was generalizable to patients outside Denmark. DANCAMI is recommended as a standard approach for comorbidity adjustment in studies of myocardial infarction prognosis.

Validity of First-Time Diagnoses of Inherited Ichthyosis in the Danish National Patient Registry and the Danish Pathology Registry.

PURPOSE: Inherited ichthyosis is a monogenetic disease characterized by hyperkeratosis and scaling of the skin, with large interindividual variation in severity. It can affect quality of life for patients and their families. Population-based data on inherited ichthyosis are lacking, which hampers studies into its epidemiology. PATIENTS AND METHODS: Based on medical record review, we validated diagnoses of inherited ichthyosis in two nationwide population-based registries commonly used for epidemiological research: The Danish National Patient Registry and the Danish Pathology Registry. The study period was January 1, 1977, through December 31, 2015. Validation samples were taken from one regional hospital without a specialized dermatological department and two specialized dermatological departments. Positive predictive values (PPVs) were estimated overall and for each coding system (ICD-8, ICD-10 and SNOMED), including for specific ICD-10 codes. RESULTS: We identified 1772 first-time diagnoses of inherited ichthyosis; 363 patients were diagnosed at the departments selected for validation, and 307 of these patients (84.6%) had medical records enabling validation. We observed an overall PPV of 73.3% (95% CI: 68.1-77.9). For ICD-8, ICD-10, and SNOMED diagnoses, the PPVs were 73.2% (95% CI: 58.1-84.3), 74.7% (95% CI: 69.0-79.7), and 46.2% (95% CI: 22.1-71.7), respectively. In analyses for ICD-10 diagnoses, we observed much higher validity of diagnoses from the specialized departments (PPV 79.7%; 95% CI: 74.1-84.3) than the regional hospital (PPV 5.9%; 95% CI: 0.6-24.3). The PPVs for specific diagnoses were 80.1% for ichthyosis vulgaris and 96.6% for X-linked ichthyosis but below 45% for remaining, rarer, subtypes. CONCLUSION: The PPV of first-time diagnosis of inherited ichthyosis made at specialized dermatological departments in the Danish National Patient Registry is approximately 80%. Diagnoses from the Danish Pathology Registry had low PPVs precluding their use for research.

Use of antiepileptic drugs and risk of skin cancer: A nationwide case-control study.

BACKGROUND: Several antiepileptic drugs are photosensitizing; however, it is not known whether this confers an increased risk of skin cancer. OBJECTIVE: To examine the association between common antiepileptic drugs and basal cell carcinoma, squamous cell carcinoma (SCC), and malignant melanoma. METHODS: We conducted a nested case-control study identifying skin cancer patients in Denmark from 2004 through 2015 matched 1:10 with disease-free controls. We estimated odds ratios (ORs) for skin cancer associated with high cumulative use of antiepileptic drugs (≥500 defined daily doses) compared with nonuse. RESULTS: Most antiepileptic drugs were not associated with skin cancer. SCC was associated with use of carbamazepine (OR, 1.88; 95% confidence interval, 1.42-2.49) and lamotrigine (OR, 1.57; 95% confidence interval, 1.12-2.22) with evidence of a dose-response relationship for carbamazepine. The estimated absolute risks were low; for example, 6335 person-years of high cumulative exposure to carbamazepine were required for 1 additional SCC to occur. LIMITATIONS: Data on important risk factors for skin cancer, such as sun exposure, were not available. CONCLUSIONS: Most antiepileptic drugs were not associated with skin cancer; however, carbamazepine and lamotrigine were associated with SCC. These findings need to be replicated and characterized further in other settings and have no direct clinical implications.

Use of hydrochlorothiazide and risk of skin cancer: a nationwide Taiwanese case-control study.

