Suicidal behavior and all-cause mortality in depressed older adults aged 75+ treated with electroconvulsive therapy: A Swedish register-based comparison study.

OBJECTIVES: Electroconvulsive therapy (ECT) is effective in treating late-life depression. There is limited research on suicidal behavior and all-cause mortality in the oldest old after ECT. METHODS: Older adults aged 75 years and above who had been inpatients for moderate to severe depression between January 1, 2011, and December 31, 2017, were included in the study. We used exact and propensity score matching to balance groups. We compared suicidal behavior (fatal and non-fatal) and all-cause mortality in those who had received ECT and those with other depression treatments. RESULTS: Of the study population, 1802 persons who received ECT were matched to 4457 persons with other treatments. There were no significant differences in the risk of suicidal behavior between groups, (within 3 months: odds ratio 0.73; 95% confidence intervals (CI), 0.44-1.23, within 4 months to 1 year: aOR 1.34; 95% CI, 0.84-2.13). All-cause mortality was lower among ECT recipients compared to those who had received other treatments, both within 3 months (aOR, 0.35; 95% CI, 0.23-0.52), and within 4 months to 1 year (aOR 0.65; 95% CI, 0.50-0.83). CONCLUSIONS: Compared to other depression treatments, ECT is not associated with a higher risk of suicidal behavior in patients aged 75 and above. ECT is associated with lower all-cause mortality in this age group, but we advise caution regarding causal inferences.

Determinants of suicidal behavior in dementia: A Swedish national register-based study.

OBJECTIVES: To examine predictors of suicidal behavior (SB) in adults aged 75 years and above with dementia. DESIGN: Longitudinal national register-based study. PARTICIPANTS AND SETTING: Swedish residents aged ≥75 years with dementia identified in the Swedish Dementia Registry (SveDem) between 1 January 2007 and 31 December 2017 (N = 59 042) and followed until 31 December 2018. Data were linked with numerous national registers using personal identity numbers. MEASUREMENTS: Outcomes were nonfatal self-harm and suicide. Fine and Gray regression models were used to investigate demographics, comorbidities, and psychoactive medications associated with fatal and nonfatal SB. RESULTS: Suicidal behavior was observed in 160 persons after dementia diagnosis; 29 of these died by suicide. Adjusted sub-hazard ratio (aSHRs) for SB was increased in those who had a previous episode of self-harm (aSHR = 14.42; 95% confidence interval [CI] = 7.06-29.46), those with serious depression (aSHR = 4.33, 95%CI = 2.94-6.4), and in those born outside Sweden (aSHR = 1.53; 95% CI = 1.03-2.27). Use of hypnotics or anxiolytics was also associated with a higher risk of SB; use of antidepressants was not. Milder dementia and higher frailty score also increased risk of SB. Risk was decreased in those who received home care (aSHR = 0.52; 95%CI = 0.38-0.71) and in the oldest group (aSHR = 0.35; 95%CI = 0.25-0.49). CONCLUSION: In addition to established targets for suicidal behavior prevention (improved identification and treatment of depression and previous self-harm), several new risk factors were suggested. There is a need for innovative public health strategies to meet the needs of older dementia patients with a foreign background. Home care may have a potential positive effect to prevent SB in people with dementia, but this needs to be further explored.

Use of Psychoactive Medications and Risk of Suicide in Late Life (75+): A Total Population Study.

