Prescribing of opioids for chronic pain on reimbursable prescription. / Forskrivning av opioider på blå resept mot langvarige smerter.

BACKGROUND: In 2008 the reimbursable prescription scheme was amended so that patients with severe, chronic pain could be prescribed opioids on reimbursable prescription. The purpose of this study was to investigate the prescribing of opioids on reimbursable prescription, the proportion of patients who started opioid treatment on reimbursable prescription who became long-term users, and the number of patients in 2018 who received higher dosages than the reimbursable prescription scheme permits. MATERIAL AND METHOD: Data were retrieved from the Norwegian Prescription Registry. Persons aged 18 or over who were dispensed at least one opioid on reimbursable prescription for severe, chronic pain in the period 2008-2018, were included. RESULTS: The number of patients who were prescribed opioids on reimbursable prescription increased during the study period, and in 2018 the number was 17 383. Of these, 331 (1.9 %) were prescribed more than 300 mg oral morphine equivalents per day. After nine years, 48 % of the patients who started with opioids in 2009 were still being prescribed opioids on reimbursable prescription. INTERPRETATION: A high proportion of patients with severe, chronic pain who started with opioids on reimbursable prescription became long-term users. A number of patients received higher dosages than are recommended.

Menopausal hormone therapy and risk of melanoma: Do estrogens and progestins have a different role?

The association between use of menopausal hormone therapy (HT) and occurrence of skin malignant melanoma (SMM) is controversial. We investigated the issue in a nationwide cohort of 684,696 Norwegian women, aged 45-79 years, followed from 2004 to 2008. The study was based on linkage between Norwegian population registries. Multivariable Poisson regression models were used to estimate the effect of HT use, different HT types, routes of administration and doses of estrogen and progestin on the risk of SMM. During the median follow-up of 4.8 years, 178,307 (26%) women used HT, and 1,476 incident SMM cases were identified. Current use of HT was associated with increased risk of SMM (rate ratios (RR) = 1.19; 95% confidence interval (CI) 1.03-1.37). Plain estrogen therapy was associated with an increased risk of SMM (RR 1.45; 95% CI 1.21-1.73), both for oral (RR 1.45; 95% CI 1.09-1.93) and vaginal (RR 1.44; 95% CI 1.14-1.84) formulations, while combined estrogen and progestin therapy (EPT) was not (RR 0.91; 95% CI 0.70-1.19). We performed a dose-response analysis of estrogen and progestin in women using tablets, and found that use of estrogens was associated with increased risk (RR 1.24; 95% CI 1.00-1.53 per 1 mg/day) and use of progestins with decreased risk (RR 0.71; 95% CI 0.57-0.89 per 10 mg/month) of SMM. In conclusion, estrogens were associated with increased risk of SMM, while combinations of estrogens and progestins were not. Our results suggest that estrogens and progestins might affect the risk of SMM in opposite ways.

Low Calcium Intake in Midpregnancy Is Associated with Hypertension Development within 10 Years after Pregnancy: The Norwegian Mother and Child Cohort Study.

Background: Low dietary calcium intake may be a risk factor for hypertension, but studies conflict.Objective: We evaluated the ability to predict hypertension within 10 y after delivery based on calcium intake during midpregnancy.Methods: The Norwegian Mother and Child Cohort Study of women delivering in 2004-2009 was linked to the Norwegian Prescription Database (2004-2013) to ascertain antihypertensive medication usage >90 d after delivery. Women with hypertension before pregnancy were excluded, leaving 60,027 mothers for analyses. Age and energy-adjusted cubic splines evaluated dose-response curves, and Cox proportional hazard analyses evaluated HR and 95% CIs by calcium quartiles adjusting for 7 covariates. Analyses were stratified by gestational hypertension and by sodium-to-potassium intake ratio (<0.76 compared with ≥0.76).Results: Participants had a mean ± SD age of 30.5 ± 4.6 y, a body mass index (in kg/m2) of 24.0 ± 4.3 before pregnancy, and a mean follow-up duration of 7.1 ± 1.6 y. Cubic spline graphs identified a threshold effect of low calcium intake only within the range of dietary inadequacy related to increased risk. The lowest calcium quartile (≤738 mg/d; median: 588 mg/d), relative to the highest quartile (≥1254 mg/d), had an HR for hypertension of 1.34 (95% CI: 1.05, 1.70) among women who were normotensive during pregnancy, and an HR of 1.62 (95% CI: 1.14, 2.35) among women who had gestational hypertension, after adjusting for covariates. Women with gestational hypertension, who were in the lowest quartile of calcium intake, and who had a high sodium-to-potassium intake ratio had a risk of hypertension more than double that of their counterparts with a calcium intake in the highest quartile. Results were attenuated by adjusting for covariates (HR: 1.92; 95% CI: 1.09, 3.39).Conclusions: The results suggest that low dietary calcium intake may be a risk factor or risk marker for the development of hypertension, particularly for women with a history of gestational hypertension.

