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Purpose To assess the impact on exposure time and outcome misclassifications, and consequent impact on exposure-outcome associations from treatment episode construction. We investigated the dosage assumptions of 1 unit per day, and 1 DDD per day, versus actual prescribed dosage under different handling of gaps and overlaps of prescriptions. Methods Data on mirtazapine and citalopram exposure (years 2006–2014) from the Swedish Prescribed Drug register were used. Via a within individuals design we compared method A, based on actual dosage, with methods B and C based on 1 unit of drug per day and 1 DDD per day assumptions, respectively, including consideration of gaps and overlaps. Four outcomes were used, hospitalizations and outpatient visits for all and for psychiatric causes. Results Relative to method A, both alternative methods lead to misclassification of exposure time. With regard to outcome misclassifications, method B overestimates the effect of the exposure on the outcome in 77% and 100% of exposure definition comparisons for mirtazapine and citalopram respectively, while 23% of the comparisons for mirtazapine results in underestimation of exposure-outcome associations. Conversely, treatment episodes based on DDD (method C) result in underestimation of the exposure-outcome association in 100% and 87.5% of exposure definition comparisons for mirtazapine and citalopram respectively, while 12.5% of the comparisons for citalopram results in overestimation of the exposure-outcome associations. Conclusions The study provides results that have consistent clinical relevance. We have showed that a non-accurate construction of exposure time may lead to errors on outcome detection during exposed time, and consequently affect conclusions on safety or efficacy profile of a treatment.

OBJECTIVE To investigate the health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to patients with depression not meeting TRD criteria. METHODS Nationwide Swedish registers were used to identify patients 18-69 years old with incident depression and antidepressant treatment. Patients were followed prospectively and defined as having TRD at start of the third distinct consecutive treatment episode. Each of the 16,329 identified TRD patients were matched with five comparators with depression not meeting criteria for TRD. Main outcome measure was total number of inpatient days and outpatient visits, and secondary outcome was HCU in connection with a main diagnosis of depression or suicide attempt. RESULTS TRD patients had a significantly higher risk of all-cause inpatient care than comparators (first year adjusted risk ratio [aRR] 3.03 [95%CI 3.01-3.05], years 1-3 aRR 2.15 [2.13-2.16]). This was more pronounced when the main diagnosis was depression (first year aRR 4.41 [4.36-4.45]), and after suicide attempt (first year aRR 4.43 [4.26-4.60]). Outpatient visits were also markedly more frequent for patients with TRD (first year aRR 2.05 [2.03-2.07]). Higher HCU among TRD patients persisted throughout follow-up. CONCLUSIONS Patients with TRD may have a twofold to fourfold higher HCU than other patients with depression.KEYPOINTSThis register-based prospective study investigated health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to other patients with depression.Patients with TRD had a two to fourfold higher HCU regarding all measured outcomes, including inpatient hospital days and outpatient visits.The elevated HCU persisted for more than three years, although decreasing gradually. This should correspond to increased costs and individual burden for patients with TRD.

PURPOSE When defining exposure to pharmacological treatments in pharmacoepidemiology, register data often do not provide information regarding if a pharmacological treatment is a switch or an add-on. This study aims to compare two methods defining switching and add-on therapies and their impact on exposure-outcome associations. Additionally, to guide bias reduction, it aims to describe how the methods relate to immortal time bias and selection bias. METHODS Cohort study using Swedish population-based health registers to identify antidepressant (AD) prescriptions as exposures while hospitalizations for psychiatric reasons were used as an empirical outcome example. The first method for exposure definition used conditioning on future exposure (FE), the second used the concept of uncertain exposure (UE). To estimate associations between outcome and exposure categories "Use of one AD," "Use of two or more ADs", and "UE" compared to "Unexposed," hazard ratios (HRs) and 95% confidence intervals were estimated using Cox regression adjusted for age and sex. RESULTS Using the UE method, 7.2% of time periods were classified as "UE" with a notable proportion of psychiatric hospitalizations (7.7%) occurring during this time, while when using the FE method these hospitalizations were distributed over unexposed time and AD use time. The FE method resulted in slightly higher associations than the UE method. The highest HR was found during "UE": HR (95% CI) 5.54 (5.06-6.07). CONCLUSIONS This study suggests that to reduce the potential immortal time bias, selection bias, and exposure misclassification inherent to the FE method, the UE method could be used for identifying switching and add-on therapies. If not used as a main exposure definition, the UE method may be used to investigate the impact of UE time in a sensitivity analysis.

Background/Objectives Despite profound weight loss after bariatric surgery, some patients are dissatisfied with the results. Pre-surgery expectations, as well as post-surgery items of satisfaction, need to be clarified. The main objective in this study was to investigate the primary reasons to seek bariatric surgery and assess items of satisfaction 1-year post-surgery. Subjects/Methods This is a prospective cohort study of women (n = 50) undergoing bariatric surgery in Stockholm, Sweden. Presurgery assessment included reasons to seek surgery, expected weight loss, co-morbidities, and quality of life. Post-surgery assessment included items of satisfaction, weight loss, co-morbidities, and quality of life. In total, two women did not undergo surgery, and 40 women had complete data from all pre- and post-surgery assessments. Results Mean change in body mass index (BMI) pre- and post-surgery was -12.9 (3.7) kg/m(2). At 1-year post-surgery, the mean percent of excess weight loss (% EWL) was 86.9 (26.3). Pre-surgery, the most reported reason to seek surgery was "weight loss" (47.9%), while the most reported item of satisfaction post-surgery was "improved self-esteem" (55.6%). Satisfaction with the result 1-year post-surgery was associated with the extent of % EWL. Satisfied patients (n = 32) had a mean % EWL of 94.6 (22.9), while those not satisfied (n = 8) had a mean % EWL of 59.9 (17.6). Conclusions The primary reason to seek bariatric surgery was weight loss. However, despite profound weight loss, improved self-esteem was the item of most satisfaction post-surgery. Our findings may be useful in the clinical setting when informing patients pre- surgery about what to expect as well as when meeting a patient post-surgery to discuss results.

