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Data on the association of multimorbidity and functional impairment with cardiovascular (CV) and non-CV outcomes among older myocardial infarction (MI) patients are limited.Multimorbidity and functional impairment among older MI patients are associated with CV and non-CV mortality.Patients aged ≥65 years, 1-3 years post-MI, and enrolled between June 2013 and Novemeber 2014 from 349 sites in 25 countries in the global TIGRIS registry were categorized by age, number of comorbidities, and presence and degree of functional impairment. Functional impairment was calculated using five-dimension EuroQol based on three domains-mobility, self-care, and usual activities. The association between age, number of comorbid conditions, and degree of functional impairment with 2-year incidence of CV and non-CV death was evaluated using Poisson regression analysis.Older age was associated with higher number of comorbidities and functional impairment; after adjustment, increasing age was significantly associated with non-CV mortality (p = .03) but not CV mortality (p = .38). Greater functional impairment was associated with a higher rate and relatively equal magnitude risk of CV (rate ratios [RR] 1.52, 95% confidence intervals [CI]: 1.29-1.79, per one-step increase) and non-CV mortality (RR 1.42, 95% CI: 1.17-1.73). Multimorbidity was more strongly associated with CV mortality (RR 1.52, 95% CI: 1.38-1.67, per additional comorbidity) versus non-CV mortality (RR 1.29, 95% CI: 1.14-1.47, per additional comorbidity).Multimorbidity and functional impairment are prevalent among older post-MI patients and are associated with increased CV and non-CV mortality. These findings highlight the importance of considering comorbid conditions and functional impairment as predictors of risk for adverse outcomes and aspects of medical decision making. Clinical Trial Registration: NCT01866904.

In December 2021, U.S. Food & Drug Administration (FDA) will issue guidance on the use of real-world evidence (RWE) to support new indications or expanded product labeling. While difficult to foresee what FDA will require, learnings can be gleaned from previous paradigm shifts at FDA, such as for patient reported outcomes (PROs) in 2006–2009. We contrast published requirements for justifying PROs as fit-for-purpose for a specific labeling claim with a potential approach to justify RWE as fit-for-purpose to support expanded labeling or a new indication. PRO labeling claims require a PRO Evidence Dossier that includes: specific wording of claim, clinical trial hypothesis structure and endpoint model, and justification that the PRO is relevant and meaningful to patients in the target population (content validity) with adequate psychometric properties. FDA’s 2018 RWE Framework outlined critical considerations for using RWE to support regulatory decisions, including data quality, relevancy, provenance, and transparency. Strong parallels exist between the evidence required to justify that PROs are fit-for-purpose to support specific labeling claims and evidence to justify RWE as fit-for-purpose for specific research questions and labeling. Early discussion with FDA is encouraged. Drawing on parallels with use of PROs in labeling, RWE for regulatory purposes should be evaluated within the context of specific labeling or indication, specific study design and analysis plans, and the data attributes of data source. Sponsors seeking a new indication or labeling expansion based on RWE should justify that a specific data source and specific study design are fit-for-purpose.

ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.

BACKGROUND Patterns of dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI) have not been well studied. METHODS TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 24 countries), observational study of patients 1 to 3 years post-MI. We sought to identify the prevalence and determinants of DAPT use ≥1 year post-MI in patients enrolled in TIGRIS. We used multivariable logistic regression to identify determinants of DAPT use at 396 days post-MI (365 days plus a 31day overrun period to account for intended DAPT discontinuation at 1 year). Patients treated with an oral anticoagulant were excluded. RESULTS Of 7708 patients (median age 67 years, women 25%, ST-elevation MI 50%), 39% and 16% were on DAPT at 396 days and 5 years post-MI, respectively. DAPT use at 396 days post-MI was more prevalent in patients

International audience; Background: Risk prediction tools are lacking for patients with stable disease some years after myocardial infarction (MI).Hypothesis: A practical long‐term cardiovascular risk index can be developed.Methods: The long‐Term rIsk, Clinical manaGement and healthcare Resource utilization of stable coronary artery dISease in post‐myocardial infarction patients prospective global registry enrolled patients 1 to 3 years post‐MI (369 centers; 25 countries), all with ≥1 risk factor (age ≥65 years, diabetes mellitus requiring medication, second prior MI, multivessel coronary artery disease, or chronic non‐end‐stage kidney disease [CKD]). Self‐reported health was assessed with EuroQoL‐5 dimensions. Multivariable Poisson regression models were used to determine key predictors of the primary composite outcome (MI, unstable angina with urgent revascularization [UA], stroke, or all‐cause death) over 2 years.Results: The primary outcome occurred in 621 (6.9%) of 9027 eligible patients: death 295 (3.3%), MI 195 (2.2%), UA 103 (1.1%), and stroke 58 (0.6%). All events accrued linearly. In a multivariable model, 11 significant predictors of primary outcome (age ≥65 years, diabetes, second prior MI, CKD, history of major bleed, peripheral arterial disease, heart failure, cardiovascular hospitalization (prior 6 months), medical management (index MI), on diuretic, and poor self‐reported health) were identified and combined into a user‐friendly risk index. Compared with lowest‐risk patients, those in the top 16% had a rate ratio of 6.9 for the primary composite, and 18.7 for all‐cause death (overall c‐statistic; 0.686, and 0.768, respectively). External validation was performed using the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events registry (c‐statistic; 0.748, and 0.849, respectively).Conclusions: In patients >1‐year post‐MI, recurrent cardiovascular events and deaths accrue linearly. A simple risk index can stratify patients, potentially helping to guide management.

