Use of drugs for hypertension or heart failure and the risk of death in COVID-19: association with loop-diuretics.

PURPOSE: To study the association between the use of drugs for hypertension or heart failure, particularly diuretics, and risk of death in COVID-19. METHODS: We conducted a cohort study, based on record linked individual-based data from national registers, of all Swedish inhabitants 50 years and older (n = 3,909,321) at the start of the first SARS-CoV-2 wave in Sweden. The association between use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), thiazides, loop diuretics, aldosterone antagonists, beta blocking agents and calcium channel blockers at the index date 6 March 2020, and death in COVID-19 during 7 March to 31 July 2020, was analysed using Cox-proportional hazards regression, adjusted for a wide range of possible confounders. RESULTS: Use of loop diuretics was associated with higher risk [adjusted hazard ratio (HR) 1.26; 95% confidence interval (95% CI) 1.17-1.35] and thiazides with reduced risk (0.78; 0.69-0.88) of death in COVID-19. In addition, lower risk was observed for ACEI and higher risk for beta-blocking agents, although both associations were weak. For ARB, aldosterone antagonists and calcium channel blockers no significant associations were found. CONCLUSION: In this nationwide cohort of nearly 4 million persons 50 years and older, the use of loop diuretics was associated with increased risk of death in COVID-19 during the first SARS-CoV-2 wave in Sweden. This contrasted to the decreased risk observed for thiazides. As treatment with loop diuretics is common, particularly in the elderly, the group most affected by severe COVID-19, this finding merit further investigation.

Cardiometabolic multimorbidity and incident dementia: the Swedish twin registry.

AIMS: Cardiometabolic diseases (CMDs), including diabetes, heart disease, and stroke, are established risk factors for dementia, but their combined impact has been investigated only recently. This study aimed to examine the association between mid- and late-life cardiometabolic multimorbidity and dementia and explore the role of genetic background in this association. METHODS AND RESULTS: Within the Swedish Twin Registry, 17 913 dementia-free individuals aged ≥60 were followed for 18 years. CMDs [including age of onset in mid (60) or late (≥60) life] and dementia were ascertained from medical records. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. Cox regression was used to estimate the CMD-dementia association in (i) a classical cohort study design and (ii) a co-twin study design involving 356 monozygotic and dizygotic pairs. By comparing the strength of the association in the two designs, the contribution of genetic background was estimated. At baseline, 3,312 (18.5%) participants had 1 CMD and 839 (4.7%) had ≥2 CMDs. Over the follow-up period, 3,020 participants developed dementia. In the classic cohort design, the hazard ratio (95% confidence interval) of dementia was 1.42 (1.27-1.58) for 1 CMD and 2.10 (1.73-2.57) for ≥2 CMDs. Dementia risk was stronger with mid-life as opposed to late-life CMDs. In the co-twin design, the CMD-dementia association was attenuated among monozygotic [0.99 (0.50-1.98)] but not dizygotic [1.55 (1.15-2.09)] twins, suggesting that the association was in part due to genetic factors common to both CMDs and dementia. CONCLUSION: Cardiometabolic multimorbidity, particularly in mid-life, is associated with an increased risk of dementia. Genetic background may underpin this association.

Few geriatric heart failure patients investigated according to clinical guidelines: a retrospective review of patient records.

BACKGROUND: Research on heart failure (HF) has often focused on younger patients. The aim of this study was to analyze extent of investigation and treatment among older patients prior to referral to inpatient geriatric care for worsening of HF. METHODS: Data on etiology, ejection fraction (EF) by echocardiography (ECHO), level of functioning according to New York Heart Association (NYHA), analysis of N-terminal-pro-brain natriuretic peptide (NT-Pro-BNP), ongoing treatment, adherence to guidelines, and information from previous caregiver were collected from patient records prior to admission from a sample of 134 patients. RESULTS: Few patients had been examined by a cardiologist (14%) during the year prior to referral. EF assessment had been performed in 78% (n = 105). The patients were categorized as having HF with reduced (HFrEF 28%), preserved (HFpEF 53%) or mid-range (HFmrEF 19%) EF. HFpEF patients had older EF assessments (mean 517 days) than those with HFrEF (385 days). In 61% (n = 82) at least one assessment with NT-Pro-BNP had been performed, being older among patients with HFpEF (290 days vs 16 days). There was a strong positive correlation (OR 4.9, p = 0.001) between having recent assessments of EF and NT-Pro-BNP (n = 30, 21%) and being presented with etiology in the referral, adjusted for EF, age, sex, and comorbidity. Among the HFrEF patients, 78% were treated with ACEI/ARB and BB according to ESC guidelines but reaching only half of target doses. In the HFpEF group the corresponding treatment was 46%. Among patients with EF ≤ 35% only 14% were treated with mineral receptor antagonists, ie low adherence to guidelines. CONCLUSIONS: HF care in this population of older individuals showed deficiencies. There was little contact with cardiologists, lack of information of etiology in referrals and low adherence to treatment guidelines. Improving adherence to HF guidelines regarding investigation and treatment for HF in older people is therefore urgent and calls for more collaboration between specialists in cardiology and geriatric medicine.

