High risk of developing dementia in Parkinson's disease: a Swedish registry-based study.

Dementia have substantial negative impact on the affected individual, their care partners and society. Persons living with Parkinson's disease (PwP) are also to a large extent living with dementia. The aim of this study is to estimate time to dementia in PD using data from a large quality register with access to baseline clinical and patient reported data merged with Swedish national health registries. Persons with Parkinson's disease in the Swedish Neuro Registries/Parkinson's Disease Swedish PD Registry (PARKreg) in Sweden were included and linked to national health registries and matched by sex and age to controls without PD. Time to dementia was analysed with Cox regression models assuming proportional hazards, with time since diagnosis as the underlying time variable. In this large prospective cohort study, PwP had approximately four times higher risk of developing dementia as compared to age and sex-matched controls, a finding which remained after adjusting for potential confounders. The present results underline the high risk of dementia in PD and further emphasize the importance of developing symptomatic and ultimately disease modifying strategies to counteract this part of the non-motor symptomatology in PD.

Sensitivity to Change and Patient-Centricity of the Unified Multiple System Atrophy Rating Scale Items: A Data-Driven Analysis.

BACKGROUND: The Unified Multiple System Atrophy Rating Scale (UMSARS) is a commonly used semiquantitative rating scale to assess symptoms and measure disease progression in multiple system atrophy (MSA). However, it is currently incompletely understood which UMSARS items are the most sensitive to change and most relevant to the patient. OBJECTIVE: The objective of this study was to assess sensitivity to change and patient-centricity of single UMSARS items. METHODS: Data were taken from the European Multiple System Atrophy Study Group Natural History Study and the Rasagiline for Multiple System Atrophy trial. Sensitivity of change of an item of the UMSARS was assessed by calculation of a sensitivity-to-change ratio using its mean slope of progression divided by the standard deviation of the slope when modeling its progression over time. Patient-centricity was assessed through correlation of UMSARS items with quality-of-life measures. RESULTS: Progression rates above the mean in at least one of the two studies examined here were seen for seven items of UMSARS I and 11 items of UMSARS II. These items related to key motor functions such as swallowing, speech, handwriting, cutting food, hygiene, and dressing or walking, whereas items related to autonomic dysfunction were generally less sensitive to change in either data set. More UMSARS I items were identified as patient-centric compared with UMSARS II items, and items most strongly impacting patients' quality of life were those affecting verbal communication skills, personal hygiene, and walking. CONCLUSION: The present results illustrate the potential to optimize the UMSARS to enhance sensitivity to change and patient centricity. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Non-therapeutic male circumcision in infancy or childhood and risk of human immunodeficiency virus and other sexually transmitted infections: national cohort study in Denmark.

Whether male circumcision in infancy or childhood provides protection against the acquisition of human immunodeficiency virus (HIV) or other sexually transmitted infections (STIs) in adulthood remains to be established. In the first national cohort study to address this issue, we identified 810,719 non-Muslim males born in Denmark between 1977 and 2003 and followed them over the age span 0-36 years between 1977 and 2013. We obtained information about cohort members' non-therapeutic circumcisions, HIV diagnoses and other STI outcomes from national health registers and used Cox proportional hazards regression analyses to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status (i.e., circumcised v. genitally intact). During a mean of 22 years of follow-up, amounting to a total observation period of 17.7 million person-years, 3375 cohort members (0.42%) underwent non-therapeutic circumcision, and 8531 (1.05%) received hospital care for HIV or other STIs. Compared with genitally intact males, rates among circumcised males were not statistically significantly reduced for any specific STI. Indeed, circumcised males had a 53% higher rate of STIs overall (HR = 1.53, 95% CI: 1.24-1.89), and rates were statistically significantly increased for anogenital warts (74 cases in circumcised males v. 7151 cases in intact males, HR = 1.51; 95% CI: 1.20-1.90) and syphilis (four cases in circumcised males v. 197 cases in intact males, HR = 3.32; 95% CI: 1.23-8.95). In this national cohort study spanning more than three decades of observation, non-therapeutic circumcision in infancy or childhood did not appear to provide protection against HIV or other STIs in males up to the age of 36 years. Rather, non-therapeutic circumcision was associated with higher STI rates overall, particularly for anogenital warts and syphilis.

