Direction- and Angle-Assisted Buttonhole Cannulation of Arteriovenous Fistula in Hemodialysis Patients: A Multicenter Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Arteriovenous fistula cannulation with the buttonhole technique is often preferred by patients but has been associated with an increased infection risk. Guidelines disagree on whether it should be abandoned, thus we assessed a technologically simple method to facilitate gentler arteriovenous fistula cannulation with potentially less discomfort and damage to the epithelial lining of the buttonhole tract. STUDY DESIGN: 8-week, prospective, open-label, randomized controlled trial. SETTING & PARTICIPANTS: Patients with buttonhole tracts receiving hemodialysis at 7 dialysis centers in Norway were randomized to the intervention group (43 patients, 658 cannulations) or control group (40 patients, 611 cannulations). INTERVENTION: Direction and angle of the established buttonhole tract were marked on the forearm skin in the intervention group, whereas the control group had no structured cannulation information system. OUTCOMES: The primary outcome was successful cannulation, defined as correct placement of both blunt needles at the first attempt without needing to change needles, perform extra perforations, or reposition the needle. The secondary outcomes were patient-reported difficulty of cannulation (verbal rating scale: 1 = very easy, 6 = impossible) and intensity of pain (numeric rating scale: 0 = no pain, 10 = unbearable pain). RESULTS: After a 2-week run-in period, successful cannulation was achieved in 73.9% and 74.8% of the patients in the intervention and control groups, respectively (relative risk [RR], 0.99; 95% CI, 0.87-1.12; P = 0.85). However, the probability of a difficult arterial cannulation (verbal rating scale, 3-6) was significantly lower in the intervention group (RR, 0.69; 95% CI, 0.55-0.85; P = 0.001). There were no improvements for venous cannulations. Furthermore, the probability of a painful cannulation (numeric rating scale, 3-10) was lower in the intervention group (RR, 0.72; 95% CI, 0.51-1.02; P = 0.06). LIMITATIONS: Unable to evaluate hard end points such as infections and thrombosis owing to the small sample size. CONCLUSIONS: Marking direction and angle of cannulation did not improve cannulation success rates; however, patients more often reported an unproblematic procedure and less pain. FUNDING: None. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01536548).

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.

Cigarette smoking and risk of subsequent use of antibacterials: a follow-up of 365,117 men and women.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Health Alliance for prudent antibiotic prescribing in patients with respiratory tract infections (HAPPY AUDIT) -impact of a non-randomised multifaceted intervention programme.

BACKGROUND: Excessive use of antibiotics is worldwide the most important reason for development of antimicrobial resistance. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. Initiatives have been taken to improve the quality of antibiotic prescribing in primary care, but only few studies have been designed to determine the effectiveness of multifaceted strategies across countries with different practice setting. The aim of this study was to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different health organization and different prevalence of antibiotic resistance. METHODS: GPs from two Nordic countries, two Baltic Countries and two Hispano-American countries registered patients with respiratory tract infections (RTIs) in 2008 and 2009. After first registration they received individual prescriber feedback and they were offered an intervention programme that included training courses, clinical guidelines, posters for waiting rooms, patient brochures and access to point of care tests (Strep A and C-Reactive Protein). Antibiotic prescribing rates were compared before and after the intervention. RESULTS: A total of 440 GPs registered 47011 consultations; 24436 before the intervention (2008) and 22575 after the intervention (2009). After the intervention, the GPs significantly reduced the percentage of consultations resulting in an antibiotic prescription. In patients with lower RTI the GPs in Lithuania reduced the prescribing rate by 42%, in Russia by 25%, in Spain by 25%, and in Argentina by 9%. In patients with upper RTIs, the corresponding reductions in the antibiotic prescribing rates were in Lithania 20%, in Russia 15%, in Spain 9%, and in Argentina 5%. CONCLUSION: A multifaceted intervention programme targeting GPs and patients and focusing on improving diagnostic procedures in patients with RTIs may lead to a marked reduction in antibiotic prescribing. The pragmatic before-after design used may suffer from some limitations and the reduction in antibiotic prescribing could be influenced by factors not related to the intervention.

Use of prescribed opioid analgesics and co-medication with benzodiazepines in women before, during, and after pregnancy: a population-based cohort study.

