Post-traumatic stress disorder and incident fractures in the Danish population.

Psychological stress may be associated with increased risk of fractures. It is unknown whether post-traumatic stress disorder (PTSD), a marker of chronic severe psychological stress occurring in response to a traumatic event, influences fracture risk. In this nationwide cohort study, persons with PTSD had an increased risk of fractures compared to the general population. INTRODUCTION: We conducted a population-based national cohort study in Denmark to examine the association between PTSD and incident fractures. METHODS: We examined the incidence rate of overall and specific fractures among patients with clinician-diagnosed PTSD (n = 4114), compared with the incidence rate in the general population from 1995 to 2013, using Danish medical registry data. We further examined differences in associations by gender, age, psychiatric and somatic comorbidity, and follow-up time. We calculated absolute risks, standardized incidence ratios (SIRs), and 95% confidence intervals (95% CIs). RESULTS: Risk of any fracture among persons with PTSD was 24% (95% CI 20%, 28%) over the study period. The SIR for any fracture was 1.7 (95% CI 1.6, 1.9). We found little evidence of effect measure modification of the association between PTSD and fractures in our stratified analyses. CONCLUSIONS: Our findings suggest that PTSD is associated with increased fracture risk.

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.

Glucocorticoid prescriptions and breast cancer recurrence: a Danish nationwide prospective cohort study.

BACKGROUND: Treatment with synthetic glucocorticoids (GCs) depresses the immune response and may therefore modify cancer outcomes. We investigated the association between GC use and breast cancer recurrence. MATERIALS AND METHODS: We conducted a population-based cohort study to examine the risk of breast cancer recurrence associated with GC use among incident stage I-III female breast cancer patients aged >18 years diagnosed 1996-2003 in Denmark. Data on patients, clinical and treatment factors, recurrence, and comorbidities as well as data on GC prescriptions and potential confounders were obtained from Danish population-based medical registries. GCs were categorized according to administrative route: systemic, inhaled, or intestinal. Women were followed for up to 10 years or until 31 December 2008. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) to evaluate the association between GC use and recurrence. Time-varying drug exposures were lagged by 1 year. RESULTS: We included 18 251 breast cancer patients. Median recurrence follow-up was 6.9 years; 3408 women developed recurrence during follow-up. Four thousand six hundred two women filled at least one GC prescription after diagnosis. In unadjusted models, no association was observed among users of systemic, inhaled, and intestinal GCs (HRsystemic = 1.1, 95% CI 0.9-1.3; HRinhaled = 0.9, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.9-1.2) versus nonusers. In adjusted models, the results were also near null (HRsystemic = 1.1, 95% CI 0.9-1.2; HRinhaled = 0.8, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.8-1.2). CONCLUSION: We found no evidence of an effect of GC use on breast cancer recurrence.

Rosiglitazone use and post-discontinuation glycaemic control in two European countries, 2000-2010.

OBJECTIVES: To evaluate the impact of risk minimisation policies on the use of rosiglitazone-containing products and on glycaemic control among patients in Denmark and the UK. DESIGN, SETTING AND PARTICIPANTS: We used population-based data from the Aarhus University Prescription Database (AUPD) in northern Denmark and from the General Practice Research Database (GPRD) in the UK. MAIN OUTCOME MEASURES: We examined the use of rosiglitazone during its entire period of availability on the European market (2000-2010) and evaluated changes in the glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels among patients discontinuing this drug. RESULTS: During 2000-2010, 2321 patients with records in AUPD used rosiglitazone in northern Denmark and 25 428 patients with records in GPRD used it in the UK. The proportion of rosiglitazone users among all users of oral hypoglycaemic agents peaked at 4% in AUPD and at 15% in GPRD in May 2007, the month of publication of a meta-analysis showing increased cardiovascular morbidity associated with rosiglitazone use. 12 months after discontinuation of rosiglitazone-containing products, the mean change in HbA1c was -0.16% (95% CI -3.4% to 3.1%) in northern Denmark and -0.17% (95% CI -0.21% to 0.13%) in the UK. The corresponding mean changes in FPG were 0.01 mmol/L (95% CI -7.3 to 7.3 mmol/L) and 0.03 mmol/L (95% CI -0.22 to 0.28 mmol/L). CONCLUSIONS: Publication of evidence concerning the potential cardiovascular risks of rosiglitazone was associated with an irreversible decline in the use of rosiglitazone-containing products in Denmark and the UK. The mean changes in HbA1c and FPG after drug discontinuation were slight.