Socio-demographic differences in polypharmacy and potentially inappropriate drug use among older people with different care needs and in care settings in Stockholm, Sweden.

AIMS: Polypharmacy and potentially inappropriate medications (PIM) are risk factors for negative health outcomes among older people. This study aimed to investigate socio-demographic differences in polypharmacy and PIM use among older people with different care needs in a standard versus an integrated care setting. METHODS: Population-based register data on residents aged ⩾65 years in Stockholm County based on socio-demographic background and social care use in 2014 was linked to prescription drug use in 2015. A logistic regression analysis was used to estimate socio-demographic differences in polypharmacy and PIM, adjusting for education, age group, sex, country of birth, living alone, morbidity and dementia by care setting based on area and by care need (i.e. independent, home help or institutionalised). RESULTS: The prevalence of polypharmacy and PIM was greater among home-help users (60.4% and 11.5% respectively) and institutional residents (74.4% and 11.9%, respectively). However, there were greater socio-demographic differences among the independent, with those with lower education, older age and females having higher odds of polypharmacy and PIM. Morbidity was a driver of polypharmacy (odds ratio (OR)=1.19, confidence interval (CI) 1.16-1.22) among home-help users. Dementia diagnosis was associated with reduced odds of polypharmacy and PIM among those in institutions (OR=0.78, CI 0.71-0.87 and OR 0.52, CI 0.45-0.59, respectively) and of PIM among home-help users (OR=0.53, 95% CI 0.42-0.67). CONCLUSIONS: Polypharmacy and PIM were associated with care needs, most prevalent among home-help users and institutional residents, but socio-demographic differences were most prominent among those living independently, suggesting that municipal care might reduce differences between socio-demographic groups. Care setting had little effect on inappropriate drug use, indicating that national guidelines are followed.

Prevalence and initiation of statin therapy in the oldest old-a longitudinal population-based study.

PURPOSE: To investigate the prevalence and initiation of statins as well as treatment intensity in the oldest old, with younger olds as a reference. METHODS: A population-based cohort was used, including record-linked data from the Total Population Register, the Swedish Prescribed Drug Register, and the Swedish Patient Register. In each year over the study period (2009-2015), statin use was described in individuals 85 years or older and 65-84 years of age, and initiation rates were calculated among individuals with no statin treatment during a preceding 3-year period. RESULTS: A total of 1,764,836 individuals ≥ 65 years in 2009, increasing to 2,022,764 in 2015, were included in the analyses. In individuals 85 years or older, the prevalence of statin therapy increased from 11% in 2009 to 16% in 2015, the corresponding initiation rates being 1.3% and 1.7%, respectively. Corresponding prevalence and incidence figures in 65-84-year-olds were 23 to 25% and 3.0 to 3.3%, respectively. Overall, the proportion of individuals initiating statin with high-intensity treatment (atorvastatin ≥ 40 mg or rosuvastatin ≥ 20 mg) in the oldest old increased from 1 to 36% during the study period, and a similar increase was seen in the younger age group. Over the study years, the presence of an established indication for statin treatment varied between 70 and 76% in the oldest old and between 30 and 39% in the younger olds. CONCLUSION: Prevalence and initiation of statin therapy are increasing among the oldest old, despite the fact that randomized controlled trials focusing on this age group are lacking and safety signals are difficult to detect.

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.

Validating a model for medication-related dental outcomes in older people.

