Adjustment disorder and risk of Parkinson's disease.

BACKGROUND AND PURPOSE: It has been postulated that stress is part of the etiological process of Parkinson's disease (PD). The risk of PD was examined in a cohort of patients with adjustment disorders, a diagnosis made in the presence of a severe response to a stressful life event. METHODS: Using Danish medical registries, PD occurrence was examined in a nationwide population-based cohort of patients with adjustment disorder diagnosed between 1995 and 2011. The standardized incidence ratio of PD was calculated as the ratio of observed to expected cases, stratified by time and potential risk factors, including depression and anxiety. RESULTS: Our adjustment disorder cohort (67 786 patients) was followed for a median of 8 years (interquartile range 4, 12.6 years). During follow-up, 119 patients developed PD, versus 64 expected, corresponding to a standardized incidence ratio of 1.84 (95% confidence interval 1.53, 2.20). Consistent results were observed after stratification on potential risk factors, including depression and anxiety. CONCLUSION: Adjustment disorder, a diagnosis made in the presence of severe response to stressful life events, was associated with an increased risk of PD.

Pneumonia and the incidence of cancer: a Danish nationwide cohort study.

OBJECTIVES: To examine the risk of a subsequent pulmonary or extra-pulmonary cancer diagnosis following a first-time hospital-based diagnosis of pneumonia. DESIGN: Population-based cohort study using Danish medical registries. SETTING: All hospitals in Denmark. SUBJECTS: A total of 342,609 patients with a first-time hospital-based (inpatient, emergency room or outpatient clinic) diagnosis of pneumonia between 1995 and 2011. MAIN OUTCOME MEASURES: We quantified the excess risk of various cancers amongst pneumonia patients compared to the expected risk in the general population, using relative [standardised incidence ratios (SIRs)] and absolute risk calculations. Follow-up started 1 month after a hospital-based diagnosis of pneumonia and ended on 31 December 2011. RESULTS: A total of 28,496 cancers were observed, compared with 21,625 expected, amongst 342,609 pneumonia patients followed for a median of 4.2 years. The absolute risk of a cancer diagnosis 1 to <6 months following a pneumonia diagnosis was 1.4%, with a corresponding SIR of 2.48 [95% confidence interval (CI) 2.41-2.55]. This was mainly due to an increased risk of lung cancer (eightfold) and haematological cancers (fourfold). The SIR for any cancer remained increased at 1.35 (95% CI 1.30-1.40) during 6-12 months of follow-up, and 1.20 (95% CI 1.18-1.22) during 1-5 years of follow-up. Beyond 5 years, an increased risk was maintained for lung, oesophageal, liver and bladder cancers, squamous cell carcinoma of the skin, lymphoma and multiple myeloma. CONCLUSIONS: A hospital-based pneumonia diagnosis was associated with an increased risk of a cancer diagnosis, especially in the ensuing months, but the absolute risk was small.

Tuberculosis and risk of cancer: a Danish nationwide cohort study.

OBJECTIVES: To investigate the short- and long-term risk of cancer in patients with active tuberculosis (TB). DESIGN: Using Danish nationwide databases, we quantified cancer risk in TB patients during 1978-2011 compared with the general population. RESULTS: We observed 1747 cancers in 15 024 TB patients (median follow-up 8.5 years), reflecting a standardised incidence ratio (SIR) of 1.52 (95%CI 1.45-1.59). All-time SIR for extra-pulmonary cancer was 1.29 (95%CI 1.22-1.36) and for lung cancer it was 3.40 (95%CI 3.09-3.74). Absolute cancer risk 3 months after TB was 1.83% (SIR 11.09, 95%CI 9.82-12.48), with highly increased SIRs for malignant pleural mesothelioma (368.4), lung cancer (40.9), Hodgkin's lymphoma (30.6), ovarian cancer (26.4) and non-Hodgkin's malignant lymphoma (23.8). Between the 3-month and 5-year follow-up, the SIR for any cancer was 1.59 (95%CI 1.46-1.72), including 19- and 3-fold increases for malignant pleural mesothelioma and lung cancer. Beyond 5 years, the SIR of cancer was 1.17 (95%CI 1.10-1.25). Elevated long-term risks persisted for haematological (SIR 1.34, 95%CI 1.01-1.74) and tobacco-related cancers (SIR 1.78, 95%CI 1.60-1.97). CONCLUSION: TB is a marker of occult lung cancer and several extra-pulmonary cancers. TB also predicts increased long-term risk of cancer, possibly related to chronic inflammation and shared risk factors, including immunosuppression and smoking.