Introduction Lipid-lowering therapy (LLT) reduces the risk of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D). However, socioeconomic factors and gender may have an impact on the adherence to and non-persistence with LLT. Methods This was a nationwide register-based cohort study that included 6192 individuals with T1D aged ≥ 18 years who were registered in the Swedish National Diabetes Register and had initiated novel use of LLT. Information on socioeconomic parameters (source: Statistics Sweden) and comorbidity (source: National Patient Register) was collected. The individuals were followed for 36 months, and adherence to LLT was analyzed according to age, socioeconomics and gender. The medication possession ratio (MPR; categorized into ≤ 80% and > 80%) and non-persistence (discontinuation) with medication was calculated after 18 and 36 months. Results Individuals older than 53 years were more adherent to LLT (MPR > 80%) than those younger than 36 years (odds ratio [(OR] 1.30, p

ObjectiveTo assess associations of health-related quality of life (HRQoL) with patient profile, resource use, cardiovascular (CV) events and mortality in stable patients post-myocardial infarction (MI).MethodsThe global, prospective, observational TIGRIS Study enrolled 9126 patients 1–3 years post-MI. HRQoL was assessed at enrolment and 6-month intervals using the patient-reported EuroQol-5 dimension (EQ-5D) questionnaire, with scores anchored at 0 (worst possible) and 1 (perfect health). Resource use, CV events and mortality were recorded during 2-years’ follow-up. Regression models estimated the associations of index score at enrolment with patient characteristics, resource use, CV events and mortality over 2-years’ follow-up.ResultsAmong 8978 patients who completed the EQ-5D questionnaire, 52% reported ‘some’ or ‘severe’ problems on one or more health dimensions. Factors associated with a lower index score were: female sex, older age, obesity, smoking, higher heart rate, less formal education, presence of comorbidity (eg, angina, stroke), emergency room visit in the previous 6 months and non-ST-elevation MI as the index event. Compared with an index score of 1 at enrolment, a lower index score was associated with higher risk of all-cause death, with an adjusted rate ratio of 3.09 (95% CI 2.20 to 4.31), and of a CV event, with a rate ratio of 2.31 (95% CI 1.76 to 3.03). Patients with lower index score at enrolment had almost two times as many hospitalisations over 2-years’ follow-up.ConclusionsClinicians managing patients post-acute coronary syndrome should recognise that a poorer HRQoL is clearly linked to risk of hospitalisations, major CV events and death.Trial registration numberClinicalTrials.gov Registry (NCT01866904) (https://clinicaltrials.gov).

Aims THEMIS ( NCT01991795 ) demonstrated cardioprotective benefits of ticagrelor plus acetylsalicylic acid (ASA) compared with placebo plus ASA in patients with type 2 diabetes (T2D), stable coronary artery disease (CAD) and no history of myocardial infarction (MI) or stroke. To complement these findings, we assessed clinical outcomes and healthcare costs in commercially insured US patients similar to those in THEMIS. Methods This retrospective, observational study used data from Optum. The T2D-CAD cohort (n = 154,369) included patients (≥50 years old) either with high cardiovascular risk or taking a P2Y12 inhibitor. The THEMIS-like cohort (n = 126,938) comprised patients (≥50 years old) at high cardiovascular risk; the THEMIS-PCI-like cohort comprised a subset of these patients with prior percutaneous coronary intervention (PCI) (n = 18,394). Results Mean follow-up was 2.4–2.5 years. Incidence rates of the composite outcome (death, MI, and stroke) were 6.56 (95% CI 6.50–6.63), 6.21 (6.14–6.28), and 5.57 (5.39–5.74) per 100 person-years, and annualized healthcare costs per patient were US$15,848, US$16,044, and US$20,934 for the T2D-CAD, THEMIS-like, and THEMIS-PCI-like cohorts, respectively. Conclusions Commercially insured patients similar to those in THEMIS had high cardiovascular event rates and healthcare costs, highlighting a need for improved preventive strategies.

In December 2021, U.S. FoodDrug Administration (FDA) will issue guidance on the use of real-world evidence (RWE) to support new indications or expanded product labeling. While difficult to foresee what FDA will require, learnings can be gleaned from previous paradigm shifts at FDA, such as for patient reported outcomes (PROs) in 2006-2009.We contrast published requirements for justifying PROs as fit-for-purpose for a specific labeling claim with a potential approach to justify RWE as fit-for-purpose to support expanded labeling or a new indication.PRO labeling claims require a PRO Evidence Dossier that includes: specific wording of claim, clinical trial hypothesis structure and endpoint model, and justification that the PRO is relevant and meaningful to patients in the target population (content validity) with adequate psychometric properties. FDA's 2018 RWE Framework outlined critical considerations for using RWE to support regulatory decisions, including data quality, relevancy, provenance, and transparency. Strong parallels exist between the evidence required to justify that PROs are fit-for-purpose to support specific labeling claims and evidence to justify RWE as fit-for-purpose for specific research questions and labeling. Early discussion with FDA is encouraged.Drawing on parallels with use of PROs in labeling, RWE for regulatory purposes should be evaluated within the context of specific labeling or indication, specific study design and analysis plans, and the data attributes of data source. Sponsors seeking a new indication or labeling expansion based on RWE should justify that a specific data source and specific study design are fit-for-purpose.

Background THEMIS (NCT01991795) showed that in patients with type 2 diabetes (T2D) and stable coronary artery disease (CAD) but with no prior myocardial infarction (MI) or stroke, ticagrelor plus acetylsalicylic acid (ASA) decreased the incidence of ischaemic cardiovascular events compared with placebo plus ASA. To complement these findings, we assessed disease burden and healthcare resource utilization (HRU) in US patients with CAD and T2D, but without a prior MI or stroke. Methods This observational study used 2013‐2014 data from the Diabetes Collaborative Registry linked to Medicare administrative claims. Two cohorts of patients with T2D were studied: patients at high cardiovascular risk (THEMIS‐like cohort; N = 56 040) and patients at high cardiovascular risk or taking P2Y12 inhibitors (CAD‐T2D cohort; N = 69 790). Outcomes included the composite of all‐cause death, MI and stroke; the individual events from the composite endpoint; HRU; and costs. Results Median age was 73.0 years, and median follow‐up was 1.3 years in both cohorts. Event rates of the composite outcome were 16.34 (95% confidence interval: 16.31‐16.37) and 17.64 (17.61‐17.67) per 100 person‐years for the THEMIS‐like and CAD‐T2D cohorts, respectively. The incidence rate of bleeding events was 0.13 events per 100 person‐years in both cohorts. Healthcare costs per patient‐year were USD 8741 and USD 9150 in the THEMIS‐like and CAD‐T2D cohorts, respectively. Conclusions Patients in the THEMIS‐like cohort and the broader CAD‐T2D population had similarly substantial cardiovascular event rates and healthcare costs, indicating that patients with CAD and T2D similar to the THEMIS population are at an increased cardiovascular risk., Disease burden and healthcare resource utilization (HRU) were assessed in patients with coronary artery disease (CAD) and type 2 diabetes (T2D) from a US‐based diabetes registry. Patients similar to those enrolled in THEMIS have substantial cardiovascular event rates and healthcare costs, but low bleeding risk. Findings were similar in a broader CAD‐T2D population, indicating that the THEMIS population reflects high‐risk patients with CAD and T2D in clinical practice.

