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1.  Depression and risk of hospitalisations and rehospitalisations for ambulatory care-sensitive conditions in Denmark: a population-based cohort study 
BMJ Open  2015;5(12):e009878.
Objective
Hospitalisations for ambulatory care-sensitive conditions (ACSCs), a group of chronic and acute illnesses considered not to require inpatient treatment if timely and appropriate ambulatory care is received, and early rehospitalisations are common and costly. We sought to determine whether individuals with depression are at increased risk of hospitalisations for ACSCs, and rehospitalisation for the same or another ACSC, within 30 days.
Design
National, population-based cohort study.
Setting
Denmark.
Participants
5 049 353 individuals ≥18 years of age between 1 January 2005 and 31 December 2013.
Measurements
Depression was ascertained via psychiatrist diagnoses in the Danish Psychiatric Central Register or antidepressant prescription redemption from the Danish National Prescription Registry. Hospitalisations for ACSCs and rehospitalisations within 30 days were identified using the Danish National Patient Register.
Results
Overall, individuals with depression were 2.35 times more likely to be hospitalised for an ACSC (95% CI 2.32 to 2.37) versus those without depression after adjusting for age, sex and calendar period, and 1.45 times more likely after adjusting for socioeconomic factors, comorbidities and primary care utilisation (95% CI 1.43 to 1.46). After adjusting for ACSC-predisposing comorbidity, depression was associated with significantly greater risk of hospitalisations for all chronic (eg, angina, diabetes complications, congestive heart failure exacerbation) and acute ACSCs (eg, pneumonia) compared to those without depression. Compared to those without depression, persons with depression were 1.21 times more likely to be rehospitalised within 30 days for the same ACSC (95% CI 1.18 to 1.24) and 1.19 times more likely to be rehospitalised within 30 days for a different ACSC (95% CI 1.15 to 1.23).
Conclusions
Individuals with depression are at increased risk of hospitalisations for ACSCs, and once discharged are at elevated risk of rehospitalisations within 30 days for ACSCs.
doi:10.1136/bmjopen-2015-009878
PMCID: PMC4679902  PMID: 26634401
PRIMARY CARE
2.  Apgar-score in children prenatally exposed to antiepileptic drugs: a population-based cohort study 
BMJ Open  2015;5(9):e007425.
Objectives
It is unknown if prenatal exposure to antiepileptic drugs (AEDs) increases the risk of low Apgar score in offspring.
Setting
Population-based study using health registers in Denmark.
Participants
We identified all 677 021 singletons born in Denmark from 1997 to 2008 and linked the Apgar score from the Medical Birth Register with information on the women's prescriptions for AEDs during pregnancy from the Danish Register of Medicinal Product Statistics. We used the Danish National Hospital Registry to identify mothers diagnosed with epilepsy before birth of the child. Results were adjusted for smoking and maternal age.
Results
Among 2906 children exposed to AEDs, 55 (1.9%) were born with an Apgar score ≤7 as compared with 8797 (1.3%) children among 674 115 pregnancies unexposed to AEDs (adjusted relative risk (aRR)=1.41 (95% CI 1.07 to 1.85). When analyses were restricted to the 2215 children born of mothers with epilepsy, the aRR of having a low Apgar score associated with AED exposure was 1.34 (95% CI 0.90 to 2.01) When assessing individual AEDs, we found increased, unadjusted RR for exposure to carbamazepine (RR=1.86 (95% CI 1.01 to 3.42)), valproic acid (RR=1.85 (95% CI 1.04 to 3.30)) and topiramate (RR=2.97 (95% CI 1.26 to 7.01)) when compared to unexposed children.
Conclusions
Prenatal exposure to AEDs was associated with increased risk of being born with a low Apgar score, but the absolute risk of a low Apgar score was <2%. Risk associated with individual AEDs indicate that the increased risk is not a class effect, but that there may be particularly high risks of a low Apgar score associated with certain AEDs.
doi:10.1136/bmjopen-2014-007425
PMCID: PMC4567672  PMID: 26359281
EPIDEMIOLOGY; PERINATOLOGY
3.  Psychiatric disorders following fetal death: a population-based cohort study 
BMJ Open  2014;4(6):e005187.
Objectives
Women have increased risks of severe mental disorders after childbirth and death of a child, but it remains unclear whether this association also applies to fetal loss and, if so, to which extent. We studied the risk of any inpatient or outpatient psychiatric treatment during the time period from 12 months before to 12 months after fetal death.
Design
Cohort study using Danish population-based registers.
Setting
Denmark.
Participants
A total of 1 112 831 women born in Denmark from 1960 to 1995 were included. In total, 87 687cases of fetal death (International Classification of Disease-10 codes for spontaneous abortion or stillbirth) were recorded between 1996 and 2010.
