Johan Reutfors

Uppsala University, Uppsala, Uppsala, Sweden

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Publications (21)67.11 Total impact

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    ABSTRACT: Assessment of factors influencing antipsychotic prescription fills in the early phase of schizophrenia or schizoaffective disorder. 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. 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). 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.
    Journal of clinical psychopharmacology 10/2013; · 5.09 Impact Factor
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    ABSTRACT: Patients with schizophrenia are at increased risk of suicide, but data from controlled studies of pharmacotherapy in relation to suicide risk is limited. To explore suicide risk in schizophrenia in relation to medication with antipsychotics, antidepressants, and lithium. Of all patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n=4000), patients who died by suicide within five years from diagnosis were defined as cases (n=84; 54% male). Individually matched controls were identified from the same population. Information on prescribed medication was retrieved from psychiatric records in a blinded way. Adjusted odds ratios [OR] of the association between medication and suicide were calculated by conditional logistic regression. Lower suicide risk was found in patients who had been prescribed a second generation antipsychotic (clozapine, olanzapine, risperidone, or ziprasidone; 12 cases and 20 controls): OR 0.29 (95% confidence interval [CI], 0.09-0.97). When the 6 cases and 8 controls who had been prescribed clozapine were excluded, the OR was 0.23 (95% CI 0.06-0.89). No significant association was observed between suicide and prescription of any antipsychotic, depot injection antipsychotics, antidepressants, SSRI, or lithium. Lower suicide risk for patients who had been prescribed second generation antipsychotics may be related to a pharmacological effect of these drugs, to differences in adherence, or to differences in other patient characteristics associated with lower suicide risk.
    Schizophrenia Research 10/2013; · 4.59 Impact Factor
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    ABSTRACT: It is not clear which patients with a first psychotic episode will develop schizophrenia. We performed a diagnostic follow-up of patients treated for a first time non-affective, non-schizophrenia psychosis and explored potential predictors of a subsequent schizophrenia or schizoaffective diagnosis. This register-based cohort study comprises individuals born between 1973 and 1978 in Sweden, with a first hospital-treated psychosis excluding schizophrenia, schizoaffective disorder, bipolar disorder and depressive disorder with psychotic symptoms (n=1840). The patients were followed for five years regarding subsequent diagnoses. Psychiatric, social, family history of psychiatric illness, premorbid intellectual level, head injuries and obstetrical complications were investigated by logistic regression as predictors of schizophrenia or schizoaffective diagnosis. During the follow-up, 18% were diagnosed with schizophrenia or schizoaffective disorder, 5% were diagnosed with bipolar disorder, whereas 29% were not re-admitted to a psychiatric clinic. Patients with a first-degree relative hospitalized for schizophrenia and/or bipolar disorder had an increased risk of subsequent diagnosis for schizophrenia or schizoaffective disorder (odds ratio 1.9 and 95% confidence interval 1.1 to 3.0)), whereas previous severe criminality was associated with a decreased risk (odds ratio 0.5, 95% confidence interval 0.3-0.8). Diagnostic outcome was diverse after a first non-schizophrenia and non-affective psychosis. Family history of severe mental illness and no previous conviction for severe criminality were the strongest risk factors for a future schizophrenia or schizoaffective diagnosis.
    Schizophrenia Research 07/2013; · 4.59 Impact Factor
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    ABSTRACT: It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values) were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08-3.04), reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01-2.97; and OR = 2.03, 95% CI 1.32-3.13), hypertension with perphenazine (OR = 2.00, 95% CI 1.21-3.59), and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05-0.89) and positively with haloperidol (OR = 2.02, 95% CI 1.18-3.48). There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In conclusion, treatment with antipsychotic drugs is differentially associated with cardiovascular risk factors, even after adjusting for waist circumference, sex, age, and smoking.