Postmenopausal hormone therapy and the risk of breast cancer in Norway.

There is convincing evidence that combined estrogen-progestin therapy (EPT) increases the risk of breast cancer. However, the effect of different formulations, preparations and routes of administration is largely unknown. Estrogen only-therapy (ET) is, in general, not associated or weakly associated with breast cancer risk. We investigated the effect of hormone therapy (HT) with ET, EPT, and tibolone on risk of invasive breast cancer. Information on HT use was obtained from the Norwegian Prescription Database, and breast cancer incidence from the Cancer Registry of Norway. Poisson regression was used to estimate the incidence rate ratios (RR). We analyzed data from 686,614 Norwegian women, aged 45-79 years in January 2004, followed until December 2008, of whom 178,383 (26%) were prescribed HT. During the average 4.8 years of follow-up, 7,910 invasive breast cancers were registered. Compared with nonusers, current users of estradiol-norethisterone acetate (NETA)(EPT) had a RR of 2.74 (95% CI: 2.55-2.95). Users of the high dose estradiol-NETA formulation Kliogest(®) had a RR of 3.26 (95% CI: 2.84-3.73), while users of the low dose Activelle(®) had a RR of 2.76 (95% CI: 2.51-3.04). Current users of tibolone had a RR of 1.91 (95% CI: 1.61-2.28). Current users of ET with oral or transdermal estradiol had a RR of 1.40 (95% CI: 1.16-1.68), and 1.40 (95% CI: 1.00-1.95), respectively. The increased incidence rates approximates one extra invasive breast cancer case diagnosed for every 259 women using estradiol-NETA for one year, and one extra case for every 475 women using tibolone. In conclusion, use of estradiol-NETA and tibolone preparations is associated with an increased breast cancer risk.

Breast cancer incidence trends in Norway--explained by hormone therapy or mammographic screening?

A decline in breast cancer incidence has been observed in several countries after 2002. Reduced use of menopausal hormonal therapy (HT), as a consequence of the publication of results from the Women's Health Initiative, has been argued to be the main reason. In Norway, the governmentally funded Norwegian Breast Cancer Screening Program (NBCSP) was implemented during the same time period as the increased use of HT. This study investigated trends in breast cancer incidence by use of HT and introduction of the screening program. We obtained rates of breast cancer from the Cancer Registry of Norway and sales data of HT preparations from the Norwegian Institute of Public Health. Mammography rates were estimated from published reports. Breast cancer incidence rates increased steadily from 1956 to the end of the 20th century, particularly in women aged 55-69 during 1996-2002 residing in the counties where the NBCSP was first introduced. The rates declined after 2002-2003. HT use increased in 1987-2001, peaking around year 2000. In particular, sales of combined estrogen and progestogen preparations declined after 2002. Among women aged 55-59, rates of hormone receptor positive breast cancers peaked in 2000-2003. No such trend was seen in other age groups. In conclusion, the interpretation of breast cancer incidence trends in Norway from 1987 to 2009 is complicated because the NBCSP was introduced during a period with increasing HT use. Both factors likely contributed to the observed trends, and the role of each may vary across age groups.

Use of Statins in Kidney Transplant Recipients in Norway.