BACKGROUND: The antihypertensive agent hydrochlorothiazide has been associated with increased risks of non-melanoma skin cancer (NMSC) and possibly some melanoma subtypes. Previous studies were, however, conducted in predominantly Caucasian populations. We therefore examined the association between hydrochlorothiazide and skin cancer risk in an Asian population. METHODS: By using Taiwan's National Health Insurance Research Database (NHIRD), we conducted three separate case-control studies of lip cancer, non-lip non-melanoma skin cancer and melanoma. Cases (n = 29,082) with a first-ever skin cancer diagnoses (2008-2015) were matched 1:10 to population controls. We estimated odds ratios (ORs) associating hydrochlorothiazide use with skin cancer risk by using conditional logistic regression. RESULTS: Hydrochlorothiazide use showed no overall association with any of the three outcomes: ORs for high cumulative use of HCTZ (≥50,000 mg) were 0.86 (95% CI 0.09-7.81) for lip cancer, 1.16 (95% CI 0.98-1.37) for non-lip NMSC and 1.07 (95% CI 0.65-1.76) for melanoma. There was some evidence of a dose-response pattern for non-lip NMSC, with an OR of 1.66 (95% CI 0.82-3.33) for 100,000-149,999 mg of HCTZ. The null findings were robust across subgroup and sensitivity analyses. CONCLUSION: Use of HCTZ appears safe in terms of skin cancer risk in an Asian population.

The Danish health care system and epidemiological research: from health care contacts to database records.

Denmark has a large network of population-based medical databases, which routinely collect high-quality data as a by-product of health care provision. The Danish medical databases include administrative, health, and clinical quality databases. Understanding the full research potential of these data sources requires insight into the underlying health care system. This review describes key elements of the Danish health care system from planning and delivery to record generation. First, it presents the history of the health care system, its overall organization and financing. Second, it details delivery of primary, hospital, psychiatric, and elderly care. Third, the path from a health care contact to a database record is followed. Finally, an overview of the available data sources is presented. This review discusses the data quality of each type of medical database and describes the relative technical ease and cost-effectiveness of exact individual-level linkage among them. It is shown, from an epidemiological point of view, how Denmark's population represents an open dynamic cohort with complete long-term follow-up, censored only at emigration or death. It is concluded that Denmark's constellation of universal health care, long-standing routine registration of most health and life events, and the possibility of exact individual-level data linkage provides unlimited possibilities for epidemiological research.

Validity of first-time diagnoses of congenital epidermolysis bullosa in the Danish National Patient Registry and the Danish Pathology Registry.

PURPOSE: Congenital epidermolysis bullosa (CEB) is a group of rare monogenic genodermatoses. Phenotypically, the diseases vary in both severity and dissemination, which complicates studies of their epidemiology. To investigate the potential of using the Danish National Patient Registry (DNPR) for epidemiological research on CEB, we examined the positive predictive value (PPV) of a first-time diagnosis of CEB. METHODS: We identified patients with a record of CEB in DNPR and the Danish Pathology Registry (DPR) during January 1, 1977, until December 31, 2015. We restricted diagnoses from two dermatological departments and one regional hospital. Diagnoses in the DNPR are coded by the eighth and tenth revisions of the ICD (ICD-8 and ICD-10) and in the DPR by the Systematized Nomenclature of Medicine (SNOMED). We used clinical description in medical records, family history, histological findings, and molecular genetic investigations to validate diagnoses and classified them as rejected and confirmed. We estimated PPVs for any diagnosis, according to coding systems used, and for additional subdivisions of ICD-10 codes. RESULTS: We identified 116 cases from the hospital departments investigated and evaluated 96 medical records for validity. The overall PPV for probable CEB was 62.5% (95% CI: 52.5-71.5). For ICD-8, ICD-10, and SNOMED codes, the PPVs were 30.8% (95% CI: 11.4-57.7), 76.7% (95% CI: 65.8-84.9), and 0.0% (95% CI: 0.0-21.7), respectively. For the ICD-10 codes, we found the highest PPVs for diagnoses arising from the dermatological departments. For subdivisions of ICD-10 codes, PPVs were high for epidermolysis bullosa simplex and dystrophica. CONCLUSION: The PPVs for first-time diagnoses of CEB registered in the two Danish nationwide registries investigated, DNPR and DPR, ranged from low to average. We therefore recommend that these data be used with caution and restricted to ICD-10 diagnoses from specialized dermatological departments.

Social isolation and all-cause mortality: a population-based cohort study in Denmark.