Does comorbidity interact with colorectal cancer to increase mortality? A nationwide population-based cohort study.

BACKGROUND: It is unknown whether comorbidity interacts with colorectal cancer (CRC) to increase the rate of mortality beyond that explained by the independent effects of CRC and comorbid conditions. METHODS: We conducted a cohort study (1995-2010) of all Danish CRC patients (n=56963), and five times as many persons from the general population (n=271670) matched by age, gender, and specific comorbidities. To analyse comorbidity, we used the Charlson Comorbidity Index (CCI) scores. We estimated standardised mortality rates per 1000 person-years, and calculated interaction contrasts as a measure of the excess mortality rate not explained by the independent effects of CRC or comorbidities. RESULTS: Among CRC patients with a CCI score=1, the 0-1 year mortality rate was 415 out of 1000 person-years (95% confidence interval (CI): 401, 430) and the interaction accounted for 9.3% of this rate (interaction contrast=39 out of 1000 person-years, 95% CI: 22, 55). For patients with a CCI score of 4 or more, the interaction accounted for 34% of the mortality (interaction contrast=262 out of 1000 person-years, 95% CI: 215, 310). The interaction between CRC and comorbidities had limited influence on mortality beyond 1 year after diagnosis. CONCLUSION: Successful treatment of the comorbidity is pivotal and may reduce the mortality attributable to comorbidity itself, and also the mortality attributable to the interaction.

Mortality and incidence of new primary cancers in men with prostate cancer: a Danish population-based cohort study.

BACKGROUND: Prostate cancer (PC) survivors may have an increased risk of new primary cancers (NPCs) due to shared risk factors or PC-directed treatments. METHODS: Using Danish registries, we conducted a cohort study of men with (n=30,220) and without PC (n=151,100) (comparators), matched 1:5 on age and PC diagnosis/index date. We computed incidence rates of NPCs per 10,000 person years (PY) and associated 95% confidence intervals (CI), and used Cox proportional hazards regression to compute hazard ratios (HRs) and 95%CI, adjusting for comorbidities. In order to obviate any impact of shorter survival among prostate cancer patients, we censored comparator patients when the matched prostate cancer patient died or was censored. RESULTS: Follow-up spanned 113,487PY and 462,982PY in the PC and comparison cohorts, respectively. 65% of the cohorts were aged >70 years at diagnosis. Among PC patients, 51% had distant/unspecified stage, and 63% had surgery as primary treatment. The PC cohort had lower incidence of NPCs than their comparators. The adjusted HR of NPC among men with PC versus the comparators was 0.84 (95%CI=0.80, 0.88). Lowest HRs were among older men, those with distant stage, and were particularly evident for cancers of the brain, liver, pancreas, respiratory, upper gastrointestinal, and urinary systems. CONCLUSIONS: We find no evidence of an increased risk of NPCs among men with PC. The deficit of NPCs among men with PC may be a true effect but is more likely due to lower levels of risk factors (e.g., smoking) in PC patients versus comparators, clinical consideration of cancers at new organs as metastases rather than new primaries, or under-recording/under-reporting of NPCs among PC patients.

Preoperative risk factors related to bladder cancer rehabilitation: a registry study.

INTRODUCTION: Patients diagnosed with (muscle-) invasive bladder cancer (IBC) are more likely to harbour comorbidities due to their advanced age at diagnosis. Under-nutrition is a predictor for postoperative morbidity and mortality in cancer patients, but under-reported in urology. Understanding the IBC patient profile before major surgery could facilitate and optimise outcome of the surgical patient. BACKGROUND/OBJECTIVES: To identify preoperative risk factors for early rehabilitation before radical cystectomy (RC). SUBJECTS/METHODS: A historical registry-based study of 76 patients referred for RC at Aarhus University Hospital, Denmark (DK) in 2009. Early rehabilitation was defined by length of stay (LOS) postoperatively with a cutoff ≥11 days. High comorbidity was expressed by the charlson comorbidity index score (CCI) ≥3. LOS was calculated by linking the unique Civil Registration Number with the National Patient Registry. Preoperative nutritional risk was identified using the screening tool, nutritional risk score 2002 (NRS) of the European Society of Clinical Nutrition and Metabolism. Multivariate analysis was used to identify risk factors for early rehabilitation. RESULTS: The proportion of patients at preoperative nutritional risk was 26% (95% confidence interval (CI): (95% CI: 17; 37) and 43% of patients held a high CCI (95% CI: 33; 55). Prolonged LOS was independently associated with female gender (P=0.02) and age ≥70 years (P=0.04). NRS and CCI were not associated with LOS. CONCLUSIONS: Attention should be focused on women and elderly patients undergoing RC to optimise early rehabilitation and reduce LOS. It is still unknown whether preoperative nutritional risk and comorbidity are obstacles in early rehabilitation of RC patients.

