Mediating pathways between neighborhood disadvantage and cardiovascular risk: Quasi-experimental evidence from a Danish refugee dispersal policy.

Research has documented that neighborhood disadvantage is associated with increased cardiovascular disease risk, but it is unclear which mechanistic pathways mediate this association across the life course. Leveraging a natural experiment in which refugees to Denmark were quasi-randomly assigned to neighborhoods across the country during 1986-1998 and using 30 years of follow-up data from population and health registers, we assessed whether and how individual-level poverty, unstable employment, and poor mental health mediate the relation between neighborhood disadvantage and the risk of hypertension, hyperlipidemia, and type 2 diabetes among Danish refugees (N= 40,811). Linear probability models using the discrete time-survival framework showed that neighborhood disadvantage was associated with increased risk of hypertension (0.05 percentage points [pp] per year [95%CI -0.00, 0.10]); hyperlipidemia (0.03 pp per year [95%CI -0.01, 0.07]), and diabetes (0.01 pp per year (95%CI -0.02, 0.03)). The Baron-Kenny product-of-coefficients method for counterfactual mediation analysis indicated that cumulative income mediated 6%-28% of the disadvantage effect on these outcomes. We find limited evidence of mediation by unstable employment and poor mental health. This study informs our theoretical understanding of the pathways linking neighborhood disadvantage with cardiovascular disease risk and identifies income security as a promising point of intervention in future research.

Neighbourhood socioeconomic disadvantage and psychiatric disorders among refugees: a population-based, quasi-experimental study in Denmark.

PURPOSE: Refugees are vulnerable to psychiatric disorders because of risk factors linked to migration. Limited evidence exist on the impact of the neighbourhood in which refugee resettle. We examined whether resettling in a socioeconomically disadvantaged neighbourhood increased refugees' risk of psychiatric disorders. METHODS: This register-based cohort study included 42,067 adults aged 18 years and older who came to Denmark as refugees during 1986-1998. Resettlement policies in those years assigned refugees in a quasi-random fashion to neighbourhoods across the country. A neighbourhood disadvantage index was constructed using neighbourhood-level data on income, education, unemployment, and welfare receipt. Main outcomes were psychiatric diagnoses and psychiatric medication usage ascertained from nationwide patient and prescription drug registers, with up to 30-year follow-up. Associations of neighbourhood disadvantage with post-migration risk of psychiatric disorders were examined using Cox proportional hazards and linear probability models adjusted for individual, family, and municipality characteristics. RESULTS: The cumulative risk of psychiatric diagnoses and medication was 13.7% and 46.1%, respectively. Refugees' risk of psychiatric diagnoses and psychiatric medication usage was higher among individuals assigned to high-disadvantage compared with low-disadvantage neighbourhoods in analyses including fixed effects for assigned municipality (psychiatric diagnoses: hazard ratio (HR) = 1.14, 95% CI 1.04, 1.25; psychiatric medication: HR = 1.05, 95% CI 1.00, 1.11). Consistent results were found using linear probability models. Results for diagnostic categories and subclasses of medications suggested that the associations were driven by neurotic and stress-related disorders and use of anxiolytic medications. CONCLUSION: Resettlement in highly disadvantaged neighbourhoods was associated with an increase in refugees' risk of psychiatric disorders, suggesting that targeted placement of newly arrived refugees could benefit refugee mental health. The results contribute quasi-experimental evidence to support links between neighbourhood characteristics and health.

Corrigendum: Risk of reoperation due to surgical site infection in 74,771 hip fracture patients: a Danish nationwide cohort study.

Corrigendum of Acta Orthop 2022; 93: 760-766. doi: https://doi.org/10.2340/17453674.2022.4580.

Risk of reoperation due to surgical site infection in 74,771 hip fracture patients: a Danish nationwide cohort study.

