Patient-Reported Outcomes (PROs) and PRO Remission Rates in 12,262 Biologic-Naïve Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitors in Routine Care.

OBJECTIVE: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. METHODS: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. RESULTS: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. CONCLUSION: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.

One-Third of European Patients With Axial Spondyloarthritis Reach Pain Remission With Routine Care Tumor Necrosis Factor Inhibitor Treatment.

OBJECTIVE: To investigate the distribution of patient-reported outcomes (PROs) in patients with axial spondyloarthritis (axSpA) initiating a tumor necrosis factor inhibitor (TNFi), to assess the proportion reaching PRO "remission" across registries and treatment series, and to compare patients registered to fulfill the modified New York (mNY) criteria for ankylosing spondylitis (AS) vs patients with nonradiographic axSpA (nr-axSpA). METHODS: Fifteen European registries contributed PRO scores for pain, fatigue, patient global assessment (PtGA), Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Health Assessment Questionnaire (HAQ) from 19,498 patients with axSpA. Changes in PROs and PRO remission rates (definitions: ≤ 20 mm for pain, fatigue, PtGA, BASDAI, and BASFI; ≤ 0.5 for HAQ) were calculated at 6, 12, and 24 months of treatment. RESULTS: Heterogeneity in baseline characteristics and outcomes between registries were observed. In pooled data, 6 months after the start of a first TNFi, pain score was reduced by approximately 60% (median at baseline/6/12/24 months: 65/25/20/20 mm) in patients on treatment. Similar patterns were observed for fatigue (68/32/30/25 mm), PtGA (66/29/21/20 mm), BASDAI (58/26/21/19 mm), BASFI (46/20/16/16 mm), and HAQ (0.8/0.4/0.2/0.2). Patients with AS (n = 3281) had a slightly better response than patients with nr-axSpA (n = 993). The Lund Efficacy Index (LUNDEX)-adjusted remission rates at 6 months for pain/fatigue/PtGA/BASDAI/BASFI/HAQ were 39%/30%/38%/34%/35%/48% for the AS cohort and 30%/21%/26%/24%/33%/47% for the nr-axSpA cohort. Better PRO responses were seen with a first TNFi compared to a second and third TNFi. CONCLUSION: Patients with axSpA starting a TNFi achieved high PRO remission rates, most pronounced in those fulfilling the mNY criteria and for the first TNFi.

Temporal changes in the probability of live birth among female survivors of childhood cancer: A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries.

BACKGROUND: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births. METHODS: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades. RESULTS: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97]). CONCLUSIONS: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary. LAY SUMMARY: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child.

Multisystem burden of neurofibromatosis 1 in Denmark: registry- and population-based rates of hospitalizations over the life span.

PURPOSE: The aim was to assess lifetime risk for hospitalization in individuals with neurofibromatosis 1 (NF1). METHODS: The 2467 individuals discharged with a diagnosis indicating NF1 or followed in a clinical center for NF1 were matched to 20,132 general population comparisons. Based on diagnoses in 12 main diagnostic groups and 146 subcategories, we calculated rate ratios (RRs), absolute excess risks (AERs), and hazard ratios for hospitalizations. RESULTS: The RR for any first hospitalization among individuals with NF1 was 2.3 (95% confidence interval 2.2-2.5). A high AER was seen for all 12 main diagnostic groups, dominated by disorders of the nervous system (14.5% of all AERs), benign (13.6%) and malignant neoplasms (13.4%), and disorders of the digestive (10.5%) and respiratory systems (10.3%). Neoplasms, nerve and peripheral ganglia disease, pneumonia, epilepsy, bone and joint disorders, and intestinal infections were major contributors to the excess disease burden caused by NF1. Individuals with NF1 had more hospitalizations and spent more days in hospital than the comparisons. The increased risk for any hospitalization was observed for both children and adults, with or without an associated cancer. CONCLUSION: NF1 causes an overall greater likelihood of hospitalization, with frequent and longer hospitalizations involving all organ systems throughout life.

Risk factors for cardiovascular disease in 5-year survivors of adolescent and young adult cancer: A Danish population-based cohort study.