Background: Response rates after and tolerability of electroconvulsive therapy (ECT) in depressive disorders with psychiatric comorbidity are uncertain. Methods: Data on patients with a depressive episode and a first course of ECT were collected from the Swedish National Quality Register for ECT. Logistic regression analyses, adjusted for gender, age, and depressive episode severity, were used to compare patients with and without comorbidity. The clinical response assessment Clinical Global Impression - Improvement Scale was used in 4413 patients and the memory item from the Comprehensive Psychiatric Rating Scale was used for subjective memory impairment rating after ECT in 3497 patients. Results: In patients with depressive disorder and comorbid personality disorder or anxiety disorder, 62.7% and 73.5%, respectively, responded after ECT compared with 84.9% in patients without comorbidity [adjusted odds ratio (aOR) 0.43, 95% confidence interval (CI) 0.34-0.55, and aOR 0.61, 95% CI 0.51-0.73, respectively]. The proportion of responding patients with comorbid alcohol use disorder was 77.1%, which was not significantly different from that in patients without comorbidity (aOR 0.75, 95% CI 0.57-1.01). The impact of comorbidity decreased with higher age and depressive episode severity. Subjective ratings of memory impairment did not differ between patients with and without comorbidity. Limitations: Observational non-validated clinical data. Conclusions: The response rate after ECT in depression may be lower with concurrent personality disorder and anxiety disorder; however, the majority still respond to ECT. This implies that psychiatric comorbidity should not exclude patients from ECT. Funding Agencies|Uppsala Universityhospitals research fund; Swedish Research CouncilSwedish Research CouncilEuropean Commission [201602362]

Background Treatment resistant depression (TRD) is common among patients with depression, and is associated with clinical and functional disability. However, the risk and risk factors for being granted disability pension (DP) among patients with TRD have not been investigated. Methods All antidepressant initiators in Sweden with a diagnosis of depression in specialized care were identified in nationwide registers 2006–2013 and followed regarding treatment trials. TRD was defined as the start of a third sequential trial. Patients with TRD who were not on DP (N = 3204) were matched by age, sex, history of depression, calendar year, and time for treatment start with 3204 comparators with depression and ongoing antidepressant treatment. A proportional Cox Regression was performed with DP as outcome, adjusted for various sociodemographic and clinical covariates. Results Compared to the comparison cohort, TRD was associated with a doubled risk for all-cause DP (aHR 2.07; 95%CI 1.83–2.35), DP due to depression (2.28; 1.82–2.85) and to any mental disorder (2.24; 1.95–2.57) but not due to somatic diagnoses (1.25; 0.84–1.86). Among significant risk factors for DP in TRD were female sex, being > 29 years of age, unemployment and a diagnosis of comorbid personality disorder (ICD-10 codes F60.0–9). Conclusion TRD is associated with an elevated risk for DP compared to other patients with depression, with large potential costs for the affected patients and for society. Clinical and therapeutic implications for patients with TRD who are granted DP should be further investigated. Limitation: No clinical data, e.g. type of depression or reason for treatment switch, was available for this study.

Objective To investigate suicide ideation and behavior as risk factors for suicide in schizophrenia during varying time periods. Method Cases were 84 patients who died by suicide within 5 years from diagnosis in a source population of patients discharged for the first time from psychiatric hospitals in Stockholm County, Sweden, with a schizophrenia spectrum diagnosis. One control was individually matched with each suicide case. Data were retrieved from clinical records in a blind fashion. Thoughts of death, thoughts of suicide, suicide plan, and suicide attempt during varying time periods were investigated as risk factors for subsequent completed suicide. Results In adjusted analyses, thoughts of suicide, suicide plan, and suicide attempt were significantly associated with subsequent completed suicide in the following year. The highest suicide risk was found within a year following suicide attempt (adjusted OR 9.9, 95% confidence interval 2.5-39.0). The association between suicide ideation and behavior and subsequent suicide declined over time. Conclusions Several types of suicide ideation and behavior were associated with suicide, and the association was stronger for suicidal behavior. The clinical significance of suicidal communication appears highest during the following month or/and year. Many suicides occurred without recorded short-term suicidal communication.

The risk of suicide is elevated among patients with treatment-resistant depression (TRD). Risk factors for suicide and suicide attempts among cases and controls with TRD were investigated using data from nationwide Swedish registers. Among 119,407 antidepressant initiators with a diagnosis of depression, 15,631 patients who started a third sequential treatment trial during the same depressive episode were classified with TRD. A nested case-control study compared cases with suicide and suicide attempts with up to three closely matched controls. Sociodemographic and clinical risk factors were assessed using conditional logistic regression analyses. In all, 178 patients died by suicide and 1,242 experienced a suicide attempt during follow-up. History of suicide attempts, especially if1 year after the attempt, was a significant independent risk factor for suicide (adjusted odds ratio [aOR], 8.9; 95% confidence interval [CI], 5.1-15.7) as were 10 to 12 years of education compared to lower education (aOR, 1.69; 95% CI, 1.02-2.81). For attempted suicide, the strongest independent risk factors were history of suicide attempts (1 year aOR, 5.1; 95% CI, 4.0-6.5), substance abuse (aOR, 2.6; 95% CI, 2.2-3.1), personality disorders (aOR, 1.9; 95% CI, 1.5-2.3), and somatic comorbidity (aOR, 2.0; 95% CI, 1.04-3.9). Suicide attempts, especially if recent, are strong risk factors for completed suicide among patients with TRD. Established risk factors for suicide attempts were confirmed for patients with TRD.

Background Data on real-world rehospitalization risks in patients using different drugs and combination therapies for relapse prevention after a manic episode is limited. Methods We conducted a nationwide population based cohort study using data from Swedish national registers. Swedish residents aged 18–75 years who were hospitalized for a manic episode between July 1, 2006 and December 2, 2014 were included. Prescription fills of lithium, valproate, olanzapine, quetiapine and aripiprazole were recorded throughout the first four weeks after hospital discharge, after which the patients were followed for up to one year. General and treatment specific rehospitalization risks were determined and results were adjusted for clinical and sociodemographic factors. Results The study included follow-up data from 6 502 hospitalizations for mania. Pharmacologic relapse prevention was used after 78% of these hospitalizations. Monotherapies and combination therapies were equally common. The average one-year rehospitalization risk for patients who did versus did not initiate prophylactic treatment was 39% and 46%, respectively. The lowest rehospitalization risks were seen in patients on combination therapy with olanzapine and valproate or olanzapine and lithium, experiencing one year rehospitalization risks of 32% and 34% (adjusted hazard ratios 0.76 (95% confidence interval [CI] 0.62–0.93) and 0.83 (95% CI 0.70–0.98), compared to lithium monotherapy). Limitations Register data does not provide information on all clinical parameters affecting treatment choices. Conclusions One-year rehospitalization rates after a manic episode are considerable also for patients who initiate prophylactic treatment. Combination therapies including olanzapine and a classic mood-stabilizer may be beneficial for reducing rehospitalization risks after a manic episode., final draft, peerReviewed