The impact of comorbidity and stage on prognosis of Danish melanoma patients, 1987-2009: a registry-based cohort study.

BACKGROUND: Comorbid conditions may play an important role in the prognosis of melanoma patients but have received little attention. METHODS: Using data from Danish registries, we identified patients diagnosed with melanoma from 1987 to 2009. We estimated the prevalence of comorbidity and calculated mortality rate ratios and interaction risks between melanoma and comorbidity. For every melanoma patient, 10 individuals were selected for comparison. Individuals in the comparison cohort were matched to their corresponding melanoma patients on age, gender, and exact prevalent comorbidities. RESULTS: We included 23 476 patients, 81% of whom had no comorbidity. Higher prevalence of comorbidity was associated with more advanced cancer stage. The standardised mortality rate increased with increasing level of comorbidity in both cohorts and was consistently higher among melanoma patients. Melanoma and comorbidity interacted to increase the mortality rate. The highest proportional excess was seen in melanoma patients with comorbidity score 3, in whom interaction accounted for 77 deaths per 1000 person-years (40% of the total rate). We stratified by cancer stage and found that the interaction was markedly concentrated in patients with distant metastases. CONCLUSION: Interaction between melanoma and comorbidity was primarily concentrated in patients with distant metastases, which raises the possibility that comorbidity is associated with delay of melanoma diagnosis, advanced cancer stage, and less aggressive melanoma treatment.

Predictors of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study.

AIM: To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation. METHODS: We conducted a population-based study in Denmark. Patients were categorized according to age group, surgery type, and glucocorticoid use before surgery: never, current (0-90 days), and former (>90 days). We calculated the risk of re-operation due to post-surgical bleeding within 14 days after surgery, risk differences, and risk ratios of re-operation associated with age group, surgery type, and glucocorticoid use. RESULTS: 19,919 women were studied; 508 were re-operated. 3573 of the 19,919 women ever used glucocorticoids. Older age and mastectomy increased the risk of post-surgical bleeding compared with breast conserving surgery and younger age among both ever and never users of glucocorticoids. The crude risk of re-operation was 2.5% among never users of glucocorticoids, 2.6% among ever users and 4.0% among current users. Women aged ≥80 who were ever users of glucocorticoids and who had a mastectomy had 8.1% risk of re-operation due to post-surgical bleeding, whereas women <80 years old who never used glucocorticoids and who had breast conserving surgery had a 1.7% risk of re-operation. CONCLUSIONS: Older age, mastectomy, and - in some women - glucocorticoid use add an extra risk of re-operation due to bleeding. Clinicians and their patients can use this information to evaluate the patient-specific risk of this complication.

Antidepressant use and colorectal cancer risk: a Danish population-based case-control study.

BACKGROUND: Earlier research suggests that use of selective serotonin reuptake inhibitors (SSRIs), but not tricyclic antidepressants (TCAs), reduces the risk of colorectal cancer (CRC). METHODS: We conducted a population-based case-control study to investigate the association between antidepressant use and CRC risk. Cases were diagnosed with a first primary CRC from 1991 through 2008. We selected 10 population controls matched to cases on sex, birth year, and residence from the Danish Civil Registration System using risk-set sampling. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) associating antidepressant use with colorectal cancer occurrence, controlling for potential confounders. RESULTS: The study included 9,979 cases and 99,790 controls. We found no notable reduction in CRC risk in ever users (≥2 prescriptions) of TCAs (OR=0.94; 95% CI: 0.84, 1.05), SSRIs (OR=0.97; 95% CI: 0.90, 1.05), or other antidepressants (OR=0.95; 95% CI: 0.83, 1.07). Associations for recent and former use of antidepressants were also near null. Intensity of antidepressant use (number of pills divided by total duration of use), regardless of duration, was not associated with CRC risk. CONCLUSIONS: We found no evidence that antidepressant use substantially reduces the risk of colorectal cancer.

Antiplatelet drugs and risk of subarachnoid hemorrhage: a population-based case-control study.