Predicting time to relapse in patients with schizophrenia according to patients' relapse history: a historical cohort study using real-world data in Sweden.

BACKGROUND: For patients with schizophrenia, relapse is a recurring feature of disease progression, often resulting in substantial negative impacts for the individual. Although a patient's relapse history (specifically the number of prior relapses) has been identified as a strong risk factor for future relapse, this relationship has not yet been meticulously quantified. The objective of this study was to use real-world data from Sweden to quantify the relationship of time to relapse in schizophrenia with a patient's history of prior relapses. METHODS: Data from the Swedish National Patient Register and Swedish Prescribed Drug Register were used to study relapse in patients with schizophrenia with a first diagnosis recorded from 2006-2015, using proxy definitions of relapse. The primary proxy defined relapse as a psychiatric hospitalisation of ≥7 days' duration. Hazard ratios (HRs) were calculated for risk of each subsequent relapse, and Aalen-Johansen estimators were used to estimate time to next relapse. RESULTS: 2,994 patients were included, and 5,820 relapse episodes were identified using the primary proxy. As the number of previous relapses increased, there was a general trend of decreasing estimated time between relapses. Within 1.52 years of follow-up, 50% of patients with no history of relapse were estimated to have suffered their first relapse episode. 50% of patients with one prior relapse were estimated to have a second relapse within 1.23 years (HR: 1.84 [1.71-1.99]) and time to next relapse further decreased to 0.89 years (HR: 2.77 [2.53-3.03]) and 0.22 years (HR: 18.65 [15.42-22.56]) for 50% of patients with two or ten prior relapses, respectively. Supplementary analyses using different inclusion/exclusion criteria for the study population and redefined proxies of relapse reflected the pattern observed with the primary analyses of a higher number of prior relapses linked with increased risk of/reduced estimated time to the next relapse. CONCLUSIONS: The results suggested a trend of accelerating disease progression in schizophrenia, each relapse episode predisposing an individual to the next within a shorter time period. These results emphasise the importance of providing early, effective, and tolerable treatments that better meet a patient's individual needs.

The relative efficiency of schizophrenia health care systems: an international comparison using data envelopment analysis.

AIM: To compare the health economic efficiency of health care systems across nations, within the area of schizophrenia, using a data envelopment analysis (DEA) approach. METHODS: The DEA was performed using countries as decision-making units, schizophrenia disease investment (cost of disease as a percentage of total health care expenditure) as the input, and disability-adjusted life years (DALYs) per patient due to schizophrenia as the output. Data were obtained from the Global Burden of Disease 2017 study, the World Bank Group, and a literature search of the PubMed database. RESULTS: Data were obtained for 44 countries; of these, 34 had complete data and were included in the DEA. Disease investment (percentage of total health care expenditure) ranged from 1.11 in Switzerland to 6.73 in Thailand. DALYs per patient ranged from 0.621 in Lithuania to 0.651 in Malaysia. According to the DEA, countries with the most efficient schizophrenia health care were Lithuania, Norway, Switzerland and the US (all with efficiency score 1.000). The least efficient countries were Malaysia (0.955), China (0.959) and Thailand (0.965). LIMITATIONS: DEA findings depend on the countries and variables that are included in the dataset. CONCLUSIONS: In this international DEA, despite the difference in schizophrenia disease investment across countries, there was little difference in output as measured by DALYs per patient. Potentially, Lithuania, Norway, Switzerland and the US should be considered 'benchmark' countries by policy makers, thereby providing useful information to countries with less efficient systems.

Identifying and characterizing treatment-resistant schizophrenia in observational database studies.

