Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study.

BACKGROUND: Sleep disturbance is common in dementia and often treated with Z-drugs (zopiclone, zaleplon, and zolpidem). While some observational studies suggest that Z-drugs are associated with adverse events such as falls and fracture risks in older people, this has not been studied in dementia. METHODS: We used data from 27,090 patients diagnosed with dementia between January 2000 and March 2016 from the Clinical Practice Research Datalink linked to Hospital Episodes Statistics data in England. We compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines. We defined higher dose Z-drugs and benzodiazepines as prescriptions equivalent to ≥ 7.5 mg zopiclone or > 5 mg diazepam daily. Cox regression was used to estimate hazard ratios (HRs) for incident fracture, hip fracture, fall, mortality, acute bacterial infection, ischaemic stroke/transient ischaemic attack, and venous thromboembolism over a 2-year follow-up, adjusted for demographic- and health-related covariates. RESULTS: The mean (SD) age of patients was 83 (7.7) years, and 16,802 (62%) were women. Of 3532 patients prescribed Z-drugs, 584 (17%) were initiated at higher doses. For patients prescribed higher dose Z-drugs relative to non-users with sleep disturbance, the HRs (95% confidence interval) for fractures, hip fractures, falls, and ischaemic stroke were 1.67 (1.13-2.46), 1.96 (1.16-3.31), 1.33 (1.06-1.66), and 1.88 (1.14-3.10), respectively. We observed similar associations when compared to non-sedative-users with proximal GP consultation. Minimal or inconsistent excess risks were observed at ≤ 3.75 mg zopiclone or equivalent daily, and for mortality, infection, and venous thromboembolism. We observed no differences in adverse events for Z-drugs compared to benzodiazepines, except lower mortality rates with Z-drugs (HR [95% confidence interval] of 0.73 [0.64-0.83]). CONCLUSIONS: Higher dose Z-drug use in dementia is associated with increased fracture and stroke risks, similar or greater to that for higher dose benzodiazepines. Higher dose Z-drugs should be avoided, if possible, in people living with dementia, and non-pharmacological alternatives preferentially considered. Prescriptions for higher dose Z-drugs in dementia should be regularly reviewed. TRIAL REGISTRATION: ENCePP e-register of studies, EUPAS18006.

Changing prevalence and treatment of depression among older people over two decades.

BACKGROUND: Depression is a leading cause of disability, with older people particularly susceptible to poor outcomes. AIMS: To investigate whether the prevalence of depression and antidepressant use have changed across two decades in older people. METHOD: The Cognitive Function and Ageing Studies (CFAS I and CFAS II) are two English population-based cohort studies of older people aged ≥65 years, with baseline measurements for each cohort conducted two decades apart (between 1990 and 1993 and between 2008 and 2011). Depression was assessed by the Geriatric Mental State examination and diagnosed with the Automated Geriatric Examination for Computer-Assisted Taxonomy algorithm. RESULTS: In CFAS I, 7635 people aged ≥65 years were interviewed, of whom 1457 were diagnostically assessed. In CFAS II, 7762 people were interviewed and diagnostically assessed. Age-standardised depression prevalence in CFAS II was 6.8% (95% CI 6.3-7.5%), representing a non-significant decline from CFAS I (risk ratio 0.82, 95% CI 0.64-1.07, P = 0.14). At the time of CFAS II, 10.7% of the population (95% CI 10.0-11.5%) were taking antidepressant medication, more than twice that of CFAS I (risk ratio 2.79, 95% CI 1.96-3.97, P < 0.0001). Among care home residents, depression prevalence was unchanged, but the use of antidepressants increased from 7.4% (95% CI 3.8-13.8%) to 29.2% (95% CI 22.6-36.7%). CONCLUSIONS: A substantial increase in the proportion of the population reporting taking antidepressant medication is seen across two decades for people aged ≥65 years. However there was no evidence for a change in age-specific prevalence of depression.

Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis.

BACKGROUND: the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear. METHODS: we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I. RESULTS: twenty-six studies (including 621,548 participants) met our inclusion criteria. 'Any' anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09-1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17-1.29, I2 = 2%; and OR 1.50, 95% CI 1.22-1.85, I2 = 90%). 'Any' anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09-0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97-1.59, I2 = 0%). CONCLUSIONS: anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.

Increasing prevalence of anticholinergic medication use in older people in England over 20 years: cognitive function and ageing study I and II.

BACKGROUND: Anticholinergic medication use is linked with increased cognitive decline, dementia, falls and mortality, and their use should be limited in older people. Here we estimate the prevalence of anticholinergic use in England's older population in 1991 and 2011, and describe changes in use by participant's age, sex, cognition and disability. METHODS: We compared data from participants aged 65+ years from the Cognitive Function and Ageing Studies (CFAS I and II), collected during 1990-1993 (N = 7635) and 2008-2011 (N = 7762). We estimated the prevalence of potent anticholinergic use (Anticholinergic Cognitive Burden [ACB] score = 3) and average anticholinergic burden (sum of ACB scores), using inverse probability weights standardised to the 2011 UK population. These were stratified by age, sex, Mini-Mental State Examination score, and activities of daily living (ADL) or instrumental ADL (IADL) disability. RESULTS: Prevalence of potent anticholinergic use increased from 5.7% (95% Confidence Interval [CI] 5.2-6.3%) of the older population in 1990-93 to 9.9% (9.3-10.7%) in 2008-11, adjusted odds ratio of 1.90 (95% CI 1.67-2.16). People with clinically significant cognitive impairment (MMSE [Mini Mental State Examination] 21 or less) were the heaviest users of potent anticholinergics in CFAS II (16.5% [95% CI 12.0-22.3%]). Large increases in the prevalence of the use medication with 'any' anticholinergic activity were seen in older people with clinically significant cognitive impairment (53.3% in CFAS I to 71.5% in CFAS II). CONCLUSIONS: Use of potent anticholinergic medications nearly doubled in England's older population over 20 years with some of the greatest increases amongst those particularly vulnerable to anticholinergic side-effects.

Dementia Friendly Communities in England: A scoping study.

OBJECTIVES: To describe the characteristics of Dementia Friendly Communities (DFCs) across England in order to inform a national evaluation of their impact on the lives of those affected by dementia. METHODS: DFCs in England were identified through online searches and Alzheimer's Society records. A subsample (n = 100) were purposively selected for in-depth study based on online searches and, where necessary, follow-up telephone calls. Data collection and analysis were guided by a pilot evaluation tool for DFCs that addressed how DFCs are organised and resourced and how their impact is assessed. The evidence was predominantly qualitative, in addition to some descriptive quantitative information. RESULTS: Of 284 DFCs identified, 251 were defined by geographical location, while 33 were communities of interest. Among 100 sampled DFCs, 89 had been set up or started activities following policy endorsement of DFCs in 2012. In the resourcing of DFCs, statutory agencies and charities played an important role. Among DFC activities, awareness raising was cited most commonly. There was some evidence of involvement of people living with dementia in organisational and operational aspects of DFCs. Approaches to evaluation varied, with little evidence of findings having effected change. CONCLUSIONS: DFCs are characterised by variation in type, resourcing, and activities. England has policy endorsement and a recognition system for DFCs. These can be important catalysts for initiation and growth. A systematic approach to evaluation is lacking. This would enable DFCs to be consistent in how they demonstrate progress and how they enable people living with dementia to live well.

The place for dementia-friendly communities in England and its relationship with epidemiological need.