BACKGROUND: Psychoactive medications play an important role for the mental health and risk of suicidal behaviour in the oldest segment of the population (75+). A better understanding of psychoactive medication use is advocated to prevent suicide in this age group. PURPOSE: We investigated the risk of suicide associated with the use of psychoactive medications in the total population aged ≥ 75 years, with and without exposure to antidepressants. METHOD: A national population-based register study, including all Swedish residents aged ≥ 75 years between 2006 and 2014 (N = 1,413,806). A nested case-control design was used to investigate psychoactive medications associated with suicide among users and non-users of antidepressants. Risk estimates were calculated in adjusted conditional logistic regression models for the entire cohort and by gender. RESULTS: Suicide occurred in 1305 persons (907 men and 398 women). Among them, 555 (42.5%) were on an antidepressant at the time of suicide. Adjusted incidence rate ratio (aIRR) for suicide was increased in those who were on hypnotics in the total cohort (aIRR 2.05, 95% confidence interval 1.74 to 2.41), in both users and non-users of antidepressants and for both genders. Elevated suicide risk was observed in those who concomitantly used anxiolytics with antidepressants (1.51, 1.25 to 1.83). Decreased risk of suicide was observed among those who were on anti-dementia drugs, in the total cohort (0.33, 0.21 to 0.52) and in both users and non-users of antidepressants. Use of antipsychotics and mood stabilisers showed no effect on suicide risk. CONCLUSION: Use of hypnotics and concomitant use of anxiolytics with antidepressants was associated with increased risk of late-life suicide. Our findings suggest the need for careful evaluation of the benefit-risk balance of psychoactive medications as well as their availability as a possible suicide means. Future research should consider the indication of use of the psychoactive medications and the severity of psychiatric and medical illnesses of the patients.

Healthcare visits for mental disorders and use of psychotropic medications before and after self-harm in a cohort aged 75.

OBJECTIVES: Non-fatal self-harm (SH) is a major risk factor for late-life suicide. A better knowledge of the clinical management of older adults who self-harm is needed to establish where improvements could be made for the implementation of effective suicide prevention interventions. We therefore assessed contacts with primary and specialised care for mental disorders and psychotropic drug use during the year before and after a late-life non-fatal SH episode. METHOD: Longitudinal population-based study in adults aged ≥75 years with SH episode between 2007 and 2015 retrieved from the regional database VEGA. Healthcare contacts for mental disorders and psychotropic use were assessed during the year before and after the index SH episode. RESULTS: There were 659 older adults who self-harmed. During the year before SH, 33.7% had primary care contacts with a mental disorder, 27.8% had such contacts in specialised care. Use of specialised care increased sharply after the SH, reaching a maximum of 68.9%, but this figure dropped to 19.5% by the end of the year. Use of antidepressants increased from 41% before to 60% after the SH episode. Use of hypnotics was extensive before and after SH (60%). Psychotherapy was rare in both primary and specialised care. CONCLUSION: The use of specialised care for mental disorders and antidepressant prescribing increased after SH. The drop in long-term healthcare visits should be further explored to align primary and specialised healthcare to the needs of older adults who self-harmed. The psychosocial support of older adults with common mental disorders needs to be strengthened.

Time trends in depression prevalence among Swedish 85-year-olds: repeated cross-sectional population-based studies in 1986, 2008, and 2015.

BACKGROUND: Octogenarians of today are better educated, and physically and cognitively healthier, than earlier born cohorts. Less is known about time trends in mental health in this age group. We aimed to study time trends in the prevalence of depression and psychotropic drug use among Swedish 85-year-olds. METHODS: We derived data from interviews with 85-year-olds in 1986-1987 (N = 348), 2008-2010 (N = 433) and 2015-17 (N = 321). Depression diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders. Symptom burden was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Information on psychotropic drug use, sociodemographic, and health-related factors were collected during the interviews. RESULTS: The prevalence of major depression was lower in 2015-2017 (4.7%, p < 0.001) and 2008-2010 (6.9%, p = 0.010) compared to 1986-1987 (12.4%). The prevalence of minor depression was lower in 2015-2017 (8.1%) compared to 2008-2010 (16.2%, p = 0.001) and 1986-1987 (17.8%, p < 0.001). Mean MADRS score decreased from 8.0 in 1986-1987 to 6.5 in 2008-2010, and 5.1 in 2015-2017 (p < 0.001). The reduced prevalence of depression was not explained by changes in sociodemographic and health-related risk factors for depression. While psychoactive drug use was observed in a third of the participants in each cohort, drug type changed over time (increased use of antidepressants and decreased use of anxiolytics and antipsychotics). CONCLUSIONS: The prevalence of depression in octogenarians has declined during the past decades. The decline was not explained by changes in known risk factors for depression. The present study cannot answer whether changed prescription patterns of psychoactive drugs have contributed to the decline.