OBJECTIVES: Treatment-resistant schizophrenia (TRS) is clinically defined as failure to respond to two antipsychotics of adequate dose and duration. An algorithm (registry TRS) was developed, for identifying patients with TRS in claim datasets from Sweden and the United States. METHODS: Schizophrenia (SZ) patients aged ≥13 years were identified in both datasets and matched to controls. Patients were identified as having TRS by use of the registry TRS or ≥1 prescription for clozapine or use of other published criteria. The algorithm was compared for sensitivity, and patients with and without TRS were compared for psychiatric and hospital burden and Global Assessment of Functioning (GAF) scores. TRS prevalence was not assessed due to lack of clinically validated data to test the specificity of the algorithm. RESULTS: Swedish registry TRS patients ≤45 years at first SZ diagnosis had significantly lower GAF scores and earlier disease onset than non-TRS patients. SZ patients with higher psychiatric comorbidity and hospital burden were more likely identified as TRS by all algorithms. The registry algorithm was significantly more sensitive to multiple inpatient stays and all psychiatric comorbidities at identifying TRS. CONCLUSION: The registry algorithm appeared more sensitive at identifying patients with TRS, who had greater psychiatric and hospital burden.

Cultural background, non-therapeutic circumcision and the risk of meatal stenosis and other urethral stricture disease: Two nationwide register-based cohort studies in Denmark 1977-2013.

BACKGROUND: Meatal stenosis is markedly more common in circumcised than genitally intact males, affecting 5-20 per cent of circumcised boys. However, no population-based study has estimated the relative risk of meatal stenosis and other urethral stricture diseases (USDs) or the population attributable fraction (AFp) associated with non-therapeutic circumcision. METHODS: In two nationwide cohort studies (comprising 4.0 million males of all ages and 810 719 non-Muslim males aged 0-36 years, respectively), we compared hospital contact rates for USD during 1977-2013 between circumcised and intact Danish males. Hazard ratios (HRs) were obtained using Cox proportional hazards regression, and the AFp estimated the proportion of USD cases in <10 year-old boys that is due to non-therapeutic circumcision. RESULTS: Muslim males had higher rates of meatal stenosis than ethnic Danish males, particularly in <10 year-old boys (HR 3.44, 95 per cent confidence interval 2.42-4.88). HRs linking circumcision to meatal stenosis (10.3, 4.53-23.4) or other USDs (5.14, 3.48-7.60) were high, and attempts to reduce potential misclassification and confounding further strengthened the association, particularly in <10 year-old boys (meatal stenosis: 26.3, 9.37-73.9; other USDs: 14.0, 6.86-28.6). Conservative calculations revealed that at least 18, 41, 78, and 81 per cent of USD cases in <10 year-old boys from countries with circumcision prevalences as in Denmark, the United Kingdom, the United States and Israel, respectively, may be attributable to non-therapeutic circumcision. CONCLUSION: Our study provides population-based epidemiological evidence that circumcision removes the natural protection against meatal stenosis and, possibly, other USDs as well.

The validity of register data to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis.

BACKGROUND: The incidence of atopic dermatitis, wheezing, asthma and allergic rhinoconjunctivitis has been increasing. Register-based studies are essential for research in subpopulations with specific diseases and facilitate epidemiological studies to identify causes and evaluate interventions. Algorithms have been developed to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis using register information on disease-specific dispensed prescribed medication and hospital contacts, but the validity of the algorithms has not been evaluated. This study validated the algorithms vs gold standard deep telephone interviews with the caretaker about physician-diagnosed atopic dermatitis, wheezing, asthma or allergic rhinoconjunctivitis in the child. METHODS: The algorithms defined each of the three atopic diseases using register-based information on disease-specific hospital contacts and/or filled prescriptions of disease-specific medication. Confirmative answers to questions about physician-diagnosed atopic disease were used as the gold standard for the comparison with the algorithms, resulting in sensitivities and specificities and 95% confidence intervals. The interviews with the caretaker of the included 454 Danish children born 1997-2003 were carried out May-September 2015; the mean age of the children at the time of the interview being 15.2 years (standard deviation 1.3 years). RESULTS: For the algorithm capturing children with atopic dermatitis, the sensitivity was 74.1% (95% confidence interval: 66.9%-80.2%) and the specificity 73.0% (67.3%-78.0%). For the algorithm capturing children with asthma, both the sensitivity of 84.1% (78.0%-88.8%) and the specificity of 81.6% (76.5%-85.8%) were high compared with physician-diagnosed asthmatic bronchitis (recurrent wheezing). The sensitivity remained high when capturing physician-diagnosed asthma: 83.3% (74.3%-89.6%); however, the specificity declined to 66.0% (60.9%-70.8%). For allergic rhinoconjunctivitis, the sensitivity was 84.4% (78.0-89.2) and the specificity 81.6% (75.0-84.4). CONCLUSION: The algorithms are valid and valuable tools to identify children with atopic dermatitis, wheezing, asthma or allergic rhinoconjunctivitis on a population level using register data.