OBJECTIVES: The dementia-friendly community (DFC) initiative was set up to enable people living with dementia to remain active, engaged, and valued members of society. Dementia prevalence varies nationally and is strongly associated with the age and sex distribution of the population and level of social deprivation. As part of a wider project to evaluate DFCs, we examined whether there is a relationship between provision of DFCs and epidemiological need. METHODS: Dementia-friendly communities were identified through the formal recognition process of DFC status by the Alzheimer's Society and mapped against areas defined by English Clinical Commissioning Groups. We tested whether provision of a DFC was associated with: (1) dementia prevalence, (2) number of known cases, and (3) known plus estimated number of unknown cases. RESULTS: Of the 209 English Clinical Commissioning Group areas, 115 had at least one DFC. The presence of a DFC was significantly associated with number of known dementia cases (mean difference = 577; 95% CI, 249 to 905; P = 0.001) and unknown dementia cases (mean difference = 881; 95% CI, 349 to 1413; P = 0.001) but not prevalence (mean difference = 0.03; 95% CI, -0.09 to 0.16; P = 0.61). This remains true when controlling for potential confounding variables. CONCLUSIONS: Our findings suggest that DFC provision is consistent with epidemiological-based need. Dementia-friendly communities are located in areas where they can have the greatest impact. A retrospective understanding of how DFCs have developed in England can inform how equivalent international initiatives might be designed and implemented.

Comparing the predictive ability of the Revised Minimum Dataset Mortality Risk Index (MMRI-R) with nurses' predictions of mortality among frail older people: a cohort study.

OBJECTIVES: to establish the accuracy of community nurses' predictions of mortality among older people with multiple long-term conditions, to compare these with a mortality rating index and to assess the incremental value of nurses' predictions to the prognostic tool. DESIGN: a prospective cohort study using questionnaires to gather clinical information about patients case managed by community nurses. Nurses estimated likelihood of mortality for each patient on a 5-point rating scale. The dataset was randomly split into derivation and validation cohorts. Cox proportional hazard models were used to estimate risk equations for the Revised Minimum Dataset Mortality Risk Index (MMRI-R) and nurses' predictions of mortality individually and combined. Measures of discrimination and calibration were calculated and compared within the validation cohort. SETTING: two NHS Trusts in England providing case-management services by nurses for frail older people with multiple long-term conditions. PARTICIPANTS: 867 patients on the caseload of 35 case-management nurses. 433 and 434 patients were assigned to the derivation and validation cohorts, respectively. Patients were followed up for 12 months. RESULTS: 249 patients died (28.72%). In the validation cohort, MMRI-R demonstrated good discrimination (Harrell's c-index 0.71) and nurses' predictions similar discrimination (Harrell's c-index 0.70). There was no evidence of superiority in performance of either method individually (P = 0.83) but the MMRI-R and nurses' predictions together were superior to nurses' predictions alone (P = 0.01). CONCLUSIONS: patient mortality is associated with higher MMRI-R scores and nurses' predictions of 12-month mortality. The MMRI-R enhanced nurses' predictions and may improve nurses' confidence in initiating anticipatory care interventions.

Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study.

BACKGROUND: Studies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk. We tested this hypothesis using data from a UK cohort study. METHODS: We used data from the baseline (Y0), 2-year (Y2) and 10-year (Y10) waves of the Medical Research Council Cognitive Function and Ageing Study. Participants without dementia at Y2 were included (n = 8216). Use of benzodiazepines (including nonbenzodiazepine Z-drugs), anticholinergics with score 3 (ACB3) and anticholinergics with score 1 or 2 (ACB12) according to the Anticholinergic Cognitive Burden scale were coded as ever use (use at Y0 or Y2), recurrent use (Y0 and Y2), new use (Y2, but not Y0) or discontinued use (Y0, but not Y2). The outcome was incident dementia by Y10. Incidence rate ratios (IRR) were estimated using Poisson regression adjusted for potential confounders. Pre-planned subgroup analyses were conducted by age, sex and Y2 Mini-Mental State Examination (MMSE) score. RESULTS: Dementia incidence was 9.3% (N = 220 cases) between Y2 and Y10. The adjusted IRRs (95%CI) of developing dementia were 1.06 (0.72, 1.60), 1.28 (0.82, 2.00) and 0.89 (0.68, 1.17) for benzodiazepines, ACB3 and ACB12 ever-users compared with non-users. For recurrent users the respective IRRs were 1.30 (0.79, 2.14), 1.68 (1.00, 2.82) and 0.95 (0.71, 1.28). ACB3 ever-use was associated with dementia among those with Y2 MMSE> 25 (IRR = 2.28 [1.32-3.92]), but not if Y2 MMSE≤25 (IRR = 0.94 [0.51-1.73]). CONCLUSIONS: Neither benzodiazepines nor ACB12 medications were associated with dementia. Recurrent use of ACB3 anticholinergics was associated with dementia, particularly in those with good baseline cognitive function. The long-term prescribing of anticholinergics should be avoided in older people.