OBJECTIVES: To externally validate a model for medication-related dental outcomes in (a) a general older population with dementia and (b) a matched population without dementia. SUBJECTS AND METHODS: This validation study used population-based data from seven Swedish national registers (2008-2017). Individuals aged 60+ with dementia were matched to those without dementia on age, gender, and county of residence at the date of diagnosis (index date). The exposure was continuous use of xerogenic medications during the 3-year period before index date. The primary outcome was the number of tooth extraction and restorative procedures within 3 years after index date. RESULTS: A total of 334,220 individuals were included in the final sample. In the dementia cohort, the use of urological drugs (incidence rate ratio [IRR] 1.08, 95% CI 1.03-1.13), respiratory medicines (IRR 1.10, 95% CI 1.04-1.17), and proton-pump inhibitors (IRR 1.09, 95% CI 1.05-1.13) was associated with the primary outcome. In the non-dementia cohort, respiratory medicines (IRR 1.03, CI 1.00-1.05), proton-pump inhibitors (IRR 1.06, CI 1.04-1.08), opioids (IRR 1.05, CI 1.03-1.07), and antidepressants (IRR 1.06, CI 1.04-1.08) were associated with the primary outcome. CONCLUSIONS: Although there were differences in prescription patterns, the model performed similarly in both those with and without dementia.

Do Acetylcholinesterase Inhibitors Prevent or Delay Psychotropic Prescribing in People With Dementia? Analyses of the Swedish Dementia Registry.

OBJECTIVES: To investigate whether acetylcholinesterase inhibitor (AChEI) use prevents or delays subsequent initiation of psychotropic medications in people with Alzheimer's disease (AD) and Lewy body dementia (LBD). METHODS: Cohort study of 17,763 people with AD and LBD, without prior psychotropic use at time of dementia diagnosis, registered in the Swedish Dementia Registry from 2007 to 2015. Propensity score-matched regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent AChEI use and risk of psychotropic initiation. RESULTS: Compared with matched comparators, AChEI users had a lower risk of antipsychotic (HR: 0.85, 95%CI: 0.75-0.95) and anxiolytic (HR: 0.76, 95%CI: 0.72-0.80) initiation. In subanalyses, this association remained significant at higher AChEI doses, and in AD but not LBD. There were no associations between AChEI use and initiation of antidepressants or hypnotics. CONCLUSION: AChEI use may be associated with lower risk of antipsychotic and anxiolytic initiation in AD, particularly at higher doses. Further investigation into aceytylcholinesterase inhibitors in behavioral and psychological symptoms of dementia management in LBD is warranted.

Use of potentially inappropriate medication and polypharmacy in older adults: a repeated cross-sectional study.

BACKGROUND: With age, the number of chronic conditions increases along with the use of medications. For several years, polypharmacy has been found to be on the increase in western societies. Polypharmacy is associated with an increased risk of adverse drug events (ADE). Medications called potentially inappropriate medications (PIM) have also been found to increase the risk of ADEs in an older population. In this study, which we conducted during a national information campaign to reduce PIM, we analysed the prevalence of PIM in an older adult population and in different strata of the variables age, gender, number of chronic conditions and polypharmacy and how that prevalence changed over time. METHODS: This is a registry-based repeated cross-sectional study including two cohorts. Individuals aged 75 or older listed at a primary care centre in Blekinge on the 31st March 2011 (cohort 1, 15,361 individuals) or on the 31st December 2013 (cohort 2, 15,945 individuals) were included in the respective cohorts. Using a chi2 test, the two cohorts were compared on the variables age, gender, number of chronic conditions and polypharmacy. Use of five or more medications at the same time was the definition for polypharmacy. RESULTS: Use of PIM decreased from 10.60 to 7.04% (p-value < 0.001) between 2011 and 2013, while prevalence of five to seven chronic conditions increased from 20.55 to 23.66% (p-value < 0.001). Use of PIM decreased in all strata of the variables age, gender number of chronic conditions and polypharmacy. Except for age 80-84 and males, where it increased, prevalence of polypharmacy was stable in all strata of the variables. CONCLUSIONS: Use of potentially inappropriate medications had decreased in all variables between 2011 and 2013; this shows the possibility to reduce PIM with a focused effort. Polypharmacy does not increase significantly compared to the rest of the population.

Extent and quality of drug use in community-dwelling people aged ≥75 years: A Swedish nationwide register-based study.

