Umeå University's logo

PURPOSE: To assess the effect of a small economic inducement on the rate of spontaneous reporting of adverse drug reactions (ADRs) and the attitudes of general practitioners and physicians towards reporting of ADRs. METHOD: One intervention and one control county were selected for the study. Written information about the main purpose of spontaneous reporting of ADRs was personally addressed to all physicians in the two counties. The information was identical, except for the addition that during a period of 6 months two lottery tickets would be given to the receivers in the intervention area with the standard personal feedback to the reporter of the ADR. After the 6-month study period, the actual number of reported ADRs and the seriousness of the reported ADRs were assessed. To investigate the attitude towards this stimulation of reporting, a questionnaire was addressed to all physicians within the intervention area (IA). RESULTS: From the IA a total number of 57 ADR reports were received containing 62 suspected ADRs, 40% of which were assessed as serious reactions. From the control area (CA), 49 reports containing 50 suspected ADRs were received, 32% of which were assessed as serious reactions. The increase of ADR reports from the IA compared to the same time period the previous year was 59% as compared to an unchanged reporting from the CA. Of those responding to the questionnaire, 80% did not believe that a small economic bonus would be a useful tool to improve the reporting rate. CONCLUSION: A small economic inducement is associated with an increase in the reporting of suspected ADRs.

OBJECTIVES: This study was designed to investigate attitudes of general practitioners (GPs) and hospital physicians in Sweden towards spontaneous reporting of adverse drug reactions (ADRs). METHOD: Two areas in the northern region of Sweden were selected for the study. A knowledge and attitude questionnaire followed by a reminder letter 2 weeks later was addressed to all GPs and hospital physicians in the study areas. RESULT: The total response rate from the study areas was 748 of the 1274 questionnaires sent out (58.7%). Of those who responded, 236 were GPs, 433 were hospital physicians and 79 had other positions. Of the responders, 252 stated that they had never reported any ADR and 488 that they had reported at least once in their career. Issues that came out as important in the decision to report or not to report were whether the reaction was considered well-known or not, the severity of the reaction, hesitance to report only on suspicion, lack of knowledge of existing rules, giving priority to other matters and lack of time to report ADRs. Only minor differences in these regards were observed between male and female physicians. CONCLUSION: Our investigation shows that the physicians in northern Sweden have a fairly good knowledge about the existing rules for reporting ADRs in Sweden. However, the attitudes leave room for considerable under-reporting due to matters related mainly to the medical impact of the reaction and of reporting it, but also to the scientific "paradox" of reporting only on suspicion and of course due to lack of time in the health care setting.

Purpose: The survival of esophageal and gastric cancer patients treated with chemotherapy is rarely assessed outside of clinical trials. Therefore, we compared the effectiveness of various curative or palliative chemotherapy regimens on the survival of esophageal and gastric cancer patients in a "real world" clinical setting.

Methods: We identified a cohort of 966 incident esophageal and gastric cancer patients in Stockholm/Gotland County (a low-risk Western population) during 2008–2013. Patients who received chemotherapy with curative intention (n = 279) and palliative intention (n = 182) were analyzed separately. Using Cox proportional hazards regression models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted for the potential confounding factors: age, sex, TNM stage, radiotherapy, comorbidity, marital status, education, income, and country of birth.

Results: In esophageal cancer patients with curative treatment intention, we observed a higher hazard for death among patients who received carboplatin-fluorouracil compared to patients who received cisplatin-fluorouracil, corresponding to a HR of 2.18 (95% CI 1.09–4.37). Conversely, in patients with cancer in the gastroesophageal junction who had a curative treatment intention at diagnosis, we observed a reduced hazard for death among those who received fluorouracil-oxaliplatin, compared to patients who received cisplatin-fluorouracil (HR 0.28; 95% CI 0.08–0.96).

Conclusion: Among patients with esophageal cancer who received treatment with curative intention, cisplatin-fluorouracil was associated with better survival compared to carboplatin-fluorouracil, while patients with gastroesophageal junction cancer who were treated with cisplatin-fluorouracil had worse survival compared to fluorouracil-oxaliplatin.

OBJECTIVES: This study was designed to investigate attitudes to and incentive for reporting adverse drug reactions (ADRs) in general and towards nurses as reporters of ADRs in particular in a sample of hospital physicians. METHOD: A questionnaire was sent to 1,201 randomly selected hospital physicians. RESULTS: The main factors for the decision to report an ADR were the severity of the reaction, a reaction to a new drug, and an unusual reaction. The most important factor for refraining from reporting was that the reaction was well known. There were no significant differences between males and females or between age groups in these aspects. A majority were positive or neutral to nurses as reporters. Only 6% stated that their willingness to report ADRs would be affected in a negative way if nurses were involved in the program for reporting. CONCLUSIONS: The results of this survey showed that inclusion of hospital nurses as reporters will not decrease the reporting rate from the physicians.

