Caroline E. Weibull

Prostate-specific Antigen (PSA) Testing Is Prevalent and Increasing in Stockholm County, Sweden, Despite No Recommendations for PSA Screening: Results from a Population-based Study, 2003–2011

BACKGROUND Prostate-specific antigen (PSA) testing has increased in several countries. There is incomplete knowledge of PSA testing patterns. OBJECTIVE Determine the prevalence of PSA testing and explore patterns of PSA retesting in Stockholm County, Sweden. DESIGN, SETTING, AND PARTICIPANTS A population-based study was performed. Through registry linkages, we collected population information, data on PSA tests, pathology reports, and clinical information. The study population comprised males living in Stockholm County in 2011 (n=1034129), of which 229 872 had a PSA test during the period 2003-2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We determined limited-duration-point prevalence of PSA testing and performed survival analysis on PSA retesting for men aged 40-89 yr. RESULTS AND LIMITATIONS The number of PSA tests increased from 54239 in 2003 to 124613 in 2011. During the 9-yr study period, 46%, 68%, and 77% of men without a prior prostate cancer (PCa) diagnosis and aged 50-59 yr, 60-69 yr, and 70-79 yr, respectively, had a PSA test. During 2010 and 2011, 25%, 40%, and 46% of men aged 50-59 yr, 60-69 yr, and 70-79 yr, respectively, had a PSA test. The prevalence of PSA testing increased from 2003 to 2011. The probability of retesting was PSA and age dependent, with a 26-mo cumulative incidence of 0.337 (95% confidence interval, 0.333-0.341) if the first PSA value was <1 ng/ml. The main limitations were (1) that PSA data prior to 2003 were not available and (2) that the study cohort was restricted to men who were alive in 2011. CONCLUSIONS Although screening for PCa is not recommended in Sweden, PSA testing in Stockholm County was high across ages ranging from 40 to 89 yr and increased during the period 2003-2011. The probability of PSA retesting was high, regardless of the original PSA level. These results contrast with current clinical recommendations and raise calls for a change, either through structured PCa testing or more detailed guidelines on PSA testing.

Parkinson's Disease and Cancer: A Register-based Family Study

We wanted to compare cancer incidence rates between Parkinsons disease (PD) patients and persons without PD, as well as between siblings of these groups. We conducted a family-based matched cohort study based on nationwide Swedish health registries and the Swedish Multi-Generation Register. We assessed risk of incident cancer in PD patients (n = 11,786) during 1964-2009 versus a matched cohort of PD-free individuals (n = 58,930) and in siblings of PD patients (n = 16,841) versus siblings of PD-free individuals (n = 84,205). Hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards regression. Cancer occurrence was slightly higher in PD patients than in PD-free individuals (hazard ratio (HR) = 1.05, 95% confidence interval (CI): 1.00, 1.10), largely because of cancers arising within 1 year before or after the index date for PD, but risk of smoking-related cancers was lower (HR = 0.87, 95% CI: 0.79, 0.96). PD patients had a higher risk of melanoma both up to 1 year before the PD index date (HR = 1.53, 95% CI: 1.23, 1.91) and from 1 year after the index date onward (HR = 1.46, 95% CI: 1.01, 2.10). In the sibling comparison, cancer occurrence was largely similar. These results indicate that melanoma risk is higher among PD patients and that mechanisms other than familial ones explain the association.

Severe head injury and amyotrophic lateral sclerosis

Abstract Our objective was to examine whether severe head injury, subtypes of head injury, or repeated head injuries are associated with ALS risk based on the Swedish population and health registers. We conducted a case-control study, nested within a cohort of 5,764,522 individuals who were born in Sweden during 1901–1970 and followed between 1991 and 2007. The study included 4004 ALS patients identified from the Swedish Patient Register during follow-up and 20,020 randomly selected controls matched by gender and birth year. We evaluated hospitalization for severe head injury that was recorded in the inpatient register before ALS diagnosis. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results showed that there was an association of ALS risk with severe head injury ≤ 1 year before diagnosis (OR: 3.9, 95% CI 2.6–6.1). No association was observed for severe head injury > 3 years before ALS diagnosis, nor was ALS associated with subtypes of head injury or repeated injuries occurring > 3 years before diagnosis. In conclusion, our findings from the Swedish registers provide no strong support for an etiological relationship between severe head injury in adulthood and ALS risk.

Rapid increase in multidrug‐resistant enteric bacilli blood stream infection after prostate biopsy—A 10‐year population‐based cohort study

Bloodstream infection following a transrectal prostate biopsy is a well‐known and feared complication. Previous studies have shown an increase in multi‐resistant bacterial infections as a consequence of higher usage of antibiotics in investigated populations. Our aim was to analyze bacterial resistance patterns in positive blood cultures, after prostate biopsies in Stockholm, Sweden, where the use of antibiotics has been low and decreasing during the last 10 years.