BACKGROUND AND PURPOSE: Surgical site infection (SSI) after hip fracture surgery is a feared condition. We examined the trend in incidence of reoperation due to SSI up to 1 year following hip fracture surgery from 2005 to 2016 and risk factors of SSI by age, sex, comorbidity, type of fracture, and surgery. PATIENTS AND METHODS: We conducted a population-based, nationwide cohort study using data from the Danish Multidisciplinary Hip Fracture Register (DMHFR). We included 74,771 patients aged 65 and up who underwent surgery from 2005 to 2016 for all types of hip fracture. We calculated net risk of reoperation using Kaplan­Meier method, and, with Cox regression, adjusted hazard ratios (HRs) with a 95% confidence interval (CI) for reoperation due to SSI. RESULTS: Overall, the 1-year net risk of reoperation due to SSI was 1.6%. The HR was higher for patients undergoing total/hemiarthroplasty surgery versus internal fixation (HR = 1.5; 95%CI 1.3­1.8) and lower for patients with per-/subtrochanteric fracture versus femoral neck fracture (HR = 0.6; CI 0.6­0.7). The risk of reoperation due to SSI decreased over time; HR was 0.7 (CI 0.5­0.8) for 2015­2016 compared with 2005­2006. Risk of reoperation decreased with increasing age; the HR was 0.8 (CI 0.7­1.0) in the more than 85-year-olds compared with 65­74-year-old patients. Charlson Comorbidity Index of ≥ 3 was associated with a higher risk of reoperation due to SSI, HR was 1.3 (CI 1.1­1.6). INTERPRETATION: The net risk of reoperations due to SSI in our study was lower than previously assumed. We identified several risk factors for increased risk of reoperation due to SSI, most noticeably treatment with arthroplasty vs. internal fixation, as well as younger age, high comorbidity burden, and femoral neck fracture diagnosis.

Mortality and revision risk after femoral neck fracture: comparison of internal fixation for undisplaced fracture with arthroplasty for displaced fracture: a population-based study from Danish National Registries.

Background and purpose - Hemiarthroplasty has lower reoperation frequency and better mobilization compared with internal fixation (IF) in patients with undisplaced femoral neck fractures (FNF), which might translate into lower mortality. In this population-based cohort study we compare the risk of mortality and reoperation in undisplaced FNF treated with IF and displaced FNF treated with arthroplasty in patients older than 70 years old. We assume that, per se, there is no difference in mortality risk between patients with a displaced and an undisplaced FNF.Patients and methods - Hip fracture patients were identified in the Danish Multidisciplinary Hip Fracture Registry during 2005-2015. Data on medication, comorbidities, reoperation, and mortality were retrieved from other Danish medical databases. IF and arthroplasty patients were compared with regards to mortality and reoperation up to 5 years postoperatively. We calculated hazard ratios (HR) with 95% confidence intervals (CI) adjusting for relevant confounders.Results - We included 19,260 FNF treated with arthroplasty and 10,337 FNF with IF. There was an increased risk of mortality for arthroplasty within 30 days, HR 1.3 (95% CI 1.3-1.4), compared with IF but not after 1 and 5 years. Arthroplasty patients had adjusted HRs for reoperation of 0.8 (0.8-0.9) within 1 year, 0.8 (0.7-0.9) within 2 years, and 0.8 (0.8-0.9) within 5 years postoperatively compared with IF.Interpretation - Patients treated for a displaced FNF with arthroplasty had a higher risk of 30-day mortality compared with patients who had an undisplaced FNF treated with IF. It has to be considered that there were baseline differences in the groups but there was no difference in mortality risk up to 5 years post-surgery. Concerning reoperation, patients with a displaced FNF treated with arthroplasty had a lower risk of reoperation compared with IF for undisplaced FNF.

Risk of adverse birth outcomes after maternal varenicline use: A population-based observational study in Denmark and Sweden.

