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Background Benefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied. Methods A total of 344 556 individuals (20–79 years, 52 % women) recruited from population-based health screening during 1985–2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of 99 mg/dl (< 0.78, 0.78–1.01, 1.04–1.27, 1.30–1.53, 1.55–1.79, 1.81–2.04, 2.07–2.31, 2.33–2.56, >2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health. Results During a mean follow-up of 22 years, 69 505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50–59 mg/dl (1.30–1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels >99 mg/dl (>2.56 mmol/L) were 1.32 (1.21–1.43), 1.05 (0.89–1.24), 1.26 (1.09–1.46) and 1.68 (1.48–1.90) for all–cause, CVD, cancer and non–CVD/non–cancer mortality, respectively. For HDL-C levels Conclusions Higher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.

Background Several studies have shown that women and men with two children have lower mortality than the childless, but there is less certainty about mortality, including CVD mortality, at higher parities and meagre knowledge about factors underlying the parity–mortality relationship. Methods The association between parity and CVD mortality was analyzed by estimating discrete-time hazard models for women and men aged 40–80 in 1975–2015. Register data covering the entire Norwegian population were used, and the models included a larger number of relevant sociodemographic control variables than in many previous studies. To analyze the relationship between parity and seven CVD risk factors, logistic models including the same variables as the mortality models were estimated from the CONOR collection of health surveys, linked to the register data. Results Men (but not women) who had four or more children had higher mortality from CVD than those with two, although this excess mortality was not observed for the heart disease sub-group. Overweight, possibly in part a result of less physical activity, seems to play a role in this. All CVD risk factors except smoking and alcohol may contribute to the relatively high CVD mortality among childless. Conclusions Childbearing is related to a number of well-known CVD risk factors, and becoming a parent or having an additional child is, on the whole, associated with lower—or at least not higher—CVD mortality in Norway. However, for men family sizes beyond three children are associated with increased CVD mortality, with risks of overweight one possible pathway.

Aims Alcohol consumption has been linked to colorectal cancer (CRC) and also to the high-density lipoprotein cholesterol level (HDL-C). HDL-C has been associated with the incidence of CRC. The aim of this study was to investigate the association between self-reported alcohol consumption, HDL-C and incidence of CRC, separately for the two sites. Methods Altogether, 250,010 participants in Norwegian surveys have been followed-up for an average of 18 years with respect to a first-time outcome of colon or rectal cancer. During follow-up, 3023 and 1439 colon and rectal cancers were registered. Results For men, the HR per 1 drink per day was 1.05 with 95% confidence interval (0.98–1.12) for colon and 1.08 (1.02–1.15) for rectal cancer. The corresponding figures for women were 1.03 (0.97–1.10) and 1.05 (1.00–1.10). There was a positive association between alcohol consumption and HDL-C. HDL-C was inversely associated with colon cancer in men (0.74 (0.62–0.89) per 1 mmol/l) and positively associated with rectal cancer, although not statistically significant (1.15 (0.92–1.44). A robust regression that assigned weights to each observation and exclusion of weights ≤ 0.1 increased the HRs per 1 drink per day and decreased the HR per 1 mmol/l for colon cancer. The associations with rectal cancer remained unchanged. Conclusion Our results support a positive association between alcohol consumption and colon and rectal cancer, most pronounced for rectal cancer. Considering the positive relation between alcohol consumption and HDL-C, the inverse association between HDL-C and colon cancer in men remains unsettled., Short Summary: This study showed that the relation between alcohol consumption is somewhat stronger for rectal cancer than for colon cancer. Although there is a positive relation between levels of HDL and alcohol consumption, the relation between HDL and colon cancer in men is inverse. This finding warrants further studies.

AimsWhile investigators have typically quantified the health risk of passive smoking by utilising self-reported exposure, prospective studies with objective ascertainment, which are less liable to measurement error, are rare. Using data pooling, we examined the relation of a biochemical assessment of passive smoking, salivary cotinine, with mortality from a range of causes.MethodsWe combined data from twelve cohort studies from England and Scotland initiated between 1998 and 2008. Study members were linked to national death registries. A total of 36 584 men and women aged 16 to 85 years of age reported that they were non-smoking at baseline, provided baseline salivary cotinine, and consented to mortality record linkage.ResultsA mean of 8.1 years of mortality follow-up of 36 584 non-smokers (16 792 men and 19 792 women) gave rise to 2367 deaths (775 from cardiovascular disease, 780 from all cancers, and 289 from smoking-related cancers). After controlling for a range of covariates, a 10 ng/ml increase in salivary cotinine level was related to an elevated risk of total (hazard ratios; 95% confidence interval: 1.46; 1.16, 1.83), cardiovascular (1.41; 0.96, 2.09), cancer (1.49; 1.00, 2.22) and smoking-related cancer mortality (2.92; 1.77, 4.83).ConclusionsPassive smoking assessed biomedically was a risk factor for a range of health outcomes known to be causally linked to active smoking.

Aim The aim of this study was to investigate whether the coffee brewing method is associated with any death and cardiovascular mortality, beyond the contribution from major cardiovascular risk factors. Methods and results Altogether, 508,747 men and women aged 20–79 participating in Norwegian cardiovascular surveys were followed for an average of 20 years with respect to cause-specific death. The number of deaths was 46,341 for any cause, 12,621 for cardiovascular disease (CVD), 6202 for ischemic heart disease (IHD), and 2894 for stroke. The multivariate adjusted hazard ratios (HRs) for any death for men with no coffee consumption as reference were 0.85 (082–0.90) for filtered brew, 0.84 (0.79–0.89) for both brews, and 0.96 (0.91–1.01) for unfiltered brew. For women, the corresponding figures were 0.85 (0.81–0.90), 0.79 (0.73–0.85), and 0.91 (0.86–0.96) for filtered, both brews, and unfiltered brew, respectively. For CVD, the figures were 0.88 (0.81–0.96), 0.93 (0.83–1.04), and 0.97 (0.89–1.07) in men, and 0.80 (0.71–0.89), 0.72 (0.61–0.85), and 0.83 (0.74–0.93) in women. Stratification by age raised the HRs for ages ≥60 years. The HR for CVD between unfiltered brew and no coffee was 1.19 (1.00–1.41) for men and 0.98 (0.82–1.15) for women in this age group. The HRs for CVD and IHD were raised when omitting total cholesterol from the model, and most pronounced in those drinking ≥9 of unfiltered coffee, per day where they were raised by 9% for IHD mortality. Conclusion Unfiltered brew was associated with higher mortality than filtered brew, and filtered brew was associated with lower mortality than no coffee consumption.

Surprisingly few attempts have been made to quantify the simultaneous contribution of well-established risk factors to CVD mortality differences between countries. We aimed to develop and critically appraise an approach to doing so, applying it to the substantial CVD mortality gap between Russia and Norway using survey data in three cities and mortality risks from the Emerging Risk Factor Collaboration. We estimated the absolute and relative differences in CVD mortality at ages 40–69 years between countries attributable to the risk factors, under the counterfactual that the age- and sex-specific risk factor profile in Russia was as in Norway, and vice-versa. Under the counterfactual that Russia had the Norwegian risk factor profile, the absolute age-standardized CVD mortality gap would decline by 33.3% (95% CI 25.1–40.1) among men and 22.1% (10.4–31.3) among women. In relative terms, the mortality rate ratio (Russia/Norway) would decline from 9–10 to 7–8. Under the counterfactual that Norway had the Russian risk factor profile, the mortality gap reduced less. Well-established CVD risk factors account for a third of the male and around a quarter of the female CVD mortality gap between Russia and Norway. However, these estimates are based on widely held epidemiological assumptions that deserve further scrutiny.

