Casey Crump

Comorbidities and Mortality in Persons With Schizophrenia: A Swedish National Cohort Study

OBJECTIVE Schizophrenia is associated with premature mortality, but the specific causes and pathways are unclear. The authors used outpatient and inpatient data for a national population to examine the association between schizophrenia and mortality and comorbidities. METHOD This was a national cohort study of 6,097,834 Swedish adults, including 8,277 with schizophrenia, followed for 7 years (2003-2009) for mortality and comorbidities diagnosed in any outpatient or inpatient setting nationwide. RESULTS On average, men with schizophrenia died 15 years earlier, and women 12 years earlier, than the rest of the population, and this was not accounted for by unnatural deaths. The leading causes were ischemic heart disease and cancer. Despite having twice as many health care system contacts, schizophrenia patients had no increased risk of nonfatal ischemic heart disease or cancer diagnoses, but they had an elevated mortality from ischemic heart disease (adjusted hazard ratio for women, 3.33 [95% CI=2.73-4.05]; for men, 2.20 [95% CI=1.83-2.65]) and cancer (adjusted hazard ratio for women, 1.71 [95% CI=1.38-2.10; for men, 1.44 [95% CI=1.15-1.80]). Among all people who died from ischemic heart disease or cancer, schizophrenia patients were less likely than others to have been diagnosed previously with these conditions (for ischemic heart disease, 26.3% compared with 43.7%; for cancer, 73.9% compared with 82.3%). The association between schizophrenia and mortality was stronger among women and the employed. Lack of antipsychotic treatment was also associated with elevated mortality. CONCLUSIONS Schizophrenia patients had markedly premature mortality, and the leading causes were ischemic heart disease and cancer, which appeared to be underdiagnosed. Preventive interventions should prioritize primary health care tailored to this population, including more effective risk modification and screening for cardiovascular disease and cancer.

Comorbidities and Mortality in Bipolar Disorder: A Swedish National Cohort Study

IMPORTANCE Bipolar disorder is associated with premature mortality, but the specific causes and underlying pathways are unclear. OBJECTIVE To examine the physical health effects of bipolar disorder using outpatient and inpatient data for a national population. DESIGN, SETTING, AND PARTICIPANTS National cohort study of 6,587,036 Swedish adults, including 6618 with bipolar disorder. MAIN OUTCOMES AND MEASURES Physical comorbidities diagnosed in any outpatient or inpatient setting nationwide and mortality (January 1, 2003, through December 31, 2009). RESULTS Women and men with bipolar disorder died 9.0 and 8.5 years earlier on average than the rest of the population, respectively. All-cause mortality was increased 2-fold among women (adjusted hazard ratio [aHR], 2.34; 95% CI, 2.16-2.53) and men (aHR, 2.03; 95% CI, 1.85-2.23) with bipolar disorder, compared with the rest of the population. Patients with bipolar disorder had increased mortality from cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional injuries, and suicide for both women and men and cancer for women only. Suicide risk was 10-fold among women (aHR, 10.37; 95% CI, 7.36-14.60) and 8-fold among men (aHR, 8.09; 95% CI, 5.98-10.95) with bipolar disorder, compared with the rest of the population. Substance use disorders contributed only modestly to these findings. The association between bipolar disorder and mortality from chronic diseases (ischemic heart disease, diabetes, COPD, or cancer) was weaker among persons with a prior diagnosis of these conditions (aHR, 1.40; 95% CI, 1.26-1.56) than among those without a prior diagnosis (aHR, 2.38; 95% CI, 1.95-2.90; P(interaction) = .01). CONCLUSIONS AND RELEVANCE In this large national cohort study, patients with bipolar disorder died prematurely from multiple causes, including cardiovascular disease, diabetes, COPD, influenza or pneumonia, unintentional injuries, and suicide. However, chronic disease mortality among those with more timely medical diagnosis approached that of the general population, suggesting that better provision of primary medical care may effectively reduce premature mortality among persons with bipolar disorder.

