To investigate whether exposure to methadone affects the risk of motor vehicle accident with personal injury.
Cohort study linking three Norwegian administrative registries using unique person identifiers.
Information was retrieved from the Norwegian Prescription Database on any prescriptions ever received by the individuals for methadone and all prescriptions for benzodiazepines. The Norwegian Road Accident Registry provided information about motor vehicle accidents involving personal injuries on Norwegian roads. The Central Population Registry provided demographic information on all residents in Norway.
All Norwegian adults aged 18-69 years were observed for 2.5 years.
Standardized incidence ratio (SIR) was calculated by comparing the incidence of traffic accidents with personal injuries in patients exposed to methadone with the incidence in those not exposed.
During the 4626 person-years observed in patients exposed to methadone, there were 26 motor vehicle accidents. There were very few accidents among the females who received methadone and they had no increased risk of being involved in motor vehicle accidents (SIR 1.1; 95% CI 0.2-3.1). We observed an increased risk of involvement in accidents among males (SIR 2.4; 95% CI 1.5-3.6). This figure did not change significantly when exposure to benzodiazepines was excluded.
Men exposed to methadone appear to have an increased risk of being involved in motor vehicle accidents involving personal injuries. This increased risk could not be explained by exposure of benzodiazepines.
Studies have shown that lithium may cause psychomotor and cognitive impairment and impose an increased risk of traffic accidents. The antiepileptic drug valproate is also used as a mood stabilizer, but the impact on traffic safety has not been studied. The objective of the present study was to examine whether the use of lithium or valproate increased the risk of being involved in traffic accidents.
Between April 2004 and September 2006, information on prescriptions, road accidents and emigrations/deaths was obtained from three Norwegian population-based registries. Data on people between the ages 18-70 (3.1 million) were linked. Exposure consisted of receiving prescriptions for either lithium or valproate. Standardized incidence ratios (SIRs) were calculated by comparing the incidence of motor vehicle accidents during time exposed with the incidence over the time not exposed. Lithium was studied separately from valproate.
During the study period, 20,494 road accidents occurred including 36 while exposed to lithium and 31 while exposed to valproate. The overall accident risk was neither increased after having received prescriptions for lithium (SIR 1.3; 95%CI: 0.9-1.8), nor after having received a prescription for valproate (SIR 0.9; 0.6-1.3). The exception was a three-fold increase in risk for younger female drivers exposed to lithium.
We found no increase in the traffic accident risk after being exposed to lithium or valproate, except for young female drivers on lithium. This may be because these drugs carry no increased risk or because patients exposed to these drugs refrain from driving.
To examine associations between exposure to various subgroups of antipsychotic drugs and risk of hip fracture in older adults.
Nationwide cohort study.
Norway, 2005-2010.
Everyone living in Norway born before 1945 (N = 906,422).
Information was obtained on all prescriptions of antipsychotic drugs dispensed from 2004 to 2010 (Norwegian Prescription Database) and data on all primary hip fractures from 2005 to 2010 (Norwegian Hip Fracture Registry). Incidence rates of hip fracture during person-time exposed and unexposed to antipsychotic drugs were compared by calculating the standardized incidence ratio (SIR).
Thirty-nine thousand nine hundred thirty-eight (4.4%) participants experienced a primary hip fracture. Greater risk of hip fracture was associated with exposure to any antipsychotic (SIR = 2.1, 95% confidence interval (CI) = 1.9-2.1), first-generation antipsychotics (SIR = 2.0, 95% CI = 1.8-2.2), second-generation antipsychotics (SIR = 2.2, 95% CI = 1.9-2.4), prolactin-sparing antipsychotics (SIR = 2.4, 95% CI = 1.8-3.1) and prolactin-elevating antipsychotics (SIR = 2.0, 95% CI = 1.9-2.2).