Aims/hypothesisDyslipidemia is an important modifiable risk factor and lipid-lowering treatment (LLT) is essential to reduce the risk of cardiovascular disease (CVD). Studies in type 2 diabetes indicate that low adherence to statin therapy is a barrier to reach full protective potential, and less is known in type 1 diabetes (T1D). The aim was to assess risk of CVD by adherence and nonpersistence to LLT in T1D. MethodA population-based study with a retrospective longitudinal design was conducted between 2006 and 2010, with follow-up until December 2013. In total, 6192 adult individuals with T1D, initiating LLT between 2006 and 2010, were included. Information on LLT, socioeconomic characteristics, comorbidities and cardiovascular events were collected. After 18 months, refill adherence was estimated by calculating medication possession ratio (MPR). Nonpersistence was defined as being without medicines on hand for at least 180 days. Individuals were thereafter followed until CVD, death or end of follow-up in December 2013. Cox regression analyses were performed to assess adherence level and nonpersistence of LLT as predictor of CVD. Analyses were adjusted for cardiovascular risk factors and socioeconomic status. ResultsMean MPR was 72%, 52% of the participants had an MPR above 80% and 27% discontinued LLT. There were 637 nonfatal and 58 fatal CVD events, mean follow-up 3.6 and 3.9 years, respectively. MPR above 80% was associated with reduced risk for nonfatal CVD compared with lower MPR, HR 0.78 (95% CI 0.65 to 0.93)). For fatal CVD, results indicated a negative effect of high adherence but the association did not reach statistical significance, HR 1.96 (0.96 to 4.01). Individuals discontinuing LLT had higher risk of nonfatal CVD, HR 1.43 (95% CI 1.18 to 1.73). Conclusions/InterpretationIn T1D, the risk for nonfatal CVD was lower among individuals with high adherence and higher among those discontinuing LLT within 18 months. It is important to evaluate and emphasize adherence to prescribed LLT at clinical visits to achieve treatment goals and reduce the risk of CVD.

Objectives The generic substitution of medicines has been introduced in Europe since the 1990s to increase price competition and the use of cheaper equivalents. Patent expiry is assumed to be associated with changes in sales patterns, particularly when combined with generic substitution. Other changes have been observed when prescribers obtain new information on drug safety and efficacy of medicines. This article examines to what extent patent expiry and new medical information on efficacy influence the pharmaceutical sales patterns of antihypertensive medicines in Japan and Sweden. Methods Angiotensin-converting enzyme inhibitors and angiotensin Ⅱ antagonists (ARBs) were selected, since they are widely used in both Japan and Sweden. The two analysed interventions were patent expiry and published information on lower efficacy for two ARBs. Seasonal autoregressive integrated moving average modelling with intervention was used to analyse changes in sales volumes. Results Patent expiry was not associated with any significant changes in sales patterns. In Sweden, the sales rate of losartan increased following new information on lower efficacy for candesartan and telmisartan (0.77650 DDDs/1,000 inhabitants per day, p = 0.0068), whereas candesartan sales decreased (-0.50760 DDDs/1000 inhabitants per day, p = 0.0058). In Japan, the publication of new efficacy information was also associated with a significant decrease in candesartan (−1.21215 DDDs/1000 inhabitants per day, p = 0.001). Conclusions We found sales patterns of antihypertensive medicines were to a large extent affected by information on efficacy rather than patent expiry. However, further assessment is needed for other medicine groups and settings. (248 words)

Objectives To analyse attitudes towards sales and use of over-the-counter (OTC) drugs in the Swedish adult population. Methods Data were collected through the web-based Citizen Panel comprising 21 000 Swedes. A stratified sample of 4058 participants was emailed a survey invitation. Questions concerned use of OTC drugs, and attitudes towards sales and use of OTC drugs. Correlations between the attitudinal statements were assessed using Spearman’s rank correlation. Associations between attitudes and participant characteristics were analysed using multinomial logistic regression. Key findings Participation rate was 64%. Altogether 87% reported use of OTC drugs in the last 6 months. Approximately 10% of participants stated that they used OTC drugs at the first sign of illness, and 9% stated that they used more OTC drugs compared with previously, due to increased availability. The statement on use of OTC drugs at first sign of illness correlated with the statement about using more OTC drugs with increased availability. Socio-demographic factors (age, sex and education) and frequent use of OTC drugs were associated with attitudes to sales and use of OTC drugs. Conclusions Increased use due to greater availability, in combination with OTC drug use at first sign of illness illustrates the need for continuous education of the population about self-care with OTC drugs. Increased awareness of the incautious views on OTC drugs in part of the population is important. Swedish policy-makers may use such knowledge in their continuous evaluation of the 2009 pharmacy reform to review the impact of sales of OTC drugs in retail outlets on patient safety and public health. Pharmacy and healthcare staff could be more proactive in asking customers and patients about their use of OTC drugs and offering them advice.

BACKGROUND: Evidence is lacking on long-term outcomes in unselected patients surviving the first year following myocardial infarction (MI). METHODS AND RESULTS: The TIGRIS (long-Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease in post-myocardial infarction patients) prospective registry enrolled 9176 eligible patients aged ≥50 years, 1-3 years post-MI, from 25 countries. All had ≥1 risk factor: age ≥ 65 years, diabetes mellitus, second prior MI, multivessel coronary artery disease, chronic kidney disease (CKD). Primary outcome was a composite of MI, unstable angina with urgent revascularization, stroke, or all-cause death at 2-year follow-up. Bleeding requiring hospitalization was also recorded. 9027 patients (98.4%) provided follow-up data: the primary outcome occurred in 621 (7.0%), all-cause mortality in 295 (3.3%), and bleeding in 109 (1.2%) patients. Events accrued linearly over time. In multivariable analyses, qualifying risk factors were associated with increased risk of primary outcome (incidence rate ratio [RR] per 100 patient-years [95% confidence interval]): CKD 2.06 (1.66, 2.55), second prior MI 1.71 (1.38, 2.10), diabetes mellitus 1.63 (1.39, 1.92), age ≥ 65 years 1.53 (1.28, 1.83), and multivessel disease 1.24 (1.05, 1.48). Risk of bleeding events was greater in older patients (vs