SUMMARY BACKGROUND: Antiplatelet drug use increases bleeding risk, but its role in precipitating subarachnoid hemorrhage remains unclear. OBJECTIVES: We examined whether the use of low-dose acetylsalicylic acid (LDA), clopidogrel or dipyridamole increased the risk of subarachnoid hemorrhage. PATIENTS/METHODS: This population-based case-control study was conducted in northern Denmark. We used the Danish National Patient Registry to identify all persons admitted to neurosurgery or neurology departments with a first diagnosis of subarachnoid hemorrhage between 1997 and 2008 (n = 1186). Using risk-set sampling, we selected 10 population controls (n = 11 840) for each case, matched by age and sex. We obtained data on prescriptions for antiplatelet drugs, use of other medications and comorbidity from medical databases. We used conditional logistic regression to compute odds ratios with 95% confidence intervals (CIs), controlling for confounding factors. RESULTS: One hundred and nine cases (9.2%) and 910 controls (7.7%) used antiplatelet drugs. Among cases, 104 (8.8%) used LDA and 11 (0.9%) used dipyridamole. Among controls, 891 (7.5%) used LDA and 48 (0.4%) used dipyridamole. As compared with not using any antiplatelet drugs during the study period, the adjusted odds ratios were 1.03 (95% CI 0.81-1.32) for long-term LDA use, 2.52 (95% CI 1.37-4.62) for new LDA use, and 2.09 (95% CI 1.04-4.23) for long-term dipyridamole use. Owing to the low number of users, data were inconclusive for clopidogrel. CONCLUSIONS: Long-term dipyridamole use and new LDA use were associated with an increased risk of subarachnoid hemorrhage. Because of the limited precision of these risk estimates, however, caution is advised in their interpretation. Long-term LDA use was not associated with subarachnoid hemorrhage.

Statins and amyotrophic lateral sclerosis--the level of evidence for an association.

Myopathy is a known side effect of statins, but neurotoxicity is not. Two studies reported that statins and amyotrophic lateral sclerosis (ALS) appear together more than expected amongst adverse events in overlapping surveillance databases. A pooled analysis of clinical trials, many with short follow-up, showed no higher rate of ALS in the statins arms. In older age groups, statin use increased from approximately 5% in 1991 to approximately 40% in 1998 and then remained constant. There was no similar increase in ALS incidence. The initial signals of a strong association from drug surveillance systems should now be discounted, but not disregarded.

Tamoxifen's protection against breast cancer recurrence is not reduced by concurrent use of the SSRI citalopram.

Tamoxifen remains an important adjuvant therapy to reduce the rate of breast cancer recurrence among patients with oestrogen-receptor-positive tumours. Cytochrome P-450 2D6 metabolizes tamoxifen to metabolites that more readily bind the oestrogen receptor. This enzyme also metabolizes selective serotonin reuptake inhibitors (SSRI), so these widely used drugs - when taken concurrently - may reduce tamoxifen's prevention of breast cancer recurrence. We studied citalopram use in 184 cases of breast cancer recurrence and 184 matched controls without recurrence after equivalent follow-up. Cases and controls were nested in a population of female residents of Northern Denmark with stages I-III oestrogen-receptor-positive breast cancer 1985-2001 and who took tamoxifen for 1, 2, or most often for 5 years. We ascertained prescription histories by linking participants' central personal registry numbers to prescription databases from the National Health Service. Seventeen cases (9%) and 21 controls (11%) received at least one prescription for the SSRI citalopram while taking tamoxifen (adjusted conditional odds ratio=0.85, 95% confidence interval=0.42, 1.7). We also observed no reduction of tamoxifen effectiveness among regular citalopram users (>or=30% overlap with tamoxifen use). These results suggest that concurrent use of citalopram does not reduce tamoxifen's prevention of breast cancer recurrence.

Comorbidity and survival of Danish breast cancer patients from 1995 to 2005.

Comorbid diseases can affect breast cancer prognosis. We conducted a population-based study of Danish women diagnosed with a first primary breast cancer from 1995 to 2005 (n=9300), using hospital discharge registry data to quantify comorbidities by Charlson score. We examined the influence of comorbidities on survival, and quantified their impact on relative mortality rates. The prevalence of patients with a Charlson score='0' fell from 86 to 81%, with an increase in those with Charlson score='1-2' from 13 to 16%, and score='3+' from 1 to 2%. One- and five-year survival for patients with Charlson score='0' and '1-2' was better for those diagnosed in 1998-2000 than in 1995-1997. Overall, patients diagnosed in 2001-2004 (mortality ratio (MR)=0.80, 95% CI=0.68-0.95) and 1998-2000 (MR=0.92, 95% CI=0.78-1.09) had lower 1-year age-adjusted mortality compared to those diagnosed in 1995-1997 (reference period). Patients with Charlson scores '1-2' and '3+' had higher age-adjusted 1-year mortality than those with a Charlson score='0' in each time period (2001-2004: MR('1-2')=1.76, 95% CI=1.35-2.30, and MR('3+')=3.78, 95% CI=2.51-5.68; and 1998-2000: MR('1-2')=1.60, 95% CI=1.36-1.88 and MR('3+')=2.34, 95% CI=1.65-3.33). Similar findings were observed for 5-year age-adjusted mortality. Additional analyses, adjusted for stage, indicated that confounding by stage could not explain these findings. Despite continued improvements in breast cancer survival, we found a trend of poorer survival among breast cancer patients with severe comorbidities even after adjusting for age and stage. Such poorer survival is an important public health concern and can be expected to worsen as the population ages.