BACKGROUND: An increased risk of metabolic syndrome has been reported for childhood cancer survivors and for adult survivors with certain cancer types. One previous study reported on the risk for diseases in the metabolic syndrome specifically among survivors of adolescent and young adult cancers. METHODS: The study comprised 11,822 five-year survivors of adolescent and young adult cancer (ages 15-39 years at diagnosis) who were diagnosed during the period from 1994 through 2009 in Denmark and a population-based comparison cohort of 76,024 individuals. The cohorts were linked to Danish nationwide registries for information on hospital contacts and purchase of prescription drugs related to metabolic syndrome, respectively. Standardized rate ratios (RRs) for hospital contacts (SHRRs) and prescriptions (SPRRs) with 95% CIs were calculated for diabetes, hyperlipidemia, and hypertension. RESULTS: Survivors had increased risks for hospital contacts and prescriptions for diabetes (SHRR, 1.21; 95% CI, 1.03-1.43; SPRR, 1.08; 95% CI, 0.96-1.23), hyperlipidemia (SHRR, 1.18; 95% CI, 1.00-1.40; SPRR, 1.16; 95% CI, 1.08-1.25), and hypertension (SHRR, 1.27; 95% CI, 1.15-1.41; SPRR, 1.25; 95% CI, 1.20-1.31). The highest risks for hospitalizations were among survivors of brain cancer (RR, 2.94 for diabetes) and Hodgkin lymphoma (RR, 2.40 for diabetes). Survivors of brain cancer and Hodgkin lymphoma were most likely to purchase prescription drugs for diseases in metabolic syndrome. CONCLUSIONS: Survivors of adolescent and young adult cancer are at increased risk of hospital contacts and purchase of prescription drugs for diseases in metabolic syndrome. Survivors at high risk should be followed closely to improve prevention, early detection, and management of these diseases to ultimately minimize the risk of cardiovascular diseases.

Radiation Therapy for Treatment of Adolescent and Young Adult Hodgkin Lymphoma and Risk for Cardiovascular Disease and Cancer.

PURPOSE: To estimate the risk for hospitalizations among survivors of Hodgkin lymphoma diagnosed in adolescence or young adulthood according to exposure to treatment with radiation therapy. METHODS: Through the files of the Danish Cancer Registry, we identified 1684 five-year survivors of Hodgkin lymphoma, diagnosed at age 15-39 years during the period 1943-2004, and for whom information on radiation therapy was available in the Cancer Registry. Population-based comparisons were identified through the Danish Civil Registration System and matched to the survivors on year of birth and sex. Survivors of Hodgkin lymphoma and comparisons were linked to the Danish National Patient Register for information on hospitalizations. Standardized hospitalization rate ratios (RR) and absolute excess rates (AERs) were estimated for total number of hospitalizations and for hospitalizations for cardiovascular disease, cancer and several other disease groups. RESULTS: Overall, survivors of Hodgkin lymphoma who received radiation therapy had higher risk (RR 2.0) and AER (AER 588) of hospitalization than survivors not treated with radiation therapy (RR 1.8; AER 399). Especially, the risk for cardiovascular disease and cancer was high among survivors who received radiation therapy (RR 2.8 and 3.6) compared with survivors who did not receive this type of treatment (RR 2.2 and 2.3). CONCLUSION: Survivors of adolescent and young adult Hodgkin lymphoma treated with radiation therapy had a higher risk of diseases requiring hospitalization than survivors not treated with radiation therapy. Irrespective of the type of treatment received, initiatives that prevent and minimize hospital-requiring late effects in survivors of Hodgkin lymphoma are needed.

Endocrine Late Effects in Survivors of Cancer in Adolescence and Young Adulthood: A Danish Population-Based Cohort Study.