Background and Aims The time post-release from prison involves elevated mortality, especially overdose deaths. Variations in overdose mortality both by time since release from prison and time of release has not been investigated sufficiently. Our aims were to estimate and compare overdose death rates at time intervals after prison release and to estimate the effect on overdose death rates over calendar time. Design, Setting, Participants, Measurements This 15-year cohort study includes all individuals (n = 91 090) released from prison (1 January 2000 to 31 December 2014) obtained from the Norwegian prison registry, linked to the Norwegian Cause of Death Registry (2000–14). All-cause and cause-specific mortality were examined during different time-periods following release: first week, second week, 3–4 weeks and 2–6 months, and by three different time intervals of release. We calculated crude mortality rates (CMRs) per 1000 person-years and estimated incidence rate ratios (IRR) by Poisson regression analysis adjusting for time intervals after prison release, release periods and time spent in prison. Findings Overdose deaths accounted for 85% (n = 123) of all deaths during the first week following release (n = 145), with a peak during the 2 days immediately following release. Compared with week 1, the risk of overdose death was more than halved during week 2 [IRR = 0.43; 95% confidence interval (CI) = 0.31–0.59] and reduced to one-fifth in weeks 3–4 (IRR = 0.22; 95% CI = 0.16–0.31). The risk of overdose mortality during the first 6 months post-release was almost twofold higher in 2000–04 compared with 2005–09 (IRR = 0.53; 95% CI = 0.43–0.65) and 2010–14 (IRR = 0.47; 95% CI = 0.37–0.59). The risk of overdose death was highest for those incarcerated for 3–12 months compared with those who were incarcerated for shorter or longer periods, and recidivism was associated with risk of overdose death. Conclusions There is an elevated risk of death from drug overdose among individuals released from Norwegian prisons, peaking in the first week. The risk has reduced since 2000–04, but is greatest for those serving 3–12 months compared with shorter or longer periods.

Background Guidelines for the prevention of cardiovascular disease recommend the estimation of an individual's total risk. We have developed a new model for the prediction of the 10-year risk of incident acute myocardial infarction or cerebral stroke based on Norwegian data, NORRISK 2. Design The model was based on 10-year follow-up of a large population-based cohort (CONOR) through linkage to the CVDNOR project, a database of cardiovascular disease hospital discharge diagnoses and mortality in Norway in 1994-2009. Methods We used the Fine and Gray regression model to estimate the 10-year risk adjusting for competing risk. The model population consisted of participants in 1994-1999 and the external validation population of participants in 2000-2003. We validated the model by area under the receiver operating characteristic curves, calibration plots and analyses of sensitivity and specificity. Results The model population consisted of 31,445 men and 35,267 women aged 40-79 years with 3658 endpoints in men and 2459 in women. The external validation population consisted of 19,980 men and 19,309 women, of whom 1858 men and 874 women had an endpoint during follow-up. The area under the curve was 0.79 (0.79-0.80) in men and 0.84 (0.83-0.85) in women in the model population and was slightly lower in the external validation population. Calibration plots showed good agreement between observed and predicted risk. The sum of sensitivity and specificity was greatest around the suggested risk thresholds. Conclusion The NORRISK 2 model showed good validity in an external dataset and will be a valuable tool to guide decisions about preventive interventions in people without known previous cardiovascular disease.

Purpose To study the association between coffee and alcoholic beverage consumption and alcoholic liver disease mortality. Methods In total, 219,279 men and women aged 30–67 years attended cardiovascular screening in Norway from 1994 to 2003. Linkage to the Cause of Death Registry identified 93 deaths from alcoholic liver disease. Coffee consumption was categorized into four levels: 0, 1–4, 5–8, and greater than or equal to 9 cups/d and alcohol consumption as 0, greater than 0 to less than 1.0, 1.0 to less than 2.0, and greater than or equal to 2.0 units/d, for beer, wine, liquor, and total alcohol consumption. Results The hazard ratios per one category of consumption were 2.06 (95% confidence interval 1.62–2.61), 0.68 (0.46–1.00), and 2.54 (1.92–3.36) for beer, wine, and liquor, respectively. Stratification at 5 cups/d (the mean) revealed a stronger association between alcohol consumption and alcoholic liver disease at less than 5 versus 5 or more cups/d. With less than 5 cups/d, 0 alcohol units/d as reference, the hazard ratio reached to 25.5 (9.2–70.5) for greater than or equal to 2 units/d, whereas with greater than or equal to 5 cups/d, it reached 5.8 (1.9–17.9) for greater than or equal to 2 units/d. A test for interaction was significant (P = .01). Conclusions Coffee and wine consumption were inversely associated with alcoholic liver disease death. Total alcohol consumption was adversely associated with alcoholic liver disease mortality and the strength of the association varied with the level of coffee consumption.

OBJECTIVE To quantify concentrations of cartilage oligomeric matrix protein (COMP) and fibromodulin in synovial fluid from the tarsocrural joints (TCJs) of horses with osteochondritis dissecans (OCD) of the distal intermediate ridge of the tibia and determine whether concentrations would change following arthroscopic removal of osteochondral fragments. ANIMALS 115 client-owned horses with OCD of the TCJ and 29 control horses euthanized for unrelated reasons. PROCEDURES COMP and fibromodulin concentrations were measured in synovial fluid from the TCJs of the affected horses before and after osteochondral fragments were removed arthroscopically and in synovial fluid from the TCJs of the control horses after euthanasia. Synovial biopsy specimens from the TCJs of affected and control horses were examined histologically for evidence of inflammation. RESULTS Synovial fluid COMP and fibromodulin concentrations prior to surgery in horses with OCD were not significantly different from concentrations in control horses. Fibromodulin, but not COMP, concentration in horses with OCD was significantly decreased after surgery, compared with the concentration before surgery. Fibromodulin concentration was significantly correlated with joint effusion score but not with lameness score or results of a flexion test and was correlated with histologic score for number of synoviocytes on the surface of the synovium but not with score for degree of infiltration of inflammatory cells in the synovium. Synovial fluid COMP concentration was not significantly correlated with clinical or histologic findings. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that fibromodulin, but not COMP, could potentially be a biomarker of joint inflammation in horses with OCD of the TCJ.

We tested whether teetotalism explains the upturn in cardiovascular risk for non-drinkers and whether wine is a more favorable alcohol type. We studied 115,592 men and women aged 40–44 years who participated in the age 40 program in Norway in 1994–1999 and were followed for an average of 16 years with 550 cardiovascular deaths. Self-reported number of glasses of beer, wine and spirits during 14 days was transformed to alcohol units/day. One unit is approximately 8 grams of pure alcohol. The mean and median number of alcohol units/day were 0.70 and 0.46. Teetotallers had higher risk of dying from cardiovascular disease than alcohol consumers, multivariate adjusted hazard ratio (95% CI) 1.97 (1.52–2.56). The use of alcohol-related deaths as endpoint substantiated a selection of previous alcohol users to the teetotal group. Without teetotallers there was no association between alcohol consumption and cardiovascular disease mortality. However, the multivariate adjusted hazard ratio per one unit/day of wine was 0.76 (0.58–0.99). The corresponding figures for beer and spirits were 1.04 (0.94–1.15) and 0.98 (0.75–1.29). The upturn in risk for non-drinkers could be explained by a higher risk for teetotallers who likely included previous alcohol users or teetotalers who started to drink during follow-up. Wine gave the most favorable risk estimates.

