Missed opportunities in the diagnosis of heart failure: a real-world assessment.

AIMS: Heart failure (HF) is a leading cause of hospitalization worldwide. An early HF diagnosis is key to reducing hospitalizations. We used electronic health records (EHRs) to characterize HF pathways at the primary care physician (PCP) level prior to a first HF hospitalization (hHF). This study aimed to identify missed opportunities for HF diagnosis and management at the PCP level before a first hHF. METHODS AND RESULTS: This cohort study used EHRs of a large health care organization in Portugal. Patients with incident hHF between 2017 and 2020 were identified. Missed opportunities were defined by the absence of any of the following work-up in the 6 months after signs or symptoms had been recorded: lab results and electrocardiogram, natriuretic peptides, echocardiogram, referral to HF specialist, or HF medication initiation. A total of 2436 patients with a first hHF were identified. The median (interquartile range) age at the time of hospitalization was 81 (14) years, and 1361 (56%) were women. Most patients were treated with cardiovascular drugs prior or at index event. A total of 720 (30%) patients had records of HF signs or symptoms, 94% (n = 674) within 6 months prior to hHF. Among patients with recorded HF signs or symptoms, 410 (57%) had clinical management considered adequate before signs and symptoms were recorded. Of the 310 remaining patients, 155 (50%) had a follow-up that was considered inadequate. CONCLUSIONS: Relatively few patients with a first hHF had primary care records of signs or symptoms prior to admission. Of these, nearly half had inadequate management considering diagnosis and treatment. These data suggest the need to improve PCP HF awareness.

Atrial fibrillation and clinical outcomes 1 to 3 years after myocardial infarction.

OBJECTIVE: Atrial 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/RESULTS: The 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. CONCLUSIONS: In 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 NUMBER: ClinicalTrials: NCT01866904.

Impact of Socioeconomic Factors and Gender on Refill Adherence and Persistence to Lipid-Lowering Therapy in Type 1 Diabetes.

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 < 0.0001) at 36 months. Women were more adherent and less prone to discontinue LLT at 18 months (OR 1.05, p = 0.0005 and OR 0.95, p = 0.0004, respectively), but not at 36 months. Divorced individuals were less adherent than married ones (OR 0.93, p = 0.0005) and discontinued LLT more often than the latter (OR 1.06, p = 0.003). Education had no impact on adherence, but individuals with higher incomes discontinued LLT less frequently than those with lower incomes. Individuals with a country of origin other than Sweden discontinued LLT more often. CONCLUSION: Lower adherence to LLT in individuals with T1D was associated with male gender, younger age, marital status and country of birth. These factors should be considered when evaluating adherence to LLT in clinical practice, with the aim to help patients achieve full cardioprotective treatment.

Health-related quality of life 1-3 years post-myocardial infarction: its impact on prognosis.

OBJECTIVE: To 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). METHODS: The 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. RESULTS: Among 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. CONCLUSIONS: Clinicians 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 NUMBER: ClinicalTrials.gov Registry (NCT01866904) (https://clinicaltrials.gov).

Assessment of the high risk and unmet need in patients with CAD and type 2 diabetes (ATHENA): US healthcare resource utilization, cost and burden of illness in the Diabetes Collaborative Registry.

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.

Adherence to lipid-lowering therapy and risk for cardiovascular disease and death in type 1 diabetes mellitus: a population-based study from the Swedish National Diabetes Register.

AIMS/HYPOTHESIS: Dyslipidemia 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.  METHOD: A 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.   RESULTS: Mean 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/INTERPRETATION: In 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.

Risk of cardiovascular event and mortality in relation to refill and guideline adherence to lipid-lowering medications among patients with type 2 diabetes mellitus in Sweden.

Objective: To 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 methods: We 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. Results: Compared 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 <48%) had a higher risk of CV events and CV mortality. Otherwise, no difference in the risk of CV events or mortality was observed by guideline adherence level. Conclusions: Our results demonstrate the importance of high refill adherence and thus the value of individualized care among patients with T2DM.

Attitudes towards sales and use of over-the-counter drugs in Sweden in a reregulated pharmacy market: a population-based study.

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.

Prescription of lipid-lowering medications for patients with type 2 diabetes mellitus and risk-associated LDL cholesterol: a nationwide study of guideline adherence from the Swedish National Diabetes Register.