Birth outcome in women with breast cancer.

We investigated whether maternal breast cancer affects birth outcome in a nationwide cohort study of 695 births from 1973 to 2002 of women with breast cancer with respect to preterm birth, low birth weight at term, stillbirth and congenital abnormalities as well as mean birth weight, compared with the outcomes of 33 443 births from unaffected mothers. There was no excess risk of adverse birth outcome for the 216 newborns of women with breast cancer before pregnancy. Stratification by mother's treatment did not change the results. For 37 newborns of women diagnosed during pregnancy, the prevalence ratio (PR) of preterm birth was 8.1 (95% confidence interval (CI): 3.8-17). However, 10 of the 12 preterm deliveries among these women were elective early deliveries. Among 442 births of women diagnosed in the 2 years from time of delivery, the PR of preterm birth was 1.4 (95% CI: 1.0-2.0), and the PR of low birth weight at term for boys was 2.9 (95% CI: 1.3-6.3). Overall, our results are reassuring regarding the risks of adverse birth outcome for breast cancer patients.

Accuracy of ovarian cancer ICD-10 diagnosis in a Danish population-based hospital discharge registry.

OBJECTIVE: We estimated the accuracy of ICD-10 diagnosis of ovarian cancer in a Danish discharge registry (HDR) by comparing it with Cancer Registry data (DCR). STUDY DESIGN AND SETTING: Patients (N=489) living in North Jutland County, Denmark with ovarian cancer or borderline tumour registered in the HDR or the DCR. We estimated the completeness and positive predictive value (PPV) of ovarian cancer discharge diagnosis. Mortality rates were constructed for both registries. RESULTS: The completeness in the HDR for ovarian cancer was 96% (95% confidence interval [CI]: 94%-98%) and PPV was 87% (95% CI: 85%-90%). 87 (18%) of the patients coded with ovarian cancer in the HDR had borderline tumours. When borderline tumours were excluded from the DCR, the PPV declined to 69% and the completeness did not change. The mortality rate ratio for ovarian cancer registered in the HDR compared to the DCR was 1.08 (95% CI: 0.90-1.29). CONCLUSION: The discharge data (ICD-10) had some misclassification, but can be a valuable tool in assessment of the prognosis of ovarian cancer.

Medical surveillance after breast cancer diagnosis.

OBJECTIVES: To characterize the tests ordered for surveillance of breast cancer recurrence in the 4 years after breast cancer diagnosis by surgeons, medical oncologists, and radiation oncologists. RESEARCH DESIGN: 303 stage I or II breast cancer patients age 55-years or older and diagnosed at 1 of 5 Boston hospitals. Patient interviews and medical record abstracts provided the data to characterize patient demographics, the breast cancer stage and its primary therapy, and the surveillance procedures ordered. RESULTS: 279 of the 303 women had some surveillance testing. Among those who received some surveillance, a mean of 22.0 tests were ordered, most by their medical oncologists (mean = 14.4), followed by their surgeons (mean = 9.7) and their radiation oncologists (mean = 5.7). The most common test was a mammogram (mean = 3.9). Women ages 75 to 90 years old were at higher risk for failure to complete four consecutive years of surveillance and for receipt of less than guideline surveillance. Younger women, women treated at a breast cancer center with a unified patient chart, and women who worked full or part time were at lower risk for failure to complete 4 years of surveillance. CONCLUSION: Most women in this cohort received some surveillance after completing primary therapy for breast cancer. Although no woman's surveillance corresponded exactly to existing guidelines, the oldest women were least likely to receive guideline surveillance. Surveillance after breast cancer therefore joins the list of aspects of breast cancer care-breast cancer screening, diagnosis, prognostic evaluation, and primary therapy-for which older women receive less than definitive care.