Healthcare costs of adverse drug reactions and potentially inappropriate prescribing in older adults: a population-based study.

OBJECTIVES: To describe the distribution of costs based on potentially inappropriate prescribing (PIP) and adverse drug reaction (ADR) status in terms of total direct costs and costs caused by ADRs, among older adults. DESIGN: A retrospective cohort study was conducted among older adults, identified from a random sample of the general Swedish population. PIP was identified based on the Screening Tool of Older Persons' Prescriptions (STOPP) criteria and ADRs were identified using the Howard criteria. Causality between PIP and ADRs was evaluated using Hallas' criteria. Prevalence-based direct healthcare costs were calculated for the 3-month study period, including the total cost for healthcare and drugs, and the cost caused by ADRs. SETTING: All care levels, including primary care, other outpatient care and inpatient care. PARTICIPANTS: 813 adults ≥65 years. PRIMARY OUTCOME MEASURES: The prevalence and cost of PIP and ADRs. RESULTS: Total direct cost for persons with PIP was approximately twice the total cost of those without PIP (€1958 (€1428-€2616) vs €881 (€817-€1167), p=0.0020). The costs caused by ADRs was 10 times higher among persons with PIP, compared with those without PIP (€270 (€86-€545) vs €27 (€10-€61), p=0.047). For persons with ADRs caused by PIP, total direct costs were €4646 (€2617-€7931). This group represented 8% of the study population and used 25% of the costs. The main cost driver in all studied patient groups was healthcare contacts. CONCLUSIONS: Older persons with PIP and ADRs had high healthcare costs, particularly when ADRs were caused by PIP. Since these costs appear to be substantial, the potential savings by preventing their occurrence may, to a certain degree, cover the added cost of such activities. Further studies should be undertaken to provide further evidence on the costs of PIP, ADRs and ADRs caused by PIP.

Psychoactive medication use and risk of suicide in long-term care facility residents.

OBJECTIVES: To investigate psychoactive medication use and risk of suicide in long-term care facility (LTCF) residents aged 75 and above. A second aim was to investigate the role of psychiatric and medical conditions in the occurrence of suicide in LTCF residents. METHODS: A Swedish national register-based cohort study of LTFC residents aged ≥75 years between 1 January 2008 and 31 December 2015, and followed until 31 December 2016 (N = 288,305). Fine and Gray regression models were used to analyse associations with suicide. RESULTS: The study identified 110 suicides (15.8 per 100,000 person-years). Half of these occurred during the first year of residence. Overall, 54% of those who died by suicide were on hypnotics and 45% were on antidepressants. Adjusted sub-hazard ratio (aSHR) for suicide was decreased in those who were on antidepressants (aSHR 0.64, 95% confidence interval 0.42-0.97), even after the exclusion of residents who had healthcare contacts for dementia or were on anti-dementia drugs. The aSHR for suicide was more than two-fold higher in those who were on hypnotics (2.20, 1.46-3.31). Suicide risk was particularly elevated in those with an episode of self-harm prior to LTCF admittance (15.78, 10.01-24.87). Specialized care for depression was associated with increased risk, while medical morbidity was not. CONCLUSIONS: A lower risk of suicide in LTCF residents was found in users of antidepressants, while elevated risk was observed in those on hypnotics. Our findings suggest that more can be done to prevent suicide in this setting.

Use of antidepressants and risk of repeat self-harm in older adults 75+ with nonfatal self-harm: A 1-year prospective national study.