ObjectiveTo analyze the risk of cardiovascular (CV) events and mortality in relation to adherence to lipid-lowering medications by healthcare centers and patients with type 2 diabetes mellitus (T2DM).Research design and methodsWe included 121 914 patients (12% secondary prevention) with T2DM reported by 1363 healthcare centers. Patients initiated lipid-lowering medications between July 2006 and December 2012 and were followed from cessation of the first filled supply until multidose dispensed medications, migration, CV events, death or December 2016. The study period was divided into 4-month intervals through 2014, followed by annual intervals through 2016. Adherence measures were assessed for each interval. Patients’ (refill) adherence was measured using the medication possession ratio (MPR). Healthcare centers’ (guideline) adherence represented the prescription prevalence of lipid-lowering medications according to guidelines. The risk of CV events and mortality was analyzed for each interval using Cox proportional hazard regression and Kaplan-Meier.ResultsCompared with high-adherent patients (MPR >80%), low-adherent primary prevention patients (MPR ≤80%) showed higher risk of all outcomes: 44%–51 % for CV events, doubled for all-cause mortality and 79%–90% for CV mortality. Corresponding risks for low-adherent secondary prevention patients were 17%–19% for CV events, 88%–97% for all-cause and 66%–79% for CV mortality. Primary prevention patients treated by low-adherent healthcare centers (guideline adherence ConclusionsOur results demonstrate the importance of high refill adherence and thus the value of individualized care among patients with T2DM.

Background: THEMIS is a large randomized controlled trial (NCT01991795) comparing the effect of ticagrelor vs placebo (both with background acetylsalicylic acid) for the prevention of major cardiovascular (CV) events in patients with coronary artery disease (CAD) and type 2 diabetes (T2D) with no prior myocardial infarction (MI) or stroke. The current study evaluated healthcare resource utilization (HCRU) and cost in patients similar to those eligible for enrollment in THEMIS (THEMIS-like) and in a broader population (T2D-CAD). Methods: This retrospective, observational study included patients, > 50 years old, with pharmacologically treated T2D and no prior MI or stroke collected from the Optum Research Database including Medicare Advantage Part D coverage between January 1, 2007 and December 31, 2017. Both cohorts were followed until disenrollment or end of the study period. The THEMIS-like cohort included patients with evidence of CAD including percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or an angina diagnosis. In addition to CAD as above, the broader T2D-CAD cohort included use of prescription antiplatelet therapy. Selected HCRU (heart failure hospitalizations [hHF], nontraumatic bleeding hospitalizations or ED visits, medication use), annualized costs (all-cause and CV-related total, medical, and pharmacy), and secondary prevention medication (antiplatelets, statins, ACE inhibitors, ARBs, and beta-blockers) persistence were analyzed. Results: The T2D-CAD (N=203,916) and THEMIS-like (N=127,125) cohorts accounted for 3.5% and 2.2% of the total T2D population, respectively. Mean + SD ages were 68 + 9 vs 67 + 9 years and 57% vs 56% were men, respectively. Mean annual all-cause total costs for the THEMIS-like and T2D-CAD cohorts were $43,332 and $36,254, and pharmacy costs accounted for 15.3% and 19.2% of total cost, respectively. CV-related costs accounted for 38.2% of all-cause costs in the THEMIS-like cohort, and 29.1% in T2D-CAD cohort, respectively. Mean all-cause pharmacy and CV-related pharmacy costs were $6,668 and $497 for the THEMIS-like cohort and $6,985 and $739 for the T2D-CAD cohort, respectively. Medication persistence was between 55% and 61% for all medication classes for both cohorts. At least one hHF was experienced by 13.3% of patients in the THEMIS-like cohort and by 10.3% of patients in the T2D-CAD cohort. Bleeding event rates were 0.35 and 0.38 per 100 person-years in the THEMIS-like and T2D-CAD cohorts, respectively. Conclusion: Patients in a US commercially-insured population similar to those enrolled in THEMIS incurred high cost of care, which was largely attributable to CV-related causes. Nearly 1 in 7 THEMIS-like patients experienced hHF, and bleeding incidence was low. These findings identify a unique patient population that may benefit from better preventive measures.

The purpose of this study are to analyse adherence to antidepressant treatment over 2 years in Sweden among women and men who initiated treatment with citalopram and to identify groups at risk of non-adherence using trajectory models.The study population, including individuals 18-85 years who initiated citalopram use between 1 July 2006 and 30 June 2007, was identified in the Swedish Prescribed Drug Register and followed for 2 years. Adherence was estimated with continuous measure of medication acquisition (CMA) and group-based trajectory modelling, a method which describes adherence patterns over time by estimating trajectories of adherence and the individual's probability of belonging to a specific trajectory.The study population included 54,248 individuals, 64 % women. Mean CMA was 52 % among women and 50 % among men (p 0.001). Five different adherence patterns (Trajectories) were identified. Similar proportion of women and men belonged to each Trajectory. Around 29 % of the women and 27 % of the men belonged to the Trajectory which showed full adherence throughout the 2-year study period. The other four Trajectories showed adherence that declined to different degrees and at different stages in time. Having low socioeconomic status was more common among individuals in Trajectories showing declining adherence than in the adherent Trajectory.Using trajectory modelling, five Trajectories describing different patterns of adherence to citalopram treatment over time were identified. A large proportion discontinued treatment early and having low socioeconomic status increased the risk of being non-adherent.

Objectives Among OECD countries, the proportion of total expenditure on health spent on pharmaceuticals is highest in Japan, 20%. In Sweden, the corresponding proportion is 13%. Swedish pharmaceutical expenditures increased dramatically in the 1990s and policy changes were introduced to curb this. Both countries have introduced policy changes to increase cost containment. This study aims to compare the pharmaceutical policies regarding generic medicines in Japan and Sweden. Methods Information on pharmaceutical policies was collected. We compared pharmaceutical policies according to the 4E (Education, Engineering, Economics, and Enforcement) component framework developed to describe the differences in policies. Results and conclusions In Sweden, there were several organizational and managerial interventions within the Engineering class. Japan had several positive incentives for health care actors in the Economics category. The Enforcement category had a stronger legal component in Sweden compared to Japan. The Swedish policies were mainly directed towards prescribing and dispensing whereas the Japanese addressed several stakeholders to promote use of generic drugs. The countries were similar with respect to the Education category. Within the Enforcement component the Swedish policies were legally enforced whereas the Japanese to large extent were recommendations.

