Smoking history and all-cause, ischaemic heart disease and lung cancer mortality: follow-up study of 358 551 men and women aged 40-43 years.

AIMS: We studied the health consequences of quitting smoking before age 43 by time since quitting, number of years smoked and cigarettes smoked per day. The outcomes were all-cause, ischaemic heart disease and lung cancer mortality. DESIGN: Prospective study. SETTING: Norwegian counties. PARTICIPANTS: Men and women aged 40-43 years who participated in a national cardiovascular screening programme and who were followed from 1985 to 2018. MEASUREMENTS: Self-reports from questionnaire on time since quitting smoking, years smoked and number of cigarettes per day, and measurements of height, weight and blood pressure, and a blood sample where serum was analysed for total serum cholesterol and triglycerides. FINDINGS: The all-cause mortality rate was 30% higher among quitters less than 1 year ago compared with never smokers (adjusted HR=1.30, 95% CI 1.18-1.43 in men and HR=1.31, 95% CI 1.16 to 1.50 in women). Quitters who had smoked longer than 20 years had 23% higher mortality in men (HR=1.23, 95% CI 1.14 to 1.34) and 32% higher mortality in women (HR=1.32, 95% CI 1.18 to 1.49). Past smoking of more than 20 cigarettes/day was associated with HR=1.14 (1.05-1.23) in men and HR=1.16 (1.01-1.32) in women. The HR for lung cancer was 6.77 (95% CI 4.86 to 9.45) for quitting men who had smoked for more than 20 years compared with never smokers. The corresponding figure for women was 5.75 (95% CI 4.08 to 8.09). CONCLUSIONS: The mortality among quitters was close to that of never smokers, except for a higher mortality for lung cancer, which on the other hand was much lower than the lung cancer mortality in current smokers.

Associations between serum high-density lipoprotein cholesterol levels and cause-specific mortality in a general population of 345 000 men and women aged 20-79 years.

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 <30, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, 90-99 and >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 <30 mg/dl (0.78 mmol/L), the corresponding HRs (95% CIs) were 1.30 (1.24-1.36), 1.55 (1.44-1.67), 1.14 (1.05-1.23) and 1.19 (1.10-1.29). The mortality from alcoholic liver disease, cancers of mouth-oesophagus-liver, chronic liver diseases, chronic obstructive pulmonary disease, accidents and diabetes increased distinctly with increasing HDL-C above the reference level. HDL-C levels lower than the reference level were mainly associated with increased mortality of ischaemic heart disease (IHD), other CVDs, stomach cancer and diabetes. 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.

Alcohol consumption and incidence of pancreatic cancer.

Purpose: The association between alcohol consumption and pancreatic cancer is unsettled. Methods: Altogether 243,169 men and women 20-79 years, without cancer at baseline, were followed with respect to pancreatic cancer by linkage to the Cancer Registry of Norway and the Norwegian Cause of Death Registry. They participated in a cardiovascular survey where information on alcohol consumption, smoking habits, anthropometric measures, and some biological variables were recorded. During 20 years of follow-up, 991 incident pancreatic cancers were registered. We estimated the hazard ratios with the Cox proportional hazards model, and graphed spline curves between glass-units/d of alcohol and hazard ratio of incident pancreatic cancer. Results: The multivariable adjusted hazard per 1 glass-unit/d was 1.08 (95% confidence interval 1.02-1.15) for men and 1.04 (0.97-1.13) for women. The association between alcohol consumption and incident pancreatic cancer was present in ex- and current smokers, but the association could be ascribed to smoking habits. The multivariable adjusted spline curves increased with increasing glass-units/d and with confidence bands not encompassing 1.0 above one glass-unit/day. Conclusion: Our findings of an association between higher level of alcohol consumption and incident pancreatic cancer, could be attributed to confounding by smoking habits.

Biomarker-assessed passive smoking in relation to cause-specific mortality: pooled data from 12 prospective cohort studies comprising 36 584 individuals.