PURPOSE: To assess exposure to antidepressants (AD) before and after nonfatal self-harm (SH) in older adults and to examine 1-year rates and risk factors for subsequent SH. METHODS: Longitudinal national register-based retrospective cohort study of Swedish residents aged 75+ (N = 2775) with treatment at hospital or specialist outpatient clinic in connection with SH between January 1, 2006, and December 31, 2013. The cohort was followed for 1 year after the index episode. Exposure to AD was assessed at index and at subsequent SH. Cox regression analysis was used to assess factors associated with 1-year repeat SH. RESULTS: At the index episode, 51% were prevalent AD users; 23% started AD during the following year. Overall 12% of prevalent AD users, 8% of AD nonusers, and 6% of AD new users repeated SH or died by suicide. About two-thirds of these subsequent behaviors occurred within 3 months after the index episode. Men had increased risk of subsequent SH (Hazard ratio [HR] 1.38, 95% CI: 1.09-1.74); older age (>85 years) was associated with a lower risk (HR 0.72, CI 95% 0.55-0.93). Users of AD did not have an increased risk of repeat SH. CONCLUSIONS: Half of older adults who self-harmed were prevalent AD users and a further one fourth started an AD within 1 year after the index SH. Antidepressant use was not associated with increased risk of subsequent SH in this high-risk cohort of older adults.

Passive and active suicidal ideation in Swedish 85-year-olds: Time trends 1986-2015.

BACKGROUND: Older adults have high suicide rates. We investigated potential time trends in the prevalence of passive and active suicidal ideation in 85-year-olds. Further, we examined factors associated with such ideation in this age group. METHODS: Population-based samples of 85-year-olds were interviewed in 1986 (N = 347), 2008 (N = 426) and 2015 (N = 320). Past-month passive/active suicidal ideation was evaluated with the Paykel questions. RESULTS: Reporting any type of passive or active suicidal ideation was less common in 2008 (7.3%, p < 0.001) and 2015 (7.2%, p < 0.001) compared to 1986 (16.4%). The change was driven by decreases in passive ideation. Passive/active suicidal ideation was associated with higher MADRS score (OR: 1.2, 95% CI: 1.1-1.2, p < 0.001), institution residence (OR: 3.9, 95% CI: 1.7-8.9, p = 0.001) and feelings of loneliness (OR: 2.7, 95% CI: 1.4-5.2, p = 0.003). When stratified by sex, it was associated with institution residence (OR: 3.7, 95% CI: 1.4-9.9, p = 0.008) and feelings of loneliness (OR: 3.0, 95% CI: 1.4-6.3, p = 0.005) in women. In men, we observed a tenfold higher risk in those without partners (OR: 9.8, 95% CI: 2.9-33.5, p < 0.001). LIMITATIONS: While differential three-year mortality was not observed in 1986, mortality was higher among non-participants in 2008 and 2015. This might have inflated cohort differences in passive/active suicidal ideation. CONCLUSION: An initial decrease in the prevalence of passive/active suicidal ideation in 85-year-olds was observed but this positive trend did not persist. Results underline that preventive strategies targeting loneliness and focusing on institutional settings are needed, as are interventions for men without partners.

Antidepressant Use and Suicide Rates in Adults Aged 75 and Above: A Swedish Nationwide Cohort Study.

Background: The treatment of depression is a main strategy for suicide prevention in older adults. We aimed to calculate suicide rates by antidepressant prescription patterns in persons aged ≥ 75 years. A further aim was to estimate the contribution of antidepressants to the change in suicide rates over time. Methods: Swedish residents aged ≥ 75 years (N = 1,401,349) were followed between 2007 and 2014 in a national register-based retrospective cohort study. Biannual suicide rates were calculated for those with selective serotonin reuptake inhibitor (SSRI) single use, mirtazapine single use, single use of other antidepressants and use of ≥ 2 antidepressants. The contribution of antidepressants to the change in biannual suicide rates was analyzed by decomposition analysis. Results: There were 1,277 suicides. About one third of these were on an antidepressant during their last 3 months of life. In the total cohort, the average biannual suicide rate in non-users of antidepressants was 13 per 100,000 person-years. The corresponding figure in users of antidepressants was 34 per 100,000 person-years. These rates were 25, 42 and 65 per 100,000 person-years in users of SSRI, mirtazapine and ≥ 2 antidepressants, respectively. In the total cohort, antidepressant users contributed by 26% to the estimated increase of 7 per 100,000 in biannual suicide rates. In men, biannual suicide rates increased by 11 suicides per 100,000 over the study period; antidepressant users contributed by 25% of the change. In women, those on antidepressant therapy accounted for 29% of the estimated increase of 4.4 per 100,000. Conclusion: Only one third of the oldest Swedish population who died by suicide filled an antidepressant prescription in their last 3 months of life. Higher suicide rates were observed in mirtazapine users compared to those on SSRIs. Users of antidepressants accounted for only one quarter of the increase in the suicide rate. The identification and treatment of suicidal older adults remains an area for prevention efforts.