Kidney transplant recipients (KTRs) experience increased risk of cardiovascular disease. Guidelines recommend HMG-CoA reductase inhibitor (statin) therapy when tolerated. We aimed to study changes in the prescription of statins and patients' adherence to treatment over time. A population-based observational study utilizing linked data from the Norwegian Renal Registry (national coverage of 99.9%) and the Norwegian Prescription Database was performed. Data from a total of 2250 first KTRs were included (mean age-54 years, 69% men). Dispensed prescriptions of statins and immunosuppressants for the period 2004-2016 for all first KTRs engrafted in the period 2005-2015 were analyzed. Seventy-two percent received statins the first year after kidney transplantation and the proportion increased with age. The proportion receiving a statin varied according to the time frame of transplantation (77% in 2005-2010 vs. 66% in 2012-2015). Among new users of statins, 82% of the patients were adherent both the second and third year after kidney transplantation, while the corresponding figure for those already receiving statins before transplantation was 97%. Statin continuation rates in KTRs were high. In conclusion, our findings show a slightly lower overall proportion of patients receiving statins after kidney transplants than the national target level of 80%. The proportion of statin users increased with the age of the KTRs but showed a decreasing trend as time progressed.

Statin treatment in a cohort of 20 212 men and women in Norway according to cardiovascular risk factors and level of education.

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 1,620 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.

Environmental assessment of Norwegian priority pharmaceuticals based on the EMEA guideline.

An environmental risk assessment of eleven pharmaceuticals according to the guideline recommended by the European Medicines Evaluation Agency (EMEA) was performed. Cefuroxime, ciprofloxacin, cyclophosphamide, diclofenac, ethinylestradiol, ibuprofen, metoprolol, paracetamol, sulfamethoxazole, tetracycline and trimethoprim were selected for assessment by the Norwegian Pollution Control Authority. Predicted environmental concentrations (PECs) were calculated according to both the EMEA guideline and a conventional model for comparison and ranged from 0.0002 to 45 microg/L. Available acute and chronic toxicity data were collected from the literature, although no data were available for cyclophosphamide. Toxicity tests showed cyclophosphamide to have relatively low acute toxicity with an EC50 for Pseudokirchneriella subcapitata >100 mg/L and a Daphnia magna reproduction NOEC of 56 mg/L. These and the literature data were used to derive predicted no effect concentrations (PNEC). Risk quotients (PEC/PNEC) were then calculated for all 11 pharmaceutical compounds. Risk quotients greater than 1 were obtained for ciprofloxacin, diclofenac, ethinylestradiol, sulfamethoxazole and tetracycline according to the EMEA guideline. Measured environmental concentrations (MECs) confirmed that the release of ciprofloxacin from wastewater treatment works may potentially be of environmental concern in Norway.

Aspects of statin prescribing in Norwegian counties with high, average and low statin consumption - an individual-level prescription database study.

BACKGROUND: A previous study has shown that variations in threshold and intensity (lipid goal attainment) of statins for primary prevention contribute to regional differences in overall consumption of statins in Norway. Our objective was to explore how differences in prevalences of use, dosing characteristics, choice of statin and continuity of therapy in individual patients adds new information to previous results. METHODS: Data were retrieved from The Norwegian Prescription Database. We included individuals from counties with high, average, and low statin consumption, who had at least one statin prescription dispensed during 2004 (N = 40 143).1-year prevalence, prescribed daily dose (PDD), statin of choice, and continuity of therapy assessed by mean number of tablets per day. RESULTS: The high-consumption county had higher prevalence of statin use in all age groups. Atorvastatin and simvastatin were dispensed in 79-87% of all statin users, and the proportion was significantly higher in the high-consumption county. The estimated PDDs were higher than the DDDs, up to twice the DDD for atorvastatin. The high-consumption county had the highest PDD for simvastatin (25.9 mg) and atorvastatin (21.9 mg), and more users received tablets in the upper range of available strengths. Continuity of therapy was similar in the three counties. CONCLUSION: Although differences in age-distribution seems to be an important source of variation in statin consumption, it cannot account for the total variation between counties in Norway. Variations in prevalences of use, and treatment intensity in terms of PDD and choice of statin also affect the total consumption. The results in this study seems to correspond to previous findings of more frequent statin use in primary prevention, and more statin users achieving lipid goal in the highest consuming county.