Social isolation is associated with increased mortality. Meta-analytic results, however, indicate heterogeneity in effect sizes. We aimed to provide new evidence to the association between social isolation and mortality by conducting a population-based cohort study. We reconstructed the Berkman and Syme's social network index (SNI), which combines four components of social networks (partnership, interaction with family/friends, religious activities, and membership in organizations/clubs) into an index, ranging from 0/1 (most socially isolated) to 4 (least socially isolated). We estimated cumulative mortality and adjusted mortality rate ratios (MRR) associated with SNI. We adjusted for potential important confounders, including psychiatric and somatic status, lifestyle, and socioeconomic status. Cumulative 7-year mortality in men was 11% for SNI 0/1 and 5.4% for SNI 4 and in women 9.6% for SNI 0/1 and 3.9% for SNI 4. Adjusted MRRs comparing SNI 0/1 with SNI 4 were 1.7 (95% CI: 1.1-2.6) among men and 1.6 (95% CI: 0.83-2.9) among women. Having no partner was associated with an adjusted MRR of 1.5 (95% CI: 1.2-2.1) for men and 1.7 (95% CI: 1.2-2.4) for women. In conclusion, social isolation was associated with 60-70% increased mortality. Having no partner was associated with highest MRR.

Melanoma of the Skin in the Danish Cancer Registry and the Danish Melanoma Database: A Validation Study.

BACKGROUND: The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. METHODS: We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. RESULTS: The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database. CONCLUSIONS: The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies.

Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark.

BACKGROUND: Hydrochlorothiazide, one of the most frequently used diuretic and antihypertensive drugs in the United States and Western Europe, is photosensitizing and has previously been linked to lip cancer. OBJECTIVE: To examine the association between hydrochlorothiazide use and the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: From the Danish Cancer Registry, we identified patients (cases) with nonmelanoma skin cancer (NMSC) during 2004-2012. Controls were matched 1:20 by age and sex. Cumulative hydrochlorothiazide use (in 1995-2012) was assessed from the Danish Prescription Registry. Using conditional logistic regression, we calculated odds ratios (ORs) for BCC and SCC associated with hydrochlorothiazide use. RESULTS: High use of hydrochlorothiazide (≥50,000 mg) was associated with ORs of 1.29 (95% confidence interval [CI], 1.23-1.35) for BCC and 3.98 (95% CI, 3.68-4.31) for SCC. We found clear dose-response relationships between hydrochlorothiazide use and both BCC and SCC; the highest cumulative dose category (≥200,000 mg of HCTZ) had ORs of 1.54 (95% CI, 1.38-1.71) and 7.38 (95% CI, 6.32-8.60) for BCC and SCC, respectively. Use of other diuretics and antihypertensives was not associated with NMSC. LIMITATIONS: No data on sun exposure were available. CONCLUSIONS: Hydrochlorothiazide use is associated with a substantially increased risk of NMSC, especially SCC.

Use of sildenafil or other phosphodiesterase inhibitors and risk of melanoma.

BACKGROUND: Phosphodiesterase 5A inhibitors (PDEIs), a common treatment for erectile dysfunction, were recently linked to an increased risk of melanoma. METHODS: We conducted two parallel case-control studies, using the Danish Nationwide Health Registries (DNHR) and the Kaiser Permanente Northern California (KPNC) electronic health records. Identifying men with histologically verified melanoma (cases) matched on birth year to 10 cancer-free controls, we estimated odds ratios (OR) for melanoma associated with high use of PDEIs (⩾100 tablets filled), adjusting for available confounders. RESULTS: We identified 7045 DNHR and 2972 KPNC cases with invasive melanoma. The adjusted OR for invasive melanoma associated with high PDEI use was 1.22 (95% confidence interval (CI), 0.99-1.49) in DNHR and 0.95 (95% CI, 0.78-1.14) in KPNC. Odds ratios were highest for localised invasive melanoma in DNHR (OR, 1.21) and melanoma in situ in KPNC (OR, 1.15), and lowest for non-localised disease in both populations (ORs 0.75 and 0.61, respectively). The increased ORs were slightly attenuated upon adjustment for markers of health-care utilisation. CONCLUSIONS: We found little evidence for a causal association between PDEI use and risk of melanoma. The marginally increased risk of early stage disease likely resulted from more frequent health-care contacts among PDEI users.