    Neuropsychiatric Disease and Treatment 01/2013; 9:371-7. · 2.00 Impact Factor
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    ABSTRACT: Knowledge about the effects of exposure to the newer antipsychotics during pregnancy is limited. To investigate the effects of maternal use of antipsychotics during pregnancy on gestational diabetes and fetal growth. Population-based cohort study comparing women exposed and not exposed to antipsychotics during pregnancy. Exposure was defined as prescriptions filled. Swedish national health registers. All women giving birth in Sweden from July 1, 2005, through December 31, 2009, grouped by filled prescriptions for (1) olanzapine and/or clozapine, the most obesogenic and diabetogenic antipsychotics (n = 169), (2) other antipsychotics (n = 338), or (3) no antipsychotics (n = 357,696). Odds ratios (ORs) with 95% CIs for gestational diabetes and being small for gestational age (SGA) and large for gestational age for birth weight, birth length, and head circumference. Exposure to other antipsychotics was associated with an increased risk of gestational diabetes (adjusted OR, 1.77 [95% CI, 1.04-3.03]). The risk increase with olanzapine and/or clozapine was of similar magnitude but not statistical significance (adjusted OR, 1.94 [95% CI, 0.97-3.91]). Infants exposed to either group of antipsychotics had increased risks of being SGA on birth weight, whereas only exposure to other antipsychotics yielded increased risks of being SGA for birth length and head circumference. None of the risks for SGA measurements remained significant after adjusting for maternal factors. There were no increased risks of being large for gestational age for birth weight or birth length after exposure to olanzapine and/or clozapine, but the risk increased for head circumference (OR, 3.02 [95% CI, 1.60-5.71]). Women who used antipsychotics during pregnancy had increased risks of gestational diabetes. The increased risks of giving birth to an SGA infant seemed to be an effect of confounders, such as smoking. Except for macrocephaly, olanzapine and/or clozapine exposure was not associated with anabolic fetal growth.
    Archives of general psychiatry 07/2012; 69(7):715-21. · 12.26 Impact Factor
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    ABSTRACT: Makris GD, Reutfors J, Ösby U, Isacsson G, Frangakis C, Ekbom A, Papadopoulos FC. Suicide seasonality and antidepressants: a register-based study in Sweden. Objective:  Seasonality of completed suicides with a peak in spring and early summer is a well-documented finding. The circannual serotonergic functioning is hypothesized to be central in this phenomenon. Antidepressant medications exert their pharmacological action mainly by regulating serotonin. Our aim is to study the amplitude of the seasonal effect among suicide victims positive for different classes of antidepressants or without any antidepressants at the time of death. Method:  By using Swedish Registers, 12 448 suicides with forensic data for antidepressive medication and information on in-patient-treated mental disorder were identified during 1992-2003. Seasonality was estimated with a Poisson regression variant of the circular normal distribution of completed suicides. Results:  Higher suicide seasonality was found for individuals treated with selective serotonin reuptake inhibitor (SSRIs) compared to those with other antidepressant treatment or without any antidepressant treatment. The finding is more evident for men and violent suicide methods and those without history of in-patient treatment. Conclusion:  Our results provide preliminary support for the serotonergic hypothesis of suicide seasonality and raise the question of a possible accentuation of the natural suicide seasonality in patients treated with SSRIs, a hypothesis that warrants further investigation.
    Acta Psychiatrica Scandinavica 06/2012; · 4.86 Impact Factor
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    ABSTRACT: To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. Population based cohort study using data from national health registers. Sweden. 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)-those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy-or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263). Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations. Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women. Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.
    BMJ (Clinical research ed.). 01/2012; 345:e7085.
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    ABSTRACT: 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.
    Schizophrenia Research 12/2011; 133(1-3):36-41. · 4.59 Impact Factor
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2011; 21.
  • European Psychiatry - EUR PSYCHIAT. 01/2011; 26:1885-1885.
  • European Psychiatry - EUR PSYCHIAT. 01/2011; 26:1915-1915.
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    ABSTRACT: Earlier studies of patients with schizophrenia have investigated suicide risk in relation to specific psychiatric symptoms, but it remains to be better understood how suicide risk relates to the diagnostic profile in these patients. We identified all patients with a first clinical ICD-diagnosis of schizophrenia, schizophreniform or schizoaffective disorder in Stockholm County between 1984 and 2000. Patients who died by suicide within five years from diagnosis were defined as cases (n=84) and were individually matched with a similar number of living controls from the same population. Sociodemographic and clinical variables were retrieved from hospital records through a blind process. DSM-IV lifetime diagnoses for cases and controls were derived using the OPCRIT algorithm. A schizophrenia spectrum diagnosis (i.e. schizophrenia, schizophreniform or schizoaffective disorder) was assigned by OPCRIT to 50% of the suicide cases and 62% of the controls. Criteria for schizophrenia were met by 41% of the cases and 51% of the controls; for schizoaffective disorder by 8% of the cases and 10% of the controls; for other psychosis by 23% of the cases and 25% of the controls; and for mood disorder by 26% of the cases and 12% of the controls. Using the schizophrenia diagnosis as a reference, suicide risk was significantly higher in patients meeting criteria for a mood disorder diagnosis with an adjusted odds ratio of 3.3 (95% CI 1.2-9.0). In patients with a clinical schizophrenia spectrum diagnosis, a DSM-IV mood disorder diagnosis increases the suicide risk more than three-fold.