PURPOSE: The aim of the study was to describe the use of prescribed opioid analgesics for noncancer pain and the degree of possible concurrent co-medication with benzodiazepines to women in Norway before, during, and after pregnancy. METHODS: This was a population-based cohort study based on linkage of two nationwide registries: the Medical Birth Registry of Norway, and the Norwegian Prescription Database. Prescribed opioid analgesics and benzodiazepines issued to women 3 months prior to, during, and 3 months after pregnancies were identified. The study population consisted of 194,937 singleton pregnancies beginning in March 2004 or later and ending before January 2009. RESULTS: About 6% of the women were dispensed opioid analgesics before, during, or after pregnancy. Almost all these women received weak opioids (99%) with short-acting codeine in combination with paracetamol (acetaminophen) as the most frequently dispensed drug. The dispensing of codeine was reduced from 24/1,000 women before pregnancy to 10/1,000 in the last trimester, increasing to 17/1,000 during the breastfeeding period. Most women were dispensed codeine once, and treatment was of short duration (about 1 week). A small group of women (n = 271) were dispensed opioids in all trimesters. Increasing benzodiazepine use was observed as the number of opioid prescriptions increased. CONCLUSIONS: The use of opioid analgesics in pregnant women in Norway was dominated by treatment of short duration of the weak opioid codeine. As pregnancy proceeded, opioid use was reduced. However, the increase in opioid use during the nursing period has the potential for serious adverse effects.

Prevalence, incidence and persistence of etanercept and adalimumab in Norway 2005-2009.

PURPOSE: Examining the prevalence, incidence and persistence of use of etanercept and adalimumab in Norway during 2005-2009. METHODS: We retrieved data from the nationwide Norwegian Prescription Database (NorPD) for all individuals who were dispensed etanercept or adalimumab from pharmacies during 2005-2009. The NorPD covers the total Norwegian population in ambulatory care. Key measurements were one-year prevalence, incidence rate and persistence (minimum refill). RESULTS: The one-year prevalence for etanercept and adalimumab was 1.59‰ (n = 3840) for men and 1.85‰ (n = 4483) for women in 2009, an increase from 0.76‰ (n = 1752) for men and 1.21‰ (n = 2830) for women from 2005. The prevalence increased during the entire study time in all ages, with the highest prevalence for both genders among those aged 50-69. A total of 7786 individuals started therapy with etanercept or adalimumab during 2005-2009. Annual incidence of new users increased with 23.6% from 2005 to 2009. Sixty one percent of new users redeemed etanercept as the first drug, and 39% redeemed adalimumab. Sixty seven percent of all individuals who received etanercept or adalimumab in 2005 refilled their prescription at least once each of the following 4 years. CONCLUSIONS: Both prevalence and incidence of use of etanercept and adalimumab increased in Norway during 2005-2009. A high proportion of the individuals redeemed prescriptions regularly over 5 years.

Health Alliance for Prudent Prescribing, Yield and Use of Antimicrobial Drugs in the Treatment of Respiratory Tract Infections (HAPPY AUDIT).

BACKGROUND: Excessive and inappropriate use of antibiotics is considered to be the most important reason for development of bacterial resistance to antibiotics. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. The majority of respiratory tract infections (RTIs) are treated in general practice. Most infections are caused by virus and antibiotics are therefore unlikely to have any clinical benefit. Several intervention initiatives have been taken to reduce the inappropriate use of antibiotics in primary health care, but the effectiveness of these interventions is only modest. Only few studies have been designed to determine the effectiveness of multifaceted strategies in countries with different practice setting. The aim of this study is to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different prevalence of antibiotic resistance: Two Nordic countries (Denmark and Sweden), two Baltic Countries (Lithuania and Kaliningrad-Russia) and two Hispano-American countries (Spain and Argentina). METHODS/DESIGN: HAPPY AUDIT was initiated in 2008 and the project is still ongoing. The project includes 15 partners from 9 countries. GPs participating in HAPPY AUDIT will be audited by the Audit Project Odense (APO) method. The APO method will be used at a multinational level involving GPs from six countries with different cultural background and different organisation of primary health care. Research on the effect of the intervention will be performed by analysing audit registrations carried out before and after the intervention. The intervention includes training courses on management of RTIs, dissemination of clinical guidelines with recommendations for diagnosis and treatment, posters for the waiting room, brochures to patients and implementation of point of care tests (Strep A and CRP) to be used in the GPs'surgeries. To ensure public awareness of the risk of resistant bacteria, media campaigns targeting both professionals and the public will be developed and the results will be published and widely disseminated at a Working Conference hosted by the World Association of Family Doctors (WONCA-Europe) at the end of the project period. DISCUSSION: HAPPY AUDIT is an EU-financed project with the aim of contributing to the battle against antibiotic resistance through quality improvement of GPs' diagnosis and treatment of RTIs through development of intervention programmes targeting GPs, parents of young children and healthy adults. It is hypothesized that the use of multifaceted strategies combining active intervention by GPs will be effective in reducing prescribing of unnecessary antibiotics for RTIs and improving the use of appropriate antibiotics in suspected bacterial infections.