Importance: As survival rates from cancer have improved dramatically over the last decades, there is a need to explore the long-term consequences. Adolescents and young adults with cancer are at risk for several therapy-related late effects; however, these have not been studied extensively. Objective: To investigate the lifetime risks of endocrine late effects of cancer and cancer treatment in adolescent and young adult cancer survivors. Design, Setting, and Participants: This Danish, nationwide, population-based cohort study was conducted from January 1, 1976, through December 31, 2009, and included follow-up from January 1, 1977, through December 31, 2010. A total of 32 548 one-year cancer survivors diagnosed at ages 15 to 39 years were identified using the Danish Cancer Registry and 188 728 cancer-free comparison participants matched by year of birth and sex were randomly chosen from the Danish Civil Registration system. Analyses were performed from July 3, 2015, to February 27, 2018. Exposures: Individuals in the survivor cohort were diagnosed with a first primary cancer at ages 15 to 39 years and received treatment according to recommendations and guidelines at time of diagnosis. Main Outcomes and Measures: By linkage to the National Patient Register, all hospital contacts for endocrine diseases were identified, and standardized hospitalization rate ratios (RRs) and absolute excess risks (AERs) were calculated. Results: A total of 32 548 adolescent and young adult 1-year cancer survivors (14 021 [43.1%] male) in the Danish Patient Registry were followed up for 379 157 person-years (median [range]: 10 [0-34] years) and 188 728 cancer-free participants (82 669 [43.8%] male) for comparison were followed up for 2 958 994 person-years (median [range]: 15 [0-34] years). A total of 2129 survivors (6.5%) had at least 1 hospital contact for an endocrine disease, while 1232.0 (3.8%) were expected, yielding a statistically significant increased RR of 1.73 (95% CI, 1.65-1.81). The RRs were highest for testicular hypofunction (75.12; 95% CI, 45.99-122.70), ovarian hypofunction (14.65; 95% CI, 8.29-25.86), and pituitary hypofunction (11.14; 95% CI, 8.09-15.34). The leading reasons for hospital contacts were thyroid disease (38.0% of total AER), testicular dysfunction (17.1% of total AER), and diabetes (14.4% of total AER). Leukemia survivors were at a high risk for any endocrine disease (RR, 3.97; 95% CI, 3.10-5.09), while Hodgkin lymphoma survivors (RR, 3.06; 95% CI, 2.62-3.57) had the highest disease-specific excess risk for hypothyroidism (AER, 362 per 100 000 person-years; 95% CI, 280-443 per 100 000 person-years). Conclusions and Relevance: The increased risk for endocrine diseases in adolescent and young adult cancer survivors indicates the need for counseling and follow-up, and could guide future preventive measures and surveillance strategies. Additional studies are required to determine exact associations between treatment regimens and endocrine diseases.

Long-term inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study: A cohort study of 21,297 childhood cancer survivors.

BACKGROUND: Survivors of childhood cancer are at increased risk for a wide range of late effects. However, no large population-based studies have included the whole range of somatic diagnoses including subgroup diagnoses and all main types of childhood cancers. Therefore, we aimed to provide the most detailed overview of the long-term risk of hospitalisation in survivors of childhood cancer. METHODS AND FINDINGS: From the national cancer registers of Denmark, Finland, Iceland, and Sweden, we identified 21,297 5-year survivors of childhood cancer diagnosed with cancer before the age of 20 years in the periods 1943-2008 in Denmark, 1971-2008 in Finland, 1955-2008 in Iceland, and 1958-2008 in Sweden. We randomly selected 152,231 population comparison individuals matched by age, sex, year, and country (or municipality in Sweden) from the national population registers. Using a cohort design, study participants were followed in the national hospital registers in Denmark, 1977-2010; Finland, 1975-2012; Iceland, 1999-2008; and Sweden, 1968-2009. Disease-specific hospitalisation rates in survivors and comparison individuals were used to calculate survivors' standardised hospitalisation rate ratios (RRs), absolute excess risks (AERs), and standardised bed day ratios (SBDRs) based on length of stay in hospital. We adjusted for sex, age, and year by indirect standardisation. During 336,554 person-years of follow-up (mean: 16 years; range: 0-42 years), childhood cancer survivors experienced 21,325 first hospitalisations for diseases in one or more of 120 disease categories (cancer recurrence not included), when 10,999 were expected, yielding an overall RR of 1.94 (95% confidence interval [95% CI] 1.91-1.97). The AER was 3,068 (2,980-3,156) per 100,000 person-years, meaning that for each additional year of follow-up, an average of 3 of 100 survivors were hospitalised for a new excess disease beyond the background rates. Approximately 50% of the excess hospitalisations were for diseases of the nervous system (19.1% of all excess hospitalisations), endocrine system (11.1%), digestive organs (10.5%), and respiratory system (10.0%). Survivors of all types of childhood cancer were at increased, persistent risk for subsequent hospitalisation, the highest risks being those of survivors of neuroblastoma (RR: 2.6 [2.4-2.8]; n = 876), hepatic tumours (RR: 2.5 [2.0-3.1]; n = 92), central nervous system tumours (RR: 2.4 [2.3-2.5]; n = 6,175), and Hodgkin lymphoma (RR: 2.4 [2.3-2.5]; n = 2,027). Survivors spent on average five times as many days in hospital as comparison individuals (SBDR: 4.96 [4.94-4.98]; n = 422,218). The analyses of bed days in hospital included new primary cancers and recurrences. Of the total 422,218 days survivors spent in hospital, 47% (197,596 bed days) were for new primary cancers and recurrences. Our study is likely to underestimate the absolute overall disease burden experienced by survivors, as less severe late effects are missed if they are treated sufficiently in the outpatient setting or in the primary health care system. CONCLUSIONS: Childhood cancer survivors were at increased long-term risk for diseases requiring inpatient treatment even decades after their initial cancer. Health care providers who do not work in the area of late effects, especially those in primary health care, should be aware of this highly challenged group of patients in order to avoid or postpone hospitalisations by prevention, early detection, and appropriate treatments.