AIMS: While investigators have typically quantified the health risk of passive (secondhand) smoking by using self-reported data, these are liable to measurement error. By pooling data across studies, we examined the prospective relation of a biochemical assessment of passive smoking, salivary cotinine, with mortality from a range of causes. METHODS: We combined data from 12 cohort studies from England and Scotland initiated between 1998 and 2008. A total of 36 584 men and women aged 16-85 years of age reported that they were non-smoking at baseline, provided baseline salivary cotinine and consented to mortality record linkage. RESULTS: A 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, 779 from all cancers and 289 from smoking-related cancers). After controlling for a range of covariates, a 10 ng/mL increase in salivary cotinine was related to an elevated risk of total (HRs; 95% CI) (1.46; 1.16 to 1.83), cardiovascular disease (1.41; 0.96 to 2.09), cancer (1.49; 1.00 to 2.22) and smoking-related cancer mortality (2.92; 1.77 to 4.83). CONCLUSIONS: Assessed biomedically, passive smoking was a risk factor for a range of health outcomes known to be causally linked to active smoking.

Alcohol Consumption, HDL-Cholesterol and Incidence of Colon and Rectal Cancer: A Prospective Cohort Study Including 250,010 Participants.

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.

Quantifying the contribution of established risk factors to cardiovascular mortality differences between Russia and Norway.

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.

Coffee consumption and mortality from cardiovascular diseases and total mortality: Does the brewing method matter?

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.

The association between parity, CVD mortality and CVD risk factors among Norwegian women and men.

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.

Coffee and wine consumption is associated with reduced mortality from alcoholic liver disease: follow-up of 219,279 Norwegian men and women aged 30-67 years.

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.

Consumption of alcohol and cardiovascular disease mortality: a 16 year follow-up of 115,592 Norwegian men and women aged 40-44 years.

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.

High risk of overdose death following release from prison: variations in mortality during a 15-year observation period.

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.

NORRISK 2: A Norwegian risk model for acute cerebral stroke and myocardial infarction.

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.

Blood pressure changes during 22-year of follow-up in large general population - the HUNT Study, Norway.

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.

Cardiovascular risk estimation in older persons: SCORE O.P.

AIMS: Estimation of cardiovascular disease risk, using SCORE (Systematic COronary Risk Evaluation) is recommended by European guidelines on cardiovascular disease prevention. Risk estimation is inaccurate in older people. We hypothesized that this may be due to the assumption, inherent in current risk estimation systems, that risk factors function similarly in all age groups. We aimed to derive and validate a risk estimation function, SCORE O.P., solely from data from individuals aged 65 years and older. METHODS AND RESULTS: 20,704 men and 20,121 women, aged 65 and over and without pre-existing coronary disease, from four representative, prospective studies of the general population were included. These were Italian, Belgian and Danish studies (from original SCORE dataset) and the CONOR (Cohort of Norway) study. The variables which remained statistically significant in Cox proportional hazards model and were included in the SCORE O.P. model were: age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, smoking status and diabetes. SCORE O.P. showed good discrimination; area under receiver operator characteristic curve (AUROC) 0.74 (95% confidence interval: 0.73 to 0.75). Calibration was also reasonable, Hosmer-Lemeshow goodness of fit test: 17.16 (men), 22.70 (women). Compared with the original SCORE function extrapolated to the ≥65 years age group discrimination improved, p = 0.05 (men), p < 0.001 (women). Simple risk charts were constructed. On simulated external validation, performed using 10-fold cross validation, AUROC was 0.74 and predicted/observed ratio was 1.02. CONCLUSION: SCORE O.P. provides improved accuracy in risk estimation in older people and may reduce excessive use of medication in this vulnerable population.

Changes in synovial fluid biomarker concentrations following arthroscopic surgery in horses with osteochondritis dissecans of the distal intermediate ridge of the tibia.

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.

Paediatric Off-Label Use of Melatonin--A Register Linkage Study between the Norwegian Prescription Database and Patient Register.