Adherence has not been studied in male oncology populations. The aim of this study on both the prescriber and user perspectives in prostate cancer treatment was to analyse real-life prescribing patterns of anti-androgens (AA), primarily bicalutamide, and factors influencing the patients' adherence to treatment. A nationwide clinical cohort of incident prostate cancer, PCBaSe, was linked to the Swedish Prescribed Drug Register. Men with a planned first line monotherapy AA treatment were identified; dosages and extent of off-label treatment were investigated. Cumulative incidence proportions for reasons for drug discontinuation were calculated. Factors potentially influencing adherence were explored using the medical possession ratio based on the individual prescribed daily dose. First line monotherapy AA was planned in 4.4 % of all incident cases and in 2.1 % of low risk disease cases. Among 1,406 men prescribed bicalutamide, 1,109 (79 %) received the approved daily dose of 150 mg. Discontinuation reasons differed with disease severity. Off-label, low-dose prescription associated with age above 75 years and disease categorised as low risk was noted in 297 men (21 %). Sixty percent of the men adhered well, i.e. to a parts per thousand yen80 %. Age above 75 years and less severe disease were both negatively associated with adherence. Patient age and tumour risk group influenced the prescriber's choice of dose, pointing to important issues for critical reflection. Possible over-treatment was noted in low risk disease. Interventions to increase adherence in older men and in men with less severe disease are worth considering after critically reviewing the appropriateness of the treatment indication, especially in the latter case.

There were great interindividual differences in warfarin maintenance dosage (ranging from 0.6 to 8.4 mg/day) among the 127 patients with mechanical heart valve prostheses. VKORC1-1639G>A, CYP2C9, EPHX1691A>G polymorphism, body weight, and age were found to affect the dose demands. Multiple linear regression models incorporating genetic polymorphisms of VKORC1, CYP2C9, EPHX1691A>G, and the nongenetic factors of age and body weight were developed, and explained up to 76.8% of the total variation (adjusted R (2) of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses.

A double-blind, randomized cross-over trial was carried out in 50 patients undergoing surgical removal of bilaterally impacted lower wisdom teeth. Surgery in each patient was performed twice and paracetamol 1000 mg was administered once preoperatively and once postoperatively. The time interval to additional analgesic intake and the pain intensity up to and at that time were assessed. There was no difference between the 2 treatments. It was concluded that preoperative paracetamol does not offer any clinical advantage in patients who undergo surgical removal of impacted lower wisdom teeth.

PURPOSE: The use of psychotropic drugs to treat behavioral and psychological symptoms among people with dementia has been widely questioned because of its limited efficacy and risk of harmful side-effects. The objectives of this study was to compare the prevalence of behavioral and psychological symptoms and the use of psychotropic drug treatments among old people with cognitive impairment living in geriatric care units in 2007 and 2013.

METHODS: Two questionnaire surveys were performed in 2007 and 2013, comprising all those living in geriatric care units in the county of Västerbotten in northern Sweden. A comparison was made between 1971 people from 2007 and 1511 people from 2013. Data were collected concerning psychotropic and antidementia drug use, functioning in the activities of daily living (ADL), cognition, and behavioral and psychological symptoms, using the Multi-Dimensional Dementia Assessment Scale (MDDAS).

RESULTS: Between 2007 and 2013, the use of antipsychotic drugs declined from 25.4 to 18.9 %, and of anxiolytic, hypnotic, and sedative drugs from 35.5 to 29.4 %. The prevalence of people prescribed antidepressant drugs remained unchanged while antidementia drug prescription increased from 17.9 to 21.5 %. When controlled for demographic changes, 36 out of 39 behavioral and psychological symptoms showed no difference in prevalence between the years.

CONCLUSIONS: The use of antipsychotic, anxiolytic, hypnotic, and sedative drugs declined considerably between 2007 and 2013 among old people with cognitive impairment living in geriatric care units. Despite this reduction, the prevalences of behavioral and psychological symptoms remained largely unchanged.

PURPOSE: The aims of this study were to investigate trends in the prevalence of potentially inappropriate drug use among old people living in geriatric care units in the county of Västerbotten between 2007 and 2013 using six national quality indicators and to assess the impact of medication reviews on those quality indicators.

METHODS: Data were collected concerning potentially inappropriate drug use, function in the activities of daily living (ADL) and cognitive function, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). A comparison was made between the years 2007 and 2013, comprising 2772 and 1902 people, respectively, living in geriatric care in the county of Västerbotten, Sweden. We conducted a parallel investigation of a separate corresponding population in Västerbotten County from 2012, where potentially inappropriate drug use was measured before and after 895 medication reviews which involved a clinical pharmacist.