Long-term hospitalisation rates among 5-year survivors of Hodgkin lymphoma in adolescence or young adulthood: A nationwide cohort study.

In the present study, we report on the full range of physical diseases acquired by survivors of Hodgkin lymphoma diagnosed in adolescence or young adulthood. In a Danish nationwide population-based cohort study, 1,768 five-year survivors of Hodgkin lymphoma diagnosed at ages 15-39 years during 1943-2004 and 228,447 comparison subjects matched to survivors on age and year of birth were included. Hospital discharge diagnoses and bed-days during 1977-2010 were obtained from the Danish Patient Register for 145 specific disease categories gathered in 14 main diagnostic groups. The analysis was conducted separately on three subcohorts of survivors, that is, survivors diagnosed 1943-1976 for whom we had no information on rehospitalisation for Hodgkin lymphoma and survivors diagnosed 1977-2004, split into a subcohort with no expected relapses and a subcohort for whom a rehospitalisation for Hodgkin lymphoma indicated a relapse. The overall standardised hospitalisation rate ratios (RRs) were 2.0 [95% confidence interval (CI), 1.9-2.1], 1.5 (1.4-1.6) and 2.9 (2.6-3.1) respectively, and the corresponding RRs for bed-days were 3.5 (3.4-3.5), 1.8 (1.8-1.9) and 10.4 (10.3-10.6). Highest RRs were seen for nonmalignant haematological conditions (RR: 2.6; 3.1 and 9.7), malignant neoplasms (RR: 3.2; 2.5 and 4.7) and all infections combined (RR: 2.5; 2.2 and 5.3). Survivors of Hodgkin lymphoma in adolescence or young adulthood are at increased risk for a wide range of diseases that require hospitalisation. The risk depends on calendar period of treatment and on whether the survivors were rehospitalised for Hodgkin lymphoma, and thus likely had a relapse.

Long-term Risk of Hospitalization for Somatic Diseases in Survivors of Adolescent or Young Adult Cancer.