Age at Menarche and Risk of Multiple Sclerosis: A Prospective Cohort Study Based on the Danish National Birth Cohort.

Few studies have addressed the possible association between age at menarche and multiple sclerosis (MS), and results are conflicting. We studied this issue in a large prospective cohort study. The study cohort comprised 77,330 women included in the Danish National Birth Cohort (1996-2002). Information on menarcheal age was ascertained at the first interview, which took place in the 16th week of pregnancy. Women were followed for MS from the first interview to December 31, 2011. Associations between age at menarche and risk of MS were evaluated with hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Overall, 226 women developed MS during an average follow-up period of 11.7 years. Age at menarche among women with MS was generally lower than that among women without MS (Wilcoxon rank-sum test; P = 0.002). We observed an inverse association between age at menarche and MS risk. For each 1-year increase in age at menarche, risk of MS was reduced by 13% (hazard ratio = 0.87, 95% confidence interval: 0.79, 0.96). Early age at menarche appears to be associated with an increased risk of MS. The mechanisms behind this association remain to be established.

Family history of systemic lupus erythematosus and risk of autoimmune disease: Nationwide Cohort Study in Denmark 1977-2013.

Objective: To provide population-based estimates of relative risk of SLE and other autoimmune diseases (ADs) in relatives of SLE patients. Methods: A cohort of 5 237 319 Danish residents identified through the Civil Registration System was coupled to their relatives through the parental link and followed for SLE and other ADs between 1977 and 2013 through linkage to the National Patient Register. Twin zygosity was established through the Danish Twin Registry. Hazard ratios (HRs) with 95% CIs were calculated using Cox proportional hazards regression analyses. Results: During 117.5 million person-years of follow-up, 3612 persons were hospitalized with SLE. HRs of SLE were high among first-degree (HR = 10.3; 95% CI: 8.25, 12.9; n = 80) and second- or third-degree relatives of SLE patients (HR = 3.60; 95% CI: 2.20, 5.90; n = 16). HRs for any AD were elevated in first-degree (HR = 1.51; 95% CI: 1.41, 1.62; n = 785) and second- or third-degree relatives of SLE patients (HR = 1.28; 95% CI: 1.18, 1.39; n = 582). Among individuals with SLE-affected first-degree relatives, the risk was significantly increased for RA (HR = 1.64; 95% CI: 1.35, 1.99; n = 103), IBD (HR = 1.21; 95% CI: 1.02, 1.43; n = 130) and type 1 diabetes mellitus (HR = 1.23; 95% CI: 1.01, 1.48; n = 106). Risk of other ADs was significantly increased both among SLE-affected first-degree (HR = 2.08; 95% CI: 1.88, 2.31; n = 371) and second- or third-degree relatives (HR = 1.38; 95% CI: 1.23, 1.54; n = 313). Conclusion: Family history of SLE is associated with a clearly elevated risk of SLE and, to a much lesser degree, of RA and other ADs.

Acid-suppressing therapies and subsite-specific risk of stomach cancer.