PURPOSE: To examine risks of adverse birth outcomes in women exposed to varenicline during pregnancy. METHODS: Population-based cohort study including live-born and stillborn infants from 1 May 2007 to 31 December 2012. Data from health and administrative registries in Denmark and Sweden, two Nordic countries with universal health care and routine registration of major life and health events. Infants were allocated to three cohorts on the basis of their in utero exposure: the exposed cohort consisting of infants whose mothers were dispensed varenicline during pregnancy; the unexposed cohort comprised infants unexposed to varenicline, but exposed to maternal smoking in utero; and the reference cohort of infants unexposed to varenicline and maternal smoking in utero. The primary outcome was major congenital malformations diagnosed from birth to the first year of life. Secondary outcomes included stillbirth, fetal growth restriction (measured as small for gestational age), preterm delivery, preterm premature rupture of membranes, and sudden infant death syndrome. We estimated the prevalence of the primary outcome and secondary outcomes in the exposed, unexposed, and reference cohorts. Prevalence odds ratios with 95% confidence intervals (CIs) were computed using logistic regression with propensity score adjustment to control for potential confounders. RESULTS: The combined cohort included 885 185 infants. Of these, 335 infants were exposed, 78 412 were unexposed, and the remaining 806 438 comprised the reference cohort. Major congenital malformations were detected among 3.6% of exposed infants, 4.3% of unexposed infants, and 4.2% of infants in the reference cohort. The propensity score-adjusted prevalence odds ratio for major congenital malformations was 0.80 (95% CI, 0.45-1.42) for exposed vs unexposed infants. All analyses of primary and secondary outcomes comparing exposed with unexposed infants yielded odds ratio estimates below or close to unity. Use of varenicline during pregnancy does not appear to increase the risk of major congenital malformations or other adverse birth outcomes.

Open versus laparoscopic rectal cancer resection and risk of subsequent incisional hernia repair and paracolostomy hernia repair: a nationwide population-based cohort study.

OBJECTIVE: To investigate the risk of incisional hernia repair (IHR) and paracolostomy hernia repair (PHR) following open and laparoscopic rectal cancer resection with curative intent. BACKGROUND: Laparoscopic rectal cancer resection has been implemented to varying degrees around the world. IHR and PHR following open and laparoscopic rectal cancer resection have only been sparingly evaluated. METHODS: Patients who underwent rectal cancer resection were identified in the Danish Colorectal Cancer Group's database. To identify IHR and PHR following rectal cancer resection, we linked data to the Danish Ventral Hernia Database. The absolute risk of IHR and PHR was estimated as cumulative incidence proportions, treating death as competing risk. We used Cox proportional hazard regression analysis with multivariable adjustment to compute hazard ratios (HRs) comparing open and laparoscopic approach. RESULTS: The 5-year risk of IHR was 4.1% among patients undergoing open resection (n = 3090) and 3.2% among those undergoing laparoscopic resection (n = 3099), corresponding to a risk difference of 0.9% (95% CI 0.0-2.0, P = 0.057). Laparoscopic rectal resection was not associated with lower risk of IHR (adjusted HR 0.94, 95% CI 0.67-1.31, P = 0.709). A total of 2577 patients had a colostomy at rectal cancer resection and the 5-year risk of PHR was 2.1% after open surgery compared with 6.7% after laparoscopic surgery, corresponding to a risk difference of -4.6% (95% CI -6.4 to -2.7, P < 0.001). Laparoscopic surgery was associated with increased risk of PHR (adjusted HR 2.56, 95% CI 1.53-4.29, P < 0.001). CONCLUSION: We observed no association between surgical approach of rectal cancer resection and subsequent IHR. Laparoscopic surgery was associated with increased risk of PHR.

Cardiac surgery in patients with congenital heart disease is associated with acute kidney injury and the risk of chronic kidney disease.

Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of patients undergoing surgery for congenital heart disease. Here we determine if CS-AKI is associated with chronic kidney disease (CKD) in patients with congenital heart disease. Using Danish regional population-based registries, our cohort study included patients with congenital heart disease born between 1990-2010 with first cardiac surgery between 2005 and 2010 (under 15 years of age). Utilizing in- and out-patient laboratory serum creatinine data, we identified individuals fulfilling KDIGO stages of AKI within 5 days of cardiac surgery. A unique personal identifier enabled unambiguous data linkage and virtually complete follow-up. The cumulative incidences of CKD stages 2-5 according to presence of CS-AKI were computed utilizing serum creatinine values and Pottel's formula. Using Cox regression, the corresponding hazard ratios were computed, adjusting for sex, age at first cardiac surgery, calendar period of surgery, and congenital heart disease severity. Of 382 patients with congenital heart disease undergoing cardiac surgery, 127 experienced CS-AKI within 5 days of surgery. Median follow-up was 4.9 years. The five-year cumulative incidence of CKD for patients with CS-AKI was 12% (95% confidence interval 7%-20%), significantly higher than the 3% (1%-5%) for those without CS-AKI with a significant adjusted hazard ratio of 3.8 (1.4-10.4). Thus, CS-AKI in patients with congenital heart disease is common and is associated with an increased risk for CKD.

Clinical and Molecular Characteristics of Post-Colonoscopy Colorectal Cancer: A Population-based Study.

BACKGROUND & AIMS: Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy. METHODS: We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (dMMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation. RESULTS: Of 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.90-2.89) and were more likely to have dMMR (OR, 1.26; 95% CI, 1.00-1.59), but were less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89) compared with CRCs diagnosed in patients with no prior colonoscopy. The highest proportions of proximal and/or dMMR tumors were observed in CRCs diagnosed 3-6 years after colonoscopy, but these features were still more frequent among cancers diagnosed up to 10 years after colonoscopy. The relative excess of dMMR tumors was most pronounced in distal cancers. In an analysis of 85 cases detected after colonoscopy, we found BRAF mutations in 23% of tumors and that 7% of cases had features of Lynch syndrome. Colonoscopy exams were incomplete in a higher proportion of cases diagnosed within <1 year (in 38%) than in those diagnosed within 1-10 years after colonoscopy (16%). CONCLUSIONS: In a study of incident CRC cases in Denmark, we observed that tumors found in patients who have undergone colonoscopy are more often proximal and have dMMR compared to CRCs detected in patients without previous colonoscopies. The excess of right-sided tumors and the modest independent effects of dMMR reinforce the importance of proper colonoscopic examination of the proximal large bowel.

Increased Risk of Colorectal Cancer Development Among Patients With Serrated Polyps.

BACKGROUND & AIMS: Sessile serrated adenomas/polyps (SSA/Ps) and traditional serrated adenomas (TSAs) are now distinguished from hyperplastic polyps and recognized as precursors to colorectal cancer (CRC). We studied CRC risks associated with serrated polyps. METHODS: By using Danish databases (1977-2009), we conducted a nationwide population-based, case-control study nested within individuals who had received colonoscopies (n = 272,342), and identified 2045 CRC cases and 8105 CRC-free individuals (controls). For each case and control, we identified the first colorectal polyp(s) that underwent a biopsy or were excised during or after the initial colonoscopy, and obtained tissue blocks for hyperplastic lesions. Four expert pathologists reviewed these lesions using current terminology for serrated polyps. We used logistic regression to compute odds ratios (ORs) to associate the risk of CRC with polyp type and estimated the absolute risks by multiplying the risk in patients with no polyps by these ORs. RESULTS: Seventy-nine cases and 142 controls had SSA/Ps (OR, 3.07; 95% confidence interval [CI], 2.30-4.10). SSA/Ps with cytology markers of dysplasia were associated with a particularly high OR (4.76; 95% CI, 2.59-8.73). Women with SSA/P had a higher risk for CRC than men with SSA/P (OR for women, 5.05; 95% CI, 3.05-8.37 vs OR for men, 2.18; 95% CI, 1.24-3.82); patients with SSA/P proximal to the splenic flexure had the highest risk for CRC (OR, 12.42; 95% CI, 4.88-31.58). The OR for CRC was 4.84 in the 14 cases vs 17 controls with TSAs (95% CI, 2.36-9.93), 2.51 in the 757 cases vs 1698 controls with conventional adenomas (95% CI, 2.25-2.80), and 1.30 in the 55 cases vs 235 controls with hyperplastic polyps (95% CI, 0.96-1.77). The 10-year risk for CRC was 4.4% for patients with SSA/P with dysplasia, 4.5% for patients with TSAs, and 2.3% for patients with conventional adenomas. CONCLUSION: Patients with SSA/P or TSA are at increased risk for CRC; their level of risk is similar to or higher than that of patients with conventional adenomas.