[Antibiotic use in Norway]. / Antibiotikaforbruk i Norge.

BACKGROUND: Antibiotic use is a major cause of development and spread of resistant bacteria. Sensible antibiotic use should aim at decreasing total antibiotic use and replace broad-spectrum antibiotics with narrow-spectrum ones; pharmaceutical drug statistics are vital in this context. MATERIAL AND METHODS: Data were collected from the wholesaler-based drug statistics (for the period 1974 - 2007) and from the Norwegian Prescription Database (2006). The ATC/DDD methodology is used in the drug statistics. Data are presented as number of users (prevalence), number of dispensed prescriptions, defined daily doses (DDD per 1 000 inhabitants per day) and in Norwegian kroner. RESULTS AND INTERPRETATIONS: Longitudinal trends show a relatively stable and high use of narrow-spectrum antibiotics, even though broad-spectrum antibiotic use is slightly increasing. Antibiotic use varies largely by age and sex. The highest prevalences are seen among small children (0 - 5 years), women in their twenties and in people over 70 years. Over 30 % of people in these groups receive at least one antibiotic per year. The therapy profile differs between the types of prescription issued. Neither the wholesaler statistics nor the Prescription Database contains information on diagnosis, making it difficult to monitor whether the Norwegian primary health service has a rational antibiotic therapy.

Prescription drug use among fathers and mothers before and during pregnancy. A population-based cohort study of 106,000 pregnancies in Norway 2004-2006.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Mothers are using medicines during pregnancies; the extent varies across the world and is generally difficult to compare. In this registry-based study, we examined more than 100,000 Norwegian pregnancies and described the drug prescription pattern of both fathers and mothers around conception and during pregnancy (mothers). WHAT THIS STUDY ADDS: In every trimester of pregnancy, about 30% of the mothers was dispensed a drug. The total drug exposure did not seem to diminish throughout pregnancy. One-quarter of the fathers was dispensed drugs during the last 3 months prior to conception. AIMS: The primary aim of this study was to describe the use of prescribed drugs in both mothers and fathers before and during pregnancy in Norway. METHODS: This population-based cohort study was based on data retrieved from the Medical Birth Registry of Norway and the Norwegian Prescription Database. These registries cover the entire population of Norway. Information on >100,000 births during 2004-2006 in the birth registry was linked to prescription data. Prescriptions issued to mothers just prior to, during and after the pregnancies as well as prescriptions to fathers just prior to conception were identified. RESULTS: Among mothers, 83% were prescribed drugs during the period 3 months prior to estimated conception until 3 months after giving birth. The mothers who received drugs were prescribed on average 3.3 different Anatomical Therapeutic Chemical (ATC) codes (range 1-38). During pregnancy, 57% were prescribed drugs. In the first trimester, 33% of mothers were dispensed drugs, while the figure was 29% for mothers in the last trimester. Among fathers, 25% used prescribed drugs during the 3 months prior to conception, with on average 1.9 different ATC codes (range 1-22). CONCLUSION: Large proportions of both fathers and mothers were dispensed drugs prior to conception or during pregnancy. While there is a high awareness of the issues involved in maternal drug use in pregnancy, possible teratogenic effects of drug use in fathers shortly before conception should be further explored.

Switching statins in Norway after new reimbursement policy: a nationwide prescription study.