BACKGROUND: Associations of stomach cancer risk with histamine type-2 receptor antagonists (H2RA) and proton-pump inhibitors (PPI) are controversial. We hypothesised that proximal extension of Helicobacter pylori infection from acid suppression would disproportionately increase cancers at proximal subsites. METHODS: A total of 1 563 860 individuals in the Danish Prescription Drug Registry first prescribed acid-suppressive drugs 1995-2011 were matched to unexposed population-based controls. Hazard ratios (HR) were calculated by Cox proportional hazard regression for stomach cancers diagnosed more than one year after first prescription. RESULTS: There were 703 stomach cancers among H2RA-exposed individuals and 1347 among PPI-exposed. Restricted to individuals with five or more prescriptions, subsite-specific HRs for H2RA and PPI were 4.1 and 6.4 for proximal subsites vs 8.0 and 10.3 for distal subsites, respectively. CONCLUSIONS: Moderate exposures to acid-suppressive drugs did not favour proximal tumour localisation. Given confounding by indication, these findings do not resolve potential contribution to gastric carcinogenesis overall.

Socio-demographic characteristics of Danish blood donors.

BACKGROUND: Blood transfusion is an essential component of a modern healthcare system. Because knowledge about blood donor demography may inform the design of strategies for donor recruitment and retention, we used nationwide registers to characterize the entire population of blood donors in Denmark in 2010. METHODS: The study population comprised all Danes in the age range eligible for blood donation (N = 3,236,753) at the end of 2010. From the Scandinavian Donations and Transfusions (SCANDAT) register, we identified 174,523 persons who donated blood in Danish blood banks at least once in 2010. The association between sociodemographic characteristics and blood donor prevalence was examined using regression models. RESULTS: The overall prevalence of blood donation was 5.4% among both women and men. The age-specific prevalence of blood donation peaked at 25 years of age (6.8%) for women and 30 years of age (5.7%) for men. Children of any age were associated with lower prevalence of blood donation among women, while the opposite was seen for men. Middle to high income groups, but not the highest income group, had fourfold higher donor prevalence than the lowest income group (6.7% compared to 1.7%). The prevalence of blood donation was considerably lower among men living with their parents (2.9%) or alone (3.9%) than among men cohabitating with a woman (6.2%). SUMMARY: Social marginalization, as indicated by low income and being a male living without a woman, was associated with lower prevalence of blood donation. However, individuals with very high incomes and women with children were underrepresented in the Danish blood donor population.

Use of Proton Pump Inhibitors and the Risk of Listeriosis: A Nationwide Registry-based Case-Control Study.

BACKGROUND: Recent studies suggest that proton pump inhibitors (PPIs) may increase the risk for listeriosis. We investigated a potential association in cases of nonpregnancy-associated listeriosis using registry data. METHODS: We conducted a population-based, case-control study using Danish health registries. Cases (n = 721) were defined as patients aged ≥45 years notified with listeriosis from July 1994 to December 2012. We selected 34800 controls using risk-set sampling. Controls were individually matched for age, sex, and municipality. Data on use of PPIs and other drugs and hospitalization diagnoses over a 5-year period were extracted from nationwide health registries. A comorbidity index (CMI) was constructed. We calculated the association between use of PPIs and related drugs within 30 days (current use) and other time windows before the index date. Using conditional logistic regression, matched odds ratios (ORs) adjusted for CMI and confounders were estimated. RESULTS: The adjusted OR for current use of PPIs and development of listeriosis was 2.81 (95% confidence interval [CI], 2.14-3.69). PPI usage up to 90 days before the index date remained statistically significant. Subgroup analyses revealed increasing ORs with decreasing age and level of comorbidity and an increased OR for concurrent glucocorticoid treatment (OR, 4.61; 95% CI, 3.01-7.06). No significant association was found for current use of histamine-2-receptor antagonists (adjusted OR, 1.82; 95% CI, 0.89-3.71). CONCLUSIONS: Prescribed PPIs were associated with increased risk of listeriosis. The risk waned with time since last prescription redemption. PPIs may have unwanted side effects in vulnerable populations.

Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study.