Aims: It is important for district nurses and other health professionals in primary care to gain more insight into the patterns and quality of drug use in community-dwelling older people, particularly in 75-year-olds, who have been the target of preventive home visits. This study aimed to examine the extent and quality of drug use in community-dwelling older people and to compare drug use in 75-year-olds with that of older age groups. Methods: Data from 2013 on people aged ≥75 years were obtained from the Swedish Prescribed Drug Register. Those living in the community (671,940/739,734 people aged ≥75 years) were included in the study. Quality of drug use was assessed by using a selection of indicators issued by the Swedish National Board of Health and Welfare. Results: The prevalence of polypharmacy and of many drug groups increased with age, as did several indicators of inappropriate drug use. However some drug groups, as well as inappropriate drugs, were prevalent in 75-year-olds and declined with age, for example diabetes drugs, drugs with major anticholinergic effects and nonsteroidal anti-inflammatory drugs. Conclusions: The substantial use of some drugs as early as 75 years of age confirms the value of including drug use as a topic in preventive home visits to 75-year-olds. The finding that polypharmacy and many measures of inappropriate drug use increased with age in community-dwelling older people also underscores the importance of district nurses' role in continuing to promote safe medication management at higher ages.

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.

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.

Preventive drugs in the last year of life of older adults with cancer: Is there room for deprescribing?

BACKGROUND: The continuation of preventive drugs among older patients with advanced cancer has come under scrutiny because these drugs are unlikely to achieve their clinical benefit during the patients' remaining lifespan. METHODS: A nationwide cohort study of older adults (those aged ≥65 years) with solid tumors who died between 2007 and 2013 was performed in Sweden, using routinely collected data with record linkage. The authors calculated the monthly use and cost of preventive drugs throughout the last year before the patients' death. RESULTS: Among 151,201 older persons who died with cancer (mean age, 81.3 years [standard deviation, 8.1 years]), the average number of drugs increased from 6.9 to 10.1 over the course of the last year before death. Preventive drugs frequently were continued until the final month of life, including antihypertensives, platelet aggregation inhibitors, anticoagulants, statins, and oral antidiabetics. Median drug costs amounted to $1482 (interquartile range [IQR], $700-$2896]) per person, including $213 (IQR, $77-$490) for preventive therapies. Compared with older adults who died with lung cancer (median drug cost, $205; IQR, $61-$523), costs for preventive drugs were higher among older adults who died with pancreatic cancer (adjusted median difference, $13; 95% confidence interval, $5-$22) or gynecological cancers (adjusted median difference, $27; 95% confidence interval, $18-$36). There was no decrease noted with regard to the cost of preventive drugs throughout the last year of life. CONCLUSIONS: Preventive drugs commonly are prescribed during the last year of life among older adults with cancer, and often are continued until the final weeks before death. Adequate deprescribing strategies are warranted to reduce the burden of drugs with limited clinical benefit near the end of life.

Use of statins in the elderly according to age and indication-a cross-sectional population-based register study.

PURPOSE: To investigate statin use in the elderly by age (≥ 80 vs. 65-79 years) in relation to established indications. METHODS: A population-based cohort, including data from four registers, encompassing inhabitants in Region Västra Götaland, Sweden, was used. Statin users were defined as those filling statin prescriptions ≥ 75% of the year 2010. Primary care and hospital diagnoses in 2005-2010 regarding ischemic heart disease, stroke, transient ischemic attacks, and diabetes were considered established indications. RESULTS: A total of 278,205 individuals were analyzed. In individuals aged ≥ 80 and 65-79 years (n = 81,885 and n = 196,320, respectively), 17% (95% confidence interval 17%; 18%) and 23% (23%; 23%) respectively, were statin users. Among the statin users, 74% (73%; 74%) of those aged ≥ 80 and 60% (59%; 60%) of those aged 65-79 years had ≥ 1 established indication. Conversely, of those with ≥ 1 established indication, 30% (30%; 31%) and 53% (52%; 53%) were on statins in the respective age groups. Logistic regression revealed that age, nursing home residence, and multi-dose drug dispensing were the most prominent negative predictors for statin use; adjusted odds ratios (95% confidence interval): 0.45 (0.44; 0.46), 0.39 (0.36; 0.42), and 0.47 (0.44; 0.49), respectively. CONCLUSIONS: In the oldest old (≥ 80 years), statin users were fewer and had more often an established indication, suggesting that physicians extrapolate scientific evidence for beneficial effects in younger age groups to the oldest, but require a more solid ground for treatment. As the oldest old, nursing home residents, and those with multi-dose drug-dispensing were statin users to a lesser extent, physicians may often refrain from treatment in those with lower life expectancy, either due to age or to severely reduced health status. In both age groups, our results however also indicate some over- as well as undertreatment.