Objective To investigate sociodemographic and gender factors associated with suicide and suicide attempts among new users of antidepressants aged 75 and above. Design Register-based cohort study. Setting National population-based cohort of Swedish residents aged ≥75 years. Participants 185 225 patients who initiated antidepressant medication between 1 January 2007 and 31 December 2013 were followed until 31 December 2014. Main outcome measures Suicide and suicide attempts. Fine and Gray regression models were used to analyse the sociodemographic factors (age, country of birth, marital status, education level, last occupation, income and social allowance) associated with suicidal behaviours in the entire cohort and by gender. Results During follow-up, 295 suicides and 654 suicide attempts occurred. Adjusted sub-hazard ratios (aSHRs) for suicide were lower among older age groups (aSHR 0.73, 95% CI 0.53 to 0.99 for those 85–89 years; and aSHR 0.53, 95% CI 0.33 to 0.86 for those ≥90 years). A similar pattern was observed for suicide attempts. Suicide attempts were more common among those born in foreign countries (aSHR 1.58, 95% CI 1.16 to 2.15 for those born in another Nordic country; and aSHR 1.43, 95% CI 1.06 to 1.93 for those born in non-Nordic countries). In the gender-stratified analyses, being single or divorced, and born in another Nordic country was associated with a higher risk of suicide among men. Educational and occupational history and being born in a non-Nordic country influenced risk of suicidal behaviours in women. Conclusion Suicidal behaviours occurred more commonly among new users who were ‘younger’ old adults and those with foreign background, suggesting that those groups might require greater support when initiating antidepressant therapy. Our findings suggest the need for gender-specific, multifaceted approaches to the prevention of suicidal behaviours in late life.

Background: Pharmacoepidemiology is a branch of public health and had a place at the Nordic School of Public Health. Courses, Master’s theses and Doctorates of Public Health (DrPH) in Pharmacoepidemiology were a relatively minor, but still important part of the school’s activities. Methods: This paper gives a short background, followed by some snapshots of the activities at NHV, and then some illustrative case-studies. These case-studies list their own responsible co-authors and have separate reference lists. Results: In the Nordic context, NHV was a unique provider of training and research in pharmacoepidemiology, with single courses to complete DrPH training, as well as implementation of externally-funded research projects. Conclusions: With the closure of NHV at the end of 2014, it is unclear if such a comprehensive approach towards pharmacoepidemiology will be found elsewhere in the Nordic countries.

Aims To estimate the 3 month prevalence of adverse drug events (ADEs), categories of ADEs and preventable ADEs, and the preventability of ADEs among adults in Sweden. Further, to identify drug classes and organ systems associated with ADEs and estimate their seriousness. Methods A random sample of 5025 adults in a Swedish county council in 2008 was drawn from the Total Population Register. All their medical records in 29 inpatient care departments in three hospitals, 110 specialized outpatient clinics and 51 primary care units were reviewed retrospectively in a stepwise manner, and complemented with register data on dispensed drugs. ADEs, including adverse drug reactions (ADRs), sub-therapeutic effects of drug therapy (STEs), drug dependence and abuse, drug intoxications from overdose, and morbidities due to drug-related untreated indication, were detected during a 3 month study period, and assessed for preventability. Results Among 4970 included individuals, the prevalence of ADEs was 12.0% (95% confidence interval (CI) 11.1, 12.9%), and preventable ADEs 5.6% (95% CI 5.0, 6.2%). ADRs (6.9%; 95% CI 6.2, 7.6%) and STEs (6.4%; 95% CI 5.8, 7.1%) were more prevalent than the other ADEs. Of the ADEs, 38.8% (95% CI 35.8–41.9%) was preventable, varying by ADE category and seriousness. ADEs were frequently associated with nervous system and cardiovascular drugs, but the associated drugs and affected organs varied by ADE category. Conclusions The considerable burden of ADEs and preventable ADEs from commonly used drugs across care settings warrants large-scale efforts to redesign safer, higher quality healthcare systems. The heterogeneous nature of the ADE categories should be considered in research and clinical practice for preventing, detecting and mitigating ADEs.

Global data on use of evidence-based medical (EBM) therapies following myocardial infarction (MI) are rare. Therefore, we investigated regional differences in EBM therapy use and its association with CV death in patients >1 year post MI. The TIGRIS prospective global registry ([NCT01866904][1])

THEMIS is a large RCT ([NCT01991795][1]) comparing the effect of ticagrelor vs placebo (both with background ASA) for the prevention of major CV events in patients with type 2 diabetes (T2D) at high risk for such events with no prior MI or stroke. The current study assessed the burden of illness

THEMIS is a large RCT ([NCT01991795][1]) in patients with type 2 diabetes (T2D) at high risk for cardiovascular (CV) events, but without a history of MI or stroke, that compares the effect of ticagrelor vs placebo (both with background ASA) for the prevention of major CV events. The current study

Purpose To assess refill adherence to dispensed oral long-term medications among the adult population and to investigate whether the percentages of self-reported adverse drug reactions (ADRs) and sub-therapeutic effects (STEs) differed for medications with adequate refill adherence, oversupply, and undersupply. Method Survey responses on self-reported ADRs and STEs were linked to the Swedish Prescribed Drug Register in a cross-sectional population-based study. Refill adherence to antihypertensive, lipid-lowering, and oral anti-diabetic medications was measured using the continuous measure of medication acquisition (CMA). The percentages of self-reported ADRs and STEs were compared between medications with adequate refill adherence (CMA 0.8–1.2), oversupply (CMA > 1.2), and undersupply (CMA 0.5) for ADRs and 1.1%, 1.6%, and 1.5% (p > 0.5) for STEs. Conclusions Adequate refill adherence was found in two thirds of the medication therapies. ADRs and STEs were unexpectedly equally commonly reported for medications with adequate refill adherence, oversupply, and undersupply. These results suggest that a better understanding of patients' refill behaviors and their perceived medication adverse outcomes is needed and should be considered in improving medication management. The impact of individual and healthcare factors that may influence the association between refill adherence and reported medication adverse outcomes should be investigated in future studies. Copyright © 2013 John Wiley & Sons, Ltd.