IMPORTANCE: Survivors of adolescent and young adult cancers are at risk for treatment-induced late adverse effects; however, to our knowledge, the long-term risk of hospitalization in this specific group of cancer survivors has not been thoroughly evaluated. OBJECTIVE: To examine relative and absolute excess risk for hospitalizations up to 34 years after diagnosis of adolescent and young adult cancer compared with population comparisons. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study, conducted in Denmark, of 33,555 five-year survivors of adolescent or young adult cancer, diagnosed from 1943 through 2004, when they were 15 to 39 years of age, and 228,447 population comparisons, matched to the survivors by sex and year of birth. MAIN OUTCOMES AND MEASURES: Cancer survivors and comparisons were followed up for hospitalizations in the Danish Patient Register through December 2010. Standardized hospitalization rate ratios (RRs) and absolute excess risks (AERs) were calculated. RESULTS: After a median follow-up of 14 years, we identified 53,032 hospitalizations in cancer survivors, whereas 38,423 were expected, resulting in an overall RR of 1.38 (95% CI, 1.37-1.39). The data analysis was started in January 2015 and ended in June 2015. Additional data analyses requested by the reviewers were conducted in August 2015. The highest risks were found for the main diagnostic groups of diseases of blood and blood-forming organs (RR, 2.00; 95% CI, 1.87-2.14), infectious and parasitic diseases (RR, 1.69; 95% CI, 1.61-1.77), and malignant neoplasms (RR, 1.63; 95% CI, 1.59-1.68). The overall AER was 2803 (95% CI, 2712-2893) per 100,000 person-years; the highest AERs were found for malignant neoplasms, diseases of digestive organs, and diseases of the circulatory system (18%, 15%, and 14% of total AER, respectively). Survivors of the 10 most common cancers in adolescents and young adults were at significantly increased risk for diseases in the 12 main diagnostic groups. The highest risks were those of survivors of leukemia (RR, 2.21; 95% CI, 2.02-2.42), brain cancer (RR, 1.93; 95% CI, 1.86-2.00), and Hodgkin lymphoma (RR, 1.87; 95% CI, 1.80-1.94). CONCLUSIONS AND RELEVANCE: The large number of survivors and the use of hospital discharge diagnoses made it possible to draw a comprehensive picture of the complex inpatient disease burden experienced by survivors of adolescent and young adult cancer. The findings underscore a great diversity of cancer-related health problems that physicians and patients should be knowledgeable about.

Head injury and risk for Parkinson disease: results from a Danish case-control study.

OBJECTIVE: To examine the association between head injuries throughout life and the risk for Parkinson disease (PD) in an interview-based case-control study. METHODS: We identified 1,705 patients diagnosed with PD at 10 neurologic centers in Denmark in 1996-2009 and verified their diagnoses in medical records. Patients were matched to 1,785 controls randomly selected from the Danish Central Population Register on sex and year of birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. RESULTS: We observed no association between any head injury before first cardinal symptom and PD (OR 1.02; 95% CI 0.88, 1.19). Examination of number of head injuries (1: OR 1.02; 95% CI 0.87, 1.20; ≥2: OR 1.03; 95% CI 0.72, 1.47) or hospitalization for a head injury (OR 0.89; 95% CI 0.70, 1.12) did not show an association with PD. For 954 study subjects with at least one head injury, there was no evidence of an association between loss of consciousness (OR 0.89; 95% CI 0.67, 1.17), duration of loss of consciousness (≤1 minute: OR 0.93; 95% CI 0.58, 1.49; 1-5 minutes: OR 0.74; 95% CI 0.51, 1.08; ≥5 minutes: OR 0.81; 95% CI 0.53, 1.24), or amnesia (OR 1.31; 95% CI 0.88, 1.95) and risk for PD. Application of a lag time of 10 years between head injury and first cardinal symptom resulted in similar risk estimates. CONCLUSIONS: The results do not support the hypothesis that head injury increases the risk for PD.

Cardiovascular disease in survivors of adolescent and young adult cancer: a Danish cohort study, 1943-2009.