Gestational Age at Birth and Mortality in Young Adulthood

CONTEXT Preterm birth is the leading cause of infant mortality in developed countries, but the association between gestational age at birth and mortality in adulthood remains unknown. OBJECTIVE To examine the association between gestational age at birth and mortality in young adulthood. DESIGN, SETTING, AND PARTICIPANTS National cohort study of 674,820 individuals born as singletons in Sweden in 1973 through 1979 who survived to age 1 year, including 27,979 born preterm (gestational age <37 weeks), followed up to 2008 (ages 29-36 years). MAIN OUTCOME MEASURES All-cause and cause-specific mortality. RESULTS A total of 7095 deaths occurred in 20.8 million person-years of follow-up. Among individuals still alive at the beginning of each age range, a strong inverse association was found between gestational age at birth and mortality in early childhood (ages 1-5 years: adjusted hazard ratio [aHR] for each additional week of gestation, 0.92; 95% CI, 0.89-0.94; P < .001), which disappeared in late childhood (ages 6-12 years: aHR, 0.99; 95% CI, 0.95-1.03; P = .61) and adolescence (ages 13-17 years: aHR, 0.99; 95% CI, 0.95-1.03; P = .64) and then reappeared in young adulthood (ages 18-36 years: aHR, 0.96; 95% CI, 0.94-0.97; P < .001). In young adulthood, mortality rates (per 1000 person-years) by gestational age at birth were 0.94 for 22 to 27 weeks, 0.86 for 28 to 33 weeks, 0.65 for 34 to 36 weeks, 0.46 for 37 to 42 weeks (full-term), and 0.54 for 43 or more weeks. Preterm birth was associated with increased mortality in young adulthood even among individuals born late preterm (34-36 weeks, aHR, 1.31; 95% CI, 1.13-1.50; P < .001), relative to those born full-term. In young adulthood, gestational age at birth had the strongest inverse association with mortality from congenital anomalies and respiratory, endocrine, and cardiovascular disorders and was not associated with mortality from neurological disorders, cancer, or injury. CONCLUSION After excluding earlier deaths, low gestational age at birth was independently associated with increased mortality in early childhood and young adulthood.

Sociodemographic, psychiatric and somatic risk factors for suicide: a Swedish national cohort study.

BACKGROUND More effective prevention of suicide requires a comprehensive understanding of sociodemographic, psychiatric and somatic risk factors. Previous studies have been limited by incomplete ascertainment of these factors. We conducted the first study of this issue using sociodemographic and out-patient and in-patient health data for a national population. METHOD We used data from a national cohort study of 7,140,589 Swedish adults followed for 8 years for suicide mortality (2001-2008). Sociodemographic factors were identified from national census data, and psychiatric and somatic disorders were identified from all out-patient and in-patient diagnoses nationwide. RESULTS There were 8721 (0.12%) deaths from suicide during 2001-2008. All psychiatric disorders were strong risk factors for suicide among both women and men. Depression was the strongest risk factor, with a greater than 15-fold risk among women or men and even higher risks (up to 32-fold) within the first 3 months of diagnosis. Chronic obstructive pulmonary disease (COPD), cancer, spine disorders, asthma and stroke were significant risk factors among both women and men (1.4-2.1-fold risks) whereas diabetes and ischemic heart disease were modest risk factors only among men (1.2-1.4-fold risks). Sociodemographic risk factors included male sex, unmarried status or non-employment; and low education or income among men. CONCLUSIONS All psychiatric disorders, COPD, cancer, spine disorders, asthma, stroke, diabetes, ischemic heart disease and specific sociodemographic factors were independent risk factors for suicide during 8 years of follow-up. Effective prevention of suicide requires a multifaceted approach in both psychiatric and primary care settings, targeting mental disorders (especially depression), specific somatic disorders and indicators of social support.

Risk of Hypertension Among Young Adults Who Were Born Preterm: A Swedish National Study of 636,000 Births

Previous studies have reported an association between preterm birth and elevated blood pressure in adolescence and young adulthood. These studies were based on single-day blood pressure measurements and had limited ability to estimate risk of hypertension measured over a longer period and across the full range of gestational ages. The authors conducted a national cohort study of all infants born in Sweden from 1973 through 1979 (n = 636,552), including 28,220 born preterm (<37 weeks), followed to ages 25.5-37.0 years to determine whether individuals born preterm were more likely to be prescribed antihypertensive medications in 2005-2009 than those born full term. Antihypertensive medication data were obtained from all outpatient and inpatient pharmacies throughout Sweden. Young adults who were born preterm had an increased relative rate of antihypertensive medication prescription that increased monotonically by earlier gestational age and that was independent of fetal growth. The adjusted odds ratio for ≥1 antihypertensive medications/year ranged from 1.25 (95% confidence interval: 1.12, 1.39) for those born near term (35-36 weeks) to 2.51 (95% confidence interval: 1.11, 5.68) for those born extremely preterm (23-27 weeks) relative to those born full term. These findings suggest that preterm birth is strongly associated with hypertension in young adulthood, including an increased risk among those born near term.