Background: There is insufficient epidemiological evidence on the relationship between type of coffee and the risk of prostate cancer. Methods: The risk of prostate cancer by use of boiled vs not boiled coffee were assessed in a prospective study of 224,234 men 20–69 years. 5740 incident prostate cancers were identified. Results: With no coffee as reference group the hazard ratios of

Hip fractures are associated with increased mortality and their incidence in Norway is one of the highest worldwide. The aim of this nationwide study was to examine short- and long-term mortality after hip fractures, burden of disease (attributable fraction and potential years of life lost), and time trends in mortality compared to the total Norwegian population. Information on incident hip fractures between 1999 and 2008 in all persons aged 50. years and older was collected from Norwegian hospitals. Death and emigration dates of the hip fracture patients were obtained through 31 December 2010. Standardized mortality ratios (SMRs) were calculated and Poisson regression analyses were used for the estimation of time trends in SMRs. Among the 81,867 patients with a first hip fracture, the 1-year excess mortality was 4.6-fold higher in men, and 2.8-fold higher in women compared to the general population. Although the highest excess mortality was observed during the first two weeks post fracture, the excess risk persisted for twelve years. Mortality rates post hip fracture were higher in men compared to women in all age groups studied. In both genders aged 50. years and older, approximately 5% of the total mortality in the population was related to hip fractures. The largest proportion of the potential life-years lost was in the relatively young-old, i.e. less than 80. years. In men, the 1-year absolute mortality rates post hip fracture declined significantly between 1999 and 2008, by contrast, the mortality in women increased significantly relatively to the population mortality.

A potential link between intimate partner violence (IPV) and cardiovascular disease (CVD) has been suggested, yet evidence is scarce. We assessed cardiovascular risk and incident prescription of cardiovascular medication by lifetime experiences of physical and/or sexual IPV and psychological IPV alone in women.A population-based cohort study of women aged 30-60 years was performed using cross-sectional data and clinical measurements from the Oslo Health Study (2000-2001) linked with prospective prescription records from the Norwegian Prescription Database (January 1, 2004 to December 31, 2009). We used age-standardized chi-square analyses to compare clinical characteristics by IPV cross-sectionally, and Cox proportional hazards regression to examine cardiovascular drug prescription prospectively.Our study included 5593 women without cardiovascular disease or drug use at baseline. Altogether 751 (13.4%) women disclosed IPV experiences: 415 (7.4%) physical and/or sexual IPV and 336 (6.0 %) psychological IPV alone. Cross-sectional analyses showed that women who reported physical and/or sexual IPV and psychological IPV alone were more often smokers compared with women who reported no IPV. Physical and/or sexual violence was associated with abdominal obesity, low high-density lipoprotein cholesterol, and elevated triglycerides. The prospective analysis showed that women who reported physical and/or sexual IPV were more likely to receive antihypertensive medication: incidence rate ratios adjusted for age were 1.27 (95% confidence interval 1.02-1.58) and 1.36 (CI 1.09-1.70) after additional adjustment for education and systolic and diastolic blood pressure, respectively. No significant differences were found for cardiovascular drugs overall or lipid modifying drugs.Our findings indicate that clinicians should assess the cardiovascular risk of women with a history of physical and/or sexual IPV, and consider including CVD prevention measures as part of their follow-up.

Overweight-obesity and smoking are two main preventable causes of premature death. Because the relationship between smoking and body mass index (BMI) complicates the interpretation of associations between BMI and death risks, direct estimates of risks associated with joint exposures are helpful. We have studied the relationships of BMI and smoking to middle age (40-69 years) death risk-overall and by causes-in a Norwegian cohort of 32,727 women and 33,475 men who were 35-49 years old when baseline measurements and lifestyle information were collected in 1974-1988. Individuals with a history of cancer, cardiovascular disease or diabetes at baseline were excluded. Mortality follow-up was through 2009. The relationship between BMI and middle age death risk was U-shaped. Overall middle age death risks were 11% in women and 21 % in men. The combination of obesity and heavy smoking resulted in fivefold increase in middle age death risks in both women and men: For women middle age death risk ranged from 6 % among never smokers in the 22.5-24.9 BMI group to 31% (adjusted 28%) in obese (BMI > 30 kg/m(2)) heavy smokers (≥20 cigarettes/day). The corresponding figures in men were 10% and 53% (adjusted 45%). Obese never smokers and light (1-9 cigarettes/day) smokers in the 22.5-24.9 BMI groups both experienced a twofold increase in middle age risks of death. For women, cancer (56%) was the most common cause of death followed by cardiovascular disease (22%). In men, cardiovascular disease was most common (41%) followed by cancer (34%). Cardiovascular disease deaths were more strongly related to BMI than were cancer deaths.

The time post-release from prison involves elevated mortality, especially overdose deaths. Variations in overdose mortality both by time since release from prison and time of release has not been investigated sufficiently. Our aims were to estimate and compare overdose death rates at time intervals after prison release and to estimate the effect on overdose death rates over calendar time.This 15-year cohort study includes all individuals (n = 91 090) released from prison (1 January 2000 to 31 December 2014) obtained from the Norwegian prison registry, linked to the Norwegian Cause of Death Registry (2000-14). All-cause and cause-specific mortality were examined during different time-periods following release: first week, second week, 3-4 weeks and 2-6 months, and by three different time intervals of release. We calculated crude mortality rates (CMRs) per 1000 person-years and estimated incidence rate ratios (IRR) by Poisson regression analysis adjusting for time intervals after prison release, release periods and time spent in prison.Overdose deaths accounted for 85% (n = 123) of all deaths during the first week following release (n = 145), with a peak during the 2 days immediately following release. Compared with week 1, the risk of overdose death was more than halved during week 2 [IRR = 0.43; 95% confidence interval (CI) = 0.31-0.59] and reduced to one-fifth in weeks 3-4 (IRR = 0.22; 95% CI = 0.16-0.31). The risk of overdose mortality during the first 6 months post-release was almost twofold higher in 2000-04 compared with 2005-09 (IRR = 0.53; 95% CI = 0.43-0.65) and 2010-14 (IRR = 0.47; 95% CI = 0.37-0.59). The risk of overdose death was highest for those incarcerated for 3-12 months compared with those who were incarcerated for shorter or longer periods, and recidivism was associated with risk of overdose death.There is an elevated risk of death from drug overdose among individuals released from Norwegian prisons, peaking in the first week. The risk has reduced since 2000-04, but is greatest for those serving 3-12 months compared with shorter or longer periods.

Background: While hypertension still is a major health problem worldwide, some studies have indicated that the blood pressure level has decreased in some populations. This population based cohort study aims at analysing blood pressure changes in a large Norwegian population over a 22 year period. Methods: Data is acquired from three comprehensive health surveys of the HUNT Study conducted from 1984–86 to 2006–08. All citizens of Nord-Trøndelag County, Norway, >20 years were invited: 74,549 individuals participated in 1984–86; 64,523 in 1995–97; and 43,905 in 2006–08. Results: Both systolic and diastolic blood pressure levels decreased substantially from mid 1980s to mid 2000s, with the most pronounced decrease from 1995–97 to 2006–08 (from 136.0/78.9 to 128.3/70.9 mmHg in women and from 140.1/82.1 to 133.7/76.5 mmHg in men). Although the use of blood pressure lowering medication increased, there was a considerable decrease even in those who reported never use of medication (mean decrease 6.8/7.2 mmHg in women and 6.3/5.3 mmHg in men), and the decrease was most pronounced in the elderly (mean decrease 16.1/12.4 mmHg in women and 14.7/10.4 mmHg in men aged 80+). Mean heart rate, total cholesterol and daily smoking decreased, self-reported hard physical activity increased, while body weight and the prevalence of diabetes increased during the same period. Conclusions: The BP decrease might seem paradoxically, as body weight and prevalence of diabetes increased during the same period. Salt consumption might have decreased, but no salt data is available. The parallel decrease in mean heart rate might indicate reduction in the white-coat phenomenon, or increased use of beta blockers or calcium channel blockers for other diagnosis than hypertension. Additionally, the data could support the “healthy obese” hypothesis, i.e., that subgroups in the population can sustain obesity without serious health consequences. © 2016 Holmen et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Declining incidences of hip fractures are reported from western countries. Norway has among the highest rates in the world. The aim of this study was to investigate trends in total hip fracture rates in Norway between 1999 and 2008 and risk of second hip fractures. All hospitalizations given a hip fracture diagnosis code (International Classification of Diseases (ICD) 9 or ICD 10) (cervical, trochanteric or subtrochanteric) in Norwegian hospitals were retrieved with accompanying surgical procedure codes and additional diagnoses. A total of 93,123 hip fractures were identified between 1999 and 2008 in persons ≥50 years. Annual incidences of hip fractures were calculated and tested for trends. Rates of first and second hip fractures (2006-2008) were compared. The age-standardized total incidence of hip fracture decreased by 13.4 % (95 % confidence interval (CI): 11.0-15.6) in women and 4.8 % (95 % CI: 0.7, 8.7) in men. Age-adjusted rates of second hip fractures did not change in the observation period. In those with a prior hip fracture, the age-standardized risk of a subsequent hip fracture was 2.5-fold (95 % CI: 2.5, 2.6) in women, and 4.6-fold (95 % CI: 4.5, 4.7) in men. Total hip fracture rates declined in both genders during 1999-2008, whereas rates of second hip fractures did not change.