Use of azithromycin and risk of ventricular arrhythmia.

BACKGROUND: There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia. METHODS: We conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders. RESULTS: We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis. INTERPRETATION: Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.

Hospitalization rates and prognosis of patients with anaphylactic shock in Denmark from 1995 through 2012.

BACKGROUND: Anaphylactic shock (AS) is an acute, potentially life-threatening hypersensitivity reaction. There are limited population-based data on changes in the hospitalization rate and prognosis of AS. OBJECTIVES: We sought to examine the proportion of patients with AS admitted to an intensive care unit (ICU), the prognosis of AS, and time trends in AS hospitalization rates in Denmark from 1995 through 2012. METHODS: We performed a population-based cohort study in Denmark from 1995 through 2012 (cumulative population, 7.1 million) using the Danish National Patient Registry and the Danish Civil Registration System. Outcomes included time trends in first-time AS hospitalization rates, percentage admitted to an ICU, and 30-day mortality overall and stratified by year. RESULTS: We included 6,707 patients with a first-time hospitalization for AS during 103,747,997 person-years of observation time. The average AS hospitalization rate was 64.6 (95% CI, 63.1-66.2) per 1,000,000 person-years. From 1995 to 2012, the annual AS hospitalization rate increased more than 2-fold (rate ratio, 2.6; 95% CI, 2.2-3.0). However, the annual hospitalization rate in children increased 10-fold (rate ratio, 10.75; 95% CI, 5.59-20.67). Only 0.7% of patients died within 30 days after admission (50 deaths), and most fatal AS cases occurred among patients aged 30 years or older. During the 2005-2012 period, 14.5% of patients hospitalized with AS were admitted to an ICU. CONCLUSION: The AS hospitalization rate increased from 1995 to 2012; however, the 30-day mortality was less than 1%.

Mortality in myasthenia gravis: A nationwide population-based follow-up study in Denmark.

INTRODUCTION: In previous studies of myasthenia gravis (MG), increased mortality has been reported. The aim of this study was to estimate mortality in patients with acetylcholine receptor antibody-positive (AChR-Ab-seropositive) MG in a nationwide population-based, long-term follow-up study. METHODS: All AChR-Ab-seropositive MG patients, diagnosed between 1985 and 2005, were identified. Defined by age at diagnosis (≤ 50 or >50 years), patients were classified as having early- or late-onset MG. For comparison, 10 non-MG individuals from the general population were matched with each patient. All patients and controls were followed until January 1, 2009. Mortality rates and estimated mortality rate ratios (MRRs) were calculated. RESULTS: Of 702 AChR-Ab-seropositive MG patients, 302 died during follow-up. Overall mortality was higher for patients with MG (MRR = 1.41, range 1.24-1.60). In late-onset women and men, the MRRs were 1.64 (1.36-1.99) and 1.22 (1.02-1.46), respectively. Total MRR was highest during the first 5 years after diagnosis. CONCLUSIONS: MG diagnosis is still associated with increased mortality.

Change in bone mineral density during adjuvant chemotherapy for early-stage breast cancer.