    Schizophrenia Research 11/2010; 123(2-3):251-6. · 4.59 Impact Factor
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    ABSTRACT: Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increasing use of antidepressants. To investigate on the individual level the hypothesis that antidepressant medication was a causal factor. Data on the toxicological detection of antidepressants in 18 922 suicides in Sweden 1992-2003 were linked to registers of psychiatric hospitalization as well as registers with sociodemographic data. The probability for the toxicological detection of an antidepressant was lowest in the non-suicide controls, higher in suicides, and even higher in suicides that had been psychiatric in-patients but excluding those who had been in-patients for the treatment of depression. The finding that in-patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.
    Acta Psychiatrica Scandinavica 04/2010; 122(6):454-60. · 4.86 Impact Factor
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    ABSTRACT: The aim of this study was to estimate suicide risk during hospitalization and in the year following discharge for patients with mental disorders. All suicide cases in Sweden 18 years and older, between 1991 and 2003 (N=20,675; 70% male), were individually matched to 10 controls from the general Swedish population. Discharge diagnoses in the year before suicide of any mental disorder, mood disorder, schizophrenia spectrum disorder, and alcohol use disorder were identified from the Swedish Patient Register. Highest suicide risk during hospitalization and in the year following discharge was found for mood disorder [odds ratio (OR) 55 (95% CI, 47-65) for men and 86 (95% CI, 70-107) for women], with the risk peaking in the first week following discharge [OR 177 (95% CI, 78-401) for men and OR 268 (95% CI, 85-846) for women]. Compared to that for mood disorder, the suicide risk for schizophrenia spectrum disorder and alcohol use disorder was about half and more constant over time. The majority of suicide victims with a psychiatric diagnosis had been discharged from psychiatric treatment more than a month before the suicide. Over time, a constant proportion of 25% of the suicide victims had been hospitalized with a mental disorder in the year before suicide (23% of males and 31% of females), despite a significant decrease in psychiatric hospitalizations in the population. In conclusion, suicide risk was found to vary by type of mental disorder, time since discharge, and sex. This should be taken into account when planning suicide preventive efforts.
    Journal of psychiatric research 02/2010; 44(12):741-7. · 3.72 Impact Factor
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    ABSTRACT: Little is known as to whether suicide seasonality is related to psychiatric disorders affecting suicide risk/incidence. The present study aims to assess suicide seasonality patterns with regard to the history of psychiatric morbidity among suicide victims. The history of psychiatric inpatient diagnoses in the five years prior to suicide was identified among all suicides in Sweden from 1992 to 2003. Suicide seasonality was estimated as the relative risk of suicide during the month of highest to that in the month of lowest suicide incidence. Analyses were performed with respect to sex, suicide method and history of inpatient treatment of psychiatric disorder. Among both male (n=9,902) and female (n=4,128) suicide victims, there were peaks in suicide incidence in the spring/early summer. This seasonal variation was more evident in suicide victims with a psychiatric inpatient diagnosis than in those without such a diagnosis. A seasonal variation was found in most diagnostic groups, with significant peaks in males with a history of depression and in females with a history of a neurotic, stress-related, or somatoform disorder. Overall, suicide seasonality was more evident in violent than in non-violent suicide methods. Only psychiatric disorders severe enough to require hospital admission were studied. A history of inpatient-treated psychiatric disorder appears to be associated with an increase in suicide seasonality, especially in violent suicide methods. This increase is found in several psychiatric disorders.
    Journal of affective disorders 04/2009; 119(1-3):59-65. · 3.76 Impact Factor
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    ABSTRACT: Previous reports regarding risk factors for suicide in schizophrenia have been inconclusive. We performed a matched case-control study of in-patient-treated schizophrenia patients in order to assess the suicide risk associated with socioeconomic, demographic, and psychiatric factors. The cases were 84 patients who died by suicide within five years after diagnosis in a cohort of all patients discharged for the first time from psychiatric hospitals in Stockholm County, Sweden, with a diagnosis of schizophrenia, schizophreniform disorder or schizoaffective disorder between the years 1984 and 2000. One control was individually and randomly matched with each case from the same cohort by date (+/-1 year) and age (+/-5 years) at index diagnosis. Data were retrieved from clinical records of the case-control pairs in a blind fashion. Of the suicides, 54% were men and 46% were women. In multivariate analyses, higher educational attainment (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.03-8.0), age >or=30 years at onset of symptoms (OR 4.8, CI 1.1-21.2), and a history of a suicide attempt requiring non-psychiatric medical treatment (OR 5.0, CI 1.6-15.4) were found to be significantly associated with an increased suicide risk. Gender did not significantly affect the suicide risk, nor did a history of self-discharge, compulsory in-patient treatment, substance-use disorder or a family history of mental disorders or suicide. In schizophrenia, certain suicide risk factors may differ from those in the general population. Clinical suicide risk assessment for schizophrenia patients should be performed taking this into account.