Cancer incidence among patients with a hospital diagnosis of pruritus: a nationwide Danish cohort study.

BACKGROUND: Pruritus is a frequent complaint in patients with cancer. However, no large study has examined pruritus as a marker of undiagnosed cancer. OBJECTIVES: To examine the association between inpatient, outpatient and emergency hospital diagnoses of pruritus and subsequent cancer diagnoses. METHODS: In this nationwide Danish cohort study, we used medical databases to identify all patients (n = 12,813) with a diagnosis of pruritus during the period 1978-2011 and followed them until a first-time cancer diagnosis, emigration, death or 31 December 2011. We computed standardized incidence ratios (SIRs) for cancer as the observed to expected number of cancers based on national cancer incidence rates. We calculated the 1-year absolute risk of cancer, treating death as a competing risk. RESULTS: The overall SIR of cancer was 1.13 [95% confidence interval (CI) 1.07-1.20]: 1.22 (95% CI 1.13-1.33) among men and 1.05 (95% CI 0.97-1.14) among women. The SIR was 1.20 (95% CI 1.08-1.33) among patients with a previous diagnosis of dermatological disease and 1.10 (95% CI 1.02-1.18) among patients without such a diagnosis. Both haematological and various solid cancers were observed at increased rates. Overall, the highest SIRs were observed during the first 3 months of follow-up, declining rapidly thereafter. The 1-year absolute risk of a cancer diagnosis was 1.63% and 155 patients with pruritus would have needed to be examined to detect one excess cancer. CONCLUSIONS: Pruritus may be a marker of occult cancer. Further studies are needed to assess the prognostic benefit of screening for cancer in patients with pruritus.

Prenatal exposure to acid-suppressive drugs and the risk of childhood asthma: a population-based Danish cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) may activate the immune system and cause asthma. AIM: To investigate the association of prenatal exposure to PPIs and histamine 2-receptor antagonists (H2RAs) with risk of asthma. METHODS: In this cohort study, 197,060 singletons born between 1996 and 2008 in northern Denmark were followed until the end of 2009. Data were obtained through Danish medical registries. Asthma in offspring was defined as at least two prescriptions of both a ß-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during the follow-up. Cox proportional-hazard regression was used to compute incidence rate ratios, adjusting for covariates. RESULTS: A total of 2238 (1.1%) children were prenatally exposed to PPIs and 24,506 (12.4%) children developed asthma during follow-up (median follow-up = 6.8 years). The adjusted IRR (aIRR) of asthma associated with prenatal exposure to PPIs was 1.41 (95% confidence interval (CI): 1.27-1.56), compared with those unexposed. The association did not vary by trimester of exposure, and prenatal exposure to H2RAs was associated with similar increase in risk. The aIRR for maternal PPI and H2RA use in the year after, but not during pregnancy was 1.32 (95% CI: 1.20-1.46) and 1.13 (0.93-1.36), respectively, compared with non-use during and in the year after pregnancy. CONCLUSIONS: Prenatal exposure to both PPIs and H2RAs was associated with an increased risk of asthma in our study. Because the observed association is not drug specific and also observed for maternal postnatal use it may be explained by a 'class effect' or maternal underlying condition.

Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study.