BACKGROUND: Cardiovascular disease has emerged as a serious late effect in survivors of adolescent and young adult cancer, but risk has not been quantified comprehensively in a population-based setting. METHODS: In the Danish Cancer Registry, we identified 43153 1-year survivors of cancer diagnosed at ages 15 to 39 years (1943-2009) and alive in 1977; from the Danish Civil Registration System, we randomly selected a comparison cohort of the same age and sex. Subjects were linked to the Danish Patient Register, and observed numbers of first hospitalizations for cardiovascular disease (International Classification of Diseases, Tenth Revision codes I10-I79) were compared with the expected numbers derived from the comparison cohort. We calculated the absolute excess risks attributable to status as a survivor of cancer and standardized hospitalization rate ratios (RRs). All statistical tests were two-sided. RESULTS: During follow-up, 10591 survivors (24.5%) were discharged from the hospital with cardiovascular disease, whereas 8124 were expected (RR = 1.30; 95% confidence interval [CI)] = 1.28 to 1.33; P < .001). The absolute excess risks were 400 and 350 extra cases of cardiovascular disease per 100000 person-years for people aged 20 to 59 and 60 to 79 years at discharge, respectively. Survivors of Hodgkin lymphoma experienced high risks for being hospitalized with valvular disease (RR = 12.2; 95% CI = 9.9 to 15.0; P < .001). Survivors of leukemia had high risks for cerebral hemorrhage (RR = 10.3; 95% CI = 5.5 to 19.1; P < .001) and cardiomyopathy (RR = 8.6; 95% CI = 4.3 to 17.3; P < .001). CONCLUSIONS: Survivors of adolescent and young adult cancer are at increased risk for cardiovascular disease throughout life, although each main type of adolescent and young adult cancer had its own risk profile.

Parkinson's disease and occupation: differences in associations by case identification method suggest referral bias.

METHODS: We used a population-based sample of 403 Parkinson's disease cases and 405 controls to examine risks by occupation. Results were compared to a previous clinic-based analysis. RESULTS: With censoring of jobs held within 10 years of diagnosis, the following had significantly or strongly increased risks: social science, law and library jobs (OR = 1.8); farming and horticulture jobs (OR = 2.0); gas station jobs (OR = 2.6); and welders (OR = 3.0). The following had significantly decreased risks: management and administration jobs (OR = 0.70); and other health care jobs (OR = 0.44). CONCLUSIONS: These results were consistent with other findings for social science and farming occupations. Risks for teaching, medicine and health occupations were not elevated, unlike our previous clinic-based study. This underscores the value of population-based over clinic-based samples. Occupational studies may be particularly susceptible to referral bias because social networks may spread preferentially via jobs.

Exposure to estrogen and women's risk for Parkinson's disease: a prospective cohort study in Denmark.

BACKGROUND: Studies have suggested that estrogen is protective against Parkinson's disease; however, the results have been inconsistent. METHODS: Our cohort comprised 27,466 women from the prospective Diet, Cancer and Health study. At inclusion, all the cohort members filled in questionnaires on diet and lifestyle, including reproductive factors, use of hormone products, and smoking habits. The cohort was followed up for Parkinson's disease in the Danish Hospital Register, and risks associated with indicators of exposure to estrogen were estimated in a Cox proportional hazards model. RESULTS: No significant association was found between reproductive factors and risk for Parkinson's disease. Use of oral contraceptives was associated with a nonsignificantly increased risk (hazard ratio, 1.30; 95% confidence interval, 0.81-2.09), as was use of hormone replacement therapy (1.41; 0.90-2.21). CONCLUSIONS: Our data do not support the hypothesis of a protective effect of estrogen on the risk for Parkinson's disease in women.

Malignant melanoma, breast cancer and other cancers in patients with Parkinson's disease.

Previous studies report an atypical cancer pattern among patients with Parkinson's disease. Here, we evaluate the cancer pattern among people diagnosed with Parkinson's disease in an extension of our previous cohort study. For this Danish population-based cohort study, we identified 20,000 people with Parkinson's disease diagnosed in 1977-2006, from the National Danish Hospital Register. Cohort members were followed up for cancer in the Danish Cancer Registry until December 31, 2008, and their incidence rates of cancer were compared to age-, sex- and calendar period-specific rates in the general population as standardized incidence rate ratios (SIRs). In subanalyses, we estimated the risk for cancer among patients with early onset Parkinson's disease and we also compared breast tumor characteristics among women with Parkinson's disease to that of a control group. The overall cancer risk in our cohort was decreased [SIR = 0.86; 95% confidence interval (CI) = 0.83-0.90], as were those for smoking-related (SIR = 0.65; 95% CI = 0.60-0.70) and nonsmoking-related cancers (SIR = 0.79; 95% CI = 0.71-0.86). The cohort had increased risks for malignant melanoma (SIR = 1.41; 95% CI = 1.09-1.80), nonmelanoma skin cancer (SIR = 1.29; 95% CI = 1.18-1.39) and female breast cancer (SIR = 1.17; 95% CI = 1.02-1.34). Among patients with early onset Parkinson's disease, the risk for cancer was comparable to that of the general population. Of breast tumor characteristics, only grade of malignancy differed between Parkinson's disease women and controls. This study confirms a lower cancer risk among people with Parkinson's disease. Increased risks for malignant melanoma, nonmelanoma skin cancer and breast cancer might be due to shared risk factors with Parkinson's disease.