AIMS: To assess the changes in prescribing of statins in Norway after implementation of the new reimbursement regulations for statins in June 2005. METHODS: Data were retrieved from the Norwegian Prescription Database covering the total population in Norway (4.6 million). Outcome measures were the proportion of atorvastatin users switching to simvastatin and changes in the proportion of new statin users receiving simvastatin. Based on retail costs for all statin prescriptions dispensed in Norway, expenditure was measured in Norwegian currency. RESULTS: One-year prevalences of statin use increased from 6.3 to 6.8% for women and from 7.5 to 8.1% for men from the year before to the year after the new statin regulations. Of atorvastatin users (N = 131,222), 39% switched to simvastatin during the 13-month period after the implementation. The proportion of switching was higher in women (41%) than in men (36%). In May 2005, 48% of the new statin users received simvastatin. The proportion of new users receiving simvastatin increased rapidly after implementation of the new regulations to 68% in June 2005 and reached 92% in June 2006. Expenditure was reduced from 120 million to 95 million Euro when comparing the year before with the year after the new statin regulations. CONCLUSIONS: The new reimbursement policy for statins has had a great impact on physicians' prescribing of statins in Norway. Physicians in Norway acknowledge the importance of contributing to cost containment.

Age- and gender-specific antibacterial prescribing in Norway.

OBJECTIVES: To describe the use of antibacterials among outpatients in Norway and to explore patterns of age- and gender-specific use. METHODS: Data were extracted from the Norwegian Prescription Database (NorPD), a complete register of all dispensed prescriptions in Norway, in the period 1 July 2005-30 June 2006. NorPD contains data at an individual level. We extracted patients who had received an antibacterial for systemic use. Results were shown as population prevalences for the total population. RESULTS: A total of 1.1 million persons had at least one prescription for an antibacterial dispensed. The mean population prevalence of antibacterial use was 24% in total (28% and 19% for women and men, respectively). Population prevalence changed markedly between different age groups and between genders. Children (<5 years) and older elderly people (>or=75 years) were high consumers. Females, in general, used more than males. Use by the different subgroups of antibacterials differed between gender and between different age groups. beta-Lactamase-sensitive penicillins was the most prevalent antibacterial group in all age groups except for women >or=75 years, for whom penicillins with extended spectrum were the most frequently used. Individuals defined as high users (using more than 60 DDDs/year) represented 3% of the population who were using antibacterials. These patients were older and used co-medication more often than other users of antibacterials. CONCLUSIONS: Over 1 year, a quarter of the total population used antibacterials. Patterns of use and types of drugs used differed markedly between genders and between different age groups.

[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.

[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.

[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.

Problems in collecting comparable national drug use data in Europe: the example of antibacterials.

OBJECTIVE: To describe the methodological problems in collecting retrospectively comparable data on drug use and to compare the use of antibacterials in some European countries. METHODS: A spreadsheet was distributed in 2000 through the European Drug Utilisation Research Group (EuroDURG) network, requesting 1994-1999 data on use of antibacterials for systemic use (ATC group J01), from ambulatory, hospital, or total care, aggregated at ATC 4th level, and presented in defined daily doses per 1000 inhabitants per day (in the 1999 ATC/DDD version or specified other version). RESULTS: The network was able to provide national utilization data for two or more years in the requested period from 16 countries (4 only from primary care, 3 both from primary care and total use, and 9 only total use data). The main methodological problems identified were: use of divergent ATC/DDD versions, divergent assignment of DDDs for combination products and the use of unofficial or national DDDs. It was possible to correct for the different ATC/DDD versions to some extent, except for the cephalosporin group (not included in the analysis), as the collection of data at the ATC 4th level precluded recalculation of DDDs. In the seven countries with primary care data the total J01 antibacterials use varied by a factor of 2.5 (Belgium 23.4 and The Netherlands 9.5 DDDs per 1000inhabitants per day). The use of J01A tetracyclines varied fourfold, and the use of J01C penicillins and J01F macrolides and lincosamides approximately threefold. Significant reduction over time was seen in J01A and an increase in J01F. CONCLUSIONS: In the scientific and regulatory community it is still difficult to perform a valid and comprehensive cross-national collection of utilization data on antibacterials. White spots on the European map persist for ambulatory care data, and data are missing for the hospital sector in most countries. For a thorough explanation of the considerable intercountry variability (especially in antibacterial subgroups and time trends analysis) a sustained and concerted effort is necessary to implement a validation process of the ATC/DDD use in the various countries and to adopt a common methodological approach to the collection of utilization data at the substance level (ATC 5th level).