The aims were, for the entire Norwegian population aged 4-17 years, to study the prevalence of melatonin use during 2004-2012, recurrent use in incident users and psychiatric and neurological morbidity in recurrent users. Data on dispensed melatonin were retrieved from the Norwegian Prescription Database and linked to diagnostic data from the Norwegian Patient Register. Outcome measures were the following: 1-year prevalence of use, proportion of recurrent use (use over three consecutive 365-day periods among incident users in 2009) and annual number of milligrams and number of prescriptions dispensed in recurrent users. The prevalence of registered ICD-10 diagnoses during the period of 2008-2012 was given for the recurrent users. The prevalence of melatonin use increased annually in both genders during 2004-2012 (boys: 3.4-11.0 per 1000; girls: 1.5-7.7 per 1000). Twenty-nine per cent of boys and 23% of girls were recurrent melatonin users, with highest level of recurrent use among the youngest (aged 4-8 years; boys: 47%, girls: 42%). In the third year, the median annual amount of melatonin dispensed was 1080 (IQR 586-1800) milligrams in boys and 900 (IQR 402-1620) milligrams in girls. Among recurrent users, 91% had a diagnosis of either psychiatric (84%) or neurological (32%) disorder. Off-label recurrent use of melatonin seems to have acquired a role mainly in treating secondary sleep problems in children and adolescents with psychiatric and neurological disorders. Once melatonin has been started, a large proportion of patients continue for at least 3 years, in doses corresponding to daily use in the majority.

Smoking increases rectal cancer risk to the same extent in women as in men: results from a Norwegian cohort study.

BACKGROUND: Smoking has recently been established as a risk factor for rectal cancer. We examined whether the smoking-related increase in rectal cancer differed by gender. METHODS: We followed 602,242 participants (49% men), aged 19 to 67 years at enrollment from four Norwegian health surveys carried out between 1972 and 2003, by linkage to Norwegian national registries through December 2007. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazard models and adjusting for relevant confounders. Heterogeneity by gender in the effect of smoking and risk of rectal cancer was tested with Wald χ2. RESULTS: During a mean follow-up of 14 years, 1,336 men and 840 women developed invasive rectal cancer. Ever smokers had a significantly increased risk of rectal cancer of more than 25% for both men (HR = 1.27, 95% CI = 1.11-1.45) and women (HR = 1.28, 95% CI = 1.11-1.48) compared with gender-specific never smokers. Men smoking ≥20 pack-years had a significantly increased risk of rectal cancer of 35% (HR = 1.35, 95% CI = 1.14-1.58), whereas for women, it was 47% (HR = 1.47, 95% CI = 1.13-1.91) compared with gender-specific never smokers. For both men and women, we observed significant dose-response associations between the risk of rectal cancer for four variables [Age at smoking initiation in years (both ptrend <0.05), number of cigarettes smoked per day (both ptrend <0.0001), smoking duration in years (ptrend <0.05, <0.0001) and number of pack-years smoked (both ptrend <0.0001)]. The test for heterogeneity by gender was not significant between smoking status and the risk of rectal cancer (Wald χ2, p -value; current smokers = 0.85; former smokers = 0.87; ever smokers = 1.00). CONCLUSIONS: Smoking increases the risk of rectal cancer to the same extent in women as in men.

Cigarette smoking and colorectal cancer mortality among 602,242 Norwegian males and females.

BACKGROUND: Colorectal cancer (CRC) is one of the main cancer types, with high incidence and mortality in Norway. We examined the association between different measures of smoking exposure and CRC mortality overall and by subsite in a large Norwegian cohort. METHODS: We followed 602,242 participants from four Norwegian health surveys, aged 19-67 years at enrollment between 1972 and 2003 by linkage to the national registries through December 2007. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) by smoking categories for different CRC endpoints. RESULTS: During a mean follow-up of 14 years, 2,333 Norwegian males and females died of CRC (60% men). Male and female ever smokers had a 20% (HR 1.23, CI 1.08-1.40 and HR 1.22, 95% CI 1.06-1.40, respectively) increased risk of death from CRC compared with sex-specific never smokers. For proximal colon cancer mortality, female ever smokers had a 50% (HR 1.49, 95% CI 1.20-1.87) increased risk compared with female never smokers. The increased risk of rectal cancer mortality was about 40% higher for male ever smokers (HR 1.43, 95% CI 1.14-1.81) compared with male never smokers. A test for heterogeneity by sex showed an increased risk of rectal cancer mortality among men which was significant for former smokers (Wald χ(2) =0.02) and an increased risk of proximal colon cancer mortality among women which was significant for ever and former smokers (Wald χ(2) =0.02 and χ(2) =0.04, respectively). CONCLUSION: Smoking is associated with increased CRC mortality in both sexes. The risk of rectal and proximal colon cancer mortality was most pronounced among male and female smokers respectively.