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

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

Temporal Trends in Incidence of Myocardial Infarction and Ischemic Stroke by Socioeconomic Position in Sweden 1987–2010

Background We analyzed temporal trends in the incidence of myocardial infarction and ischemic stroke in Sweden by socioeconomic position and investigated whether social inequalities in incidence of these diseases changed over time. Materials and Methods We studied a cohort of almost three million Swedish residents born between 1932 and 1960 followed from 1987 until 2010. Incident cases of myocardial infarction and ischemic stroke were identified in the Swedish National Inpatient Register and Cause of Death Register. Socioeconomic position was retrieved from the Population and Housing Censuses. Incidence rates of myocardial infarction and ischemic stroke and incidence rate ratios comparing levels of socioeconomic position were estimated using flexible parametric survival models adjusted for calendar year, attained age, sex, and birth country. Results The overall incidences of myocardial infarction and ischemic stroke decreased over time among men, but were stable over time among women. With regard to ischemic stroke incidence, socioeconomic inequality increased over time in the age group 55 to 59: the incidence rate ratios for low manual compared to high non-manual increased from 1.3 (95% CI: 1.2–1.4) in 1997 to 1.5 (1.4–1.7) in 2010 among men, and from 1.4 (1.3–1.6) in 1997 to 2.1 (1.8–2.5) in 2010 among women. The socioeconomic inequality in incidence of myocardial infarction was stable over time for both men and women. Conclusion There was a decrease in myocardial infarction and ischemic stroke incidence over time among men but no significant change for women. Our study highlights existing, and in some cases increasing, social inequalities in the incidence of cardiovascular diseases.

Association Between Maternal Smoking During Pregnancy and Severe Mental Illness in Offspring

Importance Several recent population-based studies have linked exposure to maternal smoking during pregnancy to increased risk of severe mental illness in offspring (eg, bipolar disorder, schizophrenia). It is not yet clear, however, whether this association results from causal teratogenic effects or from confounding influences shared by smoking and severe mental illness. Objective To examine the association between smoking during pregnancy and severe mental illness in offspring, adjusting for measured covariates and unmeasured confounding using family-based designs. Design, Setting, and Participants This study analyzed population register data through December 31, 2013, for a cohort of 1 680 219 individuals born in Sweden from January 1, 1983, to December 31, 2001. Associations between smoking during pregnancy and severe mental illness in offspring were estimated with adjustment for measured covariates. Cousins and siblings who were discordant on smoking during pregnancy and severe mental illness were then compared, which helped to account for unmeasured genetic and environmental confounding by design. Exposures Maternal self-reported smoking during pregnancy, obtained from antenatal visits. Main Outcomes and Measures Severe mental illness, with clinical diagnosis obtained from inpatient and outpatient visits and defined using International Classification of Diseases codes for bipolar disorder and schizophrenia spectrum disorders. Results Of the 1 680 219 offspring included in the analysis, 816 775 (48.61%) were female. At the population level, offspring exposed to moderate and high levels of smoking during pregnancy had greater severe mental illness rates than did unexposed offspring (moderate smoking during pregnancy: hazard ratio [HR], 1.25; 95% CI, 1.19-1.30; high smoking during pregnancy: HR, 1.51; 95% CI, 1.44-1.59). These associations decreased in strength with increasing statistical and methodologic controls for familial confounding. In sibling comparisons with within-family covariates, associations were substantially weaker and nonsignificant (moderate smoking during pregnancy: HR, 1.09; 95% CI, 0.94-1.26; high smoking during pregnancy: HR, 1.14; 95% CI, 0.96-1.35). The pattern of associations was consistent across subsets of severe mental illness disorders and was supported by further sensitivity analyses. Conclusions and Relevance This population- and family-based study failed to find support for a causal effect of smoking during pregnancy on risk of severe mental illness in offspring. Rather, these results suggest that much of the observed population-level association can be explained by measured and unmeasured factors shared by siblings.

Occupational exposures and the risk of amyotrophic lateral sclerosis.