The repeated use of prescription opioids may lead to serious side effects. It is therefore important to examine factors associated with such repeated use. The aim of this study was to investigate the association between the maternal use of prescription opioids and their use by offspring of these mothers. Data were extracted from two nationwide registers linked by unique personal identity numbers: the 2001 Norwegian Population and Housing Census and the Norwegian Prescription Database 2004–2009. The study population consisted of 97,574 adolescents aged 15–16 years in 2001 and their mothers. The repeated use of opioids was defined as the issuing of >4 and >15 prescriptions to an adolescent and his/her mother, respectively, during the period 2004–2009. Non-steroidal anti-inflammatory drugs (NSAIDs) are not potentially addictive, and individuals issued prescriptions for NSAIDs were used as the reference analgesic drug group. The proportion of repeated prescription opioid users was higher among adolescents whose mother was registered as a repeated user of prescription opioids (8.4 %) than among those whose mother did not repeatedly use prescription opioids (2.4 %). The odds ratio (OR) was 3.1 [95 % confidence interval (CI) 2.7–3.6] when adjusted for the mother’s socioeconomic characteristics and the gender of the offspring. A lower socioeconomic position of the mother increased the risk of repeated opioid use by her offspring. Maternal repeated use of NSAIDs was associated with repeated use of NSAIDs among offspring (OR 1.8, 95 % CI 1.7–2.0). Among our study population, the maternal use of opioids was associated with the repeated use of prescription opioids among the respective offspring. The same association was seen with NSAIDs, but to a lesser extent.

Purpose To examine whether socioeconomic factors influence adherence to alendronate drug treatment among incident users in Norway during 2005–2009. Methods The study included 7610 incident alendronate users in 2005 (40–79 years), followed until 31 December 2009. Mean age was 66.6 years, and 86.7% of the patients were women. Data were drawn from the Norwegian Prescription Database and linked to marital status, education and income. Adherence was measured by the medication possession ratio (MPR). MPR was defined as the number of dispensed defined daily doses divided by the number of days each patient was included in the study. A patient was adherent if MPR ≥ 80%. ORs with 95%CI were estimated using logistic regression. Results Among all patients, 45.5% was adherent throughout 4.2 years. A slightly higher proportion of women than men were adherent. Adjusted for all covariates, women aged 70–79 years had an OR of 1.27 (95%CI 1.10–1.45) for adherence compared with those 40–59 years. In women, high household income predicted adherence of alendronate use. In men, a middle educational level compared with a low level, predicted adherence (adjusted OR = 1.47 (95%CI 1.10–1.96)). After adjustments, previous marriage reduced the odds of being adherent compared with present marriage, in both men and women. Conclusions In women, the most important factors for being adherent were high age and high income. In men, a middle educational level predicted adherence. Previous marriage reduced the odds of being adherent in both women and men. Copyright © 2012 John Wiley & Sons, Ltd.

Background: The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. Methods: We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. Results: For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators. Conclusion: Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved.

BACKGROUND Many studies have demonstrated that a low socioeconomic status is associated with poor health. The aim of the study was to investigate whether use of prescription drugs, generally and within selected categories, varies with education. MATERIAL AND METHOD Data on education from the 2001 Population and Housing Census for 645,023 men and women born in the period 1960-1969 and living in Norway in 2001 were linked to data from the Norwegian Prescription Database on drugs dispensed in the period 2004-2009. The overall frequency of drug dispensing was compared with six levels of education. The relative risk associated with limited education (≤ 10 years) compared with long education (> 10 years) of having at least one drug dispensed during the period was calculated for 42 selected drug categories. RESULTS There was a dose-response relationship between education and the number of drug prescriptions dispensed. Subjects with lower secondary education collected prescription drugs about three times as often on average as subjects with researcher education. The average relative risk of drug dispensing for subjects with short education (≤ 10 years) compared with long (>10 years) for the 42 selected drug categories was 1.29 for men and 1.31 for women. INTERPRETATION Given that dispensing of drugs is an expression of state of health, our findings support earlier studies that have shown that there is social inequality in the health of the adult population.

Purpose To examine the occurrence of chronic diseases and antimicrobial treatment in an asthma population 8–29 years old, compared with the general population. Methods In this cross-sectional study, the asthma population was identified from the general population (retrieved from a census covering the entire Norwegian population) using filled prescriptions on asthma drugs as a proxy measure of current asthma. The outcome was excess occurrence of specific diseases (comorbidity) among people with asthma, compared with the age-specific general population. Diseases were defined by filled prescriptions with specific diagnostic codes (International Classification of Primary Care 2nd edition [ICPC-2] or International Classification of Diseases 10th revision [ICD-10]) during a 1-year period in the Norwegian Prescription Database. Nine chronic diseases were examined: attention deficit/hyperactivity disorder, epilepsy, migraine, mental illness, cardiovascular disease, diabetes, autoimmune disorders, gastro-oesophageal reflux disease (GORD), and allergy. Additionally, antibacterials recommended for respiratory tract infections and antivirals were examined (defined by Anatomical Therapeutic Chemical codes). Standardized morbidity ratios (SMR) for each disease were calculated. Results Fifty-nine percent of the population with asthma had at least one of nine chronic diseases examined, compared with 18% in the general population. Few individuals with asthma had more than one additional chronic disease (6% of male subjects and 8% of female subjects). SMRs were increased for all diseases except diabetes, implying higher than expected occurrence of the specific diseases in people with asthma. This pattern was observed in both age groups (8–19 and 20–29 years) and genders. Allergy and GORD had highest SMR (range 3.2–4.8), whereas the other diseases were in the range 1.2–2.5. Conclusions An excess occurrence of comorbidities was found in the population with asthma. A majority of people with asthma had one additional chronic disease, and few had more than one. Copyright © 2011 John Wiley & Sons, Ltd.