Purpose This study aimed to describe and compare refill adherence and persistence to lipid‐lowering medicines in patients with type 2 diabetes by previous cardiovascular disease (CVD). Methods We followed 97 595 patients (58% men; 23% with previous CVD) who were 18 years of age or older when initiating lipid‐lowering medicines in 2007–2010 until first fill of multi‐dose dispensed medicines, death, or 3 years. Using personal identity numbers, we linked individuals' data from the Swedish Prescribed Drug Register, the Swedish National Diabetes Register, the National Patient Register, the Cause of Death Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. We assessed refill adherence using the medication possession ratio (MPR) and the maximum gap method, and measured persistence from initiation to discontinuation of treatment or until 3 years after initiation. We analyzed differences in refill adherence and persistence by previous CVD in multiple regression models, adjusted for socioeconomic status, concurrent medicines, and clinical characteristics. Results The mean age of the study population was 64 years, 80% were born in Sweden, and 56% filled prescriptions for diabetes medicines. Mean MPR was 71%, 39% were adherent according to the maximum gap method, and mean persistence was 758 days. Patients with previous CVD showed higher MPR (3%) and lower risk for discontinuing treatment (12%) compared with patients without previous CVD (P

Background: Early discontinuation of anti-depressant treatment is common. This study analysed whether socio-economic factors influence early discontinuation among new anti-depressant users aged 20–34 years. Methods: Our study population included all Swedes aged 20–34 years who purchased anti-depressants in 2006 and had not purchased such drugs in the preceding 6 months ( n = 25 003). We obtained prescription data from the Swedish Prescribed Drug Register. Information about demographic and socio-economic factors (country of birth, marital status, household size, education level, occupation, income and social assistance) was collected from Statistics Sweden by record linkage. We defined early discontinuation as filling only one anti-depressant prescription within a 6-month period. We used multiple logistic regression analysis to analyse the socio-economic factors associated with early discontinuation. Results: We identified 6536 individuals (26.1%) as early discontinuers. Early discontinuation was less common among women [odds ratio (OR) = 0.82; 95% confidence intervals (CI) 0.75–0.87] and in those with at least two years of higher education (OR = 0.71; 95% CI 0.61–0.83), whereas it was more common among those born outside Sweden (OR = 1.76; 95% CI 1.48–2.10) and those who received social assistance (OR = 1.26; 95% CI 1.11–1.44). Compared with selective serotonin re-uptake inhibitors, SSRI, early discontinuation was more common among individuals who started treatment with a tri-cyclic anti-depressant, TCA, (OR = 2.58; 95% CI 2.24–2.98) or an anti-depressant other than SSRIs, TCAs or selective serotonin-norepinephrine re-uptake inhibitors/norepinephrine (noradrenaline) re-uptake inhibitors (OR = 2.90; 95% CI 2.05–4.10). Conclusion: Early discontinuation occurred more commonly among social assistance recipients and those with immigrant background, suggesting that those groups might require greater support when initiating anti-depressant therapy.

Purpose To analyse and compare refill adherence to statins estimated with two different methods with a focus on sensitivity to definitions. less thanbrgreater than less thanbrgreater thanMethods In ...

Following a large regulatory reform in 2009, which ended the state's pharmacy monopoly, non-pharmacy retailers in Sweden today sell certain over-the-counter (OTC) drugs. The aim of this study was to investigate consumer preferences regarding OTC drug retailers and the reasons for choosing a pharmacy versus non-pharmacy retailer. We conducted a web survey aimed at Swedish adults. Out of a stratified sample of 4058 persons, 2594 agreed to take part (48% women; mean age: 50.3 years). Questions related to OTC drug use, retailer choice and factors affecting the participants' preferences for OTC drug retailers. Logistic regression was conducted to analyse OTC drug use and reasons for retailer choice in relation to sex, age and education. Nine in ten participants reported OTC drug use in the 6 months prior to the study. For their last OTC purchase, 76% had gone to a pharmacy, 20% to a grocery shop and 4% to a convenience store, gas station or online. Geographic proximity, opening hours and product range were reported as the most important factors in retailer choice. Counselling by trained staff was important to 57% of participants. The end of the state's pharmacy monopoly and the increase in number of pharmacies seem to have impacted more on Swedish consumers' purchase behaviours compared with the deregulation of OTC drug sales.

Objective To analyze the durability of monotherapy with different classes of oral hypoglycemic agents (OHAs) in drug naive patients with type 2 diabetes mellitus (T2DM) in real life. Methods Men and women with T2DM, who were new users of OHA monotherapy and registered in the Swedish National Diabetes Register July 2005–December 2011, were available (n=17 309) and followed for up to 5.5 years. Time to monotherapy failure, defined as discontinuation of continuous use with the initial agent, switch to a new agent, or add-on treatment of a second agent, was analyzed as a measure of durability. Baseline characteristics were balanced by propensity score matching 1:5 between groups of sulfonylurea (SU) versus metformin (n=4303) and meglitinide versus metformin (n=1308). HRs with 95% CIs were calculated using Cox regression models. Results SU and meglitinide, as compared with metformin, were associated with increased risk of monotherapy failure (HR 1.74; 95% CI 1.56 to 1.94 and 1.66; 1.37 to 2.00 for SU and meglitinide, respectively). When broken down by type of monotherapy failure, SU and meglitinide were associated with an increased risk of add-on treatment of a second agent (HR 3.14; 95% CI 2.66 to 3.69 and 2.52; 1.89 to 3.37 for SU and meglitinide, respectively) and of switch to a new agent (HR 2.81; 95% CI 2.01 to 3.92 and 3.78; 2.25 to 6.32 for SU and meglitinide, respectively). The risk of discontinuation did not differ significantly between the groups. Conclusions In this nationwide observational study reflecting clinical practice, SU and meglitinide showed substantially increased risk of switch to a new agent or add on of a second agent compared with metformin. These results indicate superior glycemic durability with metformin compared with SU and also meglitinide in real life.