PURPOSE: Adjuvant chemotherapy has been associated with loss of bone mineral density (BMD) either as a direct effect or due to glucocorticoids used as supportive care medication. A prospective cohort study was conducted to evaluate changes in BMD from baseline to right after completion of chemotherapy, i.e., 4 months. METHODS: Dual-imaging X-ray absorptiometry (DXA) was performed at baseline and after completing anthracycline- and taxane-based chemotherapy to measure BMD in the spine, hip, and forearm in early-stage breast cancer patients. High-dose prednisolone was used at three weekly intervals to reduce nausea and vomiting. Patients were advised a daily calcium/vitamin D supplement. Linear regression was used to assess mean percentage change in BMD and 95 % confidence intervals (95 % CI) according to doses of prednisolone, menopausal status, smoking, and BMI. RESULTS: Eight patients were excluded: seven because of initiation of bisphosphonate treatment due to osteoporosis at baseline, and one had non-interpretable DXA. The final cohort included 97 patients with a mean age of 53 years (range 34-72). Mean cumulative prednisolone dose was 1308 mg (95 % CI 1255; 1362). BMD increased 1.36 % (95 % CI 0.7; 2.0, p < 0.001) in the spine and 1.27 % (95 % CI 0.9; 1.7, p < 0.001) in the hip. Forearm BMD did not change. Postmenopausal women had increases in spine BMD of 2.35 % (95 % CI 1.1; 3.6, p < 0.001) compared to premenopausal women. The spine BMD of current smokers decreased 1.67 % (95 % CI -3.3; -0.1, p = 0.04) compared to never/former smokers. CONCLUSIONS: Adjuvant chemotherapy supplemented with prednisolone was not associated with loss of BMD. Postmenopausal women gained bone mass, whereas current smokers lost bone mass.

Antibiotic use varies substantially among adults: a cross-national study from five European Countries in the ARITMO project.

PURPOSE: To examine patterns of outpatient and community antibiotic use among adults in five European countries. METHODS: We used healthcare data of 28.8 million adults from six population-based ARITMO project databases to ascertain information on systemic antibiotic use in Denmark (2000-2008), the Netherlands (1999-2010), Italy (2000-2010), the UK (1996-2009), and Germany (2004-2008). We estimated overall, and age-group and sex specific antibiotic use as defined daily doses (DDD) per 1000 inhabitants per day. We computed annual age- and sex-standardized population prevalence of antibiotic use per 1000 persons-years (p-y) and the mean duration (in days) of antibiotic use. RESULTS: The overall antibiotic use varied from 8.7 DDD per 1000 inhabitants per day in the UK to 18.1 DDD in Denmark, representing a 2.1-fold geographical variation. In all countries, prescribing was relatively high among individuals aged 15-19 years; lower in those aged 20-50 years; and then increased steadily reaching 41.8 DDD per 1000 inhabitants per day in individuals ≥ 85 years in Denmark. After age- and sex-standardization, prevalence of antibiotic use varied threefold from 160.2/1000 p-y in the UK to 421.1/1000 p-y in Italy. The ratio of broad- to narrow-spectrum penicillin, cephalosporin, and macrolide use varied from 0.6 in Denmark to 120.2 in Italy. Women used more antibiotics than men did in all countries. Across countries, the mean duration of antibiotic use varied 1.3 to 21.1-fold for different antibiotics. CONCLUSIONS: Antibiotic use is high in women and the elderly. Prescribing patterns vary substantially across European countries, both according to overall consumption, user prevalence, duration, and narrow- versus broad-spectrum antibiotics.

The association of neighborhood socioeconomic characteristics with cardiovascular health: A quasi-experimental study of refugees to Denmark.