Antibacterial prescribing is driving antibiotic resistance. We aimed to analyse whether smoking habits are associated with susceptibility to be prescribed antibacterials in primary care and to examine whether patients' smoking habits influence physicians' choice of therapy.Information on smoking habits from health surveys in 1985-99 was related to use of antibacterials 5-25 years later by linkage to the Norwegian Prescription Database. The study population included 365 117 men and women, 40-45 years old. Individuals likely to have chronic obstructive airway disease were excluded. Relative risk (RR) of being dispensed antibacterials for systemic use was calculated for five levels of smoking intensity with never smokers as reference. Adjustments were made for age, education, marital status, household size, body mass index and residence (rural/urban).Fifty-six percent of the male and 69% of the female never smokers received at least one antibacterial prescription in the whole period, increasing to 68% and 82%, respectively, in heavy smokers (19 cigarettes/day) (adjusted RR 1.17 and 1.16). The percentage receiving at least one antibacterial prescription every year was 0.5% in male and 1.9% in female never smokers, increasing to 1.1% and 4.0%, respectively, in heavy smokers (adjusted RR 2.07 and 1.89). The proportion of antibacterial users who were prescribed broad-spectrum antibacterials increased with increasing cigarette consumption.Smoking habits influenced the usage of antibacterials years later with a dose-response relationship. Prescribers seem to acknowledge smoking as a risk factor for resistant bacteria since broad-spectrum antibacterials are more frequently prescribed to smokers than never smokers.

Purpose To examine whether young adults with asthma are at higher risk of initiating hypnotic use. Methods The study population was participants from the Norwegian youth health surveys, where all 10th grade students (15–17 years old) in five counties were invited. 10 164 participants with no prior use of hypnotics were linked to the Norwegian Prescription Database. Four groups were defined based on survey data about ever having had asthma and prescription data on asthma drugs received in the year prior to start of follow-up: (1) no asthma; (2) not active asthma; (3) active recently developed asthma; and (4) still active asthma. Incidence proportions were estimated as share of participants filling hypnotic prescriptions during 2005–July 2010. Incidence rate ratios (IRR), adjusted for potential confounders (illnesses, lifestyle and sociodemographic factors), were estimated with the number of hypnotic prescriptions filled during 2005–July 2010 as outcome. Results The incidence proportion of filling hypnotic prescriptions was 6.1%, ranging from 5.7% in no asthma group to 9.5% in active recently developed asthma group. Crude IRR was 1.35 (95%CI 0.93–1.95) for not active asthma, 4.18 (1.83–9.55) for active recently developed asthma, and 1.63 (0.85–3.14) for still active asthma, with no asthma as reference. Adjusted IRR for active recently developed asthma group changed to 4.72 (2.07–10.75) while the other groups remained statistically not significant. Conclusions In this prospective study of young adults without prior use of hypnotics, an increased risk of initiating hypnotic use was present in asthmatics, especially among those who recently had received asthma drugs. Copyright © 2011 John Wiley & Sons, Ltd.

Background The use of prescribed opioids for chronic non-cancer pain is increasing in many countries. It is, therefore, important to investigate predictors for repeated use of opioids in young non-cancer patients. Objective The aim of this study was to prospectively evaluate adolescent smoking and its association with repeated use of prescription opioids in adolescents/young adults without cancer. Methods The study population consisted of 11,809 15–16 year old participants (86% participation rate) in the Norwegian Youth Health Surveys carried out in 2000–2003. The exposure variable, self reported smoking status, was registered in the youth surveys along with potential confounders. Repeated use of opioids, defined as 4+ prescriptions recorded in the nationwide Norwegian Prescription Database during 2004–2008, was used as outcome measure. Results Among the participants included in our study, 161 had redeemed 4+ prescriptions for opioids. Daily adolescent smoking was associated with repeated use of opioids with an adjusted OR of 2.2 (95% CI 1.3–3.5). Conclusions Daily smoking at 15–16 years of age was associated with increased risk of incident repeated use of prescribed opioids later in life. Our study suggests that smoking dependence in adolescents may predict longer lasting and/or higher levels of opioid use. Copyright © 2010 John Wiley & Sons, Ltd.

The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974–2007, initially aged 20–50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13–1.20), 1.20 (1.14–1.27), 1.26 (1.19–1.34) and 1.09 (0.96–1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01–1.04), 1.03 (1.00–1.05), 1.03 (1.00–1.06) and 0.99 (0.92–1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women.

Background Meta-analysis of individual participant time-to-event data from multiple prospective epidemiological studies enables detailed investigation of exposure–risk relationships, but involves a number of analytical challenges. Methods This article describes statistical approaches adopted in the Emerging Risk Factors Collaboration, in which primary data from more than 1 million participants in more than 100 prospective studies have been collated to enable detailed analyses of various risk markers in relation to incident cardiovascular disease outcomes. Results Analyses have been principally based on Cox proportional hazards regression models stratified by sex, undertaken in each study separately. Estimates of exposure–risk relationships, initially unadjusted and then adjusted for several confounders, have been combined over studies using meta-analysis. Methods for assessing the shape of exposure–risk associations and the proportional hazards assumption have been developed. Estimates of interactions have also been combined using meta-analysis, keeping separate within- and between-study information. Regression dilution bias caused by measurement error and within-person variation in exposures and confounders has been addressed through the analysis of repeat measurements to estimate corrected regression coefficients. These methods are exemplified by analysis of plasma fibrinogen and risk of coronary heart disease, and Stata code is made available. Conclusion Increasing numbers of meta-analyses of individual participant data from observational data are being conducted to enhance the statistical power and detail of epidemiological studies. The statistical methods developed here can be used to address the needs of such analyses.

Studies of clinical cohorts and retrospective reports have identified psychiatric disorders as paramount risk factors for suicide. Much less is known about how self-reported mental health is related to completed suicide. To study the relation between self-reported mental health and risk of completed suicide, the authors prospectively followed a population-based Norwegian cohort of 61,588 men and 69,774 women aged 39-44 years for an average of 10.4 years between 1994 and 2007. Self-reported mental health was measured using an instrument based on the Hopkins Symptom Checklist and the General Health Questionnaire. Completed suicides were registered in the official Norwegian Cause of Death Registry. Females reported higher levels of mental distress than males. In comparison with persons reporting the fewest mental health symptoms, the adjusted hazard ratio for suicide increased from 1.8 (95% confidence interval (CI): 1.1, 2.9) in the moderately depressed group to 8.9 (95% CI: 4.4, 18.2) in the most depressed group. The risk difference was greatest in males. At each level of the mental health index, males had double the risk of suicide of females (hazard ratio = 2.3, 95% CI: 1.5, 3.3). This study shows a dose-response effect of self-reported mental health problems on completed suicide and replicates the gender paradox observed in the general population with prospective data.

The original publication is available at: http://dx.doi.org/10.1016/j.socscimed.2009.11.015 The proportion of Norwegians on disability pensions has doubled since the 1980s. The Norwegian Government wants action to stimulate the working capacity in those disability pensioners who have the potential to work. Information on factors that may impair rehabilitation efforts, including the unfavourable use of benzodiazepines, may be useful in this context. A longitudinal design, including data on 40–42 year old participants in Norwegian health surveys (year 1985–1989) linked to a prescription database (year 2004–2006), was used to describe risk of long-term use of benzodiazepines among disability pension recipients. The study population constituted benzodiazepine users at baseline. More than half of those on disability pensions, 57% of all men and 65% of all women, retrieved benzodiazepine prescriptions 20 years later, a span covering a large part of the potential active workforce period. Further, the observed amount of benzodiazepines dispensed over a three-year period indicated more than sporadic use e.g. half of the female disability pensioners were dispensed an amount of benzodiazepines corresponding to the use of a daily dose every second day over a three year period (median 450 daily doses). The majority of those who were dispensed benzodiazepines, were dispensed opioids as well: half of all men and 3 out of four women. And last, being on a disability pension was a predictor of benzodiazepine use 20 years later. Our study suggests that benzodiazepines are extensively and unfavourably used among disability pensioners, and that disability pension may have an independent effect on long-term use. Improved management of benzodiazepine use may be one alternative to get disability pensioners with the potential to work back into employment.