Long-term Use of Z-Hypnotics and Co-medication with Benzodiazepines and Opioids.

Benzodiazepine-like drugs (z-hypnotics) are the most commonly used drugs for treatment of insomnia in Norway. Z-hypnotics are recommended for short-term treatment not exceeding 4 weeks. We aimed to study the use of z-hypnotics in the adult population in Norway with focus on recurrent use in new users, treatment intensity and co-medication with benzodiazepines and opioids in long-term users. Data were obtained from the Norwegian Prescription Database. New users in 2009 were followed through 2013. Recurrent z-hypnotic use was defined as new fillings at least once in each of the four 365-day follow-up periods. Age groups of 18-39, 40-64 and 65+ years were analysed separately for men and women. In 2013, 354,571 (8.9%) of the population filled at least one prescription of z-hypnotics and the prevalence was relatively stable over time. Among the 92,911 new users of z-hypnotics in 2009, 13,996 (16.8%) received z-hypnotics all four 365-day periods of follow-up. In these long-term recurrent users, the treatment intensity was high already the second year, with mean annual amounts of 199 and 169 DDDs per patient in men and women, respectively. The interquartile differences were greatest in the youngest age group. 27.9% of the long-term recurrent users of z-hypnotics used benzodiazepines the fourth year and 33.9% used opioids. The proportions with co-medication increased with level of z-hypnotic treatment intensity. Overall, many z-hypnotic users had medicines dispensed for longer periods than recommended, and co-medications with drugs that may reinforce the central depressing and intoxicating effects were common.

Menopausal hormone therapy and colorectal cancer: a linkage between nationwide registries in Norway.

OBJECTIVES: With the present study, we aimed to investigate the association between menopausal hormone therapy (HT) and risk of colorectal cancer (CRC). SETTING: Cohort study based on the linkage of Norwegian population-based registries. PARTICIPANTS: We selected 466822 Norwegian women, aged 55-79, alive and residing in Norway as of 1 January 2004, and we followed them from 2004 to 2008. Each woman contributed person-years at risk as non-user, current user and/or past HT user. OUTCOME MEASURES: The outcome of interest was adenocarcinoma of the colorectal tract, overall, by anatomic site and stage at diagnosis. Incidence rate ratios (RRs) with 95% CIs were estimated by Poisson regression and were used to evaluate the association between HT and CRC incidence. RESULTS: During the median follow-up of 4.8 years, 138 655 (30%) women received HT and 3799 (0.8%) incident CRCs occurred. Current, but not past, use of HT was associated with a lower risk of CRC (RR 0.88; 95% CI 0.80 to 0.98). RRs for localised, regionally advanced and metastatic CRC were 1.13 (95% CI 0.91 to 1.41), 0.81 (95% CI 0.70 to 0.94) and 0.79 (95% CI 0.62 to 1.00), respectively. RRs for current use of oestrogen therapy (ET) were 0.91 (95% CI 0.80 to 1.04) while RR for current use of combined oestrogen-progestin therapy (EPT) was 0.85 (95% CI 0.70 to 1.03), as compared with no use of HT. The same figures for ET and EPT in oral formulations were 0.83 (95% CI 0.68 to 1.03) and 0.86 (95% CI 0.71 to 1.05), respectively. CONCLUSIONS: In our nationwide cohort study, HT use lowered the risk of CRC, specifically the most advanced CRC.

[How many and who are receiving medication for diabetes mellitus?]. / Hvor mange og hvem behandles medikamentelt for diabetes mellitus?

BACKGROUND: This study presents data on the prevalence and incidence of drug-treated diabetes mellitus in Norway based on the new Norwegian Prescription Database (NorPD). MATERIAL AND METHODS: We used data from the NorPD (2004-June 2005) and the official wholesales statistics (2000-2004). The number of patients with at least one prescription for drugs used in diabetes was recorded, together with gender and age distribution among the users. RESULTS: The one-year prevalence in 2004 of drug-treated diabetes was 2.6% for men and 2.2% for women. 9% of men in the 70-79 year age-group received antidiabetic drugs. 46 000 patients were recorded with at least one prescription on insulin, while 79,000 patients collected at least one prescription on tablets. The one-year prevalence of insulin users in the age-group younger than 15 years was estimated to 2.0 per 1000. The incidence rate, calculated from data from the first half of 2005, was 35 per 100,000 person-years. INTERPRETATION: The NorPD represents a new data source which offers good estimates for the number of patients diagnosed with diabetes mellitus who receive antidiabetic drugs outside hospitals or nursing homes. The 2004 prevalence was in accordance with previous surveys, while the incidence rate of type 1 diabetes in children younger than 15 years was higher than previously shown.