How many older adults receive drugs of questionable clinical benefit near the end of life? A cohort study.

BACKGROUND: The high burden of disease-oriented drugs among older adults with limited life expectancy raises important questions about the potential futility of care. AIM: To describe the use of drugs of questionable clinical benefit during the last 3 months of life of older adults who died from life-limiting conditions. DESIGN: Longitudinal, retrospective cohort study of decedents. Death certificate data were linked to administrative and healthcare registries with national coverage in Sweden. SETTING: Older adults (≥75 years) who died from conditions potentially amenable to palliative care between 1 January and 31 December 2015 in Sweden. We identified drugs of questionable clinical benefit from a set of consensus-based criteria. RESULTS: A total of 58,415 decedents were included (mean age, 87.0 years). During their last 3 months of life, they received on average 8.9 different drugs. Overall, 32.0% of older adults continued and 14.0% initiated at least one drug of questionable clinical benefit (e.g. statins, calcium supplements, vitamin D, bisphosphonates, antidementia drugs). These proportions were highest among younger individuals (i.e. aged 75-84 years), among people who died from organ failure and among those with a large number of coexisting chronic conditions. Excluding people who died from acute and potentially unpredictable fatal events had little influence on the results. CONCLUSION: A substantial share of older persons with life-limiting diseases receive drugs of questionable clinical benefit during their last months of life. Adequate training, guidance and resources are needed to rationalize and deprescribe drug treatments for older adults near the end of life.

Adequate, questionable, and inadequate drug prescribing for older adults at the end of life: a European expert consensus.

BACKGROUND: Clinical guidance is needed to initiate, continue, and discontinue drug treatments near the end of life. AIM: To identify drugs and drug classes most often adequate, questionable, or inadequate for older people at the end of life. DESIGN: Delphi consensus survey. SETTING/PARTICIPANTS: Forty European experts in geriatrics, clinical pharmacology, and palliative medicine from 10 different countries. Panelists were asked to characterize drug classes as "often adequate," "questionable," or "often inadequate" for use in older adults aged 75 years or older with an estimated life expectancy of ≤ 3 months. We distinguished the continuation of a drug class that was previously prescribed from the initiation of a new drug. Consensus was considered achieved for a given drug or drug class if the level of agreement was ≥ 75%. RESULTS: The expert panel reached consensus on a set of 14 drug classes deemed as "often adequate," 28 drug classes deemed "questionable," and 10 drug classes deemed "often inadequate" for continuation during the last 3 months of life. Regarding the initiation of new drug treatments, the panel reached consensus on a set of 10 drug classes deemed "often adequate," 23 drug classes deemed "questionable," and 23 drug classes deemed "often inadequate". Consensus remained unachieved for some very commonly prescribed drug treatments (e.g., proton-pump inhibitors, furosemide, haloperidol, olanzapine, zopiclone, and selective serotonin reuptake inhibitors). CONCLUSION: In the absence of high-quality evidence from randomized clinical trials, these consensus-based criteria provide guidance to rationalize drug prescribing for older adults near the end of life.

Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia.

INTRODUCTION: The aim of this study was to investigate the association between acetylcholinesterase inhibitor (AChEI) use and risk of ischemic stroke and death in people with dementia. METHODS: A cohort study of 44,288 people with dementia registered in the Swedish Dementia Registry from 2007 to 2014. Propensity score-matched competing risk regression models were used to compute hazard ratios and 95% confidence intervals for the association between time-dependent AChEI use and risk of stroke and death. RESULTS: Compared with matched controls, AChEI users had a lower risk of stroke (hazard ratio: 0.85, 95% confidence interval: 0.75-0.95) and all-cause death (hazard ratio: 0.76, 95% confidence interval: 0.72-0.80). After considering competing risk of death, high doses (≥1.33 defined daily doses) of AChEI remained significantly associated with reduced stroke risk. DISCUSSION: The use of AChEIs in people with dementia may be associated with reduced risk of ischemic stroke and death. These results call for a closer examination of the cardiovascular effects of AChEIs.

Psychotropic drugs and the risk of fall injuries, hospitalisations and mortality among older adults.