Diabetes and the risk of developing Parkinson's disease in Denmark.

OBJECTIVE: Insulin contributes to normal brain function. Previous studies have suggested associations between midlife diabetes and neurodegenerative diseases, including Parkinson's disease. Using Danish population registers, we investigated whether a history of diabetes or the use of antidiabetes drugs was associated with Parkinson's disease. RESEARCH DESIGN AND METHODS: From the nationwide Danish Hospital Register hospital records, we identified 1,931 patients with a first-time diagnosis of Parkinson's disease between 2001 and 2006. We randomly selected 9,651 population control subjects from the Central Population Registry and density matched them by birth year and sex. Pharmacy records comprising all antidiabetes and anti-Parkinson drug prescriptions in Denmark were available. Odds ratios (ORs) were estimated by logistic regression models. RESULTS: Having diabetes, as defined by one or more hospitalizations and/or outpatient visits for the condition, was associated with a 36% increased risk of developing Parkinson's disease (OR 1.36 [95% CI 1.08-1.71]). Similarly, diabetes defined by the use of any antidiabetes medications was associated with a 35% increased Parkinson's disease risk (1.35 [1.10-1.65]). When diabetes was defined as the use of oral antidiabetes medications, effect estimates were stronger in women (2.92 [1.34-6.36]), whereas when diabetes was defined as any antidiabetes drug prescription, patients with early-onset Parkinson's disease were at highest risk (i.e., Parkinson's disease diagnosed before the age of 60 years; 3.07 [1.65-5.70]). CONCLUSIONS: We found that a diagnosis of, or treatment received for, diabetes was significantly associated with an increased risk of developing Parkinson's disease, especially younger-onset Parkinson's disease. Our results suggest a common pathophysiologic pathway between the two diseases. Future studies should take age at Parkinson's disease onset into account.

Pesticide exposure and risk of Parkinson's disease--a population-based case-control study evaluating the potential for recall bias.

OBJECTIVE: The aim of this study was to investigate whether pesticide exposure was associated with Parkinson's disease in a population-based case-control study in British Columbia, Canada. METHODS: Patients reimbursed for anti-parkinsonian agents were identified and screened for eligibility as cases. Controls were selected from the universal health insurance database, frequency-matched to the case sample on birth year, gender, and geographic region. A total of 403 cases and 405 controls were interviewed about their job, medical and personal habits histories, and beliefs about disease risk factors. Among those reporting pesticide exposure, an occupational hygiene review selected participants exposed "beyond background" (ie, above the level expected in the general population). Unconditional logistic regression was used to estimate associations for different pesticide categories. RESULTS: Of the cases, 74 (18%) self-reported pesticide exposure and 37 (9%) were judged to be exposed beyond background. Self-reported exposure was associated with increased risk [odds ratio (OR) 1.76, 95% confidence interval (95% CI) 1.15-2.70], however the risk estimate was reduced following the hygiene review when restricted to those considered exposed (OR, 1.51, 95% CI, 0.85-2.69). When agricultural work was added to the model, the risk for hygiene-reviewed pesticide exposure was not elevated (OR 0.83, 95% CI 0.43-1.61), but agricultural work was (OR 2.47, 95% CI 1.18-5.15). More than twice as many cases as controls thought chemicals cause Parkinson's disease. Discussion This study provides little support for pesticide exposure as a cause of Parkinson's disease. The observed pattern of step-wise decreases in risk estimates might indicate differential recall by case status. The relationship to agricultural jobs suggests that farming exposures--other than pesticides--should be considered as risk factors for Parkinson's disease.