Sociodemographic and gender determinants of late-life suicide in users and non-users of antidepressants.

BACKGROUND: The treatment of depression is a main strategy for suicide prevention in older adults. Our aim was to examine factors related to suicide in older adults (75+) with and without antidepressant (AD) therapy. METHODS: A national population-based register study, including all Swedish residents aged ≥75 years between 2006 and 2014 (N = 1 413 806). A nested case-control design was used to investigate sociodemographic factors associated with suicide among users and non-users of ADs. Risk estimates were calculated in adjusted conditional logistic regression models for the entire cohort and by gender. RESULTS: In all, 1305 individuals died by suicide (70% men). The suicide rate in men who used ADs was over four times higher than women with such treatment. Being unmarried was a risk factor for suicide in men but not in women. Being born outside of Nordic countries was associated with increased suicide risk; a 3-fold risk increase was observed in non-Nordic women without AD treatment. Lower suicide risk was observed in blue-collar women who used ADs, whereas a higher risk was found in blue-collar men who did not. CONCLUSIONS: Our differential findings on factors associated with suicide can offer clues for gender-specific preventive strategies that go beyond the healthcare sphere.

What are the sociodemographic and gender determinants of non-fatal self-harm in older adult users and non-users of antidepressants? A national population-based study.

BACKGROUND: Late-life self-harm (SH) is often linked to depression. However, very few studies have explored the role of other factors and their interaction with depression in the occurrence of late-life SH. The objective of this research was to examine sociodemographic and gender factors associated with non-fatal SH, in older adults with and without antidepressant therapy. METHODS: We used national longitudinal register data from a total cohort of all Swedish residents aged ≥75 years between 2006 and 2014 (N = 1,413,806). Using personal identity numbers, we linked individuals' data from numerous national registers. We identified all those with at least one episode of non-fatal self-harm (regardless of level of intent to die) and matched 50 controls to each case. A nested case-control design was used to investigate sociodemographic factors associated with non-fatal SH in the total cohort and among antidepressant users and non-users. Risk factors were analysed in adjusted conditional logistic regression models for the entire cohort and by gender. RESULTS: In all, 2242 individuals had at least one episode of a non-fatal SH (980 men and 1262 women). Being unmarried was a risk factor for non-fatal SH in men but not in women. Among users of antidepressants, higher non-fatal SH risk was observed in those born outside the Nordic countries (IRR: 1.44; 95% CI: 1.11-1.86), whereas in AD non-users increased risk was seen in those from Nordic countries other than Sweden (IRR: 1.58; 95% CI: 1.08-2.29). Antidepressant users with higher education had an increased risk of non-fatal SH (IRR: 1.34; 95% CI: 1.12-1.61), in both men and women. CONCLUSIONS: Foreign country of birth was associated with increased risk for non-fatal SH in older adults with and without AD therapies. Being married was a protective factor for non-fatal SH in men. The complex association between sociodemographic factors and use of antidepressants in the occurrence of self-harm in older men and women indicates the need for multifaceted tailored preventive strategies including healthcare and social services alike.

Clinical relevance of alerts from a decision support system, PHARAO, for drug safety assessment in the older adults.