The aim of this study was to examine risk of self-harm, hospitalization for depression and death by suicide after gastric bypass surgery (GBP).Concerns regarding severe adverse psychiatric outcomes after GBP have been raised.This nationwide, longitudinal, self-matched cohort encompassed 22,539 patients who underwent GBP during 2008 to 2012. They were identified through the Swedish National Patient Register, the Prescribed Drug Register, and the Causes of Death Register. Follow-up time was up to 2 years. Main outcome measures were hazard ratios (HRs) for post-surgery self-harm or hospitalization for depression in patients with presurgery self-harm and/or depression compared to patients without this exposure; and standardized mortality ratio (SMR) for suicide post-surgery.A diagnosis of self-harm in the 2 years preceding surgery was associated with an HR of 36.6 (95% confidence interval [CI] 25.5-52.4) for self-harm during the 2 years of follow up, compared to GBP patients who had no self-harm diagnosis before surgery. Patients with a diagnosis of depression preceding GBP surgery had an HR of 52.3 (95% CI 30.6-89.2) for hospitalization owing to depression after GBP, compared to GBP patients without a previous diagnosis of depression. The SMR for suicide after GBP was increased among females (n = 13), 4.50 (95% CI 2.50-7.50). The SMR among males (n = 4), was 1.71 (95% CI 0.54-4.12).The increased risk of post-surgery self-harm and hospitalization for depression is mainly attributable to patients who have a diagnosis of self-harm or depression before surgery. Raised awareness is needed to identify vulnerable patients with history of self-harm or depression, which may be in need of psychiatric support after GBP.

Purpose: To study the differences in attitudes towards hypertension and drug treatment between patients persistent and non-persistent to antihypertensive drug treatment.Materials and methods: Cross...

Despite profound weight loss after bariatric surgery, some patients are dissatisfied with the results. Pre-surgery expectations, as well as post-surgery items of satisfaction, need to be clarified. The main objective in this study was to investigate the primary reasons to seek bariatric surgery and assess items of satisfaction 1-year post-surgery.This is a prospective cohort study of women (n = 50) undergoing bariatric surgery in Stockholm, Sweden. Pre-surgery assessment included reasons to seek surgery, expected weight loss, co-morbidities, and quality of life. Post-surgery assessment included items of satisfaction, weight loss, co-morbidities, and quality of life. In total, two women did not undergo surgery, and 40 women had complete data from all pre- and post-surgery assessments.Mean change in body mass index (BMI) pre- and post-surgery was - 12.9 (3.7) kg/mThe primary reason to seek bariatric surgery was weight loss. However, despite profound weight loss, improved self-esteem was the item of most satisfaction post-surgery. Our findings may be useful in the clinical setting when informing patients pre-surgery about what to expect as well as when meeting a patient post-surgery to discuss results.

Adherence to treatment is one of the most consistent factors associated with a favorable addiction treatment outcome. Little is known about factors associated with treatment adherence in individuals affected with comorbid attention-deficit/hyperactivity disorder and substance use disorders (SUD). This study aimed to explore whether treatment-associated factors, such as the prescribing physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were associated with adherence to MPH treatment. Swedish national registers were used to identify adult individuals with prescriptions of MPH and medications specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting psychiatric diagnoses. Primary outcome measure was days in active MPH treatment in stratified dose groups (≤36 mg, ≥37 mg to ≤54 mg, ≥55 mg to ≤72 mg, ≥73 mg to ≤90 mg, ≥91 mg to ≤108 mg, and ≥109 mg). Lower MPH doses (ie, ≤36 mg day 100) were associated with treatment discontinuation between days 101 and 830 (HR≤36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR≥108mg, 1.09). The results showed a linear trend (P < 0.0001) toward decreased risk of treatment discontinuation along with increase of MPH doses. In conclusion, this study shows that higher MPH doses were associated with long-term treatment adherence in individuals with attention-deficit/hyperactivity disorder and SUD.

OBJECTIVE: This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication. METHODS: Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression. RESULTS: A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk. CONCLUSIONS: A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John Wiley & Sons, Ltd.Copyright © 2016 John Wiley & Sons, Ltd. Language: en

Behavioral differences between native and introduced species may contribute to the invasiveness of certain species. This includes differences at the species level, consistent variation among individuals (“personality”) and within-individual variation (e.g., behavioral plasticity). Here, we investigated swimming activity of individuals from four different amphipod species occurring in the river Rhine system, three of which were native or naturalized (>100 years present) while one is a recent invader (Dikerogammarus villosus

In recent years, the use of atypical antipsychotics and combination therapy for relapse prevention in bipolar disorder has increased substantially. However, real-world data on the comparative effectiveness of these treatment options are largely non-existent. We conducted a population-based cohort study, using data from Swedish national registers. All patients aged 18–75 years who were hospitalized for mania 2006–2014 and filled at least one prescription of lithium, valproate, olanzapine, quetiapine, aripiprazole or any combination of these drugs were included, and followed for up to one year after hospital discharge, generating follow-up data from 5 713 hospitalizations. We used Cox proportional hazard regression models to study time to treatment failure for each individual drug and combination therapy, using lithium as comparator. Treatment failure was defined as treatment discontinuation, switch, or rehospitalization, and the results were adjusted for clinical and sociodemographic factors. We found that treatment failure occurred in 85% of cases and that the majority of combination therapies were associated with lower risks of treatment failure compared to monotherapies. Patients combining lithium + valproate + quetiapine had the lowest risk of treatment failure (adjusted HR [AHR] 0.40, 95% CI 0.30–0.54), followed by patients on lithium + valproate + olanzapine (AHR 0.55, 95% CI 0.45–0.68). In contrast, monotherapies with antipsychotics were associated with significantly higher risks of treatment failure compared to single use of lithium. In conclusion, our results support experimental findings, suggesting that combination therapy is more effective than monotherapy after a manic episode.