An association between sperm DNA integrity and fertility was recently shown for frozen-thawed Norwegian Red (NRF) bull semen diluted in skimmed milk egg yolk (SMEY). In general the fertility of NRF cattle is high, however, in comparison with NRF semen in SMEY, NRF semen diluted in Tris EY based extenders has shown reduced fertility. The aim of the present study was to do a split-sample comparison of sperm DNA integrity of NRF bull semen (n=20) in SMEY and Triladyl (Tris EY based) during routine cryopreservation procedure and during in vitro incubation of frozen-thawed semen in modified synthetic oviduct fluid (mSOF). In contrast to the high fertility of NRF cattle, Holstein cattle are experiencing a marked decline in fertility. Therefore, the present study also aimed to compare sperm DNA integrity of NRF (n=20) and Holstein (n=20) semen diluted in Triladyl during in vitro incubation. The sperm DNA integrity was measured by susceptibility to in situ acid induced denaturation by the Sperm chromatin structure assay (SCSA). Compared to initial values of frozen neat semen, an increase in DNA damage was observed after dilution and cooling (5 degrees C) and after freezing-thawing of NRF semen in SMEY, but only after freezing-thawing for NRF semen diluted in Triladyl. Sperm DNA damage of NRF semen increased during in vitro incubation in mSOF; the increase in percentage of spermatozoa with DNA damage was more prominent in SMEY than in Triladyl, while the degree of damage was higher in Triladyl, throughout the incubation period. However, while the correlation between DNA damage and sperm survival was negative in SMEY throughout the incubation period, a positive correlation was observed in Triladyl after 9h of incubation, indicating a higher presence of DNA damage in the live sperm population. In comparison with Holstein spermatozoa, the sperm DNA integrity of NRF semen reflected a better ability to withstand alterations induced during in vitro incubation in mSOF. In conclusion, sperm DNA integrity of NRF bull semen was altered during the cryopreservation procedure and in vitro incubation in mSOF. Dilution in Triladyl maintained bull sperm DNA integrity better than dilution in SMEY. Furthermore, alterations in Holstein sperm DNA integrity was more pronounced during in vitro incubation in mSOF compared to NRF bull spermatozoa.

Objective—To develop a scoring system for histopathologic changes in the synovium of tarsocrural joints (TCJs) of horses with osteochondritis dissecans (OCD) and to test for association between histopathologic changes and joint effusion or lameness. Animals—93 horses with OCD of the intermediate ridge of the tibia of 1 or both TCJs (134 joints) and 38 control horses without disease of TCJs (38 joints). Procedures—For OCD-affected horses, pretreatment lameness, TCJ effusion, and results of pelvic limb flexion test were scored. Synovial biopsy specimens were obtained from TCJs of OCD-affected horses during arthroscopy, and similar postmortem tissue specimens were obtained from control horses through a small arthrotomy. Histologic signs of synovitis in 172 biopsy specimens were scored by 2 pathologists (A and B) by use of 2 criteria: synoviocyte proliferation and cellular infiltration. Results—Analysis of scoring revealed good to very good intraobserver agreement within pathologist A (weighted kappa [WK], 0.76 to 0.81), and moderate to good agreement within pathologist B (WK, 0.56 to 0.63). Interobserver agreement for synoviocyte proliferation (WK, 0.34 to 0.52) and cellular infiltration (WK, 0.38 to 0.48) scores was fair to moderate. Joint effusion and synoviocyte proliferation were significantly associated, as were joint effusion and cellular infiltration. There was no association between histopathologic changes and the other clinical signs evaluated. Conclusions and Clinical Relevance—The scoring system was helpful for evaluating synovial inflammation caused by OCD of the intermediate ridge of the tibia in horses. Histopathologic signs of synovial inflammation were associated with effusion but not with lameness.

The purpose of this study was to examine gender- and age-specific prevalence, incidence, and the type of anti-asthma medications used in the Norwegian population aged 2-29 years during 2005-2007 and to estimate the share of individuals who regularly redeemed medications over a 3-year period.We retrieved data from the nationwide Norwegian Prescription Database for all individuals 2-29 years old (n = 1.7 million) who received anti-asthma medications during 2005-2007. Medications included inhaled short- and long-acting beta(2)-agonists, inhaled corticosteroids, fixed-dose combinations of inhaled beta(2)-agonists and corticosteroids, and leukotriene antagonists.In 2007, 5.5% (92,074 individuals) of Norwegians aged 2-29 years received anti-asthma medication, and this figure was stable throughout 2005-2007. Prevalence and incidence were higher among males than females but shifted to female dominance during adolescence. The share of anti-asthma medication users who received inhaled corticosteroids was high in preschool children but decreased by age. Conversely, use of inhaled beta(2)-agonists as monotherapy and of fixed combinations increased with age. Fewer than half the individuals were "persistent" to medication treatment for 3 years by redeeming prescriptions regularly (at least once a year).In this nationwide study, annual prevalence of anti-asthma medication use was stable during 2005-2007. The gender- and age-specific profile of prevalence and incidence correspond well with other studies. Fewer than half the individuals redeemed prescriptions regularly over 3 years.

BACKGROUND From 1948 to 1975, Norway had a mandatory tuberculosis (TB) screening programme with Pirquet testing, X-ray examinations and BCG vaccination. Electronic data registration in 1963-75 enabled the current study aimed at revealing (i) the relations between socioeconomic factors and tuberculosis infection and (ii) differences in later all-cause mortality according to TB infection status. METHODS TB screening data were linked to information from the Norwegian Cause of Death Registry (1975-98) and the National Population and Housing Censuses (1960, 1970 and 1980). Analyses were done for 10 years cohorts born 1910-49, separately for men (approximately 534,000 individuals) and women (608,000), using logistic and Cox regressions. RESULTS TB infection and X-ray data confirmed the strong regional pattern seen for TB mortality, with the highest rates in the three northernmost counties and higher rates in urban than rural areas. High socioeconomic status relates to lower odds both for TB infection and TB-related chest X-ray findings (odds ratios 0.6-0.7 for highest vs lowest educational groups). Those infected by TB, and especially those with chest X-ray findings, have increased all-cause mortality in at least a 20 years period following determination of tuberculin status (hazard ratios approximately 1.15 and 1.30, respectively, higher for late than early cohorts). CONCLUSIONS TB particularly affected lower socioeconomic strata, but even those in higher strata were at high risk. The differences in all-cause mortality could partly be attributed to socioeconomic factors, but we hypothesize that developing TB infection may also indicate biological frailness.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Use of statins reduces cardiovascular morbidity and mortality. • Little is known about educational inequalities in use of statins. WHAT THIS STUDY ADDS • In Norway in patients with no history of cardiovascular disease or diabetes, start of statin treatment was not associated with educational level after adjustment for cardiovascular risk factors. • In patients with a history of cardiovascular disease or diabetes, especially highly educated women tended to start statin treatment more often than women of low educational level. • Persistence of statin treatment did not vary by educational level. AIMS To study the influence of patients' education and cardiovascular risk factors on the probability of statin treatment. METHODS A prospective cohort study of participants in regional health surveys in Norway 2000–2002 with statin use recorded in the Norwegian Prescription Database 2004–2006 as outcome measure. Information on history of cardiovascular disease (CVD) and diabetes, lipid levels, blood pressure, use of cardiovascular drugs, body mass index, family history, smoking, physical activity, marital status and place of residence was obtained at baseline. A total of 20 212 men and women aged 40–41, 45–46 and 59–61 years who reported never use of statins were included. Educational level was retrieved from Statistics Norway. Adjusted relative risks (RR) were estimated by Poisson regression. RESULTS Whereas 655 participants reported a history of CVD or diabetes, 19 557 reported no such history. In the non-CVD/diabetes group 1620 persons (8%) became statin users and 222 persons (34%) in the CVD/diabetes group. RR of becoming a statin user for high vs. low education increased from 0.64 [95% confidence interval (CI) 0.55, 0.73] to 0.91 (95% CI 0.79, 1.05) after adjustment in the non-CVD/diabetes group and from 0.94 (95% CI 0.70, 1.26) to 1.35 (95% CI 1.00, 1.81) in the CVD/diabetes group. CONCLUSIONS Patients with no history of CVD/diabetes were prescribed statins according to cardiovascular risk independent of education. There was a tendency to a higher probability of statin treatment among highly educated compared with people of lower educational level in the group with a history of CVD or diabetes, after adjustment for other CVD risk factors, particularly in women.