OBJECTIVE: To investigate whether psychotropics are associated with an increased risk of fall injuries, hospitalizations, and mortality in a large general population of older adults. METHODS: We performed a nationwide matched (age, sex, and case event day) case-control study between 1 January and 31 December 2011 based on several Swedish registers (n = 1,288,875 persons aged ≥65 years). We used multivariate conditional logistic regression adjusted for education, number of inpatient days, Charlson co-morbidity index, dementia and number of other drugs. RESULTS: Antidepressants were the psychotropic most strongly related to fall injuries (ORadjusted : 1.42; 95% CI: 1.38-1.45) and antipsychotics to hospitalizations (ORadjusted : 1.22; 95% CI: 1.19-1.24) and death (ORadjusted : 2.10; 95% CI: 2.02-2.17). Number of psychotropics was associated with increased the risk of fall injuries, (4 psychotropics vs 0: ORadjusted : 1.53; 95% CI: 1.39-1.68), hospitalization (4 psychotropics vs 0: ORadjusted : 1.27; 95% CI: 1.22-1.33) and death (4 psychotropics vs 0: ORadjusted : 2.50; 95% CI: 2.33-2.69) in a dose-response manner. Among persons with dementia (n = 58,984), a dose-response relationship was found between number of psychotropics and mortality risk (4 psychotropics vs 0: ORadjusted : 1.99; 95% CI: 1.76-2.25). CONCLUSIONS: Our findings support a cautious prescribing of multiple psychotropic drugs to older patients. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons, Ltd.

Cognitive performance in unipolar old-age depression: a longitudinal study.

OBJECTIVE: Previous studies on cognitive deficits in acute and remitted states of old-age depression have shown mixed findings. The episodic nature of depression makes repeated assessment of cognitive performance important in order to address reversibility and stability of cognitive deficits. METHODS: Dementia-free older participants (≥60 years) from the population-based Swedish National Study on Aging and Care in Kungsholmen who completed neuropsychological testing at baseline (T1) and follow-up (T2) formed the basis of the study sample. Participants were grouped according to depression status at T1 and T2: depressed-remitted (n = 32), remitted-depressed (n = 45), and nondepressed-depressed (n = 29). These groups were compared with a group of randomly selected and matched (age, gender, education, and follow-up time) healthy controls (n = 106) over a period of maximum 6 years. RESULTS: Mixed ANCOVAs, controlling for age and gender, revealed depression-related deficits for processing speed, attention, executive function, and category fluency. In remitted states, only processing speed and attention were affected. However, these deficits were attenuated after exclusion of persons using benzodiazepine medications. A general pattern of cognitive decline was observed across all groups for processing speed, executive function, category fluency, and episodic and semantic memory; persons transitioning from a nondepressed to depressed state tended to show exacerbated cognitive decline. CONCLUSIONS: The results support the notion that cognitive deficits in depression may be more transient than stable. Consequently, cognitive deficits in depression might be regarded as potential treatment targets rather than stable vulnerabilities. As such, repeated assessment of cognitive functioning may provide an additional marker of treatment response.

Long-term use of proton pump inhibitors and prevalence of disease- and drug-related reasons for gastroprotection-a cross-sectional population-based study.

PURPOSE: To analyse the prevalence of long-term use of proton pump inhibitors (PPI) with respect to underlying diseases and drugs, and to find predictors for such treatment when an evident rationale for the PPI treatment is lacking. METHODS: The study cohort consisted of individuals, ≥65 years in 2010, residing in the Region Västra Götaland during 2005-2010. For individuals with and without long-term use of PPI in 2010, we investigated the prevalence of an underlying diagnosis, that is, an acid-related disease during the five preceding years, as well as concomitant long-term use of antiplatelet agents or cyclooxygenase inhibitors. RESULTS: In all, 278 205 individuals (median age: 74 years; 55% female; median 3 drugs per person; 5% nursing home residents, 11% with multi-dose drug dispensing) were included in the analyses, 32 421 (12%) of whom were on long-term treatment with PPI in 2010. For 12 253 individuals (38%) with such treatment, no underlying rationale was found. In individuals without a disease- or a drug-related reason for PPI use, nursing home residence, number of drugs, female sex, but not multi-dose drug dispensing, were associated with long-term use of PPI; adjusted odds ratios (95% confidence interval): 1.63 (1.49; 1.78), 1.27 (1.26; 1.28), 1.24 (1.19; 1.29), and 0.94 (0.88; 1.01), respectively. CONCLUSIONS: Long-term use of PPI occurs in one out of nine individuals in the older population. For four out of ten of these, no reason for PPI use can be identified. Nursing home residence, female sex, and greater number of drugs predict non-rational long-term use of PPI. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.