Background In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD. Methods Patients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 141 ± 60 days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS). Results A total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42 years), had a higher proportion of men (49% vs 37%, p

Background The impact of treatment resistant depression (TRD) on mortality is not established. Methods Using Swedish national registers, 118,774 patients between 18–69 years of age who had been prescribed an antidepressant and been diagnosed with depression in specialized care were identified. Patients with at least two additional treatment trials during the same depressive episode were classified as having TRD. Data on the covariates of sex, age, history of depression, self-harm, substance use disorders, and other psychiatric and somatic comorbidities was also used. Relative risks comparing TRD patients with other depressed patients were calculated as hazard ratios (HR) for all-cause mortality and for external and non-external causes of death, as well as excess mortality rate ratios (EMRR), with 95% confidence intervals (CI). Results In total 15,013 patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was 1.35 (95% CI 1.21–1.50). Mortality from external causes (including suicides and accidents) was markedly higher in TRD patients than in other depressed patients (HR 1.97; 1.69–2.29), while mortality from non-external causes was similar. The adjusted EMRR was 1.52 (1.31–1.76), highest among patients 18–29 years old (EMRR 2.03; 1.31–1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63–2.43). Limitations Severity of depression and adherence to treatment were not available in the data. Conclusions Patients with TRD may have an increased all-cause mortality compared to other depressed patients, mainly for external causes of death. The relative mortality is highest among young and physically healthy patients.

Background: Breast milk is associated with a lower risk of neonatal morbidity in very preterm infants. Despite the benefits, the duration of breastfeeding is shorter in very preterm infants than in term infants. Objective: This study aimed to investigate how early provision of mother’s own milk (MOM) and maternal and infant characteristics are related to breast milk feeding (BMF) between 36 and 40 weeks postmenstrual age (PMA) after very preterm birth. Methods: A regional observational study of 138 singleton infants born at < 32 weeks of gestation in Stockholm, Sweden, was conducted. Data were derived from medical charts to investigate the association between early provision of MOM; maternal and infant characteristics; and exclusive, partial, or no BMF at 36 weeks PMA. Moreover, changes in BMF between 36 and 40 weeks PMA were studied. Results: Most infants (80%) received MOM at 36 weeks PMA (55% exclusively, 25% partial). High provision of MOM at postnatal day 7 was associated with exclusive BMF at 36 weeks PMA, odds ratio (OR) 1.18 per 10 mL/kg MOM (95% confidence interval [CI], 1.06-1.32). Mothers born in non-Nordic countries provided MOM exclusively less often, adjusted OR 0.27 (95% CI, 0.10-0.69), compared to Nordic mothers. Between 36 and 40 weeks PMA, BMF decreased overall. This change was not associated with investigated predictors. Conclusion: It is possible to achieve high rates of BMF in very preterm infants. High intake of MOM early in the postnatal period is strongly related to exclusive BMF at 36 weeks PMA.

Treatment guidelines state that all patients with bipolar disorder should use pharmacological prophylaxis; however the actual use of prophylactic drugs after bipolar disorder diagnosis is unknown. Our aim was to assess the use of, and predictors for, pharmacoprophylaxis in newly diagnosed bipolar disorder patients.Data from three Swedish nationwide registers were obtained. We identified patients aged 18-75 with a first time diagnosis of bipolar disorder between 2006 and 2012 (n=31,770) and reviewed subsequent mood-stabilizer and antipsychotic prescription fills. In multivariable Cox regression models, we studied demographic and illness related factors as predictors of prescription fills after diagnosis.In total, 72.2% (95% confidence interval [CI] 71.7-72.7%) of the patients filled a prescription of a prophylactic drug within 3 months after diagnosis. Pharmacological prophylaxis was mainly associated with a longer duration of hospitalization at bipolar disorder diagnosis (adjusted hazard ratio [AHR] 2.18; CI 2.02-2.35 for a hospitalization of ≥28 days compared to7 days) and previous use of any mood-stabilizer or antipsychotic (inpatients: AHR 1.24; CI 1.17-1.31 and outpatients: AHR 1.78; CI 1.73-1.84).We had no information on drug prescriptions that were never filled.The proportion of newly diagnosed bipolar disorder patients without pharmacological prophylaxis is substantial. Patients who are naïve to mood-stabilizers and antipsychotics and are hospitalized for a brief period at diagnosis are the ones least likely to initiate pharmacoprophylaxis, suggesting that this group deserves attention in order to improve the long term prognosis.

Objective To compare the incidence of hypertension, stroke, coronary heart disease, and diabetes in women who have delivered after in vitro fertilization (IVF) with those who delivered after natural conception. Design A cohort study in Sweden between 1990 and 2008. Setting Sweden. Patient(s) 23,498 women who had given birth to a child after IVF and 116,960 individually matched women. Intervention(s) None. Main Outcome Measure(s) Incidence rates of hypertension, diabetes, stroke, and coronary heart disease in both groups. Result(s) Inpatient and outpatient diagnoses of hypertension, stroke, coronary heart disease, and diabetes were identified by linkage to the Swedish National Patient Register. The mean time of follow-up was 8.6 years in both groups. Multivariable analysis showed that hypertension had a higher incidence in IVF mothers with a hazard ratio (HR) of 1.27, 95% confidence interval (CI) 1.13–1.41, as compared with mothers from the Medical Birth Register. There was a trend to a higher incidence of stroke (HR 1.27; 95% CI, 0.96–1.68), but the incidence of coronary heart disease and diabetes did not differ. Conclusion(s) Hypertension was more prevalent in the IVF group, which suggests that these women should be aware of their blood pressure and cardiovascular risk profile.

Introduction and aims To assess opioid-related mortality and correlation with filled prescriptions for buprenorphine and methadone. Design and methods A register study, including data from the Swedish Forensic Pathology and Forensic Toxicology databases 2003-2010, the Prescribed Drug Register and the National Patient Register. Results A total of 1301 deaths, assessed as related to buprenorphine, methadone or heroin, or a combination of them, were studied. The largest number of fatalities was related to intake of heroin (n = 776), followed by methadone (n = 342) and buprenorphine (n = 168). The total annual number of fatal cases related to the studied drugs more than doubled (116 to 255) during the study period. There were increases in mortality related to both buprenorphine and methadone: from 1 to 49 cases for buprenorphine, and from 19 to 81 cases for methadone. Only one-fifth of the fatal cases had a filled prescription for the maintenance drug assessed as the cause of death. Discussion and conclusion This study showed that most fatalities were not related to filled prescriptions of maintenance drugs, and a substantial illicit use of buprenorphine and methadone resulting in deaths was revealed. To prevent opioid toxicity deaths it is important to make efforts not only to reduce drug diversion from maintenance programs, but also to improve the control of drug trafficking and other illegal sources.