Neighborhood socioeconomic disadvantage is associated with cardiovascular health, although it is unclear which specific aspects of neighborhoods matter most. We leveraged a natural experiment in which refugees to Denmark were quasi-randomly assigned to neighborhoods across the country during 1986-1998, creating variation in exposure to various aspects of neighborhood disadvantage. The cohort was followed through December 2018. Exposures included neighborhood-level family income, educational attainment, unemployment, and welfare transfers measured in the first neighborhood after arrival to Denmark. Outcomes included cardiovascular risk factors (hyperlipidemia, hypertension, diabetes and anxiety/depression) and cardiovascular disease (acute myocardial infarction and ischemic heart disease). Neighborhood-level income and education were most consistently associated with cardiovascular risk factors, whereas welfare transfers were most consistently associated with cardiovascular disease. Addressing these specific aspects of neighborhood disadvantage could therefore lower the risk of poor cardiovascular health among refugees. Future research is warranted to examine if results are generalizable to other immigrant groups, countries or time periods.

Neighborhood disadvantage and the risk of dementia and mortality among refugees to Denmark: A quasi-experimental study.

Objectives: Neighborhood disadvantage may increase the risk of adverse health outcomes among older refugees. Yet few studies rigorously estimate the effects of place-based factors on later-life health, particularly dementia and mortality. Evidence about refugees is especially sparse. Methods: This study leveraged a natural experiment in the form of a Danish policy (1986-1998) that dispersed refugees quasi-randomly across neighborhoods upon arrival. We used longitudinal registers allowing 30 years of follow-up among refugees aged 40+ years upon arrival in Denmark (N = 9,854). Cox models assessed the association between neighborhood disadvantage and risk of dementia and mortality. We examined heterogeneous effects by sex, age, and family size. We also examined associations among non-refugee immigrants and native-born Danes. Results: Neighborhood disadvantage was not associated with dementia in any group. One unit increase in neighborhood disadvantage index (ranges -8 to 5.7) was associated with greater mortality risk among non-refugee immigrants (HR 1.06, 95%CI: 1.02, 1.10) and native-born Danes (HR 1.11, 95%CI: 1.06, 1.17). In contrast, neighborhood disadvantage was associated with lower mortality risk among refugees (HR 0.96, 95%CI: 0.93, 0.99). Neighborhood disadvantage remained negatively associated with mortality risk in subgroups: refugees who are female (on moderate-disadvantage compared to low-disadvantage), aged 60+, and who arrived with families. Discussion: While neighborhood disadvantage was associated with lower mortality risk among refugees, it was associated with greater mortality risk among non-refugee immigrants and native-born Danes, perhaps due to confounding in the latter groups or different place-based experiences by immigration status. Future research is warranted to explain the reasons for contrasting findings.

Risk of Psychiatric Disorders Among Refugee Children and Adolescents Living in Disadvantaged Neighborhoods.

Importance: Refugee children and adolescents are at increased risk of mental health difficulties, but little is known about how the characteristics of the neighborhood in which they resettle may affect vulnerability and resilience. Objective: To test whether neighborhood socioeconomic disadvantage is associated with risk of psychiatric disorders among refugee children and adolescents and examine whether the association differs by sex, age at arrival, and family structure. Design, Setting, and Participants: This quasi-experimental register-based cohort study included refugees in Denmark aged 0 to 16 years at the time of resettlement from 1986 to 1998. A refugee dispersal policy implemented during those years assigned housing to refugee families in neighborhoods with varying degrees of socioeconomic disadvantage in a quasi-random (ie, arbitrary) manner conditional on refugee characteristics observed by placement officers. Cox proportional hazard models were used to examine the association between neighborhood disadvantage and risk of psychiatric disorders, adjusting for relevant baseline covariates. Exposures: A neighborhood disadvantage index combining information on levels of income, education, unemployment, and welfare assistance in the refugees' initial quasi-randomly assigned neighborhood. Main Outcomes and Measures: First-time inpatient or outpatient diagnosis of a psychiatric disorder before age 30 years. Results: Median (IQR) baseline age in the sample of 18 709 refugee children and adolescents was 7.9 (4.7-11.7) years; 8781 participants (46.9%) were female and 9928 (53.1%) were male. During a median (IQR) follow-up period of 16.1 (10.2-20.8) years, 1448 refugees (7.7%) were diagnosed with a psychiatric disorder (incidence rate, 51.2 per 10 000 person-years). An increase of 1 SD in neighborhood disadvantage was associated with an 11% increase in the hazard of a psychiatric disorders (hazard ratio [HR], 1.11; 95% CI, 1.03-1.21). This association did not differ between male and female individuals, refugees who arrived at different ages, or those from single- vs dual-parent households. In secondary analyses using prescribed psychiatric medication as the outcome, a similar association with neighborhood disadvantage was found (HR, 1.08; 95% CI, 1.03-1.14). Conclusions and Relevance: In this cohort study, neighborhood disadvantage was associated with an increase in risk of psychiatric disorders. The results suggest that placement of refugee families in advantaged neighborhoods and efforts to enhance the neighborhood context in disadvantaged areas may improve mental health among refugee children and adolescents.