Objectives: To estimate the risk of dying from all causes and from specified smoking-related diseases in people who were ex-smokers at two consecutive examinations, compared with never smokers and with people who were ex-smokers at the first examination but who had resumed smoking at the following examination. Design: A prospective cohort study. Setting: Three counties in Norway. Participants: A total of 23 560 men and 25 122 women, aged 20–49, screened for cardiovascular disease risk factors in the mid 1970s, rescreened after 3–13 years and followed throughout 2005 participated in this study. Outcomes: Absolute mortality and relative risks adjusted for confounding variables, of dying from all causes, cardiovascular disease, ischaemic heart disease, stroke, lung cancer and other smoking-related cancer. Results: With sustained never smokers as reference, the sustained ex-smokers had adjusted relative risk (95% CI), of dying from any cause, for men 0.97 (0.80 to 1.18), for women 0.98 (0.65 to 1.48). Corresponding risk for ex-smokers who resumed smoking was for men 1.59 (1.32 to 1.91), for women 1.40 (1.08 to 1.81). For the specified smoking-related diseases, the risk in sustained ex-smokers was not significantly different from the risk in sustained never-smokers, except for lung cancer in men. For ex-smokers who resumed smoking, the corresponding risk was on the whole significantly higher. Conclusions: A more valid and favourable picture of ex-smokers’ risk will be obtained if exposure is being based upon people with two consecutive examinations, years apart. The study confirms clearly the large health benefit of quitting smoking for good.

The present study is the first complete presentation of the prognosis of all histological types of canine vascular tumours, using population-based data. A retrospective, longitudinal, population-based study of 420 dogs was carried out in 2001-2002 using updated histologically verified diagnoses of vascular tumours and tumour-like lesions recorded in Norwegian Canine Cancer Register (NCCR) 1990-1998. Data on clinical signs and outcome of the vascular tumour, and causes of death, were obtained from dog owners and veterinary practitioners by mailed questionnaires. The a priori set inclusion criteria required that both questionnaire forms were completed, which was the case for 162 of the 420 dogs (39%). A benign tumour was diagnosed in 61%, whereas 15% had a tumour of intermediate malignancy and 24% had a malignant one. Survival time was estimated by the method of Kaplan-Meier (product limit) survival plot, and the survival time for three histological diagnoses was compared by a log-rank test. Hazard ratios were estimated by Cox proportional hazards model. A p-value0.05 was considered statistically significant. Median survival time of dogs with malignant vascular tumour wasor = one day, and the respective median survival times for intermediate malignant and benign types were 101 andor = 1095 days (P0.0001). The median survival time of dogs with splenic vascular tumours wasor = 1095 days, 110 days andor = one day for benign, intermediate malignant and malignant tumour forms, respectively (P0.0001). Since the histological diagnosis was made without any knowledge of the outcome, the present study confirms that the new histological criteria and methods employed have indeed a prognostic value. This is the first time it has been shown that a histopathological differentiation of malignant tumours into two well-defined subgroups differentiates the survival time correspondingly: dogs with less grave tumour diagnoses live 100-110 days longer than dogs with the obvious malignant tumours, if surgery alone is the treatment regime.

BACKGROUND The lean phenotype of cystathionine beta-synthase-deficient homocystinuria and the positive association of plasma total cysteine (tCys) with body mass index (BMI) suggest that total homocysteine (tHcy) and tCys are associated with body composition. OBJECTIVES We aimed to study associations of tCys and tHcy with body composition in the general population. DESIGN Using data from 7038 Hordaland Homocysteine Study participants, we fitted regression models and dose-response curves of tCys and tHcy with BMI. In 5179 participants, we investigated associations of tCys and tHcy with fat mass and lean mass and examined whether changes in these aminothiols predicted body composition 6 y later. RESULTS tCys showed positive associations with BMI (partial r = 0.28, P < 0.001), and fat mass (partial r = 0.25, P < 0.001), independent of diet, exercise, and plasma lipids. Women in the highest tCys quintile had fat mass 9 kg (95% CI: 8, 10 kg; P < 0.001) greater than that of women in the lowest quintile. The corresponding values for men were 6 kg (95% CI: 5, 7 kg; P < 0.001; P < 0.001 in both sexes, ANOVA across quintiles). The rise in tCys over 6 y was associated with greater fat mass at follow-up (P < 0.001), but there was no effect on lean mass. tHcy was not associated with lean mass, and it became significantly inversely associated with BMI and fat mass only after adjustment for tCys. The association between tHcy and lean mass was not significant. CONCLUSIONS tCys concentrations show a strong positive association with BMI, mediated through fat mass. The link between cysteine and lipid metabolism deserves further investigation.

Aim To study the relationship between heart rate and (a) all deaths and (b) cardiovascular deaths in a large cohort of middle-aged Norwegian men and women. Methods and results A prospective study of participants in cardiovascular surveys that were carried out in 1985–1999 and covered men and women aged 40–45 years in all counties except the capital, Oslo. In total, 180 353 men and 199 490 women aged 40–45 years without cardiovascular history or diabetes accrued 4 775 683 years of follow-up. There was a positive and graded association between heart rate and mortality from all causes, as well as between heart rate and deaths from cardiovascular disease (CVD), ischaemic heart disease, and stroke. However, these associations were greatly reduced when we adjusted for the main risk factors of disease. The hazard ratios for any death were reduced from 3.14 to 1.82 for men (95% CI, 1.62–2.04) and from 2.14 to 1.37 for women (95% CI, 1.19–1.59), when we compared ≥95 b.p.m. with

Purpose To evaluate the effect of the consumption of benzodiazepines at age 40–42 years on prescription of opioids later in life. Methods A cohort of 6707 men and 6683 women aged 40–42 years reported no use of analgesics in health surveys in 1985–1989. This cohort was linked to the Norwegian prescription database (NorPD) and their prescriptions of opioids during 2004–2006 were analysed. Low–high, moderate–high and high prescription frequency of opioids were defined as at least 6, 12 or 16 prescriptions during January 2004–December 2006. Non-steroid anti-inflammatory drugs (NSAIDs) were used as comparators. Results The unadjusted odds ratios (ORs) for low–high prescription frequency of opioids for men and women using benzodiazepines were 3.8 (95%CI 2.5–5.7) and 3.4 (2.6–4.4), respectively, as compared with non-users. After adjustment for alcohol, smoking habits and socio-economic variables, the ORs were lowered for both sexes: 2.6 (1.7–4.0) in men and 2.5 (1.9–3.3) in women. The adjusted OR for those with high prescription of opioids was higher for both sexes: 4.5 (2.4–8.5) in men and 3.7 (2.4–5.7) in women. A stratified analysis revealed no relationship between benzodiazepine use and later low and moderate prescription frequency of opioids among teetotallers. The adjusted ORs for low–high prescription frequency NSAID use for men and women using benzodiazepines were 1.6 (1.1–2.4) and 1.6 (1.3–2.0), respectively. Conclusion In this study population, a history of benzodiazepine use raised the chance of being prescribed opioids later in life among those who also used alcohol. Copyright © 2008 John Wiley & Sons, Ltd.