Introduction: In Scandinavia, portable monitoring has virtually replaced standard polysomnography for diagnosis of obstructive sleep apnea syndrome (OSAS). Because waiting times for specialized OSA ...

Objective Assessment of factors influencing antipsychotic prescription fills in the early phase of schizophrenia or schizoaffective disorder. Methods We used the Swedish Patient Register to identify patients younger than 45 years with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 (904 patients). Data on medication were obtained from the Prescribed Drug Register. Filling a prescription of an antipsychotic drug after discharge was used to estimate medication adherence. In Cox regression models, we studied sex, country of birth, metropolitan residence, educational level, age, duration of hospitalization, history of substance use disorder, and previous use of antipsychotic drugs as predictors for antipsychotic fills. Results Among all patients, 53.1% (95% confidence interval [CI] 49.9%–56.4%) had filled an antipsychotic prescription within 1 week from discharge. After 6 months, the proportion had increased to 80.2% (95% CI, 77.4%–82.8%) with no further increase thereafter. Prescription filling of an antipsychotic drug was primarily associated with antipsychotic use before the hospitalization (hazard ratio, 1.64; 95% CI, 1.33–2.03; for patients with access to antipsychotic drugs at admission compared with no previous use) and with longer hospitalization (hazard ratio, 1.60; 95% CI, 1.27–2.02 for 15–28 days compared with shorter hospitalization). Conclusions Among patients who filled a prescription of an antipsychotic drug after discharge, the majority did so within 1 week. Previous adherent use of antipsychotic drugs and longer hospitalization may be predictors of primary adherence to antipsychotic drug treatment in schizophrenia or schizoaffective disorder.

Caloric restriction in animals is an effective way to reduce carcinogenesis. Anorexia nervosa (AN) is considered a model of extreme caloric restriction in humans. The aim of our study was to assess cancer incidence and mortality in women with AN. A total of 6,009 women with at least one inpatient treatment for AN during the period 1973-2003 were included in the study. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were calculated. Overall, there was no statistically significant difference in cancer incidence compared to women in the general population. At a statistically significant or borderline significant level, a higher incidence for lung cancer and cancer of lymphoid, hematopoietic and related tissue was observed along with a reduced breast cancer incidence. Women with AN had twice as high mortality from cancer in general, and more specifically from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites. The increased lung cancer incidence may be due to smoking habits among women with AN. The worse prognosis with higher mortality from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites may be explained by AN-specific attitudes toward seeking medical care, adherence to treatment or worse biological precondition due to starvation and cachexia.

AIM: To assess prescribing patterns, sociodemographic characteristics and previous disease history in patients receiving pregabalin.METHODS: An observational study using register data on dispensed drugs and recorded diagnoses for all patients in Stockholm, Sweden, who filled at least one prescription of pregabalin between July 2005 and December 2009. Analyses focused on prevalence, incidence, diagnosis patterns, prior dispensing of other analgesics/psychotropics and persistence to treatment over time.RESULT: A total of 18,626 patients (mean age 55 years, 63% women) were initiated on treatment between July 2006 and December 2009. Approved indications were recorded in hospital and/or primary care within 1 year prior to the first dispensing for 40% of the patients (epilepsy 1.3%, neuropathic pain 35.5% and generalised anxiety disorder (GAD) 3.6%). Antidepressants were used by 55%, opioids by 49% and sedatives by 48% prior to initiation of pregabalin. One-third (34%) only purchased one prescription and the proportion purchasing pregabalin 1 year after initiation was 42.1% for epilepsy, 36.3% for GAD, 21.5% for neuropathic pain and 25.6% for those without any of the included diagnoses.CONCLUSION: Pregabalin was mainly used as a second-line drug for the treatment of GAD or neuropathic pain and to a lesser extent as add-on therapy in epilepsy. However, a large proportion of all patients only purchased one prescription and the persistence declined rapidly over time. The issue of potential off-label prescribing or poor registration of diagnoses should also be noted as a high proportion had been prescribed the drug without a record of any of the approved indications.

Patients with Attention Deficit/Hyperactivity Disorder (ADHD) and comorbid Substance Use Disorders (SUD) are increasingly being treated with central stimulant medication despite limited evidence for its effectiveness. Lack of longitudinal follow-up studies of dosing and adverse effects has resulted in conflicting treatment guidelines. This study aims to explore whether individuals with ADHD and comorbid SUD are treated with higher stimulant doses than individuals with ADHD only, and whether doses increase over time as a sign of tolerance, a core symptom of addiction. Information on methylphenidate doses for 14 314 Swedish adults, including 4870 individuals with comorbid SUD was obtained through linkages of Swedish national registers between 2006 and 2009. Differences in doses between patients with and without SUD were estimated using logistic regression while a linear regression model calculated time trends in mean doses. Individuals with SUD were prescribed higher methylphenidate doses than those without (OR day365 ; 2.12, 95% CI 1.81–2.47: OR day730 2.65, 95% CI 2.13–3.30). Patients with SUD were, two years after initiating stimulant treatment, prescribed approximately 40% higher doses compared to individuals with ADHD only. The results may suggest a need for increased doses in this population to achieve optimal ADHD symptom control. A tendency towards increasing doses during the first years of treatment, more pronounced in individuals with comorbid SUD, may reflect a reluctance to prescribe adequate doses due to lack of clinical guidelines. Mean doses stabilized after about two years in both groups, which does not lend support to continuously increasing tolerance over time.

Background Several antipsychotics, especially risperidone, are known to increase serum prolactin. Hyperprolactinemia has been linked to the development of mammary gland tumors in animal studies. We therefore investigated the risk of breast cancer in a nationwide cohort of women using risperidone or other antipsychotics. Methods All women, 18 years or older, who initiated treatment with risperidone or any other antipsychotic between 2006 and 2012 were identified in Swedish nationwide registers. Patients with two consecutive dispensations of the same antipsychotic within 3 months, no previous cancer diagnosis, and no previous dispensations of paliperidone were included. The final cohort consisted of 55976 women of whom 22908, 24524, and 8544 were exposed to risperidone, other atypical antipsychotics, and typical antipsychotics, respectively. A Cox regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between antipsychotics and breast cancer. Results Patients were followed prospectively, the mean follow-up time ranging from 2.4 to 2.8 years between treatment groups. After adjusting for age, there was no increased risk for breast cancer among risperidone users compared to patients exposed to another atypical antipsychotic (HR 0.94, 95% CI 0.72–1.22) or a typical antipsychotic (HR 1.25, 95% CI 0.94–1.66). Analyses stratified by tumor stage, using active treatment follow-up time, or including only treatment naive patients did not reveal any noteworthy change in the results. Conclusion Risperidone use does not confer an increased short-term risk of breast cancer compared to other antipsychotic agents.