Objectives To examine the associations of specific occupations and occupational exposures with the risk of amyotrophic lateral sclerosis (ALS) in the Swedish population. Methods A nested case–control study was conducted in Sweden. Patients with ALS diagnosed during 1991–2010 (n=5020) were identified from the National Patient Register and 5 controls per case (n=25 100) were randomly selected from the general Swedish population, individually matched to cases by birth year and sex. Occupational history was obtained from the Swedish censuses in 1970, 1980 and 1990. The Nordic Occupational Cancer Study Job Exposure Matrix was used to identify exposures related to individual occupations. Conditional logistic regression was used to estimate ORs and their 95% CIs. Results Higher risk of ALS was associated with precision-tool manufacturing (OR 1.68, 95% CI 1.11 to 2.52) and glass, pottery and tile work (OR 1.76, 95% CI 1.03 to 3.00), whereas lower risk was associated with textile work (OR 0.44, 95% CI 0.21 to 0.91). None of the examined occupational exposures were associated with ALS risk overall. However, among individuals younger than 65 years of age, an association with a higher risk of ALS was found for formaldehyde (OR 1.29, 95% CI 1.00 to 1.65), and an association with a lower risk of ALS was found for methylene chloride (OR 0.49, 95% CI 0.26 to 0.93). Conclusions We identified several occupations and occupational exposures that may be associated with the risk of ALS in Sweden. Occupational history obtained from censuses every 10 years remains a limitation of the study.

Childbearing and the Risk of Bladder Cancer: A Nationwide Population-based Cohort Study

BACKGROUND The incidence of bladder cancer (BCa) is substantially lower in women than in men, a difference that cannot be fully explained by established risk factors. Several studies suggest that hormonal and reproductive factors play a role in the development of BCa. OBJECTIVE To examine possible associations between patterns of childbearing and the risk of BCa. DESIGN, SETTING, AND PARTICIPANTS This cohort study encompassed >2 million women for whom information on reproductive history and BCa incidence was retrieved from Swedish population-based registers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Incidence rate ratios (IRRs) of BCa were estimated using Cox proportional hazards modelling. The exposures under investigation were parity and age at first birth, adjusted for education and history of chronic obstructive lung disease (COLD). RESULTS AND LIMITATIONS Among 2 009 811 women in the cohort, 2860 incident cases of BCa were identified. Parous women had lower incidence of BCa compared with nulliparous women (adjusted IRR: 0.80; 95% confidence interval [CI], 0.72-0.89). Moreover, the incidence was 15% lower in women with two children and 24% lower in women with three or more children compared with uniparous women. Compared with women aged 20-24 at first childbirth, the incidence was elevated in women with a first birth before age 20 (adjusted IRR: 1.16; 95% CI, 1.05-1.29). The risk of BCa was elevated in women with low education and among women with a history of COLD. Absence of data on menstrual history, use of exogenous hormones, and smoking was a limitation of the study. CONCLUSIONS The incidence of BCa decreased with increasing parity and older age at first birth. Although smoking habits may partly explain some of the associations, our findings provide support for yet-to-be-identified protective mechanisms associated with childbearing, possibly mediated by hormonal or structural changes following pregnancy.

Agreement between diagnoses of childhood lymphoma assigned in Uganda and by an international reference laboratory

Background Correct diagnosis is key to appropriate treatment of cancer in children. However, diagnostic challenges are common in low-income and middle-income countries. The objective of the present study was to assess the agreement between a clinical diagnosis of childhood non- Hodgkin lymphoma (NHL) assigned in Uganda, a pathological diagnosis assigned in Uganda, and a pathological diagnosis assigned in The Netherlands. Methods The study included children with suspected NHL referred to the Mulago National Referral Hospital, Kampala, Uganda, between 2004 and 2008. A clinical diagnosis was assigned at the Mulago National Referral Hospital, where tissue samples were also obtained. Hematoxylin and eosin-stained slides were used for histological diagnosis in Uganda, and were re-examined in a pathology laboratory in The Netherlands, where additional pathological, virological and serological testing was also carried out. Agreement between diagnostic sites was compared using kappa statistics. Results Clinical and pathological diagnoses from Uganda and pathological diagnosis from The Netherlands was available for 118 children. The agreement between clinical and pathological diagnoses of NHL assigned in Uganda was 91% (95% confidence interval [CI] 84–95; kappa 0.84; P < 0.001) and in The Netherlands was 49% (95% CI 40–59; kappa 0.04; P = 0.612). When Burkitt’s lymphoma was considered separately from other NHL, the agreement between clinical diagnoses in Uganda and pathological diagnoses in Uganda was 69% (95% CI 59–77; kappa 0.56; P < 0.0001), and the corresponding agreement between pathological diagnoses assigned in The Netherlands was 32% (95% CI 24–41; kappa 0.05; P = 0.326). The agreement between all pathological diagnoses assigned in Uganda and The Netherlands was 36% (95% CI 28–46; kappa 0.11; P = 0.046). Conclusion Clinical diagnosis of NHL in Uganda has a high probability of error compared with pathological diagnosis in Uganda and in The Netherlands. In addition, agreement on the pathological diagnosis of NHL between Uganda and The Netherlands is very low.