Antibiotic resistance is a collective action dilemma. Individuals may request antibiotics, but an overall reduction in use is necessary to limit resistance. A reoccurring theoretical claim is that social capital increase cooperation in social dilemmas. The aim of this paper is to investigate the link between generalized trust and reciprocity and the willingness to postpone antibiotic treatment in order to limit overuse in a scenario-based study. A between-subject scenario experimental approach with hypothetical scenarios was utilized. Participants were asked to imagine that they were seeing a doctor for a respiratory infection. The doctor prescribes antibiotics, but advise postponing therapy to see if the disease resolves by itself, for the sake of limiting overuse. Respondents were asked to answer how long they could accept postponing antibiotic treatment, from 0 to 7 days. The number of days that most people would be able to accept postponing treatment was considered the between-subject factor. In total, the study sample included 981 respondents with a mean age of 51 years. A majority of respondents were men (65.7%). The mean number of days that the respondents stated they were willing to postpone antibiotic treatment was positively associated with the number of days the respondents were told that most people were willing to postpone antibiotic treatment, p

Background Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated. Objective Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP. Methods A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC≥80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated. Results Non-adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 [95% CI, 1.18–6.43]) and with the lowest income (OR 2.05 [95% CI, 1.01–4.16]). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 [95% CI, 1.32–3.15]), persons using specialized healthcare (OR 1.63, [95% CI, 1.14–2.32]), and having multiple antihypertensive medications (OR 1.85 [95% CI, 1.25–2.75] and OR 5.22 [95% CI, 3.48–7.83], for 2 and ≥3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP. Conclusion Sociodemographic factors were associated with non-adherence to any antihypertensive medication while clinical factors with non-adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients' refill adherence prior to healthcare visit may facilitate interpreting elevated BP.

This chapter provides an overview of the organization of pricing, reimbursement of medicines, and the organization of the pharmaceutical systems in the two Scandinavian countries Norway and Sweden. The two countries have many similarities; however, they have also chosen different roads in several aspects. Both countries have a comprehensive tax-based public health insurance covering health services for all inhabitants. This includes medicines provided to cure, alleviate or prevent diseases that have been judged to be in the interest of the public. Pricing of prescribed medicines is strictly regulated in the two countries. More than 70 % of the total pharmaceutical expenditures are paid by a public third-party payer. Both countries experienced dramatic increase in pharmaceutical expenditures in the early 1990s. This set off a series of reforms concerning the pricing and reimbursement of medicines. The fundamental principle for pricing of prescription medicines is maximum pricing at the retail level. Norway applies international reference pricing while Sweden’s pricing system is based on health economic evaluations. Pricing is tied to the process of marketing in Norway and to reimbursement in Sweden. Both countries have applied mandatory generic substitution for more than 10 years.

Background: In the Swedish reimbursement scheme, the co-payment is based on the price of the product and decreases in a stepwise manner as the total accumulated co-payment increases. The aim of this study was to analyse how refill adherence in Sweden varies according to patient’s co-payment level for medicines, with antiepileptic drug (AED) use as an example. Methods: Prevalent AED users aged 18–85 years who purchased an AED between 1 January and 30 June 2007 were identified in the Swedish Prescribed Drug Register and followed for a maximum of 2 years. Patient time was categorized based on patient’s accumulated co-payment for all drugs per reimbursement period. The continuous measure of medication acquisition (CMA) was used to estimate refill adherence in relation to the patients’ co-payment level. Associations between patients’ co-payment for all medicines and refill adherence were assessed with multilevel mixed-effects linear regression, accounting for clustering within patients. Results: The study population included 2210 patients (mean age: 56 years; 54% men). CMA for AED was 91% for patients where the co-payment corresponded to 100% of the price. Compared with these patients, refill adherence for AED was 2–4% higher ( P < 0.001) for patients with reduced co-payment (co-payment of ≤50% of the price). Higher age, higher income and fenytoin use were also associated with a higher refill adherence for AED. Conclusions: Using AED as an example, a higher level of reimbursement was associated with a higher refill adherence compared with full co-payment in Sweden.

Objectives: To estimate the cost of illness (COI) of individuals with self-reported adverse drug events (ADEs) from a societal perspective and to compare these estimates with the COI for individuals without ADE. Furthermore, to estimate the direct costs resulting from two ADE categories, adverse drug reactions (ADRs) and subtherapeutic effects of medication therapy (STE). Design: Cross-sectional study. Setting: The adult Swedish general population. Participants: The survey was distributed to a random sample of 14 000 Swedish residents aged 18 years and older, of which 7099 responded, 1377 reported at least one ADE and 943 reported an ADR or STE. Main outcome measures: Societal COI, including direct and indirect costs, for individuals with at least one self-reported ADE, and the direct costs for prescription drugs and healthcare use resulting from self-reported ADRs and STEs were estimated during 30 days using a bottom-up approach. Results: The economic burden for individuals with ADEs were (95% CI) 442.7 to 599.8 international dollars (Int$), of which direct costs were Int$ 279.6 to 420.0 (67.1%) and indirect costs were Int$ 143.0 to 199.8 (32.9%). The average COI was higher among those reporting ADEs compared with other respondents (COI: Int$ 442.7 to 599.8 versus Int$ 185.8 to 231.2). The COI of respondents reporting at least one ADR or STE was Int$ 468.9 to 652.9. Direct costs resulting from ADRs or STEs were Int$ 15.0 to 48.4. The reported resource use occurred both in hospitals and outside in primary care. Conclusions: Self-reported ADRs and STEs cause resource use both in hospitals and in primary care. Moreover, ADEs seem to be associated with high overall COI from a societal perspective when comparing respondents with and without ADEs. There is a need to further examine this relationship and to study the indirect costs resulting from ADEs.

To assess refill adherence to dispensed oral long-term medications among the adult population and to investigate whether the percentages of self-reported adverse drug reactions (ADRs) and sub-therapeutic effects (STEs) differed for medications with adequate refill adherence, oversupply, and undersupply.Survey responses on self-reported ADRs and STEs were linked to the Swedish Prescribed Drug Register in a cross-sectional population-based study. Refill adherence to antihypertensive, lipid-lowering, and oral anti-diabetic medications was measured using the continuous measure of medication acquisition (CMA). The percentages of self-reported ADRs and STEs were compared between medications with adequate refill adherence (CMA 0.8-1.2), oversupply (CMA 1.2), and undersupply (CMA 0.8).The study included 1827 persons, and the refill adherence was measured for 3014 antihypertensive, 839 lipid lowering, and 253 oral anti-diabetic medications. Overall, 65.7% of the medications had adequate refill adherence, 21.9% oversupply, and 12.4% undersupply. The percentages of self-reported ADRs and STEs were respectively 2.6%, 2.7%, and 2.1% (p 0.5) for ADRs and 1.1%, 1.6%, and 1.5% (p 0.5) for STEs.Adequate refill adherence was found in two thirds of the medication therapies. ADRs and STEs were unexpectedly equally commonly reported for medications with adequate refill adherence, oversupply, and undersupply. These results suggest that a better understanding of patients' refill behaviors and their perceived medication adverse outcomes is needed and should be considered in improving medication management. The impact of individual and healthcare factors that may influence the association between refill adherence and reported medication adverse outcomes should be investigated in future studies.