RESULTS: After controlling for age, sex, ADL and cognitive impairment, there was a significant improvement in five out of six quality indicators between 2007 and 2013. While 44 % of the people were exposed to one or more potentially inappropriate medications in 2007, this number had declined to 26 % by 2013. In the separate population from 2012, the frequency of potentially inappropriate drug use was significantly reduced amongst the people who had a medication review performed.

CONCLUSION: The extent of potentially inappropriate drug use declined between 2007 and 2013 according to the quality indicators used. Medication reviews involving clinical pharmacists might be an important factor in reducing potentially inappropriate drug use and improving drug treatment among old people.

PURPOSE: Drug treatment associated problems are common and are the cause of a large proportion of hospitalizations in oldpeople. People with dementia are especially at risk of drug-related problems. The objectives of this study were to assess the occurrence and character of drug-related problems that lead to acute hospital admissions among old people (≥65 years) with dementia or cognitive impairment.

METHODS: This study was conducted in orthopedic and internal medicine wards in two hospitals in Northern Sweden. Information about acute admissions was collected from the medical records. A total of 458 people aged 65 years or older with dementia or cognitive impairment were included in the study. The contribution of drug-related problems to each hospitalization was assessed.

RESULTS: Of 458 acute hospital admissions, 189 (41.3 %) were determined to be drug-related. The most common drug-relatedproblem (86/189; 45.5 %) was an adverse drug reaction. In total, 264 drugs were judged to be involved in 189 drug-relatedadmissions, of which cardiovascular (29.5 %) and psychotropic (26.9 %) drugs were the most commonly involved drug classes. The relationship between the drug-related problem and the admission was judged certain in 25 cases, probable in 78 cases, and possible in 86 cases. Drug-related admissions were more common among people taking more drugs (p = 0.035) and among younger patients (p = 0.031).

CONCLUSION: Drug-related problems appear to be responsible for a major proportion of hospitalizations among old peoplewith dementia or cognitive impairment. Targeted interventions such as education and medication reviews may be warranted to reduce drug-related problems.

Purpose: To assess whether comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team reduce drug-related hospital readmission rates among people with dementia or cognitive impairment.

Methods: This randomized controlled trial was carried out between January 9, 2012, and December 2, 2014. Patients aged ≥65 years with dementia or cognitive impairment admitted to three wards at two hospitals located in Northern Sweden were included.

Results: Of the 473 deemed eligible for participation, 230 were randomized to intervention and 230 to control group by block randomization. The primary outcome, risk of drug-related hospital readmissions, was assessed at 180 days of follow-up by intention-to-treat analysis.

During the 180 days of follow-up, 18.9% (40/212) of patients in the intervention group and 23.0% (50/217) of those in the control group were readmitted for drug-related reasons (HR = 0.80, 95% CI = 0.53–1.21, p = 0.28, univariable Cox regression). Heart failure was significantly more common in the intervention group. After adjustment for heart failure as a potential confounder and an interaction term, multiple Cox regression analysis indicated that pharmacist participation significantly reduced the risk of drug-related readmissions (HR = 0.49, 95% CI = 0.27–0.90, p = 0.02). A post-hoc analysis showed a significantly reduced risk of 30-day readmissions due to drug-related problems in the total sample (without adjustment for heart failure).

Conclusion: Participation of clinical pharmacists in healthcare team conducting comprehensive medication reviews did not significantly reduce the risk of drug-related readmissions in patients with dementia or cognitive impairment; however, post-hoc and subgroup analyses indicated significant effects favoring the intervention. More research is needed.

Trial registration: Clinical trials NCT01504672.

Purpose: Many elderly people living in nursing homes experience pain and take analgesic medication. The aim of this study was to analyze the prevalence of pain and pharmacological pain treatment among people living in nursing homes in Sweden, in two large, comparable, samples from 2007 to 2013.

Methods: Cross-sectional surveys were performed in 2007 and 2013, including all residents in nursing homes in the county of Västerbotten, Sweden. A total of 4933 residents (2814 and 2119 respectively) with a mean age of 84.6 and 85.0 years participated. Of these, 71.1 and 72.4% respectively were cognitively impaired. The survey was completed by the staff members who knew the residents best.

Results: The prescription of opioids became significantly more common while the use of tramadol decreased significantly. The staff reported that 63.4% in 2007 and 62.3% in 2013 had experienced pain. Of those in pain, 20.2% in 2007 and 16.8% in 2013 received no treatment and 73.4 and 75.0% respectively of those with pain, but no pharmacological treatment, were incorrectly described by the staff as being treated for pain.

Conclusions: There has been a change in the pharmacological analgesic treatment between 2007 and 2013 with less prescribing of tramadol and a greater proportion taking opioids. Nevertheless, undertreatment of pain still occurs and in many cases, staff members believed that the residents were prescribed analgesic treatment when this was not the case.