BACKGROUND: Little is known about the risk of colorectal cancer among patients with irritable bowel syndrome (IBS). METHODS: We conducted a nationwide cohort study using data from the Danish National Registry of Patients and the Danish Cancer Registry from 1977 to 2008. We included patients with a first-time hospital contact for IBS and followed them for colorectal cancer. We estimated the expected number of cancers by applying national rates and we computed standardised incidence ratios (SIRs) by comparing the observed number of colorectal cancers with the expected number. We stratified the SIRs according to age, gender, and time of follow-up. RESULTS: Among 57,851 IBS patients, we identified 407 cases of colon cancer during a combined follow-up of 506,930 years (SIR, 1.14 (95% confidence interval (CI): 1.03-1.25) and 115 cases of rectal cancer, corresponding to a SIR of 0.67 (95% CI: 0.52-0.85). In the first 3 months after an IBS diagnosis, the SIR was 8.42 (95% CI: 6.48-10.75) for colon cancer and 4.81 (95% CI: 2.85-7.60) for rectal cancer. Thereafter, the SIRs declined and 4-10 years after an IBS diagnosis, the SIRs for both colon and rectal cancer remained below 0.95. CONCLUSION: We found a decreased risk of colorectal cancer in the period 1-10 years after an IBS diagnosis. However, in the first 3 months after an IBS diagnosis, the risk of colon cancer was more than eight-fold increased and the risk of rectal cancer was five-fold increased. These increased risks are likely to be explained by diagnostic confusion because of overlapping symptomatology.

Systemic sclerosis and the risk of cancer: a nationwide population-based cohort study.

BACKGROUND: Earlier studies reported an increased cancer risk among patients with systemic sclerosis. Study size limitations and paucity of population-based study designs may have resulted in imprecise risk estimates. OBJECTIVES: To assess cancer risk among patients with systemic sclerosis in a nationwide follow-up study. METHODS: Patients with a first diagnosis of systemic sclerosis from 1977 to 2006 were identified from the nationwide Danish National Registry of Patients (DNRP), whose records encompass all hospitalizations and outpatient visits. Patients' DNRP records were linked to the Danish Cancer Registry. We compared their cancer incidence with that expected from cancer incidence in the general population, calculating standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: Two thousand and forty patients with systemic sclerosis were identified and followed for 16,003 person-years, with a median follow-up time of 6·4 years (interquartile range 2·2-11·5). Among these patients, 222 cases of cancer were identified. The overall SIR for cancer was 1·5 (95% CI 1·3-1·7), with a gender-specific SIR of 2·2 (95% CI 1·7-2·8) for men and 1·3 (95% CI 1·1-1·6) for women. The most frequent cancers were smoking- and alcohol-related cancers including lung cancer (SIR = 1·6, 95% CI 1·2-2·0), haematological cancers (SIR = 2·5, 95% CI 1·5-4·0) and immune-related cancers (SIR = 1·4, 95% CI 1·0-1·9). CONCLUSIONS: Systemic sclerosis is a risk factor for cancer, particularly smoking- and alcohol-related cancers. Men with systemic sclerosis generally are at higher cancer risk than women. Both primary and secondary cancer preventive measures are needed in the care of patients with systemic sclerosis.

Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study.

OBJECTIVE: The aim of the study was to examine whether exposure to abacavir increases the risk for myocardial infarction (MI). DESIGN, SETTING AND SUBJECTS: This was a prospective nationwide cohort study which included all Danish HIV-infected patients on highly active antiretroviral therapy (HAART) from 1995 to 2005 (N = 2952). Data on hospitalization for MI and comorbidity were obtained from Danish medical databases. Hospitalization rates for MI after HAART initiation were calculated for patients who used abacavir and those who did not. We used Cox's regression to compute incidence rate ratios (IRR) as a measure of relative risk for MI, while controlling for potential confounders (as separate variables and via propensity score) including comorbidity. MAIN OUTCOME: Relative risk of hospitalization with MI in abacavir users compared with abacavir nonusers. RESULTS: Hospitalization rates for MI were 2.4/1000 person-years (PYR) [95% confidence interval (CI) 1.7-3.4] for abacavir nonusers and 5.7/1000 PYR (95% CI 4.1-7.9) for abacavir users. The risk of MI increased after initiation of abacavir [unadjusted IRR = 2.22 (95% CI 1.31-3.76); IRR adjusted for confounders = 2.00 (95% CI 1.10-3.64); IRR adjusted for propensity score = 2.00 (95% CI 1.07-3.76)]. This effect was also observed among patients initiating abacavir within 2 years after the start of HAART and among patients who started abacavir as part of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen. CONCLUSIONS: We confirmed the association between abacavir use and increased risk of MI. Further studies are needed to control for potential confounding not measured in research to date.