In people aged 60 and older in Norway, those who took an antipsychotic drug had twice the risk of sustaining a hip fracture during exposure than during nonexposure. Although confounding by indication, comorbidity, or other drugs used cannot be excluded, this association is relevant for clinical practice because hip fracture and antipsychotic drug use are prevalent in vulnerable older individuals. Clinical studies examining mechanisms or causality of the observed association between antipsychotic drug use and excess risk of hip fracture are needed.
Several recent cohort studies have found an association between smoking and breast cancer, but the association between lifetime smoking exposure and breast cancer mortality is less well described. We examined whether smoking before breast cancer diagnosis is a predictor of breast cancer mortality in a large cohort with more than 4.1 million years of follow-up, with a special focus on women who initiated smoking before first childbirth. Information on smoking status was collected before breast cancer diagnosis and used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of breast cancer mortality in a cohort of 302,865 Norwegian women with 1106 breast cancer deaths. Women were enrolled between 1974 and 2003 and followed up through linkages to national registries until 31 December 2007. We found that breast cancer mortality was slightly but significantly increased for current (HR = 1.15, 95% CI 1.01-1.32) and ever (HR = 1.15, 95% CI 1.02-1.30) smokers as compared to never smokers. No statistically significantly increased mortality was found for women who initiated smoking before first childbirth, and no dose-response association was revealed for any of the different measures of smoking exposure. A large proportion of heavy smokers may have died from other causes than breast cancer during follow-up, possibly diluting our results. This study found that lifetime smoking exposure had a significantly increased risk of breast cancer mortality compared with never smokers.
Notes
Cites: Int J Cancer. 2013 Jan 15;132(2):401-1022539012
Cites: Br J Cancer. 2012 Nov 20;107(11):1901-723079577
Cites: Int J Cancer. 2007 Jun 15;120(12):2672-717278091
Cites: Lancet. 2013 Jan 12;381(9861):133-4123107252
Brain tumour has few established determinants. We assessed to which extent risk of brain tumour was related to metabolic syndrome factors in adults.
In the Me-Can project, 580?000 individuals from Sweden, Austria, and Norway were followed for a median of 10 years after baseline measurement. Data on brain tumours were obtained from national cancer registries. The factors of metabolic syndrome (BMI, SBP and DBP, and blood levels of glucose, cholesterol, and triglycerides), separately and combined, were analysed in quintiles and for transformed z-scores (mean transformed to 0 and standard deviation to 1). Cox proportional hazards multivariate regression models were used, with corrections for measurement error.
During follow-up, 1312 primary brain tumours were diagnosed, predominantly meningioma (n?=?348) and high-grade glioma (n?=?436). For meningioma, the hazard ratio was increased for z-scores of SBP [hazard ratio?=?1.27 per unit standard deviation, 95% confidence interval (CI) 1.03-1.57], of DBP (hazard ratio?=?1.29, 95% CI 1.04-1.58), and of the combined metabolic syndrome score (hazard ratio?=?1.31, 95% CI 1.11-1.54). An increased risk of high-grade glioma was found for DBP (hazard ratio?=?1.23, 95% CI 1.01-1.50) and triglycerides (hazard ratio?=?1.35, 95% CI 1.05-1.72). For both meningioma and high-grade glioma, the risk was more than double in the fifth quintiles of DBP compared to the lowest quintile. For meningioma this risk was even larger for SBP.
Increased blood pressure was associated with risk of brain tumours, especially of meningiomas.
Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment: 1.07 [95% CI: 1.04-1.09]) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI: 1.08-1.15) for men and 1.06 (95% CI: 1.02-1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women.
A large number of studies have explored the relation between body mass index (BMI) and mortality in adults. The relation between BMI in adolescence and mortality has been investigated to a lesser extent. It has been suggested that all-cause mortality is elevated among those who were overweight during adolescence, but the limitation of previous studies has been study size. The present study explored this relation in a Norwegian cohort of 227,003 boys and girls, aged 14-19 years, whose height and weight were measured during tuberculosis screening in 1963-1975. These persons were followed for an average of 31.5 years (about 7.2 million person-years). A total of 7,516 deaths were registered. Multivariate Cox proportional hazards regression models were used in the analyses. An increasing risk of death by increasing BMI in adolescence was observed. Mortality among males whose baseline BMI was between the 85th and 95th percentiles and above the 95th percentile in the US reference population was 30% and 80% higher, respectively, than that among those whose baseline BMI was between the 25th and 75th percentiles. The corresponding rates among females were 30% and 100%. The excess mortality among adolescents whose BMI was high was not clearly manifested before they reached their thirties. Hence, BMI in adolescence is predictive of adult mortality.