Background: People with intermediate CVD risk constitute most of the population. Within this group, the proportion of events is lower compared to the high-risk group, but they contribute with the largest absolute number of events. Atherosclerosis is a dynamic process and progression can be slowed or even reversed with medication and lifestyle changes, but adherence to prescribed treatment is crucial.

Aim: To investigate the long-term effects of interventions with pictorial risk communication of cardiovascular (CVD) risk on average adherence in a group of statin users. Compare response in adherence over time between men and women after intervention.

Methods: Participants on active statin treatment were followed up to 5 years after being randomly assigned to an intervention program aimed at raising CVD risk awareness among participants and their physicians. Merging prescribed medication databases with VIPVIZA study to study adherence over time. A moving average adherence was used to compare groups.

Results: Generally, the average adherence to statins among the 512 participants was high. Men had a higher average adherence over time, while women had a sharper increase in adherence in conjuncture with the intervention program.

Conclusions: Both men and women were receptive to pictorial information regarding CVD risk, but the intervention effect was more pronounced in women. Sex differences are important when considering risk communication strategies. Periodically repeating the intervention was beneficial for maintaining the intervention effect over time.

Patients suffering from critical limb ischemia (CLI) have poor wound healing in the ankle and foot areas. Secondary wound infections are frequent and often treated with prolonged courses of antibiotics. This study set out to investigate to what extent the unbound fraction of 4 g of cloxacillin i.v. reaches its target organ in poorly vascularized tissues, i.e., the calf and foot of patients suffering from CLI. Cloxacillin concentrations were measured by HPLC in serum and in microdialysis samples from skin and muscle of the lower part of the calf and as reference subcutaneously at the pectoral level in eight patients suffering from CLI (four males, four females, mean age 78 years, range 66-85 years) and in three healthy controls (two females, one male, mean age 67, range 66-68 years). In patients suffering from CLI, the tissue penetration of cloxacillin after a single 4 g dose was comparable to that of healthy controls, despite impaired blood circulation. The reduced blood flow in the peripheral vessels of the CLI patients presented here apparently is not the rate-limiting factor for delivery or tissue penetration of cloxacillin.

In March 2007, a legislative amendment was issued in Sweden compelling nurses to report all suspected adverse drug reactions (ADRs) to the national pharmacovigilance system. The aims of this study were to describe the status of ADR reporting, before and after the implementation of the legislative changes, and to describe the general characteristics of suspected ADRs reported by nurses. The Swedish pharmacovigilance system during the study period constituted six regional centres responsible for the handling of all spontaneous ADR reports within their region. In this study, we identified all individual ADR reports from 2005 and 2010, analysed in depth the ADR reports from two regional centres and collated information about the reporter and the nature of the reported ADR. From the two regional centres, a total of 898 and 1074 reports were submitted in 2005 and 2010 respectively. Nurses submitted 31 % (275 reports) of the reports in 2005 and 24 % (260 reports) in 2010. Nurses' reporting of serious ADRs was 3 % (seven reports) in 2005 and 7 % (17 reports) in 2010 with reporting of unlabelled ADRs at 4 % (11 reports) in 2005 and 17 % (45 reports) in 2010. Most of the serious and/or unlabelled reactions were related to vaccine administration (14 reports in 2005 and 36 reports in 2010). The overall ADR reporting by nurses did not appear to increase after the change in reporting legislation. The proportion of serious and/or unlabelled ADRs reported by nurses did however appear to increase during the same period. Taken together, our data suggests that further pro-active measures should be considered in order to involve nurses in the reporting of suspected ADRs.

Aim: Psychotropic medications include many drugs that may be inappropriate for older individuals with cognitive impairment. In Sweden, many people become registered in the Swedish Dementia Registry when they are diagnosed with major neurocognitive disorder (NCD). In this study, we aim to describe psychotropic drug use and associated factors among older Swedish people with major NCD.

Methods: This study included 38,251 people ≥ 65 years from the Swedish registry for cognitive/dementia disorders diagnosed during 2007–2017. Drug use was defined as one or more filled prescription(s) recorded in the Swedish Prescribed Drug Register during 1 July to 31 December 2017. Associations between psychotropics and age, sex, diagnosis date, Mini-Mental State Examination score and major NCD subtype were analysed through multiple logistic regression.

Results: We found that 12.0% of the individuals filled at least one prescription for antipsychotics, 22.0% for anxiolytics, 23.0% for sedatives or hypnotics, 43.2% for antidepressants and 56.7% for antidementia drugs. In brief, psychotropic use was associated with female sex, higher age, longer time since diagnosis and specific subtypes of major NCD; the strongest association was found between antipsychotics and Lewy body dementia (odds ratio 2.40, 95% confidence interval 2.04–2.82).

