The introduction of second-generation antipsychotic drugs during the 1990s is widely believed to have adversely affected mortality of patients with schizophrenia. Our aim was to establish the long-term contribution of antipsychotic drugs to mortality in such patients.
Nationwide registers in Finland were used to compare the cause-specific mortality in 66 881 patients versus the total population (5.2 million) between 1996, and 2006, and to link these data with the use of antipsychotic drugs. We measured the all-cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs, and exposure to the six most frequently used antipsychotic drugs compared with perphenazine use.
Although the proportional use of second-generation antipsychotic drugs rose from 13% to 64% during follow-up, the gap in life expectancy between patients with schizophrenia and the general population did not widen between 1996 (25 years), and 2006 (22.5 years). Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine (adjusted hazard ratio [HR] 1.41, 95% CI 1.09-1.82), and the lowest risk for clozapine (0.74, 0.60-0.91; p=0.0045 for the difference between clozapine vs perphenazine, and p
Comment In: Lancet. 2009 Nov 7;374(9701):1591; author reply 1592-319897117
Comment In: Lancet. 2009 Nov 7;374(9701):1591; author reply 1592-319897118
Comment In: Lancet. 2009 Aug 22;374(9690):590-219595448
Comment In: Lancet. 2009 Nov 7;374(9701):1592; author reply 1592-319897121
Comment In: Lancet. 2009 Nov 7;374(9701):1592; author reply 1592-319897120
It has been suggested that abortions leave the breast epithelium in a proliferative state with an increased susceptibility to carcinogenesis. Results from previous studies of induced or spontaneous abortions and risk of subsequent breast cancer are contradictory, probably due to methodological considerations. We investigated the relationship between abortions and subsequent breast cancer risk in a case-control study using prospectively recorded exposure information. The study population comprised women recorded in the population-based Swedish Medical Birth Register between 1973-91. Cases were defined by linkage of the birth register to the Swedish Cancer Register and controls were randomly selected from the birth register. From the subjects' antenatal care records we abstracted prospectively collected information on induced and spontaneous abortions, as well as a number of potential confounding factors. Relative risk of breast cancer was estimated by odds ratios (OR) with 95% confidence intervals (95% CI). A reduced risk of breast cancer was observed for women with a history of at least 1 compared to no abortions (adjusted OR = 0.84, 95% CI = 0.72-0.99). The adjusted OR decreases step-wise with number of abortions to 0.59 (95% CI = 0.34-1.03) for 3 or more compared to no abortions. The patterns are similar for induced and spontaneous abortions. In conclusion, neither a history of induced nor spontaneous abortions is associated with an increased risk of breast cancer. Our data suggest a protective effect of pregnancies regardless of outcome.
Comment In: Int J Cancer. 2004 May 10;109(6):945-6; author reply 947-815027130
The focus of this study was to determine whether there were any significant differences in academic achievement between students with a cleft and the general population of Swedish students at the typical time of graduation from compulsory school (usually 16 years of age).
A retrospective population-based study. Data were obtained from the Swedish Medical Birth Register for the years 1973 through 1986 and were linked to the Swedish School-Grade Register.
A total of 511 individuals with cleft palate (CP), 651 individuals with cleft lip (CL), and 830 individuals with cleft lip and palate (CLP) were compared with a control group consisting of 1,249,404 individuals.
(1) Not receiving school leaving certificate; (2) odds of receiving lowest grade and reduced odds of receiving a high grade in the following subjects: (a) Mathematics, (b) English, (c) Swedish, (d) Physical Education, and (e) grade point average (GPA).
The group with cleft had higher odds of not receiving leaving certificates in comparison with the general population. They also had higher odds of receiving the lowest grade and/or reduced odds of receiving a high grade in the subjects analyzed together, with strong evidence of lower GPA in comparison with the general population. Individuals with CP were affected the most, followed by individuals with CLP; least affected were individuals with CL.
This study clearly indicates that adolescents with cleft lip and/or palate in Sweden experience significant deficits in their educational achievements in compulsory school.
This paper reports register data on a consecutive series of 141 children and teenagers hospitalized due to firearm injuries during a 21-year period in a community with restrictive firearm laws. Most of the injuries were minor and hospitalization was short. Shot by an air gun resulting in an eye injury was the most frequent reason for hospitalization. The patients hospitalized due to firearm injuries were compared with a control group composed of 141 individuals matched pair-wise for sex and age. The total morbidity during the follow-up period of on average 10 years was higher among patients compared with controls concerning both somatic diseases and injuries. All cases of severe psychopathology were found in the patient group. Criminality was higher among patients compared with controls and the former were younger at the time of the first crime compared with the latter. This study indicates that, irrespective of firearm laws, young people suffering from firearm injuries, even if the injury is classified as accidental, run a higher risk of becoming psychosocially disadvantaged and criminal as adults. This makes preventative measures highly necessary not only from a societal point of view, but also to avoid individual suffering in this high-risk group of youngsters.
We evaluated whether the association between low education and greater risk of dementia is explained by genetic influences, using three different types of analyses. The HARMONY study (Swedish for "health" (Hälsa), "genes" (ARv), "environment" (Miljö), "and" (Och), and "new" (NY)) includes members of the Swedish Twin Registry who were aged 65 and older and alive in 1998, and who were screened and clinically assessed for dementia. There were 394 cases with dementia and 7786 unrelated controls. Analyses included co-twin control, tests for association between education and a measured genotype, and bivariate twin modeling. Low education was a significant risk factor for dementia both in case-control analyses (odds ratio=1.77, 95% confidence interval 1.38 to 2.28) and co-twin control analyses with monozygotic twin pairs (odds ratio=3.17, 95% confidence interval 1.26 to 7.93). Apolipoprotein E genotype was not associated with education and did not account for the relationship between education and dementia. Bivariate twin modeling showed that the association between education and dementia was not mediated by genetic influences in common between education and dementia. The association was mediated by shared environmental influences that were related to both dementia and to education. Low education is confirmed as a risk factor for dementia. Findings from three different analytic approaches showed that genetic influences did not explain this association.