Antidepressant use and risk of adverse outcomes in people aged 20-64 years: cohort study using a primary care database.

BACKGROUND: Antidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20-64 years diagnosed with depression. METHODS: We conducted a cohort study in 238,963 patients aged 20-64 years registered with practices across the UK contributing to the QResearch primary care database. Only patients with a first diagnosis of depression were included. Outcomes were falls, fractures, upper gastrointestinal bleed, road traffic accidents, adverse drug reactions and all-cause mortality recorded during follow-up. Cox proportional hazards models were used to estimate hazard ratios associated with antidepressant exposure adjusting for potential confounding variables. RESULTS: During 5 years of follow-up, 4651 patients had experienced a fall, 4796 had fractures, 1066 had upper gastrointestinal bleeds, 3690 had road traffic accidents, 1058 had experienced adverse drug reactions, and 3181 patients died. Fracture rates were significantly increased for selective serotonin reuptake inhibitors (adjusted hazard ratio 1.30, 95% CI 1.21-1.39) and other antidepressants (1.28, 1.11-1.48) compared with periods when antidepressants were not used. All antidepressant drug classes were associated with significantly increased rates of falls. Rates of adverse drug reactions were significantly higher for tricyclic and related antidepressants (1.54, 1.25-1.88) and other antidepressants (1.61, 1.22-2.12) compared with selective serotonin reuptake inhibitors. Trazodone was associated with a significantly increased risk of upper gastrointestinal bleed. All-cause mortality rates were significantly higher for tricyclic and related antidepressants (1.39, 1.22-1.59) and other antidepressants (1.26, 1.08-1.47) than for selective serotonin reuptake inhibitors over 5 years but not 1 year, and were significantly reduced after 85 or more days of treatment with selective serotonin reuptake inhibitors. Mirtazapine was associated with significantly increased mortality rates over 1 and 5 years of follow-up. CONCLUSIONS: Selective serotonin reuptake inhibitors had higher rates of fracture than tricyclic and related antidepressants but lower mortality and adverse drug reaction rates than the other antidepressant drug classes. The association between mirtazapine and increased mortality merits further investigation. These risks should be carefully considered and balanced against potential benefits for individual patients when the decision to prescribe an antidepressant is made.

A comparison of health expectancies over two decades in England: results of the Cognitive Function and Ageing Study I and II.