Conclusion: Psychotropic drugs were frequently dispensed among older Swedish people with major NCD. The use of antipsychotics and medications with sedative properties warrants concern, especially among those with Lewy body dementia who are severely sensitive to antipsychotics. A more restrictive prescribing pattern regarding these medications might reduce the risk of drug-related problems in this vulnerable group of people.

Purpose To investigate the association between maternal use of antihypertensives in early pregnancy and delivery outcome, notably infant congenital malformations.

Methods A cohort study of 1,418 women who had used antihypertensive drugs in early pregnancy but had no diabetes diagnosis were identified from the Swedish Medical Birth Register.

Results There was an excess risk for placental abruption, caesarean section, delivery induction, and post-delivery hemorrhage in women taking hypertensives. Infants were more often than expected born preterm, were small for gestational age, and had an excess of various neonatal symptoms. Cardiovascular defects occurred with an adjusted odds ratio of 2.59 (95% CI 1.92-3.51). The results were similar when the woman had used ACE inhibitors or other antihypertensives, notably beta blockers. Stillbirth rate was increased (risk ratio 1.87, 95% CI 1.02-3.02), again without any clear drug specificity.

Conclusions There seems to be little drug specificity in the association between maternal use of antihypertensives and an increased risk for infant cardiovascular defects.

Objective: To assess a systematic implementation approach for introducing dapagliflozin to individuals with heart failure and reduced ejection fraction in an outpatient clinical setting.

Methods: Retrospective medical record data were analysed. All individuals diagnosed with heart failure who resided within the hospital catchment area and had visited cardiology or internal medicine department between 2010 and 2019 were screened by using the main inclusion criteria from the DAPA-HF trial. The effectiveness of the previously described seven-step systematic implementation approach was assessed by the proportion receiving information letter, dapagliflozin treatment, follow-ups at 2–12 weeks and 12 months post-dapagliflozin initiation, persistence on dapagliflozin, adverse events, and reasons for discontinuation.

Results: Of the 2433 individuals, 352 met the main DAPA-HF trial criteria in step 2. After exclusions in steps 3 and 4, 191 individuals remained. Of these, 158 were invited for eligibility discussion in step 5, with 107 having received an information letter beforehand. In step 6, dapagliflozin was prescribed to 69 individuals, and in step 7, follow-ups were conducted with 56 individuals at 2–12 weeks and 62 individuals at 12 months. Sixty out of 69 persisted on dapagliflozin after 12 months. Adverse events were reported by nine individuals. Discontinuation was attributed to reasons such as urinary tract infections, genital or abdominal discomfort, and hypotension.

Conclusion: The systematic introduction of dapagliflozin to heart failure patients was effective. Despite this, challenges in uniformly implementing procedures across patients were evident, emphasizing the necessity for a systematic implementation approach.

Purpose: To develop a model for systematic introduction and to test the feasibility in a chronic disease population. We also investigated how the approach was received by the patients.

Methods and results: The systematic introduction approach is a seven-step procedure: step 1, define a few main criteria; step 2, primary scan patients with the one or two main criteria using computerized medical records/databases/clinical registries; step 3, identify patients applying the other predefined criteria; step 4, evaluate if any examinations/laboratory test updates are required; step 5, summon identified patients to the clinic with an information letter; step 6, discuss treatment with the patient and prescribe if appropriate; and step 7, follow up on initiated therapy and evaluate the applied process. The model was tested in a case study during introduction of the new drug sacubitril-valsartan in a heart failure population. In total, 76 out of 1924 patients were identified to be eligible for sacubitril-valsartan and summoned to the clinic to discuss treatment. Patient experiences with the approach were investigated in an interview study with general inductive approach using qualitative content analysis. This resulted in three final categories: a good approach, role of the information letter, and trust in care.

Conclusions: The systematic introduction approach ensures that strict criteria are used in the selection process and that a treatment can be implemented in eligible patients within a specified population with limited resources and time. The model was effective in our case study and maintained the patient's confidence in healthcare.

Purpose: The aims of this study were to examine sex differences in a heart failure population with regards to treatment and patient characteristics and to investigate the impact of sex on achieved doses of heart failure medications.

Methods and results: A total of 1924 patients with heart failure in a regional hospital were analysed, 622 patients had ejection fraction <= 40% of which 30% were women. In patients with reduced ejection fraction, women were older (79 +/- 11 vs. 74 +/- 12 years, P < 0.001), had lower body weight (70 +/- 17 vs. 86 +/- 18 kg, P < 0.001), lower estimated glomerular filtration rate (eGFR) (49 +/- 24 vs. 71 +/- 30 ml/min, P < 0.001) and received lower doses of heart failure medications than men. Multivariable linear regression on patients with reduced ejection fraction showed that sex was not associated with achieved dose of any heart failure medication. For angiotensin-converting enzyme inhibitors and angiotensin receptor blockers associated factors were eGFR, systolic blood pressure, age, ejection fraction, and heart rate. For beta-blockers associated factors were body weight, atrial fibrillation and age. For mineralocorticoid receptor antagonists associated factors were eGFR, serum potassium, age, systolic blood pressure, ejection fraction and heart rate.