Objective: To assess the association between childbearing and mortality from anorexia nervosa (AN). Method: A total of 5,251 females, from a population-based Swedish registry, admitted with an AN diagnosis during the period 1973–2003 were included. Standardized mortality ratios (SMR) were estimated and hazard ratios (HR) were calculated using Cox regression. Results: Nulliparous women had a sixfold higher mortality due to natural causes and ninefold higher mortality due to unnatural causes compared to the general population. Parous women had higher mortality compared to the general population only due to unnatural causes. Suicide was the most common cause of death. Childbearing was associated with a 65% lower mortality. One hundred forty four women out of 1,941 parous women were hospitalized perinatally for any psychiatric disorder (7.4%). Discussion: Childbearing is associated with lower mortality among women with AN. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)

This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication.Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression.A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk.A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John WileySons, Ltd.

Non-adherence to antipsychotic medication and hospitalization in psychotic disorders are common and costly problems. Our aim was to identify risk factors for rehospitalization of patients with recent onset schizophrenia or schizoaffective disorder in a population-based cohort study. All patients with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 were included (n = 861). Patients were identified through and data retrieved from national Swedish health and population registers. We investigated how socio-demographic variables, duration of first hospitalization and prescription fills of antipsychotics were associated with rehospitalization in Cox regression models. A higher risk for rehospitalization within 28 days was observed in patients with a first hospitalization that was shorter than two weeks compared with patients who were hospitalized for more than four weeks: hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.42 to 3.74. Further, patients who did not fill a prescription of antipsychotics within the first week after discharge had a higher risk of early rehospitalization than patients who were given antipsychotics (HR 1.75, 95% CI 1.13 to 2.72). More than 12 years of education was associated with a lower risk of early rehospitalization (HR 0.44, 95% CI 0.26 to 0.77). Sex, age, being born in Sweden, urban area residence and prescription fills of antipsychotics prior to first admission did not significantly affect the risk of early rehospitalization. In conclusion, we identified two potentially modifiable risk factors for rehospitalization: short duration of initial hospitalization and early non-adherence to medication.

To assess the effectiveness of brief alcohol intervention on hazardous and harmful drinking in the 12-month period after a voluntary alcohol screening.At a large transport company, employees presenting to the occupational health services for a routine health and lifestyle check-up were offered to undertake an alcohol screening by means of self-report (the Alcohol Use Disorders Identification Test-AUDIT) and a biomarker (carbohydrate-deficient transferrin in serum-CDT). Those screening positive for the AUDIT and/or CDT were randomized to a brief or comprehensive intervention group or to a control group. An identical follow-up session was performed 12 months later.Of 990 employees (68% men) that volunteered for the alcohol screening, 194 (20%) tested positive for the AUDIT and/or CDT. Among the 158 (81%) subjects who also attended the follow-up session, the frequency of positive screening results at baseline/follow-up were 51%/23% for the AUDIT (P0.0001) and 58%/34% (P0.0001) for CDT. However, there were no significant differences between the brief and comprehensive intervention groups or between the intervention groups and the control group.The results suggested that alcohol screening and brief intervention performed in connection with routine health and lifestyle examinations in the workplace may be effective in reducing alcohol consumption. Given the lack of difference in outcome between the intervention groups and the control group, alcohol screening may in itself cause reduction in drinking. In addition, at least some of the positive effect may be explained by regression towards the mean.

Background & Aims Inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). There have been marked changes in the management and treatment of IBD over the past decades, but little is known about how these changes have impacted morbidity and mortality (time trends in risk) of CRC in patients with IBD. Methods We assessed cancer occurrence and mortality in a large population-based cohort of patients with IBD who were diagnosed from 1954 to 1989 (n = 7607). Through register links, we collected data on vital status of all registered cases of CRC, as well as intestinal surgeries and mortalities from CRC through 2004. Relative risks for CRC incidence and mortality, by calendar period of follow-up evaluation, were assessed within the cohort (using Poisson regression and taking age, sex, extent of IBD, and time since IBD diagnosis into account) and also compared with the general population using standardized incidence and mortality ratios. Results During 198,227 person-years of follow-up evaluation for the 7607 patients with IBD, 188 new cases of CRC were observed (crude incidence, 95 per 100,000; 95% confidence interval, 82–109); 92 deaths from CRC were registered. Within the IBD cohort, as well as vs the general population, the incidence of CRC showed a tendency towards a decline whereas the mortality from CRC decreased several-fold from the 1960s through 2004. Conclusions Over the past 35 years, the risk of diagnosis of CRC in patients with IBD has not declined significantly, but the risk of dying of CRC has decreased substantially.

OBJECTIVES: Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population. DESIGN AND PATIENTS: A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964-2004. MEASUREMENTS: Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR). RESULTS: A more than 2-fold increased mortality risk was observed in both women (SMR 2.9, 95% CI 2.7-3.0) and men (SMR 2.5, 95% CI 2.3-2.7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4.6, 95% CI 3.5-6.0) compared with patients with APS2 (SMR 2.1, 95% CI 1.9-2.4). Cancer incidence was increased (SIR 1.3, 95% CI 1.2-1.5). When tumours observed during the first year of follow-up were excluded, only the cancer risk among APS1 patients remained increased. Cause-specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population. CONCLUSIONS: Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency.

