Jonas Hällgren

Excess mortality, causes of death and life expectancy in 270,770 patients with recent onset of mental disorders in Denmark, Finland and Sweden.

Background Excess mortality among patients with severe mental disorders has not previously been investigated in detail in large complete national populations. Objective To investigate the excess mortality in different diagnostic categories due to suicide and other external causes of death, and due to specific causes in connection with diseases and medical conditions. Methods In longitudinal national psychiatric case registers from Denmark, Finland, and Sweden, a cohort of 270,770 recent-onset patients, who at least once during the period 2000 to 2006 were admitted due to a psychiatric disorder, were followed until death or the end of 2006. They were followed for 912,279 person years, and 28,088 deaths were analyzed. Life expectancy and standardized cause-specific mortality rates were estimated in each diagnostic group in all three countries. Results The life expectancy was generally approximately 15 years shorter for women and 20 years shorter for men, compared to the general population. Mortality due to diseases and medical conditions was increased two- to three-fold, while excess mortality from external causes ranged from three- to 77-fold. Mortality due to diseases and medical conditions was generally lowest in patients with affective disorders and highest in patients with substance abuse and personality disorders, while mortality due to suicide was highest in patients with affective disorders and personality disorders, and mortality due to other external causes was highest in patients with substance abuse. Conclusions These alarming figures call for action in order to prevent the high mortality.

The incidence of narcolepsy in Europe: Before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns

BACKGROUND In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification. METHODS We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000-2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom. RESULTS Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90-0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women>men) and around 60 years of age. In the age group 5-19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1-3.1) in Denmark, 6.4 (95% CI: 4.2-9.7) in Finland and 7.5 (95% CI: 5.2-10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time. CONCLUSIONS The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.

Life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in the Nordic countries.

Objective Excess mortality from diseases and medical conditions (natural death) in persons with psychiatric disorders has been extensively reported. Even in the Nordic countries with well-developed welfare systems, register based studies find evidence of an excess mortality. In recent years, cardiac mortality and death by diseases of the circulatory system has seen a decline in all the Nordic countries, but a recent paper indicates that women and men in Denmark, Finland, and Sweden, who had been hospitalised for a psychotic disorder, had a two to three-fold increased risk of dying from a cardiovascular disease. The aim of this study was to compare the mortality by diseases of the circulatory system among patients with bipolar disorder or schizophrenia in the three Nordic countries Denmark, Sweden, and Finland. Furthermore, the aim was to examine and compare life expectancy among these patients. Cause specific Standardized Mortality Rates (SMRs) were calculated for each specific subgroup of mortality. Life expectancy was calculated using Wiesler’s method. Results The SMR for bipolar disorder for diseases of the circulatory system was approximately 2 in all countries and both sexes. SMR was slightly higher for people with schizophrenia for both genders and in all countries, except for men in Denmark. Overall life expectancy was much lower among persons with bipolar disorder or schizophrenia, with life expectancy being from 11 to 20 years shorter. Conclusion Our data show that persons in the Nordic countries with schizophrenia or bipolar disorder have a substantially reduced life expectancy. An evaluation of the reasons for these increased mortality rates should be prioritized when planning healthcare in the coming years.

Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden

Objective To estimate the cardiovascular mortality among persons with bipolar disorder in Sweden compared to the general population. Design Population register-based cohort study with a 20-year follow-up. Setting Sweden. Participants The entire population of Sweden (n=10.6 million) of whom 17 101 persons were diagnosed with bipolar disorder between 1987 and 2006. Main outcome measures Mortality rate ratios (MRR), excess mortality (excess deaths), cardiovascular disorder (CVD) and specifically cerebrovascular disease, coronary heart disease, acute myocardial infarction, sudden cardiac deaths and hospital admission rate ratio (ARR). Results Persons with bipolar disorder died of CVD approximately 10 years earlier than the general population. One third (38%) of all deaths in persons with bipolar disorder were caused by CVD and almost half (44%) by other somatic diseases, whereas suicide and other external causes accounted for less than a fifth of all deaths (18%). Excess mortality of both CVD (n=824) and other somatic diseases (n=988) was higher than that of suicide and other external causes (n=675 deaths). MRRs for cerebrovascular disease, coronary heart disease and acute myocardial infarction were twice as high in persons with bipolar disorder compared to the general population. Despite the increased mortality of CVD, hospital admissions (ARR) for CVD treatment were only slightly increased in persons with bipolar disorder when compared to the general population. Conclusions The increased cardiovascular mortality in persons with bipolar disorder calls for renewed efforts to prevent and treat somatic diseases in this group. Specifically, our findings further imply that it would be critical to ensure that persons with bipolar disorder receive the same quality care for CVD as persons without bipolar disorder.

Mortality and life expectancy of people with alcohol use disorder in Denmark, Finland and Sweden.

To analyse mortality and life expectancy in people with alcohol use disorder in Denmark, Finland and Sweden.

Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: population based cohort study of long term incidence and mortality

Objective To determine factors influencing long term risks for acquiring or dying from invasive cervical or vaginal cancer in women previously treated for cervical intraepithelial neoplasia grade 3 (CIN3). Design Population based cohort study conducted in 1958-2008, followed up until 2009 in the Swedish Cancer Registry and Swedish Cause of Death Register, linked to the Swedish Population Register. Standardised incidence and mortality ratios were calculated for the risk of acquiring or dying from vaginal or cervical cancer, with the general female population in Sweden as reference. Relative risks in multivariable regression models were also calculated, adjusting for follow-up duration, treatment period, and age at CIN3 treatment or attained age. Setting Entire female population of Sweden. Participants 150 883 women in Sweden diagnosed and treated with CIN3 and followed up for invasive cervical or vaginal cancer, and related mortality. The cohort comprised 3 148 222 woman years. Main outcome measures Standardised incidence and mortality ratios, stratified by period for treatment. Relative standardised incidence ratios and standardised mortality ratios for age at acquiring or dying from cervical or vaginal cancer (attained age), adjusted for preset variables. Results Women previously diagnosed with CIN3 had an increased risk of dying from invasive cervical or vaginal cancer, compared with the general female population (standardised mortality ratio 2.35, 95% confidence interval 2.11 to 2.61). After age 60 years, these women had an accelerated increased risk of acquiring invasive cancer; a similar steep increase in mortality risk was seen after age 70. Regression analyses indicated that the increase in risk over time is highly attributable to ageing. Conclusions Women previously treated for CIN3 are at increased risk of developing and dying from cervical or vaginal cancer, compared with the general female population. The risk accelerates above age 60 years, suggesting a need for lifelong surveillance of these women.

Mortality trends in cardiovascular causes in schizophrenia, bipolar and unipolar mood disorder in Sweden 1987–2010

Introduction: People with severe mental illness have increased risk for premature mortality and thus a shorter life expectancy. Relative death rates are used to show the excess mortality among patients with mental health disorder but cannot be used for the comparisons by country, region and time. Methods: A population-based register study including all Swedish patients in adult psychiatry admitted to hospital with a main diagnosis of schizophrenia, bipolar or unipolar mood disorder in 1987–2010 (614 035 person-years). Mortality rates adjusted for age, sex and period were calculated using direct standardization methods with the 2010 Swedish population as standard. Data on all residents aged 15 years or older were used as the comparison group. Results: Patients with severe mental health disorders had a 3-fold mortality compared to general population. All-cause mortality decreased by 9% for people with bipolar mood disorder and by 26–27% for people with schizophrenia or unipolar mood disorder, while the decline in the general population was 30%. Also mortality from diseases of the circulatory system declined less for people with severe mental disorder (−35% to − 42%) than for general population (−49%). The pattern was similar for other cardiovascular deaths excluding cerebrovascular deaths for which the rate declined among people with schizophrenia (−30%) and unipolar mood disorder (−41%), unlike for people with bipolar mood disorder (−3%). Conclusions: People with mental health disorder have still elevated mortality. The mortality declined faster for general population than for psychiatric patients. More detailed analysis is needed to reveal causes-of-death with largest possibilities for improvement.

Psychiatric admissions and hospitalization costs in bipolar disorder in Sweden

a Department of Psychiatry, Danderyd University Hospital, Sweden b Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden c Medical Management Centre (MMC), LIME, Karolinska Institutet, Stockholm, Sweden d Bristol-Myers Squibb, Global Epidemiology and Outcomes Research (GEOR;4), Belgium e Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Risk of presentation to hospital with epileptic seizures after vaccination with monovalent AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix): self controlled case series study

Objective To assess the risk of epileptic seizures in people with and without epilepsy after vaccination with a monovalent AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix; Glaxo SmithKline, Sweden). Design Register based self controlled case series. Setting Three Swedish counties (source population 750 000). Participants 373 398 people (age 0-106, median 41.2) who were vaccinated. Vaccinated people with epileptic seizures, diagnosed as inpatients or outpatients, at any time from 90 days before until 90 days after any dose of vaccine. Main outcome measures Endpoints were admission to hospital or outpatient hospital care with epileptic seizures as the main diagnosis. The effect estimate of relative incidence was calculated as the incidence of epileptic seizures in period after exposure relative to the incidence of epileptic seizures in two control periods, one before and one after vaccination. Results 859 people experienced epileptic seizures during the study period. There was no increased risk of seizures in people with previously diagnosed epilepsy (relative incidence 1.01, 95% confidence interval 0.74 to 1.39) and a non-significant decrease in risk for people without epilepsy (0.67, 0.27 to 1.65) during the day 1-7 risk period (where day 1 is the day of vaccination). In a second risk period (day 8-30), there was a non-significant increased risk of seizures in people without epilepsy (1.11, 0.73 to 1.70) but no increase in risk for those with epilepsy (1.00, 0.83 to 1.21). Conclusions This study found no evidence of an increase in risk of presentation to hospital with epileptic seizures after vaccination with a monovalent AS03 adjuvanted pandemic H1N1 influenza vaccine.

Lithium treatment and cancer incidence in bipolar disorder

To investigate whether there is an increased risk of cancer associated with lithium treatment in patients with bipolar disorder compared to the general population.