Conclusion: Women with heart failure and reduced ejection fraction were prescribed lower doses of heart failure medications, were older, had worse renal function, and lower body weight than men. Sex was not independently associated with achieved doses of heart failure medications, instead age, renal function and body weight explained the differences in treatment.

Purpose: To describe and compare self-reported medication adherence assessed with the 5-item version of Medication Adherence Report Scale (MARS-5) and pharmacy refill adherence based on data from the Swedish Prescribed Drug Register (SPDR) among persons with ischemic stroke, and to investigate independent predictors associated with respective assessments.

Methods: A study questionnaire was sent to persons with ischemic stroke registered in the Swedish Stroke Register between Dec 2011 and March 2012, and who lived at home 3 months after discharge. The primary outcome was dichotomized to adherent/non-adherent based on MARS-5 and SPDR and analyzed with multivariable logistic regression. Adherence according to MARS-5 was defined as score 23 or higher (out of 25). Adherence according to SPDR was defined as at least one filled statin prescription recorded in SPDR in each 6-month interval during 2 years of follow-up.

Results: Of 420 participants, 367 (87%) and 329 (78%) were adherent according to MARS-5 and SPDR, respectively, and 294 (70%) participants were adherent according to both assessments. A significant association was shown between medication adherence according to the two assessments (p = 0.020). Independent predictors associated with medication adherence according to MARS-5 were female sex, while factors associated with SPDR were male sex and being younger.

Conclusions: The majority of participants were classified as adherent, 87% according to MARS-5 and 78% based on data from SPDR. However, only 70% were adherent according to both MARS-5 and SPDR, and different predictors were associated with the different measurements, suggesting that these assessments are measuring different aspects of adherence.

Background and Objective The establishment of national guidelines is one approach to creating equity in terms of access to care, and both internationally and in Sweden, guidelines have been developed for coronary heart disease. We have analysed drug treatment in Sweden according to national guidelines after acute myocardial infarction (AMI). The aim was to investigate whether there are differences between population groups according to sex, education, country of birth and diabetes.

Methods Information was obtained from the Swedish Prescribed Drug Register on drugs dispensed between July and October 2005 for incident cases of AMI during the period 2003-2004 (n=28,168). Data on socio-economic and demographic conditions were included. Dispensed drugs after AMI were compared to the recommended drug treatment according to Swedish and European guidelines - acetylsalicylic acid (ASA), beta-blockers, lipid-lowering drugs and angiotensin-converting enzyme inhibitors (ACE inhibitors).

Results We found that, in general, there were only small differences between the sexes and between educational groups. The greatest differences were found in comparisons between regions of birth. In particular, foreign-born patients resident in Sweden but originally from outside the EU25 countries used fewer drugs than Swedish-born patients. The OR (odds ratio) for ASA was 0.73 [95% confidence interval (CI) 0.63-0.85], for beta-blockers, 0.72 (0.63-0.83), for lipid-lowering drugs, 0.75 (0.65-0.86) and for ACE inhibitors, 0.76 (0.67-0.86).

Conclusions In general, we found only slight differences - or none at all - between population groups in terms of drug treatment after AMI. Only among immigrants from outside the EU25 countries was there a tendency towards a lesser use of the recommended drugs according to the national guidelines.

To evaluate the pharmacokinetic parameters of a single oral dose of vardenafil in patients with pulmonary hypertension (PH). Sixteen patients with PH received vardenafil in single oral doses (20, 10 or 5 mg), and repeated blood sampling for up to 9 h was performed. Vardenafil plasma concentration was determined using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using model-independent analysis. The plasma vardenafil concentration increased rapidly and exhibited a median time to maximum plasma concentration (t(max)) of 1 h and a mean elimination half-life (t(1/2)) of 3.4 h. The geometric mean and standard deviation of (1) the peak plasma concentration (C-max) was 21.4 +/- 1.7 mu g/L, (2) the normalized C-max (C-max,C- norm) 79.1 +/- 1.6 g/L, (3) the area under the time-concentration curve (AUC) 71.5 +/- 1.6 mu g center dot h/L and (4) the normalized AUC (AUC(norm)) 261.6 A +/- 1.7 g center dot h/L. Patients co-medicated with bosentan reached t(max) later and had a 90% reduction of C-max, C-max,C- norm, AUC and AUC(norm). The pharmacokinetic profile of vardenafil overall revealed considerable inter-individual variability in patients with PH. Co-medication with bosentan resulted in a pharmacokinetic drug interaction, leading to significantly decreased plasma concentrations of vardenafil. Therapeutic drug monitoring for individual dose optimization may be warranted.

