Previous research updated the mortality experience of North American synthetic rubber industry workers during the period 1944-1998, determined if leukemia and other cancers were associated with several employment factors and carried out Poisson regression analysis to examine exposure-response associations between estimated exposure to 1,3-butadiene (BD) or other chemicals and cancer. The present study used Cox regression procedures to examine further the exposure-response relationship between several unlagged and lagged, continuous, time-dependent BD exposure indices (BD parts per million (ppm)-years, the total number of exposures to BD concentrations >100 ppm ("peaks") and average intensity of BD) and leukemia, lymphoid neoplasms and myeloid neoplasms. All three BD exposure indices were associated positively with leukemia. Using continuous, untransformed BD ppm-years the regression coefficient (beta) from an analysis that controlled only for age was 2.9 x 10(-4) (p
The incidence of cardiovascular events remains high in patients with myocardial infarction (MI) despite advances in current therapies. New and better methods for identifying patients at high risk of recurrent cardiovascular (CV) events are needed. This study aimed to analyze the predictive value of an oral glucose tolerance test (OGTT) in patients with acute myocardial infarction without known diabetes mellitus (DM).
The prospective cohort study consisted of 123 men and women aged between 31-80 years who had suffered a previous MI 3-12 months before the examinations. The exclusion criteria were known diabetes mellitus. Patients were followed up over 6.03???1.36 years for CV death, recurrent MI, stroke and unstable angina pectoris. A standard OGTT was performed at baseline.
Randomized clinical trials have shown that use of 5a-reductase inhibitors (5-ARIs) lowers overall prostate cancer (PCa) risk compared to placebo, while the proportion of Gleason 8-10 tumors is elevated. It is unknown whether this affects PCa-specific survival. We studied disease-specific survival by 5-ARI usage in a cohort of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancer-specific deaths. For comparison, survival among alpha-blocker users was also evaluated. During the median follow-up of 7.5 years after diagnosis a total of 2,478 men died; 617 due to prostate cancer and 1,861 due to other causes. The risk of prostate cancer death did not differ between 5-ARI users and nonusers (multivariable adjusted HR 0.94, 95% CI 0.72-1.24 and HR 0.98, 95% CI 0.69-1.41 for usage before and after the diagnosis, respectively). Alpha-blocker usage both before and after diagnosis was associated with increased risk of prostate cancer death (HR 1.29, 95% CI 1.08-1.54 and HR 1.56, 95% CI 1.30-1.86, respectively). The risk increase vanished in long-term alpha-blocker usage. Use of 5-ARIs does not appear to affect prostate cancer mortality when used in management of benign prostatic hyperplasia. Increased risk associated with alpha-blocker usage should prompt further exploration on the prognostic role of lower urinary tract symptoms.
Drug dependency may develop during long-term benzodiazepine use, indicated, for example, by dose escalation. The first benzodiazepine chosen may affect the risk of dose escalation.
To detect possible differences in benzodiazepine use between new users of diazepam and oxazepam over time.
This 5-year prescription database study included 19 747 new benzodiazepine users, inhabitants of Norway, aged 30-60 years, with first redemption for diazepam or oxazepam.
Individuals starting on diazepam versus oxazepam were analysed by logistic regression with sex, age, other drug redemptions, prescriber's specialty, household income, education level, type of work, and vocational rehabilitation support as background variables. Time to reach a daily average intake of =1 defined daily doses (DDD) over a 3-month period was analysed using a Cox proportional hazard regression model.
New users of oxazepam had a higher risk for dose escalation compared with new users of diazepam. This was true even when accounting for differences in sociodemographic status and previous drug use (hazard ratio [HR] 1.33, 95% confidence interval = 1.17 to 1.51).
Most doctors prescribed, according to recommendations, oxazepam to individuals they may have regarded as prone to and at risk of dependency. However, these individuals were at higher risk for dose escalation even when accounting for differences in sociodemographic status and previous drug use. Differences between the two user groups could be explained by different preferences for starting drug, DDD for oxazepam being possibly too low, and some unaccounted differences in illness.
To determine the risk of injury associated with the new use of individual benzodiazepines and dosage regimens in the elderly.
Prospective database cohort study with 5 years of follow-up.
Two hundred fifty-three thousand two hundred forty-four persons aged 65 and older who were nonusers of benzodiazepines in the year before follow-up.
Population-based hospitalization and prescription and medical services claims databases were used to compare the risk of injury during periods of benzodiazepine use with those of nonuse. Periods of use were measured for 10 insured benzodiazepines by drug and dose as time-dependent covariates. Injury was defined as the first occurrence of a nonvertebral fracture, soft-tissue injury, or accident-related hospital admission. Patient age, sex, previous injury history, concomitant medication use, and comorbidity were measured as fixed and time-dependent confounders. Cox proportional hazards models were used to estimate the risk of injury with benzodiazepine use and to determine the extent to which patient characteristics, differences in dosage, or in the effect of increasing dosage for individual drugs explained differences between drugs.
More than one-quarter (27.6%) of 253,244 elderly were dispensed at least one prescription for a benzodiazepine, and 17.7% of elderly were treated for at least one injury during follow-up, of which fractures were the most common. Patient characteristics, systematic differences in the risk of injury in elderly prescribed different benzodiazepines, and differences in dosage prescribed for individual drugs confounded the risk of injury with benzodiazepine use. The risk of injury with increasing dosage varied by drug from a hazard ratio of 0.92 (95% confidence interval (CI)=0.60, 1.42) for alprazolam to 2.20 (95% CI=1.39, 3.47) for flurazepam per 1 standardized adult dose increase.