BACKGROUND: Management of type 2 diabetes mellitus (T2DM) encompasses intensive glycaemic control, along with treatment of comorbidities and complications to handle the increased risk of cardiovascular disease (CVD). Improved control of LDL-cholesterol (LDL-C) with lipid-lowering medications is associated with reduced CVD risk in T2DM patients. Thus, treatment guidelines recommend lipid-lowering medications for T2DM patients with LDL-C above risk-associated thresholds. This study aimed to assess healthcare provider adherence to guidelines regarding lipid-lowering medication prescription among T2DM patients and to analyse factors associated with lipid-lowering medication prescription. METHODS: Observations in 2007 - 2014 for T2DM patients age ≥ 18 were collected from the Swedish National Diabetes Register. Observations were excluded if they lacked information about LDL-C, lipid-lowering medication prescription or CVD. Observations with established CVD were attributed to secondary prevention; remaining observations were attributed to primary prevention. The analyses included primary and secondary prevention observations with LDL-C above risk-associated thresholds (LDL-C ≥ 2.5 mmol/l and LDL-C ≥ 1.8 mmol/l respectively). Guideline adherence was analysed as the probability of prescribing lipid-lowering medications using mixed-effect model regression adjusted for potential confounders. Factors associated with prescribing lipid-lowering medications were analysed for patient and healthcare provider characteristics using mixed-effect model regression and odds ratio. RESULTS: A total of 1,204,376 observations from 322,046 patients reported by 1352 healthcare providers were included. Primary prevention accounted for 63%; 52% were men, mean age was 64 and mean LDL-C was 3.4 mmol/l. For secondary prevention, 60% were men, mean age was 72 and mean LDL-C was 2.7 mmol/l. During 2007-2014, guideline adherence ranged from 36 to 47% for primary prevention and 59 to 69% for secondary prevention. In general, concomitant prescription of diabetes medications, antiplatelets and antihypertensives along with smoking and specialised care were associated with higher prescription of lipid-lowering medications. Patients age ≥ 80 were associated with lower prescription of lipid-lowering medications. Higher prescription was associated with longer diabetes duration in primary prevention and men in secondary prevention. CONCLUSIONS: Adherence to treatment guidelines levelled off after an initial increase in both prevention groups. Lipid-lowering medication prescription was based on individualised CVD risk.

Late-life suicidal behaviours among new users of antidepressants: a prospective population-based study of sociodemographic and gender factors in those aged 75 and above.

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.

Association between refill adherence to lipid-lowering medications and the risk of cardiovascular disease and mortality in Swedish patients with type 2 diabetes mellitus: a nationwide cohort study.

OBJECTIVES: To analyse the association between refill adherence to lipid-lowering medications, and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes mellitus. DESIGN: Cohort study. SETTING: National population-based cohort of Swedish patients with type 2 diabetes mellitus. PARTICIPANTS: 86 568 patients aged ≥18 years, registered with type 2 diabetes mellitus in the Swedish National Diabetes Register, who filled at least one prescription for lipid-lowering medication use during 2007-2010, 87% for primary prevention. EXPOSURE AND OUTCOME MEASURES: Refill adherence of implementation was assessed using the medication possession ratio (MPR), representing the proportion of days with medications on hand during an 18-month exposure period. MPR was categorised by five levels (≤20%, 21%-40%, 41%-60%, 61%-80% and >80%). Patients without medications on hand for ≥180 days were defined as non-persistent. Risk of CVD (myocardial infarction, ischaemic heart disease, stroke and unstable angina) and mortality by level of MPR and persistence was analysed after the exposure period using Cox proportional hazards regression and Kaplan-Meier, adjusted for demographics, socioeconomic status, concurrent medications and clinical characteristics. RESULTS: The hazard ratios for CVD ranged 1.33-2.36 in primary prevention patients and 1.19-1.58 in secondary prevention patients, for those with MPR ≤80% (p<0.0001). The mortality risk was similar regardless of MPR level. The CVD risk was 74% higher in primary prevention patients and 33% higher in secondary prevention patients, for those who were non-persistent (p<0.0001). The mortality risk was 6% higher in primary prevention patients and 18% higher in secondary prevention patients, for non-persistent patients (p<0.0001). CONCLUSIONS: Higher refill adherence to lipid-lowering medications was associated with lower risk of CVD in primary and secondary prevention patients with type 2 diabetes mellitus.

Antidepressants and suicidal behaviour in late life: a prospective population-based study of use patterns in new users aged 75 and above.