BACKGROUND: PHARAO is a decision support system developed to evaluate the risk for a set of either common or serious side-effects resulting from a combination of pharmacodynamic effects from a patient's medications. The objective of this study was to investigate the validity of the risk scores for the common side-effects generated by PHARAO in older patients. METHODS: Side-effects included were sedation, constipation, orthostatic symptoms, anticholinergic and serotonergic effects. The alerts generated by PHARAO were tested in 745 persons ≥65 years old. Dispensed prescriptions retrieved from the Swedish prescribed drug register were used to generate the pharmacological risk scores of patients' medications. Symptoms possibly related to side-effects were extracted from medical records data. RESULTS: The PHARAO system generated 776 alerts, most often for the risk of anticholinergic symptoms. The total specificity estimates of the PHARAO system were 0.95, 0.89 and 0.78 for high, intermediate and low risk alerts, respectively. The corresponding sensitivity estimates were between 0.12 and 0.37. The negative predictive value was 0.90 and the positive predictive value ranged between 0.20-0.25. CONCLUSIONS: The PHARAO system had a high specificity and negative predictive value to detect symptoms possibly associated with the of patients' medications, while the sensitivity and positive predictive value were low. The PHARAO system has the potential to minimise the risk of over-alerts in combination with a drug-drug interaction alert system, but should be used in connection with a medical evaluation of the patient.

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.

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.

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.

Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study.

PURPOSE: Potentially inappropriate prescriptions (PIPs) criteria are widely used for evaluating the quality of prescribing in elderly. However, there is limited evidence on their association with adverse drug reactions (ADRs) across healthcare settings. The study aimed to determine the prevalence of PIPs, defined by the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria, in the Swedish elderly general population and to investigate the association between PIPs and occurrence of ADRs. METHOD: Persons ≥65 years old were identified from a random sample of 5025 adults drawn from the Swedish Total Population Register. A retrospective cohort study was conducted among 813 elderly with healthcare encounters in primary and specialised healthcare settings during a 3-month period in 2008. PIPs were identified from the Swedish Prescribed Drug Register, medical records and health administrative data. ADRs were independently identified by expert reviewers in a stepwise manner using the Howard criteria. Multivariable logistic regression examined the association between PIPs and ADRs. RESULTS: Overall, 374 (46.0 %) persons had ≥1 PIPs and 159 (19.5 %) experienced ≥1 ADRs during the study period. In total, 29.8 % of all ADRs was considered caused by PIPs. Persons prescribed with PIPs had more than twofold increased odds of experiencing ADRs (OR 2.47; 95 % CI 1.65-3.69). PIPs were considered the cause of 60 % of ADRs affecting the vascular system, 50 % of ADRs affecting the nervous system and 62.5 % of ADRs resulting in falls. CONCLUSION: PIPs are common among the Swedish elderly and are associated with increased odds of experiencing ADRs. Thus, interventions to decrease PIPs may contribute to preventing ADRs, in particular ADRs associated with nervous and vascular disorders and falls.

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.

Assessment of a new instrument for detecting preventable adverse drug reactions.

BACKGROUND: Pharmacovigilance centres (PVCs) in the World Health Organization (WHO) Programme for International Drug Monitoring have demonstrated their ability to detect preventable adverse drug reactions (ADRs) in their databases. In this field, there is no gold-standard method for detecting medication errors and evaluating ADR preventability. Therefore, we developed, from existing tools, a preventability assessment method: the 'P Method' (PM). OBJECTIVE: To present the PM and to evaluate its inter-rater reliability. METHODS: The PM includes 20 explicit criteria for assessing ADR preventability. This approach is based on identification of any potentially preventable risk factor that increases the likelihood of ADR occurrence. The outcome of the preventability assessment results in one of three possible scores: 'preventable', 'non-preventable' or 'not assessable'. The PM was tested in a multicentre study involving nine national PVCs. Two experienced reviewers at each participating PVC independently analysed the preventability of 183 ADRs, applying the PM. RESULTS: The overall agreement between all reviewers for assessment of ADR preventability was 'fair', with a kappa value of 0.27 [95 % confidence interval (CI) 0.21-0.40]. The level of agreement between reviewer pairs ranged from 'slight', with a kappa value of 0.12 (95 % CI -0.03 to 0.27), to 'substantial', with a kappa value of 0.69 (95 % CI 0.48-0.89). CONCLUSION: The analysis of the agreements and disagreements between reviewers highlighted where improvements might be made. Given that no standard assessment tool exists in the WHO Programme, the transparency of the assessment process in this method provides a substantial basis for further development and for support in signalling possible preventability.

Refill adherence and self-reported adverse drug reactions and sub-therapeutic effects: a population-based 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 < 0.8). RESULTS: 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. 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.