PURPOSE: 

Acute vasodilator testing is recommended in patients with pulmonary arterial hypertension to identify individuals who may benefit from long-term treatment with oral calcium channel blockers. The aim of this study was to investigate the use of vardenafil in acute vasoreactivity testing compared to adenosine.

METHODS: 

A total of 20 patients eligible for right heart catheterisation were enrolled. Acute vasoreactivity testing was carried out with intravenous (iv) adenosine (n = 18) followed by oral vardenafil (n = 20). Haemodynamic responses were recorded at baseline and after 60 min (vardenafil). Responders were defined according to consensus guideline criteria.

RESULTS: 

Both vardenafil and adenosine significantly decreased mean pulmonary arterial pressure (mPAP, p < 0.001 and p = 0.026, respectively) and pulmonary vascular resistance (p < 0.001 and p > 0.001, respectively), and significantly increased cardiac output (p = 0.001 and p = 0.005, respectively). Vardenafil reduced mPAP more than adenosine (p = 0.044), while adenosine resulted in higher responses of cardiac index (p = 0.009) and pulmonary arterial oxygen saturation (p = 0.042). Acute adverse reactions were common with adenosine, while no side effects were observed after a single oral dose vardenafil. Vardenafil identified five responders (out of 20), while adenosine identified three responders (out of 18). During a 7-year follow-up, vardenafil responders had significantly lower NT-proBNP levels compared to non-responders.

CONCLUSIONS: 

Vardenafil may be safely used for acute vasoreactivity testing in patients with PH. A single oral dose of vardenafil is better tolerated than iv adenosine and may identify additional responders who could benefit from long-term vasodilator treatment.

Purpose: This study aimed to explore physicians’ use of drug information in professional work, with special focus on those working in primary care, and also in relation to personal characteristics of physicians.

Methods: A web-based questionnaire was distributed by e-mail to physicians in five regions in Sweden. The questions concerned drug-related queries at issue when searching for information, sources used, and factors of importance for the choice of source, as well as responder characteristics.

Results: A total of 3254 (85%) out of 3814 responding physicians stated that they searched for drug information every week. For physicians working in primary health care, the corresponding number was 585 (96%). The most common drug-related issues searched for by 76% of physicians every week concerned pharmacotherapeutic aspects (e.g., dosing), followed by adverse drug reactions (63%). For 3349 (88%) physicians, credibility was the most important factor for the choice of sources of drug information, followed by easy access online (n = 3127, 82%). Further analyses among physicians in primary care showed that some personal characteristics, like seniority, sex, and country of education, as well as research experience, were associated with usage and preferences of drug information sources.

Conclusions: This study confirms that physicians often use drug information sources in professional work, in particular those who work in primary health care. Credibility and easy access are key factors for usage. Among physicians in primary care, personal factors influenced the choice of drug information sources.

PURPOSE: Since 2005, statins have been recommended to patients with ischaemic stroke. The objective of this study was to analyse how statin treatment has been disseminated in different patient groups (age, sex, socioeconomic status and country of birth) in Sweden between 2004 and 2009.

METHODS: The Swedish Stroke Register (Riks-Stroke) has been linked to the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Approximately 85 % of stroke patients in Sweden are included in Riks-Stroke. Odds ratios for statin prescribing were calculated using a multivariable logistic regression model including age, sex, socioeconomic status and risk factors.

RESULTS: During the study period, 108,950 ischaemic stroke patients were discharged alive from hospital. The proportion with statins at discharge increased from 32.9 % in 2004 to 60.1 % in 2009. Patients with secondary school or university education had slightly higher odds [odds ratio (OR) 1.07, 95 % confidence interval (CI) 1.04-1.11 and OR 1.05, 95 % CI 1.01-1.10 respectively] than patients with primary school education. Patients on a high income were prescribed more statins than those on a low income (OR 1.24, 95 % CI 1.19-1.28). Compared with patients born in Sweden, patients born in other countries were prescribed more statins (Nordic countries excepting Sweden: OR 1.07, 95 % CI 1.01-1.14; Europe: OR 1.31, 95 % CI 1.22-1.40; Outside Europe: OR 1.20, 95 % CI 1.08-1.34).

CONCLUSIONS: Statin prescribing after ischaemic stroke has increased from 2004 to 2009. Our results also show a social stratification in the dissemination of statins, with patients having a higher income and patients with higher education receiving statins more often than those with a lower income and education, and patients born in Sweden receiving statins less often than those born outside of Sweden.

Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. Twenty-three patients on SHD were included to perform haemodialysis with four modes of low-dose anticoagulation. For comparative analyses, patients served as their own control. Haemodialysis with a single bolus of tinzaparin at the start was compared to haemodialysis initiated without i.v. heparin but priming with (1) heparin in saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in combination with a citrate-containing dialysate (HAC), (4) saline and usinga heparin-coated filters (EvodialA (R)). The priming fluid was discarded before dialysis started. Blood samples were collected at 0, 30 and 180 min during haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed during the modes to avoid interruption by clotting. The mean activated partial thromboplastin (APTT) time as well as the doses of anticoagulation administered was highest with SHD and least with HAC and EvodialA (R). Mode H versus SHD had the highest rate of prematurely interrupted dialyses (33%, p = 0.008). The urea reduction rate was less with EvodialA (R) vs. SHD (p < 0.01). One hypersensitivity reaction occurred with EvodialA (R). Changes in blood cell concentrations and triglycerides differed between the modes. If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and EvodialA (R) appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode.

Purpose: The aim of this study was to describe changes in the pattern of cardiovascular agents used in elderly people living in nursing homes between 2007 and 2013. Further, the aim was to analyse the use of cardiovascular drugs in relation to cognitive impairment and associated factors within the same population, where prescription of loop diuretics was used as a proxy for heart failure.

Methods: Two questionnaire surveys were performed including 2494 people in 2007 and 1654 people in 2013 living in nursing homes in northern Sweden. Data were collected concerning drug use, functioning in activities of daily living (ADL) and cognition, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). The use of different drugs and drug classes among people at four different levels of cognitive function in 2007 and 2013 were compared.

Results: The proportion of people prescribed ASA and diuretics was significantly lower at all four levels of cognitive function in 2013 compared to 2007. Among people prescribed loop diuretics, the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARBs) increased from 37.8 to 45.6%, β-blockers from 36.0 to 41.8% and warfarin from 4.4 to 11.4%. The use of warfarin, ACEI/ARBs, β-blockers and mineralocorticoid receptor antagonists (MRAs) were less common among individuals with more severe cognitive impairment.

Conclusion: The results indicate that cardiovascular drug treatment has improved between 2007 and 2013, but there is room for further improvement, especially regarding adherence to guidelines for heart failure. Increasing cognitive impairment had an effect on treatment patterns for heart failure and atrial fibrillation.

Purpose As people get older, their sensitivity to drugs and adverse drug reactions can increase due to pharmacokinetic and pharmacodynamic changes. Older people with dementia are a particularly vulnerable group of people. They are at an increased risk of being prescribed potentially inappropriate medications, which may lead to harmful consequences. The aim of this study was to investigate the prevalence of potentially inappropriate medications among older patients with cognitive impairment. Methods Medical records for patients aged ≥65 years admitted to two hospitals in Northern Sweden were reviewed. Potentially inappropriate medications were identified using the EU(7)-PIM list as an identification tool. Results Of 428 patients included in the study, 40.9% had one or more potentially inappropriate medication prescribed. The most commonly represented potentially inappropriate medication classes were hypnotics and sedatives, cardiovascular drugs and laxatives. The most commonly involved potentially inappropriate medications were zopiclone, digoxin and sodium picosulfate. There was an association seen between having a higher number of medications prescribed and having one or more potentially inappropriate medication. Conclusion Potentially inappropriate medications are prevalent among older people with cognitive impairment living in Northern Sweden. It is important to continuously evaluate the need for potentially inappropriate medications in this patient group, in order to prevent adverse drug reactions, especially among those who have a higher number of medications prescribed.

Purpose: Increased numbers of drugs and changes in pharmacokinetic and pharmacodynamic parameters among elderly people contribute to increased prevalence of adverse drug reactions. Drug-drug interactions (DDIs) are an important reason for admission to hospital and elderly people with dementia are particularly vulnerable. The aims of the present study were to assess the occurrence and characteristics of clinically relevant DDIs and to investigate potential risk factors associated with DDIs among elderly people with dementia.

Methods: People 65 years with dementia, admitted to two hospitals in Northern Sweden, were included. The medical records of 458 patients were reviewed. Clinically relevant DDIs were identified using the Janusmed interactions database. Pharmacological classification was conducted using Stockley's classification system.

Results: A total of 401 DDIs were identified among 43.2% of the study population, of which 98.5% had interactions that may require dose adjustment and 7.6% had drug combinations that should be avoided. Pharmacodynamic interactions were most common, of which furosemide-citalopram (n=35) were most frequently observed. Omeprazol-citalopram (n=25) was the most common drug combination among pharmacokinetic interactions. Citalopram and warfarin were the most commonly involved drug substances. An association was found between a higher number of medications being prescribed and having at least one DDI.

Conclusion: Clinically relevant drug-drug interactions are prevalent among elderly people with dementia living in Northern Sweden. Drug-drug interactions should be identified in order to manage and prevent adverse outcomes. This is particularly important among this group of people especially when multiple medications are being prescribed.