Weight loss resulting from low-calorie diets is often less than expected. We hypothesized that energy restriction would influence proton leakage and improve mitochondrial efficiency, leading to reduced energy expenditure, partly explaining the difficulties in weight loss maintenance.Eleven women with a median BMI of 38.5 kg/m(2) (q-range 37-40), and referred to gastric bypass surgery participated. Before surgery, and at 6 months of follow-up, muscle biopsies were collected from the vastus lateralis muscle. Mitochondria were isolated and analyzed for coupled (state 3) and uncoupled (state 4) respiration and mitochondrial capacity (P/O ratio).At follow-up, the participants had a median BMI of 29.6 kg/m(2) (28.3-32.0). State 3 increased from 20.6 (17.9-28.9) to 34.9 nmol O2/min/U citrate synthase (CS) (27.0-49.0), p = 0.01, while state 4 increased from 2.8 (1.8-4.2) to 4.2 nmol O2/min/U CS (3.1-6.1), although not statistically significant. The P/O ratio increased from 2.7 (2.5-2.8) to 3.2 (3.0-3.4), p = 0.02, indicating improved mitochondrial efficiency.Six months after gastric bypass surgery, the mitochondrial capacity for coupled, i.e., ATP-generating, respiration increased, and the P/O ratio improved. Uncoupled respiration was not enhanced to the same extent. This could partly explain the decreased basal metabolism and the reduced inclination for weight loss during energy restriction.

Background: Patients with rheumatoid arthritis are at increased risk of death from cardiovascular disease (CVD). This risk is influenced by the inflammatory activity of the rheumatoid arthritis as well as by traditional risk factors for CVD. However, little is known about whether or to what extent hereditary factors for CVD contribute additional risk in patients with rheumatoid arthritis. Objective: To assess the clinical impact of a parental history of CVD in patients with rheumatoid arthritis. Methods: Population based cohort study of 10 805 Swedish patients with rheumatoid arthritis aged 16–67 years during follow up (1990–2000). Parents, and cardiovascular deaths among patients and parents, were identified through register linkages. Relative risk of death v the general population was assessed using standardised mortality ratios (SMR), which were compared by Poisson regression. Results: Rheumatoid patients with a parental history of fatal CVD had an SMR of death from CVD of 2.9 (95% confidence interval, 2.5 to 3.4). By contrast, rheumatoid patients without a parental history of fatal CVD had an SMR of 1.7 (1.2 to 2.3). A parental death from CVD was associated with a 70% increase in the risk of fatal CVD in rheumatoid arthritis (SMR ratio = 1.7 (1.2 to 2.4), and an increase in the 10 year mortality from CVD from 5% to 10% in men and from 2% to 4% in women aged 50 to 67 years. Conclusions: Parental history of death from CVD is an important (and easily assessable) risk factor for fatal CVD in rheumatoid arthritis.

Liver cirrhosis may be complicated by the development of esophageal varices. The treatment of esophageal varices has changed radically during the last 30 years. Our aim was to study whether the prognosis for patients with esophageal varices had improved in Sweden between 1969 and 2002. We linked register data from the Hospital Discharge Register and from the Causes of Death Register at The National Board of Health in Sweden between 1969 and 2002 to identify and follow-up all patients with esophageal varices according to International Classification of Diseases-8, -9, and -10. There were 12,281 patients hospitalized with esophageal varices, and for all patients there was an increase in the 5-year survival in the years between 1969 and 1979 as opposed to the years between 1990 and 2002. Better survival occurred for women compared with men, for younger patients compared with older, and for patients hospitalized in the latest decade compared with the earlier decades. We found a significant decrease in the mortality caused by esophageal varices during the years studied but no decrease attributable to other causes. In conclusion, mortality for patients hospitalized with esophageal varices in Sweden decreased between 1969 and 2002. The decrease is seen for both 1- and 5-year mortality, and this suggests that the use of new treatment strategies both for acute variceal hemorrhage and secondary prophylaxis has had an impact on prognosis.

In Sweden, there is stable or slightly increased total alcohol consumption but a decrease in mortality in liver disease. The aim of the study was to determine the temporal relation between alcohol-related liver disease morbidity and mortality and type of alcohol beverage consumption.Data on patients with liver disease from the Swedish Hospital Discharge Register and from the Causes of Death Register between 1969 and 2001 were analysed. Data on the registered sales of the different beverages were taken from the Swedish State Monopoly.Liver disease mortality increased from 1969 to 1976, coinciding with the increase in sales of spirits. Both mortality and spirits sales decreased thereafter, whereas there was no decrease in beer or wine sales. Hospitalization rates were reduced after 1987. Depending on age and gender, there was a 30-80% 5-year mortality rate following discharge. Among men, but not among women, differences in the alcohol and non-alcohol-related liver diagnoses in the Hospital Discharge Register and in the Cause of Death Register were sometimes recorded in the same patient.There was a reduction in hospitalization rates and mortality in liver diseases, and the reduction in mortality in liver diseases in Sweden from 1969 to 2001 seems to be associated with sales of spirits. Patients hospitalized for liver disease have a poor prognosis. There were difficulties in differentiating between alcohol and non-alcohol liver diseases.

In Scandinavia, portable monitoring has virtually replaced standard polysomnography for diagnosis of obstructive sleep apnea syndrome (OSAS). Because waiting times for specialized OSAS care remain long, an accurate screening tool to exclude low-risk patients from diagnostic testing would be valuable.To examine the diagnostic accuracy of the Karolinska Sleep Questionnaire (KSQ) for OSAS.Consecutive patients, 30–66 years old, attending a large sleep clinic in Sweden for OSAS evaluation completed the KSQ and underwent in-home portable monitoring and medical history evaluation. OSAS was defined as apnea-hypopnea index ≥5 with symptoms of disease. We calculated sensitivity and specificity of apnea/snoring and sleepiness indices of the KSQ. Retrospectively, we combined six KSQ items (snoring, breathing cessations, disturbed sleep, etc.) and four clinical variables (age, sex, body mass index, smoking status) predictive of OSAS into a new instrument, which we also evaluated. Instrument score ranged between 0 and 21; a higher score indicated more severe symptoms.Of 103 patients, 62 were diagnosed with OSAS. Sensitivity and specificity of the indices were 0.56 and 0.68 (apnea/snoring), and 0.37 and 0.71 (sleepiness). The new instrument performed optimally at a score of 9. Sensitivity was 0.76 (95% confidence interval 0.63–0.86) and specificity 0.88 (0.74–0.96). Between 19.4% and 50.5% of patients were unaware of having apnea/snoring symptoms.Diagnostic accuracy of the apnea/snoring and sleepiness indices for OSAS was poor but could be improved by combining clinical and KSQ items. The usefulness of the apnea/snoring index and the combined instrument was questionable because of extensive symptom unawareness.