OBJECTIVE: As previous research has suggested that exposure to vitamin D insufficiency in utero may have relevance for the risk of multiple sclerosis (MS), we aimed to examine the direct association between level of neonatal vitamin D and risk of MS. METHODS: We carried out a matched case-control study. Dried blood spots samples (DBSS) belonging to 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, 1-2 controls with the same sex and birth date were retrieved from the Biobank (n = 972). Level of 25-hydroxyvitamin D (25[OH]D) in the DBSS was measured using liquid chromatography tandem mass spectroscopy. The association between different levels of 25(OH)D and risk of MS was evaluated by odds ratios (OR) calculated in conditional logistic regression models. RESULTS: We observed that lower levels of 25(OH)D in neonates were associated with an increased risk of MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile (<20.7 nmol/L) and lowest among those in the top quintile of 25(OH)D (≥48.9 nmol/L), with an OR for top vs bottom of 0.53 (95% confidence interval [CI] 0.36-0.78). In the analysis treating 25(OH)D as a continuous variable, a 25 nmol/L increase in neonatal 25(OH)D resulted in a 30% reduced risk of MS (OR 0.70, 95% CI 0.57-0.84). CONCLUSION: Low concentrations of neonatal vitamin D are associated with an increased risk of MS. In light of the high prevalence of vitamin D insufficiency among pregnant women, our observation may have importance for public health.

Erythema nodosum and the risk of tuberculosis in a high incidence setting.

OBJECTIVE: This study estimates the erythema nodosum (EN) incidence in a tuberculosis (TB) endemic setting and evaluates the likelihood of a subsequent TB diagnosis among individuals with Mycobacterium tuberculosis infection (MTI) with or without EN. DESIGN: We estimated EN incidence rates (IRs) in East Greenland in 2010-2011 and conducted a cohort study following all individuals who tested positive for MTI from 1 January 2010 until 31 December 2012. A personal identifier allowed individual follow-up in the mandatory TB register. MTI was defined by a positive interferon-gamma release assay. TB incidence rate ratios (IRRs) among participants with or without EN were estimated with the Cox proportional hazard model. RESULTS: We identified 38 EN cases corresponding to an IR of 500/100,000 inhabitants/year. All cases were among individuals with MTI. The EN IR was 11.79 (95% CI 5.73-24.27) times higher for BCG-unvaccinated compared with BCG-vaccinated individuals. The TB IRR was 25 (95% CI 11-60) within 1 month of EN compared to individuals without EN. CONCLUSION: This study documents a high EN incidence in a TB endemic region. EN occurred only in individuals with MTI, and predominantly among BCG-unvaccinated individuals. EN was significantly associated with a TB diagnosis within 1 month of diagnosis.

Self-rated health in women prior to clinical onset of multiple sclerosis: A study within the Danish National Birth Cohort.

BACKGROUND: It has been suggested that onset of multiple sclerosis (MS) is preceded by a clinically silent period of up to 10 years. OBJECTIVES: Examine whether such a period should be associated with poor self-rated health (SRH). METHODS: Information on SRH before pregnancy was ascertained among 80,848 women participating in the Danish National Birth Cohort (DNBC) 1996-2002. Women were followed for MS from enrolment in DNBC in the 16th week of pregnancy until 31 December 2011. Associations between SRH and MS were evaluated by means of hazard ratios (HR) with 95% confidence intervals (CIs) using Cox proportional hazard models. RESULTS: During on average 11.7 years of follow-up, 239 women were diagnosed with MS. Overall, neither women with fair (HR = 1.09 (95% CI = 0.83-1.41), n = 113) nor poor pre-pregnancy SRH (HR = 0.94 (95% CI = 0.47-1.87), n = 9) were at an increased risk of MS compared with women reporting very good pre-pregnancy SRH. Supplementary analyses showed no significant differences in MS risk in consecutive periods of follow-up. CONCLUSION: In this first prospective cohort study assessing MS risk as a function of SRH, we found no indication of a long period of poor SRH prior to MS. Our findings based on pregnant women may not necessarily apply to all women.

Association between pregnancy losses in women and risk of atherosclerotic disease in their relatives: a nationwide cohort study†.