[Changes in the sale and use of flunitrazepam in Norway after 1999]. / Endringer i salg og bruk av flunitrazepam etter 1999.

BACKGROUND: In Norway there has in later years been much discussion of misuse of flunitrazepam. From 1 January 2003 the drug was moved up one level in the schedule of controlled substances. On 1 August 2004 the manufacturer of the Rohypnol brand withdrew it from the Norwegian market. How did these two events influence the sales and use of drugs containing flunitrazepam? MATERIALS AND METHODS: Sales figures for drugs containing flunitrazepam from the statistics database at the Norwegian Institute of Public Health were studied. The Norwegian prescription database was used to describe new (incident) users of flunitrazepam and the two brands of this drug sold in Norway in 2004. RESULTS AND DISCUSSION: Restrictions on the prescription status of flunitrazepam lead to a decrease in sales from 7.2 defined daily doses (DDD) per 1000 inhabitants per day in 2002 to 3.0 DDD per 1000 inhabitants per day in 2003. This decrease was only partly compensated for by an increase in the sales of nitrazepam (from 5.0 to 6.0 DDD per 1000 inhabitants per day). During the years 1999 to 2004 there was a steady increase in the sales of benzodiazepine-related hypnotics (zopiclone and zolpidem). This shift could mean a change from flunitrazepam to zopiclone. The withdrawal of Rohypnol in August 2004 had only minor effects on the total sales of flunitrazepam. The decline in sales of Rohypnol was almost compensated for by the increase in the overall sales of Flunipam. This was reflected in the fact that in the later months of 2004 there were many new (incident) users of Flunipam, but few new users of flunitrazepam-containing drugs in total. It could be concluded that the restrictions on prescription status of flunitrazepam had a much higher impact than the withdrawal of the Rohypnol brand.

Postmenopausal Hormone Therapy and Breast Cancer Prognostic Characteristics: A Linkage between Nationwide Registries.

BACKGROUND: The effects of use of different types of hormone therapy on breast cancer risk according to prognostic factors are largely unknown. METHODS: We linked data from the Norwegian Prescription Database and the Cancer Registry of Norway during 2004 to 2009 on all women ages 45 to 79 years (N = 686,614). We estimated rate ratios and 95% confidence intervals for breast cancer in relation to hormone therapy using Poisson regression. RESULTS: During an average 4.8 years of follow-up, 7,910 invasive breast cancers were diagnosed. Compared with nonusers of hormone therapy, users of estradiol and tibolone were more likely to be diagnosed with grade I, lymph node-negative, and estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+) tumors. However, compared with nonusers, users of the most common estrogen and progestin combinations [estradiol-norethisterone acetate (NETA) preparations (Kliogest, Activelle or Trisekvens)] were at a 4- to 5-fold elevated risk of grade I tumors, 3-fold elevated risk of lymph node-negative tumors, and 3- to 4-fold elevated risk of ER+/PR+ tumors. Importantly, estradiol-NETA users were also at a 2- to 3-fold increased risk of medium differentiated (grade II) tumors and tumors with lymph node involvement. CONCLUSIONS: Use of oral estradiol, tibolone, and estradiol-NETA predominantly increases the risk of breast cancer with favorable prognosis characteristics. However, use of estradiol-NETA preparations also increases the risk of breast cancers with less favorable characteristics. IMPACT: The hormone therapy preparations most commonly used in the Nordic countries are associated with both breast cancers with good and less favorable prognosis characteristics. Cancer Epidemiol Biomarkers Prev; 25(11); 1464-73. ©2016 AACR.

[Prescription of selective serotonin reuptake inhibitors 1990-2004]. / Forskrivning av selektive serotoninreopptakshemmere 1990-2004.