Parkinson disease and malignant melanoma in first-degree relatives of patients with early-onset melanoma.

BACKGROUND: In a recent study, the link between Parkinson disease and malignant melanoma in patients was also observed in nuclear families, suggesting a possible genetic link between the 2 diseases. METHODS: To clarify the strength of the association, we used the nationwide Danish cancer and population registers to identify 8567 parents and 7310 siblings of patients in whom malignant melanoma was diagnosed at age 50 years or less. Hospital register data were used to follow relatives for a primary diagnosis of Parkinson disease between 1977 and 2008, and to calculate hospitalization rates for Parkinson disease in the general Danish population for comparison. Similarly, cancer registry data were used to trace cases of malignant melanoma. RESULTS: The hospitalization rate ratio for Parkinson disease among the melanoma cohort was slightly increased (ratio of observed to expected hospitalizations = 1.2 [95% confidence interval = 0.9-1.5]) on the basis of 54 observed cases. In contrast, the risk among relatives for malignant melanoma was markedly increased. There was no overlap between families affected by multiple cases of Parkinson disease and those affected by multiple cases of malignant melanoma. CONCLUSIONS: For the age range investigated, our data do not support a genetic link between Parkinson disease and malignant melanoma.

Risk for Parkinson's disease among patients with osteoarthritis: a Danish cohort study.

It has been suggested that use of nonsteroidal anti-inflammatory drugs (NSAID) protects against Parkinson's disease, although the results are not consistent. We investigated the risk for Parkinson's disease in patients with osteoarthritis, who are typically intensive users of NSAID. By using the files of the National Danish Hospital Register for the period 1977-2006, we identified a cohort of 134,176 patients with osteoarthritis severe enough to have required subsequent hip or knee implant surgery. The number of first hospital contacts for Parkinson's disease among cohort members in 1986-2007 was compared with that expected from the age-, gender- and period-specific hospital contact rates of the general Danish population, and standardized incidence ratios (SIRs) and associated 95% confidence intervals (CIs) were derived. Cohort members were also linked to the Danish Cancer Register to estimate the SIRs for colorectal and lung cancer. We observed a slightly increased risk for Parkinson's disease among patients with osteoarthritis and subsequent implant surgery (SIR, 1.07; 95% CI, 0.99-1.16). Decreased SIRs were found for both colorectal cancer (0.92; 95% CI, 0.88-0.97), consistent with a high prevalence of NSAID use among cohort members, and lung cancer (0.77; 95% CI, 0.73-0.80), indicating a lower prevalence of smoking than usual. Our results do not support the hypothesis that patients with prolonged use of NSAID and other analgesics are at reduced risk for Parkinson's disease. A possible lower smoking prevalence among patients with osteoarthritis might explain the slightly increased risk for Parkinson's disease.

Risk of Parkinson's disease after hospital contact for head injury: population based case-control study.

OBJECTIVE: To determine whether a hospital contact for a head injury increases the risk of subsequently developing Parkinson's disease. DESIGN: Population based case-control study. SETTING: Denmark. PARTICIPANTS: 13 695 patients with a primary diagnosis of Parkinson's disease in the Danish national hospital register during 1986-2006, each matched on age and sex to five population controls selected at random from inhabitants in Denmark alive at the date of the patient's diagnosis (n=68 445). MAIN OUTCOME MEASURES: Hospital contacts for head injuries ascertained from hospital register; frequency of history of head injury. RESULTS: An overall 50% increase in prevalence of hospital contacts for head injury was seen before the first registration of Parkinson's disease in this population (odds ratio 1.5, 95% confidence interval 1.4 to 1.7). The observed association was, however, due almost entirely to injuries that occurred during the three months before the first record of Parkinson's disease (odds ratio 8.0, 5.6 to 11.6), and no association was found between the two events when they occurred 10 or more years apart (1.1, 0.9 to 1.3). CONCLUSIONS: The steeply increased frequency of hospital contacts for a head injury during the months preceding the date at which Parkinson's disease was first recorded is a consequence of the evolving movement disorder rather than its cause.