Risk of Diabetes Among Young Adults Born Preterm in Sweden

OBJECTIVE Previous studies have suggested that preterm birth is associated with diabetes later in life. These studies have shown inconsistent results for late preterm births and have had various limitations, including the inability to evaluate diabetic outpatients or to estimate risk across the full range of gestational ages. Our objective was to determine whether preterm birth is associated with diabetes medication prescription in a national cohort of young adults. RESEARCH DESIGN AND METHODS This was a national cohort study of 630,090 infants born in Sweden from 1973 through 1979 (including 27,953 born preterm, gestational age <37 weeks), followed for diabetes medication prescription in 2005–2009 (ages 25.5–37.0 years). Medication data were obtained from all outpatient and inpatient pharmacies throughout Sweden. RESULTS Individuals born preterm, including those born late preterm (gestational age 35–36 weeks), had modestly increased odds ratios (ORs) for diabetes medication prescription relative to those born full term, after adjusting for fetal growth and other potential confounders. Insulin and/or oral diabetes medications were prescribed to 1.5% of individuals born preterm compared with 1.2% of those born full term (adjusted OR 1.13 [95% CI 1.02–1.26]). Insulin without oral diabetes medications was prescribed to 1.0% of individuals born preterm compared with 0.8% of those born full term (1.22 [1.08–1.39]). CONCLUSIONS Preterm birth, including late preterm birth, is associated with a modestly increased risk of diabetes in young Swedish adults. These findings have important public health implications given the increasing number of preterm births and the large disease burden of diabetes, particularly when diagnosed in young adulthood.

Preterm birth and psychiatric medication prescription in young adulthood: a Swedish national cohort study

BACKGROUND Recent studies suggest an increased risk of adverse mental health outcomes among young adults who were born preterm. These studies have been based mainly on hospital data, thus missing large numbers of mental health problems that do not require inpatient treatment. We used national outpatient and inpatient pharmacy data to evaluate whether individuals who were born preterm were more likely to be prescribed psychiatric medications during young adulthood than individuals who were born full term. METHODS A national cohort of all infants born in Sweden from 1973 through 1979 [N = 635,933, including 28,799 who were born preterm (<37 weeks)] was followed to ages 25.5-34.0 years to determine whether psychotropic medications (antidepressants, antipsychotics, anxiolytics, hypnotics/sedatives and/or psychostimulants) were prescribed in 2005-06. RESULTS A trend of increasing rate of prescriptions for antipsychotics, antidepressants and hypnotics/sedatives in young adulthood was observed by earlier gestational age at birth. Young adults who were extremely preterm at birth (23-27 weeks) were 3.1 times more likely to be prescribed antipsychotics [95% confidence interval (CI) 1.66-5.93], 1.8 times more likely to be prescribed antidepressants (95% CI 1.26-2.64) and 1.8 times more likely to be prescribed hypnotics/sedatives (95% CI 1.15-2.96) than individuals who were full term at birth, after adjusting for potential confounders. CONCLUSIONS This national cohort study, using outpatient and inpatient pharmacy data, suggests that preterm birth has important independent effects on mental health that extend at least into young adulthood.