Background and aims: Several chronic inflammatory conditions are associated with an increased risk of lymphoma. Whether this applies to inflammatory bowel disease (IBD) is still unclear but of paramount interest, particularly in the safety evaluation of newer immunosuppressive drugs. Reports also indicate a possible increase in the risk of leukaemia in IBD. We therefore assessed the risk of haematopoietic cancers in a large cohort of patients with IBD. Subjects and methods: We performed a population based cohort study using prospectively recorded data, including 47 679 Swedish patients with Crohn’s disease (CD) or ulcerative colitis (UC) assembled from regional cohorts of IBD from 1955 to 1990 (n = 8028) and from the Inpatient Register of 1964–2000 (n = 45 060), with follow up until 2001. Relative risks were expressed as standardised incidence ratios (SIR). Results: Overall, we observed 264 haematopoietic cancers during follow up, which corresponded to a borderline significant 20% increased risk in both UC and CD. In UC, lymphomas occurred as expected (SIR 1.0, n = 87) but myeloid leukaemia occurred significantly more often than expected (SIR 1.8, n = 32). In CD, there was a borderline significant increased lymphoma risk (SIR 1.3, n = 65), essentially confined to the first years of follow up. Proxy markers of disease activity had little impact on lymphoma risk. Conclusion: On average, patients with IBD have a marginally increased risk of haematopoietic cancer. In UC, this is accounted for by an excess of myeloid leukaemia. In CD, a modest short term increase in the risk of lymphoma of unknown significance cannot be excluded but any long term risk increase seems unlikely.

Hyperparathyroidism onset at a young age is one feature in multiple endocrine neoplasia (MEN) type 1 and MEN type 2A cancer syndromes. There are several case reports of MEN Type 1-associated central nervous system (CNS) tumors. To determine if there is an association between parathyroid adenomas and CNS tumors, we used Swedish registry data to identify all individuals operated on for parathyroid adenomas between 1958-99 (n = 12,468). Follow-up for the occurrence of CNS tumors in these individuals was through linkage with the Swedish Cancer Registry. There were 70 observed cases of a CNS tumor diagnosed after a parathyroid adenoma, to be compared to 35 expected (standard incidence ratio [SIR] = 2.0; 95% confidence interval [CI] = 1.5-2.5). This increased risk was independent of duration of follow-up and was confined to meningiomas (SIR = 2.4, 95% CI = 1.7-3.4) and neurinomas (SIR = 3.4, 95% CI = 1.5-6.8). These results strongly indicate an association between these tumor forms that may be genetic, environmental (such as radiation) or a combination of both.

This study investigates personality traits and psychiatric status among 174 methadone patients (121 men and 53 women) and 387 untreated controls (191 men and 196 women) in Sweden in 1993 and 1994. The methadone patients were followed up to 1998 with respect to being expelled from treatment. Pretreatment factors, like home background and behavioral factors, were studied in relation to treatment outcome. The methadone patients were interviewed using a structured questionnaire about alcohol and drug use and psychological, social, and behavioral factors. To obtain data about personality traits, the patients were asked to fill in a questionnaire, the Karolinska Scales of Personality (KSP) questionnaire. The male methadone patients had significantly (p < 0.0001) higher scores on somatic anxiety, muscular tension, impulsiveness, and psychasthenia, and significantly lower scores with regard to socialization, social desirability, and inhibited aggression compared with the controls. Compared with the female controls, the female methadone patients differed most significantly (p < 0.0001) in respect of socialization. Low socialization, social desirability, detachment, feelings of guilt, and suspicion were most predictive for later expulsion from treatment. Nearly half of the methadone patients who suffered from human immunodeficiency virus (HIV) infection had difficulties with compliance with the treatment and were later expelled. The results suggest that awareness of personality traits and psychiatric status may be crucial for a better methadone treatment outcome.

Background Alcohol consumption levels and drinking patterns have been reported to vary between day and shift workers, although the results have been conflicting. Previous results indicate that questions about alcohol habits may be asked in the workplace. However, no studies have evaluated the Alcohol Use Disorders Identification Test (AUDIT) or the alcohol biomarker carbohydrate-deficient transferrin (CDT) in serum for this purpose. Aim To investigate, in conjunction with routine health examinations, whether there is any difference between permanent day and shift workers in high-risk alcohol consumption, according to the AUDIT and CDT. Gamma-glutamyl transferase (GGT) in serum was included mainly as a comparison test. Methods The employees who attended for a regular health examination during the study period were offered voluntary alcohol screening with the AUDIT and CDT. Results Altogether, 990 employees (day, two-shift, and three-shift workers) participated in the study, 194 (20%) of whom screened positive with the AUDIT and/or CDT. There were no significant differences in the screening results between day and shift workers, whereas significantly fewer of the two-shift workers (odds ratio = 0.5, 95% confidence interval = 0.3–0.9) screened positive with CDT. Conclusions The present findings on employees who attended for regular health examinations suggest that shift workers did not show a higher level of risky alcohol consumption than day workers, according to the results with the AUDIT, CDT and GGT. On the contrary, the two-shift workers appeared to drink significantly less.

Aims To detect risk factors for sudden death from heroin injection. Design Evaluation of data from forensic investigations of all fatal cases of suspected heroin death in a metropolitan area. Only cases with detectable morphine and 6-monoacetylmorphine (6-MAM) in blood were included in order to select heroin intoxication cases. Setting Stockholm, Sweden. Measurements Autopsy investigation and toxicological analysis of blood and urine; and police reports. Findings In two-thirds of the 192 cases, death occurred in public places, and mostly without any time delay. Blood concentrations of morphine ranged from 50 to 1200 ng/g, and of 6-MAM from 1 to 80 ng/g. Codeine was detected in 96% of the subjects. In the majority of cases the forensic investigation indicated polydrug use, the most common additional findings being alcohol and benzodiazepines. However, in one-quarter of the cases other drug combinations were found. Previous abstinence from heroin and use of alcohol were identified as risk factors. For 6-MAM there was also a correlation with the presence of THC and benzodiazepines. Despite a high frequency of heart abnormalities (e.g. myocarditis and focal myocardial fibrosis), these conditions did not correlate with morphine or 6-MAM blood concentrations. Conclusions We confirm that alcohol intake and loss of tolerance are risk factors for death from heroin use, whereas no connection to heart pathology was observed. Further, prospective, studies should focus on other possible risk factors.