The risk of injury varied by benzodiazepine, independent of half-life, as did the risk associated with increasing dosage for individual products. Higher doses of oxazepam, flurazepam, and chlordiazepoxide are associated with the greatest risk of injury in the elderly.
To prospectively explore the significance of sense of humor for survival over 7 years in an adult county population.
Residents in the county of Nord-Trøndelag, Norway, aged 20 and older, were invited to take part in a public health survey during 1995-97 (HUNT-2), and 66,140 (71.2 %) participated. Sense of humor was estimated by responses to a cognitive (N = 53,546), social (N = 52,198), and affective (N = 53,132) item, respectively, taken from the Sense of Humor Questionnaire (SHQ). Sum scores were tested by Cox survival regression analyses applied to gender, age, and subjective health.
Hazard ratios were reduced with sense of humor (continuous scale: HR = 0.73; high versus low by median split: HR = 0.50) as contrasted with increase of HR with a number of classical risk factors (e.g., cardiovascular disease: HR = 6.28; diabetes: HR = 4.86; cancer: HR = 4.18; poor subjective health: HR = 2.89). Gender proved to be of trivial importance to the effect of sense of humor in survival. Subjective health correlated positively with sense of humor and therefore might have presented a spurious relation of survival with humor, but sense of humor proved to reduce HR both in individuals with poor and good subjective health. However, above age 65 the effect of sense of humor on survival became less evident.
Sense of humor appeared to increase the probability of survival into retirement, and this effect appeared independent of subjective health. Age under 65 mediated this effect, whereas it disappeared beyond this age.
To report outcomes for 1,111 men treated with iodine-125 brachytherapy (BT) at a single institution.
A total of 1,111 men (median age, 63) were treated with iodine-125 prostate BT for low- or intermediate-risk prostate cancer between March 1999 and November 2008. Median prostate-specific antigen (PSA) level was 5.4 ng/ml (range, 0.9-26.1). T stage was T1c in 66% and T2 in 34% of patients. Gleason score was 6 in 90.1% and 7 or 8 in 9.9% of patients. Neoadjuvant hormonal therapy (2-6 months course) was used in 10.1% of patients and combined external radiotherapy (45 Gy) with BT (110 Gy) in 4.1% (n = 46) of patients. Univariate and multivariate Cox proportional hazards were used to determine predictors of failure.
Median follow-up was 42 months (range, 6-114), but for biochemical freedom from relapse, a minimum PSA test follow-up of 30 months was required (median 54; n = 776). There were 27 failures, yielding an actuarial 7-year disease-free survival rate of 95.2% (96 at risk beyond 84 months). All failures underwent repeat 12-core transrectal ultrasound -guided biopsies, confirming 8 local failures. On multivariate analysis, Gleason score was the only independent predictor of failure (p = 0.001; hazard ratio, 4.8 (1.9-12.4). Median International Prostate Symptom score from 12 to 108 months ranged between 3 and 9. Of the men reporting baseline potency, 82.8% retained satisfactory erectile function beyond 5 years.
Iodine-125 prostate BT is a highly effective treatment option for favorable- and intermediate-risk prostate cancer and is associated with maintenance of good urinary and erectile functions.
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
Diabetes prevalence is associated with low socioeconomic status (SES), but less is known about the relationship between SES and diabetes incidence.
Data from eight cycles of the National Population Health Survey (1994/1995 through 2008/2009) are used. A sample of 5,547 women and 6,786 men aged 18 or older who did not have diabetes in 1994/1995 was followed to determine if household income and educational attainment were associated with increased risk of diagnosis of or death from diabetes by 2008/2009. Three proportional hazards models were applied for income and for education--for men, for women and for both sexes combined. Independent variables were measured at baseline (1994/1995). Diabetes diagnosis was assessed by self-report of diagnosis by a health professional. Diabetes death was based on ICD-10 codes E10-E14.
Among people aged 18 or older in 1994/1995 who were free of diabetes, 7.2% of men and 6.3% of women had developed or died from the disease by 2008/2009. Lower-income women were more likely to develop type 2 diabetes than were those in high-income households. This association was attenuated, but not eliminated, by ethno-cultural background and obesity/overweight. Associations with lower educational attainment in unadjusted models were almost completely mediated by demographic and behavioural variables.
Social gradients in diabetes incidence cannot be explained entirely by demographic and behavioural variables.
The mRNA expression of 17beta-hydroxysteroid dehydrogenase (17HSD) types 1 and 2 enzymes catalyzing opposite reaction of estrogen metabolism was investigated in colon cancer. Further, the significance of the 17HSD type 2 enzyme as a possible marker of colorectal cancer (CRC) prognosis was studied. In the normal mucosa, 17HSD type 2 mRNA was predominantly expressed in the surface epithelium and in the upper parts of the crypts. In the lamina propria expression was seen in endothelial cells and mononuclear phagocytes. In colorectal tumors, 17HSD type 2 expression was in most cases downregulated. Female patients had significantly more cancers with high 17HSD type 2 mRNA expression (n=11/35; 31%) than male patients (n=3/39; 8%) (P=0.02). We observed a significant impact of 17HSD type 2 mRNA expression on survival in female patients with distal colorectal cancer (n=24), with an overall cumulative 5-year survival rate of 54% in those with low 17HSD type 2 mRNA expression. None of the female patients with high 17HSD type 2 mRNA expression survived (n=11; P=0.0068; log rank 7.32). In male patients, no significant association with survival was observed. Our data provide evidence suggesting that low 17HSD type 2 mRNA expression is an independent marker of favorable prognosis in females with distal colorectal cancer, supporting the presence of gender- and location-related differences in the pathogenesis of colon cancer.