AIMS: A common underlying mechanism with a genetic component could link pregnancy losses with vascular disease. We examined whether pregnancy losses (miscarriages and stillbirths) and atherosclerotic outcomes co-aggregated in families. METHODS AND RESULTS: Using Danish registers, we identified women with pregnancies in 1977-2008, and their parents (>1 million) and brothers (>435 000). We followed parents for incident ischaemic heart disease (IHD), myocardial infarction (MI), and cerebrovascular infarction (CVI), and brothers for a broader combined atherosclerotic endpoint. Using Cox regression, we estimated hazard ratios (HRs) for each outcome by history of pregnancy loss in daughters/sisters. Overall, parents whose daughters had 1, 2, and ≥3 miscarriages had 1.01 [95% confidence interval (CI) 0.99-1.04], 1.07 (95% CI 1.02-1.11), and 1.10 (95% CI 1.02-1.19) times the rate of MI, respectively, as parents whose daughters had no miscarriages. For parents with ≥3 daughters, the HRs were 1.12 (95% CI 1.02-1.24), 1.29 (95% CI 1.13-1.48), and 1.33 (95% CI 1.12-1.57). Effect magnitudes did not differ for fathers and mothers. We observed similar patterns for IHD and CVI (parents) and the atherosclerotic endpoint (brothers). Parents whose daughters had stillbirths had 1.14 (95% CI 1.05-1.24) and 1.07 (95% CI 0.96-1.18) times the rates of MI and CVI, respectively, as parents whose daughters had no stillbirths. CONCLUSION: Certain pregnancy losses and atherosclerotic diseases in both heart and brain may have a common aetiologic mechanism. Women in families with atherosclerotic disease may be predisposed to pregnancy loss; conversely, pregnancy losses in first-degree relatives may have implications for atherosclerotic disease risk.

Was the increase in culture-confirmed Campylobacter infections in Denmark during the 1990s a surveillance artefact?

In 1991, 1999 and 2006, randomly selected individuals from the Danish Central Personal Register provided a serum sample. From individuals aged 30 years and above, 500 samples from each year were analysed for Campylobacter IgG, IgA and IgM antibodies using a direct ELISA method. We applied a seroincidence calculator available from the European Centre for Disease Prevention and Control to perform a mathematical back-calculation to estimate the annual Campylobacter seroincidence in the Danish population. The estimated Campylobacter seroincidence did not differ significantly between the 1991, 1999 and 2006 studies although the reported number of culture-confirmed cases of Campylobacter infection increased 2.5 fold from 1993 to 1999 among individuals aged 30 years and above. This suggests that Campylobacter was widely present in the Danish population before the increase in poultry-associated clinical Campylobacter infections observed from 1993 to 2001 among individuals of this age groups.

Inflammatory Bowel Disease Patients Are at Increased Risk of Invasive Pneumococcal Disease: A Nationwide Danish Cohort Study 1977-2013.

OBJECTIVES: Inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are chronic diseases characterized by an inappropriate immune response, which may also increase the risk of infections. We investigated the risk of invasive pneumococcal disease (IPD) before and after diagnosis of IBD in a population-based cohort study. METHODS: In a cohort of 74,156 IBD patients and 1,482,363 non-IBD controls included and followed during 1977-2013, hazard rate ratios (HRs) for IPD in IBD patients vs. controls were calculated by Cox regression. Within the IBD group, we also calculated the risk according to ever use of specific IBD medications. Next, using conditional logistic regression, we evaluated the odds of IPD prior to IBD diagnosis. RESULTS: The HRs for IPD within the first 6 months after IBD diagnosis were significantly and more than threefold increased and then decreased to a constant level, which for CD was significantly increased (approximately twofold, HR, 1.99; 95% confidence interval (CI), 1.59-2.49) and for UC non-significantly just above 1. IBD medication use including tumor necrosis factor alpha antagonists had limited impact on the risk of IPD, although having ever used azathioprine increased the risk of IPD in patients with UC (HR, 2.38; 95% CI, 1.00-5.67). Up to 4 years prior to IBD diagnosis, the odds ratio for IPD was significantly increased (UC HR, 1.51, 95% CI, 1.05-2.17; CD HR, 1.79, 95% CI, 1.05-3.03). CONCLUSIONS: The risk of IPD is significantly increased both before and after diagnosis of IBD, with limited impact of IBD medications. This suggests that the risk of IPD in patients with IBD is related to the underlying altered immune response in these patients.