    Schizophrenia Research 02/2009; 108(1-3):231-7. · 4.59 Impact Factor
  • European Psychiatry - EUR PSYCHIAT. 01/2008; 23.
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    ABSTRACT: Earlier research has indicated a positive association between coeliac disease (CD) and some mental disorders. Studies on CD and depression have inconsistent findings and we know of no study of CD and the risk of bipolar disorder (BD). We used Cox regression to investigate the risk of subsequent mood disorders (MD); depression and BD in 13,776 individuals with CD and 66,815 age- and sex-matched reference individuals in a general population-based cohort study in Sweden. We also studied the association between prior MD and CD through conditional logistic regression. CD was associated with an increased risk of subsequent depression (Hazard ratio (HR)=1.8; 95% CI=1.6-2.2; p<0.001, based on 181 positive events in individuals with CD and 529 positive events in reference individuals). CD was not associated with subsequent BD (HR=1.1; 95% CI=0.7-1.7; p=0.779, based on 22 and 99 positive events). Individuals with prior depression (OR=2.3; 95% CI=2.0-2.8; p<0.001) or prior BD (OR=1.7; 95% CI=1.2-2.3; p=0.001) were at increased risk of a subsequent diagnosis of CD. Study participants with CD and MD may have more severe disease than the average patient with these disorders since they were identified through a hospital-based register. CD is positively associated with subsequent depression. The risk increase for CD in individuals with prior depression and BD may be due to screening for CD among those with MD.
    Journal of Affective Disorders 04/2007; 99(1-3):117-26. · 3.30 Impact Factor
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    ABSTRACT: Childhood leukaemia incidence in Costa Rica during 1981-96, among the highest in the world, was analysed by histology, gender, birth year, time period of diagnosis, age at diagnosis and region. Numbers of cases were extracted from the database of the National Cancer Registry (RNT) of Costa Rica. Person-years at risk were calculated from census data and post-census population estimates. During the follow-up, 918 cases of leukaemia in children under 15 years (510 boys, 408 girls) were reported to the RNT (41% of all childhood malignancies), with an overall age-standardised incidence rate of 56 per million person-years. Acute lymphocytic leukaemia (ALL) represented 79% and acute non-lymphocytic leukaemia (ANLL) 16% of the cases, with rates of 43 and 9 per million person-years respectively. There were downward trends in incidence of total leukaemias, ALL and ANLL and 'not otherwise specified' (NOS) combined. Incidence of ALL was highest at 1-4 years of age in boys and girls, whereas ANLL peaked in girls during the first year of life. During 1991-96, the decrease in ALL was significant (P = 0.042). A multivariable Poisson regression model identified significant excesses of ALL for boys, for age groups 1-4 and 5-9 years and for three out of seven regions. Possible reasons for the high rates in Costa Rica are discussed.
    Paediatric and Perinatal Epidemiology 08/2002; 16(3):210-8. · 2.16 Impact Factor
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    ABSTRACT: Incidence rates of malignant central nervous system (CNS) tumours in children in Costa Rica are presented in an international perspective. For the 16-year period 1981-96, a total of 256 CNS tumours were registered in children below age 15 years by the National Tumour Registry of Costa Rica. The age-standardised incidence rate was 15.2 per million person-years, with a male-to-female ratio of 1.4. The median age-standardised incidence rates of selected registries in other Latin American countries were 19.3, in other developing countries 12.0 and in industrialised countries 29.6 per million person-years. The comparatively low incidence rates in Costa Rica were evident in all diagnostic subgroups, most notably in the youngest age group and for tumours in the brain stem. In the Central Valley, where the capital and the only specialised paediatric hospital are situated, the crude incidence rate was 18.1 [95% CI 15.1, 21.1] compared with 10.5 [95% CI 8.3, 12.8] per million person-years in the rest of the country (RR = 1.7, 95% CI 1.3, 2.3). There was no evidence of any increase over time. The data in this study cannot exclude under-diagnosis and, to a lesser degree, under-registration as a partial explanation of the low incidence rates of malignant CNS tumours in children in Costa Rica.
    Paediatric and Perinatal Epidemiology 08/2002; 16(3):219-25. · 2.16 Impact Factor

Publication Stats

117 Citations
67.11 Total Impact Points


  • 2013
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 2002–2013
    • Karolinska Institutet
      • • Center for Pharmacoepidemiology - CPE
      • • Institutionen för medicin, Huddinge
      • • Institutet för miljömedicin - IMM
      Solna, Stockholm, Sweden