Background: Preventable adverse drug events (ADEs) are common in both outpatient and inpatient settings. However, the proportion of preventable ADEs varies considerably in different studies, even when conducted in the same setting, and methods for assessing the preventability of ADEs are diverse. Objective: The aim of this article is to identify and systematically evaluate methods for assessing the preventability of ADEs. Data sources: Seven databases (Cochrane, CINAHL, EMBASE, IPA, MEDLINE, PsycINFO and Web of Science) were searched in September 2010 utilizing the databases' index terms and other common terminology on preventable ADEs. No limits for the years of publication were set. Reference lists of included original articles and relevant review articles were also screened. Study selection: After applying predetermined inclusion and exclusion criteria on 4161 unique citations, 142 (3.4%) original research articles were included in the review. One additional article was included from reference lists. Outcome measures of included studies had to include the frequency of ADEs and the assessment of their preventability. Studies were excluded if they focused on individuals with one specific type of treatment, medical condition, medical procedure or ADE. Data extraction: Measurement instruments for determining the preventability of ADEs in each article were extracted and unique instruments were compared. The process of assessing the preventability of ADEs was described based on reported actions taken to standardize and conduct the assessment, and on information about the reliability and validity of the assessment. Data synthesis: Eighteen unique instruments for determining the preventability of ADEs were identified. They fell under the following four groups: (i) instruments using a definition of preventability only (n = 3); (ii) instruments with a definition of preventability and an assessment scale for determining preventability (n = 5); (iii) instruments with specific criteria for each preventability category (n = 3); and (iv) instruments with an algorithm for determining preventability (n = 7). Of actions to standardize the assessment process, performing a pilot study was reported in 21 (15%), and use of a standardized protocol was reported in 18 (13%), of the included 143 articles. Preventability was assessed by physicians in 86 (60%) articles and by pharmacists in 41 (29%) articles. In 29 (20%) articles, persons conducting the assessment were described as trained for or experienced in preventability assessment. In 94 (66%) articles, more than one person assessed the preventability of each case. Among these 94 articles, assessment was done independently in 73 (51%) articles. Procedures for managing conflicting assessments were diverse. The reliability of the preventability assessment was tested in 39 (27%) articles, and 16 (11%) articles referred to a previous reliability assessment. Reliability ranged from poor to excellent (kappa 0.19-0.98; overall agreement 26-97%). Four (3%) articles mentioned assessing validity, but no sensitivity or specificity analyses or negative or positive predictive values were presented. Conclusions: Instruments for assessing the preventability of ADEs vary from implicit instruments to explicit algorithms. There is limited evidence for the validity of the identified instruments, and instrument reliability varied significantly. The process of assessing the preventability of ADEs is also commonly imprecisely described, which hinders the interpretation and comparison of studies. For measuring the preventability of ADEs more accurately and precisely in future, we believe that existing instruments should be further studied and developed, or that one or more new instruments should be developed, and the validity and reliability of the existing and new instruments be established. funding agencies|National Corporation of Swedish Pharmacies (Apoteket AB)

Drug-related morbidity (DRM) is common and to some extent preventable, and associated with considerable costs in patients attending hospital. In outpatients and in the general public corresponding data are limited, but pharmacists' expert opinion has suggested high rates of DRM also in US ambulatory care. It is unknown if the results are applicable in Sweden today.To estimate the proportions of patients with DRM and preventable DRM and the cost-of-illness (COI) of DRM in Sweden based on pharmacists' expert opinion.Swedish healthcare.The study applied a conceptual model of DRM based on a decision tree. An expert panel of pharmacists determined the probabilities of therapeutic outcomes of medication therapy. The COI analysis included direct costs from the healthcare perspective. Sensitivity analyses were performed for variations in probabilities and pathway costs.DRM included new medical problems (adverse drug reactions, drug dependence and intoxications) and therapeutic failures (insufficient effects of medicines and morbidity due to untreated indication).The expert panel estimated that 61 ± 14 % (mean ± SD) of all patients attending healthcare suffered from DRM, of which 29 ± 8 % suffered from new medical problems, 18 ± 6 % from therapeutic failures, and 15 ± 7 % from a combination of both. The DRM was considered preventable in 45 ± 15 % of the patients with DRM. The estimated COI was EUR 997 per patient attending healthcare, corresponding to an annual cost of EUR 6,600 million to the Swedish healthcare system. The COI ranged from EUR 490 to EUR 1,314 when varying the participants' probabilities of DRM and clinical outcomes from the first to the third quartile. Of the pathway costs, the COI was most sensitive to variation in the cost of prolonged hospital stay (COI range EUR 953-1,306).According to pharmacists' expert opinion, a large proportion of patients in Sweden experience DRM and preventable DRM, and the estimated COI of DRM is extensive. Since observational studies have not addressed the burden of DRM to the general public, this study adds the pharmacists' perception on DRM. Other healthcare professionals' perceptions on DRM need to be investigated in future studies.

Objectives To describe the use and evaluate the effectiveness of different lipid lowering therapies in unselected patients with type 1 and type 2 diabetes in clinical practice. Design Observational population-based study using the personal identification number to link information from the National Diabetes Register, the Prescribed Drug Register and the Patient register in Sweden. All patients in the NDR aged 18–75 years with diabetes more than one year were eligible, but only patients starting any lipid lowering treatment with at least three prescriptions 1 July 2006–30 June 2007 were included (n = 37182). The mean blood lipid levels in 2008 and reductions in LDL cholesterol were examined. Results Blood lipid levels were similar in patients treated with simvastatin, atorvastatin and rosuvastatin, showing similar lipid lowering effect as currently used. Users of pravastatin, fluvastatin, ezetimib and fibrate more seldom reach treatment goals. Moderate daily doses of the statins were used, with 76% of simvastatin users taking 20 mg or less, 48% of atorvastatin users taking 10 mg, 55% of pravastatin users taking 20 mg, and 76% of rosuvastatin users taking 5 or 10 mg. Conclusions This observational study shows that the LDL-C levels in patients taking simvastatin, atorvastatin or rosuvastatin are very similar as currently used, as well as their LDL-C lowering abilities. There is potential to intensify lipid lowering treatment to reduce the remaining high residual risk and achieve better fulfilment of treatment goals, since the commonly used doses are only low to moderate.