Early-Life Exposure to Antibiotics and Risk for Crohn's Disease: A Nationwide Danish Birth Cohort Study.

BACKGROUND: Early-life antibiotic use can alter the intestinal flora and modify the risk of developing Crohn disease (CD), but rigorous epidemiological evidence is limited, with inconsistent results. METHODS: We identified all children born in Denmark from 1995 to 2009 and followed them from birth until death, emigration, a diagnosis of CD, or January 1, 2013. Using Cox regression, we assessed the association between antibiotic exposure in the first year of life and subsequent risk for CD, adjusting for sex, degree of urbanization, birth order, birth year, route of delivery, gestational age, smoking during pregnancy, intake of nonsteroidal anti-inflammatory drugs in the first year of life, and family history of CD. RESULTS: During a median 9.5 years (9.3 million total person-years), CD was diagnosed in 208 of 979,039 children. Antibiotic use in the first year of life was associated with a higher risk of CD (adjusted hazard ratio, 1.4; 95% confidence interval [CI], 1.1-1.8), with the highest risk with ≥6 courses of antibiotics (adjusted hazard ratio, 4.1; 95% CI, 2.0-8.5). A family history of CD did not modify these risk associations. The cumulative risk of CD at the 11th birthday for children exposed to antibiotics in their first year of life was 0.16‰ (95% CI, 0.11‰-0.22‰) compared to 0.11‰ (95% CI, 0.08‰-0.15‰) for children unexposed to antibiotics in their first year of life. CONCLUSIONS: Antibiotic use in the first year of life is associated with a modestly increased risk for CD, although the absolute risk is very low.

Long-term statin use and the risk of gallstone disease: A population-based case-control study.

Most gallstones originate from cholesterol-supersaturated bile. Statins inhibit hepatic cholesterol biosynthesis and therefore may reduce the risk of gallstone disease. Population-based evidence, however, is sparse. Thus, the authors conducted a population-based case-control study using medical databases from northern Denmark (1.7 million inhabitants) to identify 32,494 cases of gallstones occurring between 1996 and 2008 and to identify age-, sex-, and county-matched population controls for each case. Cases and their matched controls who were exposed to lipid-lowering drugs were categorized as current users if their last prescription was redeemed ≤90 days before the case's diagnosis date; otherwise, they were categorized as former users. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals for gallstone disease in patients treated with lipid-lowering drugs. In current users, the adjusted odds ratios associating statin use with the occurrence of gallstone disease were 1.17 (95% confidence interval (CI): 1.06, 1.30) for those who had 1-4 prescriptions, 0.89 (95% CI: 0.80, 0.97) for those who had 5-19 prescriptions, and 0.76 (95% CI: 0.69, 0.84) for those who had ≥20 total prescriptions. In former users, the corresponding adjusted odds ratios were 1.24 (95% CI: 1.11, 1.39), 0.97 (95% CI: 0.86, 1.10), and 0.79 (95% CI: 0.64, 0.97), respectively. The use of other lipid-lowering drugs showed no similar association.