BACKGROUND: Antidepressant drugs are important in the treatment of major depression. The use of antidepressants in general and more specifically selective serotonin reuptake inhibitors (SSRIs) has, however, been subject to discussion since their introduction in Norway in 1990. After the introduction of paroxetin in Norway in 1993, the sales of SSRIs rose rapidly. Up until now we have had little knowledge of the patterns of use of these drugs in Norway. This article describes the sales of SSRIs and other antidepressants from 1990 to 2004. The newly established Norwegian Prescription Database (NorPD) is used to establish the figures in more detail. MATERIAL AND METHODS: Sales figures for SSRIs and other antidepressants from the Norwegian Institute of Public Health are presented. NorPD is used to describe age and gender prevalence and incidence of antidepressant use. RESULTS: After their introduction on the Norwegian drug market in the beginning of the 1990s, the SSRIs have held a leading position on this market. In the beginning, paroxetin was the prevalent drug used in Norway. When citalopram was marketed in 1995, it rapidly took over this role. From 2004 escitalopram won a growing share of the market. Two thirds of all antidepressants are prescribed to women. With increasing age, increasing shares of the population are prescribed antidepressants. Elderly people are prescribed relatively more tricyclic antidepressants than younger people. SSRIs are also prescribed to adolescents, though tricyclic antidepressants are predominant below the age of 15. INTERPRETATION: A lower increase in the sales of antidepressants in 2004 could be caused by saturation of the antidepressants market or negative media attention for these drugs. Tricyclic antidepressants are possibly still used in excess by the elderly. The number of girls 15-19 years of age using SSRIs is relatively large. Even though fluoxetin is the only drug recommended for this age group, other SSRIs are more often prescribed.

Multiple prescribers in older frequent opioid users--does it mean abuse?

BACKGROUND: Obtaining analgesic narcotics from multiple prescribers is sometimes called 'doctor-shopping,' implying abuse. If the use of multiple prescribers can be used as an indicator for abuse, it would be a convenient way to study abuse in large populations. OBJECTIVE: To assess multiple prescribers as an indicator of abuse by relating quantity of opioids obtained by older Norwegians to number of prescribers. METHODS: Data were obtained from the Norwegian Prescription database which includes all prescriptions filled in Norwegian pharmacies. The study population consisted of people aged 70-89 who filled five or more prescriptions for weak or for strong opioids in 2008. RESULTS: In 2008, 4,268 persons filled five or more prescriptions for strong opioids and 19,675 for weak opioids. More than 30% had three or more prescribers. Over half of strong opioids users and 72% of weak opioid users had medication-use-periods of over 40 weeks. For strong opioids, increasing DDDs/week was found with increasing number of prescribers. When cancer/palliative care patients were excluded, the mean DDDs/week level for strong opioids was much lower, and little association with number of prescribers remained. For weak opioids, little association between mean DDDs/week and number of prescribers was found. CONCLUSIONS: This study demonstrated that the increasing quantities of strong opioids with increasing number of prescribers are largely due to treatment of cancer/palliative care patients. While the use of multiple prescribers can be a red flag for problematic medication use, it cannot be considered synonymous with 'doctor-shopping' or abuse.

Resting heart rate and physical activity as risk factors for lone atrial fibrillation: a prospective study of 309,540 men and women.

OBJECTIVE: To study the impact of resting heart rate and leisure time physical activity at middle age on long term risk of drug treated lone atrial fibrillation (AF). DESIGN: Longitudinal cohort study of 309 540 Norwegian men and women aged 40-45 years examined during 1985-1999 followed from 2005 through 2009. SETTING: Data from a national health screening programme were linked to the Norwegian Prescription Database (NorPD). PATIENTS: The cohort comprised 162 078 women and 147 462 men; 575 (0.4%) men and 288 women (0.2%) received flecainide and 568 men and 256 women sotalol and were defined as patients with AF. INTERVENTIONS: No interventions. MAIN OUTCOME MEASURES: The outcome was lone fibrillation defined by having at least one prescription of flecainide or sotalol registered in NorPD between 2005 and 2009. Cox proportional hazard regression models were used to assess time to first prescription. RESULTS: The risk for being prescribed these drugs increased with decreasing baseline resting heart. Adjusted hazard ratio (HR) per 10 beats/min decrease in resting heart rate for flecainide prescription was 1.26 in men (95% CI 1.17 to 1.35) and 1.15 (95% CI 1.05 to 1.27) in women. Similar effects were seen for sotalol in men, but not in women. Men who reported intensive physical activity were more often prescribed flecainide than those in the sedentary group (adjusted HR=3.14, 95% CI 2.17 to 4.54). CONCLUSIONS: This population based study supports the hypothesis that the risk of drug treated lone AF increases with declining resting heart rate in both sexes, and with increasing levels of self-reported physical activity in men.