Primary and secondary outcome measures
The main outcome measures were incidence rate ratios (risk of first psychiatric inpatient or outpatient treatment).
Results
A total of 1379 women had at least one psychiatric episode during follow-up from the year before fetal death to the year after. Within the first few months after the loss, women had an increased risk of psychiatric contact, IRR: 1.51 (95% CI 1.15 to 1.99). In comparison, no increased risk of psychiatric contact was found for the period before fetal death. The risk of experiencing a psychiatric episode was highest for women with a loss occurring after 20 weeks of gestation (12 month probability: 1.95%, 95% CI 1.50 to 2.39).
Conclusions
Fetal death was associated with a transient increased risk of experiencing a first-time episode of a psychiatric disorder, primarily adjustment disorders. The risk of psychiatric episodes tended to increase with increasing gestational age at the time of the loss.
doi:10.1136/bmjopen-2014-005187
PMCID: PMC4054628  PMID: 24907247
Epidemiology; Obstetrics; Psychiatry
4.  Mental health status and risk of new cardiovascular events or death in patients with myocardial infarction: a population-based cohort study 
BMJ Open  2013;3(8):e003045.
Objective
To examine the association between mental health status after first-time myocardial infarction (MI) and new cardiovascular events or death, taking into account depression and anxiety as well as clinical, sociodemographic and behavioural risk factors.
Design
Population-based cohort study based on questionnaires and nationwide registries. Mental health status was assessed 3 months after MI using the Mental Component Summary score from the Short-Form 12 V.2.
Setting
Central Denmark Region.
Participants
All patients hospitalised with first-time MI from 1 January 2009 through 31 December 2009 (n=880). The participants were categorised in quartiles according to the level of mental health status (first quartile=lowest mental health status).
Main outcome measures
Composite endpoint of new cardiovascular events (MI, heart failure, stroke/transient ischaemic attack) and all-cause mortality.
Results
During 1940 person-years of follow-up, 277 persons experienced a new cardiovascular event or died. The cumulative incidence following 3 years after MI increased consistently with decreasing mental health status and was 15% (95% CI 10.8% to 20.5%) for persons in the fourth quartile, 29.1% (23.5% to 35.6%) in the third quartile, 37.0% (30.9% to 43.9%) in the second quartile, and 47.5% (40.9% to 54.5%) in the first quartile. The HRs were high, even after adjustments for age, sociodemographic characteristics, cardiac disease severity, comorbidity, secondary prophylactic medication, smoking status, physical activity, depression and anxiety (HR3rd quartile 1.90 (95% CI 1.23 to 2.93), HR2nd quartile 2.14 (1.37 to 3.33), HR1st quartile 2.23 (1.35 to 3.68) when using the fourth quartile as reference).
Conclusions
Low mental health status following first-time MI was independently associated with an increased risk of new cardiovascular events or death. Further research is needed to disentangle the pathways that link mental health status following MI to prognosis and to identify interventions that can improve mental health status and prognosis.
doi:10.1136/bmjopen-2013-003045
PMCID: PMC3733312  PMID: 23913773
Cardiology; Myocardial Infarction < Cardiology; Mental Health; Epidemiology
5.  The 5-minute Apgar score as a predictor of childhood cancer: a population-based cohort study in five million children 
BMJ Open  2012;2(4):e001095.
Objective
The aetiology of childhood cancer remains largely unknown but recent research indicates that uterine environment plays an important role. We aimed to examine the association between the Apgar score at 5 min after birth and the risk of childhood cancer.
Design
Nationwide population-based cohort study.
Setting
Nationwide register data in Denmark and Sweden.
Study population
All live-born singletons born in Denmark from 1978 to 2006 (N=1 771 615) and in Sweden from 1973 to 2006 (N=3 319 573). Children were followed up from birth to 14 years of age.
Main outcome measures
Rates and HRs for all childhood cancers and for specific childhood cancers.
Results
A total of 8087 children received a cancer diagnosis (1.6 per 1000). Compared to children with a 5-min Apgar score of 9–10, children with a score of 0–5 had a 46% higher risk of cancer (adjusted HR 1.46, 95% CI 1.15 to 1.89). The potential effect of low Apgar score on overall cancer risk was mostly confined to children diagnosed before 6 months of age. Children with an Apgar score of 0–5 had higher risks for several specific childhood cancers including Wilms’ tumour (HR 4.33, 95% CI 2.42 to 7.73).
Conclusions
A low 5 min Apgar score was associated with a higher risk of childhood cancers diagnosed shortly after birth. Our data suggest that environmental factors operating before or during delivery may play a role on the development of several specific childhood cancers.
doi:10.1136/bmjopen-2012-001095
PMCID: PMC3425910  PMID: 22874628
Oncology; Epidemiology; Paediatric oncology; Preventive Medicine

Results 1-5 (5)