Neighborhood Deprivation and Psychiatric Medication Prescription: A Swedish National Multilevel Study

PURPOSE Previous studies of neighborhood deprivation and mental disorders have yielded mixed results, possibly because they were based on different substrata of the population. We conducted a national multilevel study to determine whether neighborhood deprivation is independently associated with psychiatric medication prescription in a national population. METHODS Nationwide outpatient and inpatient psychiatric medication data were analyzed for all Swedish adults (N = 6,998,075) after 2.5 years of follow-up. Multilevel logistic regression was used to estimate the association between neighborhood deprivation (index of education, income, unemployment, and welfare assistance) and prescription of psychiatric medications (antipsychotics, antidepressants, anxiolytics, or hypnotics/sedatives), after adjusting for broadly measured individual-level sociodemographic characteristics. RESULTS For each psychiatric medication class, a monotonic trend of increasing prescription was observed by increasing level of neighborhood deprivation. The strongest associations were found for antipsychotics and anxiolytics, with adjusted odds ratios of 1.40 (95% confidence interval [CI], 1.36-1.44) and 1.24 (95% CI, 1.22-1.27), respectively, comparing the highest- to the lowest-deprivation neighborhood quintiles. CONCLUSIONS These findings suggest that neighborhood deprivation is associated with psychiatric medication prescription independent of individual-level sociodemographic characteristics. Further research is needed to elucidate the mechanisms by which neighborhood deprivation may affect mental health and to identify the most susceptible groups in the population.

Early-term Birth (37-38 Weeks) and Mortality in Young Adulthood.

Background: Early-term birth (gestational age, 37–38 weeks) has been associated with increased infant mortality relative to later-term birth, but mortality beyond infancy has not been studied. We examined the association between early-term birth and mortality through young adulthood. Methods: We conducted a national cohort study of 679,981 singleton births in Sweden in 1973–1979, followed up for all-cause and cause-specific mortality through 2008 (ages 29–36 years). Results: There were 10,656 deaths in 21.5 million person-years of follow-up. Among those still alive at the beginning of each age range, early-term birth relative to those born at 39–42 weeks was associated with increased mortality in the neonatal period (0–27 days: adjusted hazard ratio = 2.18 [95% confidence interval = 1.89–2.51]), postneonatal period (28–364 days: 1.66 [1.44–1.92]), early childhood (1–5 years: 1.29 [1.10–1.51]), and young adulthood (18–36 years: 1.14 [1.05–1.24]), but not in late childhood/adolescence (6–17 years: 0.97 [0.84–1.12]). In young adulthood, early-term birth was strongly associated with death from congenital anomalies and endocrine disorders, especially diabetes (2.89 [1.54–5.43]). Conclusions: In this large national cohort study, early-term birth was independently associated with increased mortality in infancy, early childhood, and young adulthood. Lowest short-term and long-term mortality was among those born at 39–42 weeks.

Associations of CYP2A6 genotype with smoking behaviors in southern China

AIMS To investigate the association of CYP2A6 genetic polymorphisms with smoking-related phenotypes in Chinese smokers. DESIGN Case-only genetic association study. SETTING Southern China. PARTICIPANTS A total of 1328 Han Chinese smokers who participated in a community-based chronic disease screening project in Guangzhou and Zhuhai from 2006 to 2007. MEASUREMENTS All participants answered a structured questionnaire about socio-demographic status and smoking behaviors and informative alleles were genotyped for the cytochrome P450 2A6 (CYP2A6) gene (CYP2A6*4,*5,*7,*9 and *10). FINDINGS The frequencies of CYP2A6*4, *5, *7, *9 and *10 alleles were 8.5, 1.2, 6.3, 13.5 and 2.4%, which corresponded to 48.9, 15.4, 24.2 and 11.5% of participants being classified as normal, intermediate, slow and poor metabolizers, respectively. Multivariate analyses in male smokers demonstrated that compared with normal metabolizers, poor metabolizers reported smoking fewer cigarettes per day [adjusted odds ratio (OR) = 0.49; 95% confidence interval (CI): 0.32-0.76], started smoking regularly later in life (adjusted OR = 1.55; 95% CI: 1.06-2.26) and, among former smokers, reported smoking for a shorter duration prior to quitting (adjusted OR = 0.33; 95% CI: 0.12-0.94). However, poor metabolizers were less likely to quit smoking and remain abstinent than normal metabolizers (adjusted OR = 0.54; 95% CI: 0.34-0.86). CONCLUSIONS Reduced metabolism function of cytochrome P450 2A6 in smokers appears to be associated with fewer cigarettes smoked, later initiation of smoking regularly, shorter smoking duration and lower likelihood of smoking cessation.