Body mass index, triglycerides, glucose, and blood pressure as predictors of type 2 diabetes in a middle-aged Norwegian cohort of men and women.

BACKGROUND: Obesity, hypertension, and hypertriglyceridemia are important risk factors for type 2 diabetes (T2D). We wanted to assess the risk associated with these three factors alone and in combination, and the relative importance of these and several other risk factors (eg, nonfasting glucose) as predictors of T2D. METHODS: Risk factors in a Norwegian population (n = 109,796) aged 40-45 years were measured in health studies in 1995-1999. Blood glucose-lowering drugs dispensed in 2004-2009 were used to estimate the incidence of T2D. Groups based on combinations of body mass index (BMI), diastolic blood pressure, and triglycerides were defined by using the 50% and 90% quantiles for each variable for men and women. The relative importance of BMI, triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose, blood pressure, and year of birth for predicting T2D was assessed using deviance from univariate and multivariate logistic regression models. Height, weight, and blood pressure were measured. All biomarkers were measured in nonfasting blood samples. RESULTS: In the various groups of BMI, triglycerides, and diastolic blood pressure, the incidence of T2D ranged from 0.5% to 19.7% in men and from 0.15% to 21.8% in women. BMI was the strongest predictor of incident T2D, followed by triglyceride levels in women and glucose levels in men. The inclusion of risk factors other than BMI, glucose, triglycerides, and blood pressure in multivariate models only marginally improved the prediction. CONCLUSION: BMI was the strongest predictor of type 2 diabetes. At defined levels of BMI, the incidence of T2D varied substantially with triglyceride levels and blood pressure. Thus, controlling triglycerides and blood pressure in middle-aged individuals should be targeted to prevent later onset of T2D.

Combination of prescribing restrictions and policies to engineer low prices to reduce reimbursement costs.

OBJECTIVES: To primarily document the influence of recent changes in the pricing policies for generics and originators in Norway, coupled with prescribing restrictions for both the proton pump inhibitors (PPIs) and statins, on subsequent prescribing efficiency, to provide possible examples to other countries. Second, to review the impact of prescribing restrictions on ezetimibe utilization in Norway compared with other European countries, again to provide guidance. METHODS: A retrospective observational study using data from the Norwegian Drug Wholesales Statistics to evaluate changes in utilization patterns for the PPIs and statins from 2001 to 2009, and the Norwegian Prescription Database for expenditure data from January 2004 to 2009. Reforms validated with key personnel at the Norwegian Medicines Agency. RESULTS: Atorvastatin utilization as measured by defined daily doses decreased after prescribing restrictions. This, coupled with increased utilization of generic simvastatin at only 15% of prepatent loss prices in recent years, led to a 55% decrease in statin expenditure in Norway between 2004 and 2009 despite appreciably increased utilization. Utilization of esomeprazole also fell following prescribing restrictions, but to a lesser extent. This reduction, coupled with low prices for generics as a result of recent pricing policies, resulted in PPI expenditure decreasing by 27% during the same period despite again appreciably increased utilization. CONCLUSIONS: Policies to reduce the price of generics have been successfully introduced in Norway despite its small population size versus a number of other Western European countries. Prescribing restrictions have also been successfully introduced, mirroring the influence with multifaceted reforms in other European countries. The same applies to ezetimibe with utilization at only 1.9% of total statin and ezetimibe utilization in 2009. However, the difference in subsequent utilization patterns for atorvastatin versus esomeprazole makes it a challenge for health authorities to predict the ultimate impact of such measures. This requires further research.