OBJECTIVE: To evaluate the reliability of self-reported family history of cancer in first-degree female relatives and to examine possible determinants of accurate reporting. METHODS: Women with ovarian cancer and controls were recruited between 1995 and 1999 and interviewed. The study comprised 579 cases and 1,564 controls with 6,265 first-degree female relatives. Self-reported familial cancer diagnoses were validated from registry data. Sensitivity, specificity, and kappa were calculated, and possible determinants were examined by logistic regression. RESULTS: The sensitivity of self-reporting ranged from 0.78 to 0.90 for all cancers but was lower for self-reporting of most site-specific cancers, ranging from 0.29 to 0.94. The specificity of self-reporting ranged from 0.91 to 0.99 for cancer in general and from 0.99 to 1.00 for site-specific cancers. Type of relative, age at interview, and length of education influenced the sensitivity and specificity significantly. The odds ratio for ovarian cancer was higher when based on registry data than on self-reported data and was significant (OR = 2.58 vs. 1.56). CONCLUSIONS: Cancer diagnoses in first-degree relatives are not always accurately reported by patients with ovarian cancer or by controls. The results indicate that studies of associations with family cancer history should validate self-reported family cancer diagnoses as carefully as possible.
To study risk factors for acute pancreatitis, here with emphasis on gastro-intestinal diseases and their treatments.
Population based case-control study covering four areas in Sweden encompassing 2.2 million inhabitants. Included were 462 incident cases of acute pancreatitis aged 20-85 years, hospitalized from 1 January 1995-31 May 1998, and 1,781 unmatched controls randomly selected from the study base using a population register. Information was captured from medical records and structured telephone interviews.
Current use of H(2) antagonists starting within 6 months of index-date was associated with acute pancreatitis with an adjusted OR of 4.9 (95% confidence interval (CI) 1.6-15), and current use of proton pump inhibitors (PPIs) with an adjusted OR of 3.2 (95%CI 1.4-7.4). For both drug classes, the ORs tended to be higher at higher doses. Gastritis/gastro-esophageal reflux disease (GERD) within the last 12 months not treated with PPIs or H(2)-antagonists and inflammatory bowel disease (IBD) not treated with anti-inflammatory or immunosuppressive drugs were associated with development of acute pancreatitis with adjusted odds ratios (OR) of 1.9 (95%CI 1.2-3.0) and 5.1 (95%CI 2.0-13) respectively.
Current IBD without treatment and gastritis/GERD without treatment were found to be associated with increased risks to develop acute pancreatitis but the nature of the latter association needs to be further evaluated. On balance, we judge that the observed associations between current use of H(2)-antagonists and PPIs and increased risk of acute pancreatitis are unlikely to be explained by bias.
Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted.
This paper discusses the misclassification that occurs when relying solely on routine register data in family studies of disease clustering. A register study of familial aggregation of schizophrenia is used as an example. The familial aggregation is studied using a regression model for the disease in the child including the disease status of the parents as a risk factor. If all the information is found in the routine registers then the disease status of the parents is only known from the time when the register started and if this information is used unquestioningly the parents who have had the disease before this time are misclassified as disease-free. Two methods are presented to adjust for this misclassification: regression calibration and an EM-type algorithm. These methods are used in the schizophrenia example where the large effect of having a schizophrenic mother hardly shows any signs of bias due to misclassification. The methods are also studied in simulations showing that the misclassification problem increases with the disease frequency.
Given the greatly elevated risks of contralateral breast cancer (CBC) observed in breast cancer patients who carry mutations in BRCA1 and BRCA2, it is critical to determine the effectiveness of standard adjuvant therapies in preventing CBC in mutation carriers. The WECARE study is a matched, case-control study of 708 women with CBC as cases and 1,399 women with unilateral breast cancer (UBC) as controls, including 181 BRCA1/BRCA2 mutation carriers. Interviews and medical record reviews provided detailed information on risk factors and breast cancer therapy. All study participants were screened for BRCA1 and BRCA2 mutations using denaturing high-performance liquid chromatography (DHPLC) to detect genetic variants in the coding and flanking regions of the genes. Conditional logistic regression was used to compare the risk of CBC associated with chemotherapy and tamoxifen in BRCA1/BRCA2 mutation carriers and non-carriers. Chemotherapy was associated with lower CBC risk both in non-carriers (RR = 0.6 [95% CI: 0.5-0.7]) and carriers (RR = 0.5 [95% CI: 0.2-1.0]; P value = 0.04). Tamoxifen was associated with a reduced CBC risk in non-carriers (RR = 0.7 [95% CI: 0.6-1.0]; P value = 0.03). We observed a similar but non-significant reduction associated with tamoxifen in mutation carriers (RR = 0.7 [95% CI: 0.3-1.8]). The tests of heterogeneity comparing carriers to non-carriers did not provide evidence for a difference in the associations with chemotherapy (P value = 0.51) nor with tamoxifen (P value = 0.15). Overall, we did not observe a difference in the relative risk reduction associated with adjuvant treatment between BRCA1/BRCA2 mutation carriers and non-carriers. However, given the higher absolute CBC risk in mutation carriers, the potentially greater impact of adjuvant therapy in reducing CBC risk among mutation carriers should be considered when developing treatment plans for these patients.