The authors estimated the association between asthma and body mass index in a 1963-2002 study of 135,000 Norwegians aged 14-60 years who were followed on average for 21 years. Cox proportional hazards regression models were fitted to estimate the relative risk of asthma adjusting for smoking, education, and physical activity. Compared with persons with a body mass index (weight (kg)/height (m)(2)) of less than 25, overweight (body mass index: 25-29) men and women had relative risks of asthma of 1.27 (95% confidence interval (CI): 1.13, 1.43) and 1.30 (95% CI: 1.17, 1.45), respectively, while obese (body mass index: >/=30) men and women had relative risks of 1.78 (95% CI: 1.35, 2.34) and 1.99 (95% CI: 1.67, 2.37), respectively. Stratified analyses revealed a similar association between body mass index and asthma for never smokers, ever smokers, persons with less than or equal to 12 years of education, and persons with more than 12 years of education. Analyses including all the covariates gave results similar to those not adjusting for these factors. The risk of asthma increased steadily with body mass index, from a body mass index of 20 in men and of 22 in women. In men, the risk of asthma increased by 10% with each unit of increased body mass index between 25 and 30. The similar value for women was 7%. Overweight or obese persons reported asthma more often than did thinner persons after adjustment for smoking, education, and physical activity.
To examine associations between birth defects and cancer from birth into adulthood.
Population based nested case-control study.
Nationwide health registries in Denmark, Finland, Norway, and Sweden.
62?295 cancer cases (0-46 years) and 724?542 frequency matched controls (matched on country and birth year), born between 1967 and 2014.
Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models.
Altogether, 3.5% (2160/62?295) of cases and 2.2% (15?826/724?542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (=20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk.
The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.
Avdeling for legemiddelepidemiologi, Divisjon for epidemiologi, Nasjonalt folkehelseinstitutt, Postboks 4404 Nydalen, 0403 Oslo. jorgen.bramness@fhi.no
In Norway there has in later years been much discussion of misuse of flunitrazepam. From 1 January 2003 the drug was moved up one level in the schedule of controlled substances. On 1 August 2004 the manufacturer of the Rohypnol brand withdrew it from the Norwegian market. How did these two events influence the sales and use of drugs containing flunitrazepam?
Sales figures for drugs containing flunitrazepam from the statistics database at the Norwegian Institute of Public Health were studied. The Norwegian prescription database was used to describe new (incident) users of flunitrazepam and the two brands of this drug sold in Norway in 2004.
Restrictions on the prescription status of flunitrazepam lead to a decrease in sales from 7.2 defined daily doses (DDD) per 1000 inhabitants per day in 2002 to 3.0 DDD per 1000 inhabitants per day in 2003. This decrease was only partly compensated for by an increase in the sales of nitrazepam (from 5.0 to 6.0 DDD per 1000 inhabitants per day). During the years 1999 to 2004 there was a steady increase in the sales of benzodiazepine-related hypnotics (zopiclone and zolpidem). This shift could mean a change from flunitrazepam to zopiclone. The withdrawal of Rohypnol in August 2004 had only minor effects on the total sales of flunitrazepam. The decline in sales of Rohypnol was almost compensated for by the increase in the overall sales of Flunipam. This was reflected in the fact that in the later months of 2004 there were many new (incident) users of Flunipam, but few new users of flunitrazepam-containing drugs in total. It could be concluded that the restrictions on prescription status of flunitrazepam had a much higher impact than the withdrawal of the Rohypnol brand.