The main objective of this study was to describe the growth patterns of 4 large dog breeds [Newfoundland (NF), Labrador retriever (LR), Leonberger (LEO), and Irish wolfhound (IW)] raised in domestic environments and concomitant changes in 2 growth-related clinical variables: total serum alkaline phosphatase (ALP) and the circumference of the distal radius and ulna (CDRU). The second objective was to investigate whether these measurements were affected by a range of independent variables like age, sex, litter number, and birth weight. Seven hundred dogs were included in the study, and BW data, separated by breed and sex, were fitted to the Gompertz function. Birth weight, adjusted for litter number, differed significantly between sexes for 3 breeds (LEO, P = 0.004; NF, P = 0.02; LR, P = 0.009) and approached significance for IW (P = 0.07). Estimated mean BW increased rapidly during the first 100 d after birth in all 4 breeds, then plateaued, with maturity being reached between 351 (female LR) and 413 d (male NF). Estimated mature BW ranged from 30.8 kg for the female LR up to 65.7 kg for the male IW. Weight gain, as expressed by the derivative of the Gompertz function, reached its peak in the smallest breed (LR) at the youngest age, 89 d for the females and 95 d for males. Log-transformed BW was significantly related to age, breed, and sex, and the age x sex and age x breed interactions. Within breeds, age, birth weight, and litter number had a significant effect on log-transformed BW. The estimated average CDRU increased from 90 d of age toward a peak at 180 d. Thereafter, CDRU declined and stabilized at about 1 yr of age. The estimated total ALP concentrations decreased from 90 to 360 d of age, after which they stabilized, at mean concentrations varying among breeds from 98 to 131 IU/L. Maximum least squares mean total ALP concentrations were found at 3 mo of age in all breeds, with the greatest least squares mean concentration in the IW breed (713 IU/L). In a mixed model analysis of the complete data set, total ALP was affected (P < 0.001) by age, breed, and the interaction of age x breed. This study described the main factors influencing growth and provided reference data for other studies, including those related to nutrition and disorders of growth.

PURPOSE: The aim of the study was to evaluate the effect of the consumption of anxiolytic or hypnotic drugs on total mortality in a general population. METHODS: We followed a cohort of 7225 men and 7726 women aged 40-42 years who underwent health surveys in 1985-1989 in two Norwegian counties, with respect to deaths. Mean follow-up period was 18 years. The subjects were categorised according to frequency of anxiolytic or hypnotic drug use during the last month: daily, every week, less than every week and not used during the last month. RESULTS: The proportion of anxiolytic or hypnotic drug users was 6.6% among men and 16.2% among women. Altogether 402 men and 290 women died. There was an increase in risk of death with an increase in frequency of use. Crude hazard ratios for men and women daily using anxiolytics or hypnotics were 3.1 (95%CI 2.0, 4.8) and 2.7 (1.9, 4.0), respectively, as compared with non-users last month. After adjusting painkiller use and smoking the hazard ratios were lowered, being 2.4 (1.5-4.0) (men) and 2.1 (1.4-3.2) (women). After additional adjustments for other possible confounders the hazard ratios were further attenuated to 1.5 (0.9-2.7) for men and 1.7 (1.1-2.6) for women. CONCLUSIONS: Daily users of anxiolytic or hypnotic drugs in our study showed higher crude mortality than non-users. However, after adjusting lifestyle and socio-economic variables the difference was markedly reduced suggesting that the remaining excess mortality is due to residual confounding. Language: en

The aim of the study was to compare educational and gender specific trends in the classical cardiovascular risk factors body mass index (BMI), cholesterol, systolic blood pressure and smoking in a Norwegian population during a period when the coronary heart disease mortality had just reached its peak in the late 1970s and 1980s. We used The Norwegian Counties study: a longitudinal study with three screenings on the same individuals in Oppland, Sogn og Fjordane and Finnmark counties in Norway in the period 1974-1988. All residents aged 35-49 were invited and 48,422 participated (89%) in the baseline screening. To estimate the cardiovascular risk factor change in individuals over time longitudinal statistical methods were used. BMI, cholesterol and blood pressure levels increased with age, while the amount of daily smokers decreased. The higher the educational level the lower the level of BMI, blood pressure, smoking and cholesterol. This pattern persisted through the whole study period. In men, however, the educational gradient in cholesterol diminished in the last screening. Among women there was an increase in inequality in systolic blood pressure, and for smoking there was a steeper decrease for men than women across all educational groups. The educational differences in classical cardiovascular risk factors persisted, except for BMI, cholesterol and daily smokers in men which tended to decrease.

Apoptosis in lymphoid follicles of the ileal Peyer's patch (IPP) in 21 sheep of two different age groups was visualized by the TdT-mediated dUTP nick end-labelling (TUNEL) method, and quantified using computer-assisted image analysis. The IPP follicle carbonic anhydrase (CA) reactivity was evaluated in the same samples. No significant differences with respect to apoptosis and CA reactivity were found between sheep aged 5 and 11 months. Individual variation in apoptotic activity correlated with the follicle centre CA reactivity. The group of animals found to have predominantly atypical ileal lymphoid follicles (more than 80% of total number of follicles) with features resembling jejunal Peyer's patch follicles, had lower number of apoptotic cells and reduced CA reactivity compared to the rest of the animals. The differences in CA reactivity in the follicle centres probably represent a variation in the presence of CA rich approximately 50 nm membrane-bounded particles known to be a feature of the sheep IPP. The present results suggest that the particles are involved in the modulation of the lymphocyte proliferation of the IPP follicles.

Objectives: To determine the risk in men and women smoking 1–4 cigarettes per day of dying from specified smoking related diseases and from any cause. Design: Prospective study. Setting: Oslo city and three counties in Norway. Participants: 23 521 men and 19 201 women, aged 35–49 years, screened for cardiovascular disease risk factors in the mid 1970s and followed throughout 2002. Outcomes: Absolute mortality and relative risks adjusted for confounding variables, of dying from ischaemic heart disease, all cancer, lung cancer, and from all causes. Results: Adjusted relative risk (95% confidence interval) in smokers of 1–4 cigarettes per day, with never smokers as reference, of dying from ischaemic heart disease was 2.74 (2.07 to 3.61) in men and 2.94 (1.75 to 4.95) in women. The corresponding figures for all cancer were 1.08 (0.78 to 1.49) and 1.14 (0.84 to 1.55), for lung cancer 2.79 (0.94 to 8.28) and 5.03 (1.81 to 13.98), and for any cause 1.57 (1.33 to 1.85) and 1.47 (1.19 to 1.82). Conclusions: In both sexes, smoking 1–4 cigarettes per day was associated with a significantly higher risk of dying from ischaemic heart disease and from all causes, and from lung cancer in women. Smoking control policymakers and health educators should emphasise more strongly that light smokers also endanger their health.

In Norwegian adult men, body mass index (BMI) increased from around 25 kg/m(2) in the late 1960s to around 26.5 kg/m(2) in the late 1990s, and the prevalence of obesity increased from about 5% to 15% in the same period. In women the prevalence of obesity actually decreased from around 13% in the late 1960s to 7% in the late 1980s. However, during the last years the prevalence has also increased reaching about 13% in the late 1990s. It is important to note that both mean and median BMI has increased with a shift in the distribution to the right. The proportion of normal weight individuals has thus decreased, whereas the proportion of obese has increased. The increase in BMI has occurred in different age groups. Although obesity is associated with low education and a sedentary lifestyle, the increase in BMI has also occurred in the more educated and physical active.