PURPOSE: To investigate associations between antidepressant use patterns and risk of fatal and non-fatal suicidal behaviours in older adults who initiated antidepressant therapy. METHOD: A national population-based cohort study conducted among Swedish residents aged ≥ 75 years who initiated antidepressant treatment. Patients who filled antidepressant prescriptions between January 1, 2007 and December 31, 2013 (N = 185,225) were followed until December 31, 2014. Sub-hazard ratios of suicides and suicide attempts associated with use patterns of antidepressants, adjusting for potential confounders such as serious depression were calculated using the Fine and Gray regression models. RESULTS: During follow-up, 295 suicides and 654 suicide attempts occurred. Adjusted sub-hazard ratios (aSHRs) were increased for both outcomes in those who switched to another antidepressant (aSHR for suicide 2.42, 95% confidence interval 1.65 to 3.55, and for attempt 1.76, 1.32 to 2.34). Elevated suicide risks were also observed in those who concomitantly filled anxiolytics (1.54, 1.20 to 1.96) and hypnotics (2.20, 1.69 to 2.85). Similar patterns were observed for the outcome suicide attempt. Decreased risk of attempt was observed among those with concomitant use of anti-dementia drugs (0.40, 0.27 to 0.59). CONCLUSION: Switching antidepressants, as well as concomitant use of anxiolytics or hypnotics, may constitute markers of increased risk of suicidal behaviours in those who initiate antidepressant treatment in very late life. Future research should consider indication biases and the clinical characteristics of patients initiating antidepressant therapy.

Refill adherence and persistence to lipid-lowering medicines in patients with type 2 diabetes: A nation-wide register-based study.

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 < 0.0001). CONCLUSIONS: Patients with previous CVD were more likely to be adherent to treatment and had lower risk for discontinuation compared with patients without previous CVD.

Direct and indirect costs for adverse drug events identified in medical records across care levels, and their distribution among payers.

BACKGROUND: Adverse drug events (ADEs) cause considerable costs in hospitals. However, little is known about costs caused by ADEs outside hospitals, effects on productivity, and how the costs are distributed among payers. OBJECTIVE: To describe the direct and indirect costs caused by ADEs, and their distribution among payers. Furthermore, to describe the distribution of patient out-of-pocket costs and lost productivity caused by ADEs according to socio-economic characteristics. METHOD: In a random sample of 5025 adults in a Swedish county, prevalence-based costs for ADEs were calculated. Two different methods were used: 1) based on resource use judged to be caused by ADEs, and 2) as costs attributable to ADEs by comparing costs among individuals with ADEs to costs among matched controls. Payers of costs caused by ADEs were identified in medical records among those with ADEs (n = 596), and costs caused to individual patients were described by socio-economic characteristics. RESULTS: Costs for resource use caused by ADEs were €505 per patient with ADEs (95% confidence interval €345-665), of which 38% were indirect costs. Compared to matched controls, the costs attributable to ADEs were €1631, of which €410 were indirect costs. The local health authorities paid 58% of the costs caused by ADEs. Women had higher productivity loss than men (€426 vs. €109, p = 0.018). Out-of-pocket costs displaced a larger proportion of the disposable income among low-income earners than higher income earners (0.7% vs. 0.2%-0.3%). CONCLUSION: We used two methods to identify costs for ADEs, both identifying indirect costs as an important component of the overall costs for ADEs. Although the largest payers of costs caused by ADEs were the local health authorities responsible for direct costs, employers and patients costs for lost productivity contributed substantially. Our results indicate inequalities in costs caused by ADEs, by sex and income.

Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?

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.

Trust, reciprocity and collective action to fight antibiotic resistance. An experimental approach.

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 < 0.001. There was a positive association between number of days they were willing to postpone antibiotic treatment and generalized trust, p = 0.001. In conclusion, the results showed that the proclaimed public willingness to postpone therapy influenced a respondent's willingness to postpone antibiotic therapy in different scenarios. Also, generalized trust was positively associated with the willingness to postpone therapy.

Pharmacoepidemiology at Nordic School of Public Health NHV: Examples from 1999 to 2014.

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.

Durability of oral hypoglycemic agents in drug naïve patients with type 2 diabetes: report from the Swedish National Diabetes Register (NDR).

OBJECTIVE: To analyze the durability of monotherapy with different classes of oral hypoglycemic agents (OHAs) in drug naïve 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.

Is the level of patient co-payment for medicines associated with refill adherence in Sweden?

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.

Prevalence, nature and potential preventability of adverse drug events - a population-based medical record study of 4970 adults.

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.