BACKGROUND: Whether rises in life expectancy are increases in good-quality years is of profound importance worldwide, with population ageing. We investigate how various health expectancies have changed in England between 1991 and 2011, with identical study design and methods in each decade. METHODS: Baseline data from the Cognitive Function and Ageing Studies in populations aged 65 years or older in three geographically defined centres in England (Cambridgeshire, Newcastle, and Nottingham) provided prevalence estimates for three health measures: self-perceived health (defined as excellent-good, fair, or poor); cognitive impairment (defined as moderate-severe, mild, or none, as assessed by Mini-Mental State Examination score); and disability in activities of daily living (defined as none, mild, or moderate-severe). Health expectancies for the three regions combined were calculated by the Sullivan method, which applies the age-specific and sex-specific prevalence of the health measure to a standard life table for the same period. FINDINGS: Between 1991 and 2011, gains in life expectancy at age 65 years (4·5 years for men and 3·6 years for women) were accompanied by equivalent gains in years free of any cognitive impairment (4·2 years [95% CI 4·2-4·3] for men and 4·4 years [4·3-4·5] for women) and decreased years with mild or moderate-severe cognitive impairment. Gains were also identified in years in excellent or good self-perceived health (3·8 years [95% CI 3·5-4·1] for men and 3·1 years [2·7-3·4] for women). Gains in disability-free years were much smaller than those in excellent-good self-perceived health or those free from cognitive impairment, especially for women (0·5 years [0·2-0·9] compared with 2·6 years [2·3-2·9] for men), mostly because of increased mild disability. INTERPRETATION: During the past two decades in England, we report an absolute compression (ie, reduction) of cognitive impairment, a relative compression of self-perceived health (ie, proportion of life spent healthy is increasing), and dynamic equilibrium of disability (ie, less severe disability is increasing but more severe disability is not). Reasons for these patterns are unknown but might include increasing obesity during previous decades. Our findings have wide-ranging implications for health services and for extension of working life. FUNDING: UK Medical Research Council.

Student nurses' experience of and attitudes towards care of the dying: A cross-sectional study.

BACKGROUND: Nurses are the professional group with the greatest contact with those at the end of life and their attitudes towards the care of the dying is important in care delivery. AIM: We investigated the relationship between student nurses' attitudes towards care of the dying and (1) demographics, (2) course factors and (3) experience of caring for people who are dying. DESIGN: A cross-sectional survey using the Frommelt's Attitude Toward Care of the Dying scale to measure respondents' attitudes. SETTING/PARTICIPANTS: Nursing students studying at a university in the United Kingdom. RESULTS: A total of 567 completed questionnaires were returned, with 91.9% of respondents being classed as having a positive attitude towards care of the dying (Frommelt's Attitude Toward Care of the Dying score ⩾65). In adjusted analysis, higher (more positive) Frommelt's Attitude Toward Care of the Dying scores were associated with time on course and experience of caring for the dying. Third-year students had a score of 2.18 points greater than those in their first year (95% confidence interval: 0.36-4.01, p = 0.017). The adjusted differences in scores were 2.22 points greater for those who had prepared a dead body (95% confidence interval: 0.57-3.87, p = 0.008), 2.95 points greater for those who had cared for a dying patient (95% confidence interval: 1.09-4.08, p = 0.002) and 2.03 points greater for those who had cared for a dying relative or friend (95% confidence interval: 0.69-3.37, p = 0.003). CONCLUSION: The length of time in education and practical experience of caring for dying individuals are independently associated with positive attitudes towards care of the dying among student nurses.

Who has undiagnosed dementia? A cross-sectional analysis of participants of the Aging, Demographics and Memory Study.

BACKGROUND: delays in diagnosing dementia may lead to suboptimal care, yet around half of those with dementia are undiagnosed. Any strategy for case finding should be informed by understanding the characteristics of the undiagnosed population. We used cross-sectional data from a population-based sample with dementia aged 71 years and older in the United States to describe the undiagnosed population and identify factors associated with non-diagnosis. METHODS: the Aging, Demographics and Memory Study (ADAMS) Wave A participants (N = 856) each underwent a detailed neuropsychiatric investigation. Informants were asked whether the participant had ever received a doctor's diagnosis of dementia. We used multiple logistic regression to identify factors associated with informant report of a prior dementia diagnosis among those with a study diagnosis of dementia. RESULTS: of those with a study diagnosis of dementia (n = 307), a prior diagnosis of dementia was reported by 121 informants (weighted proportion = 42%). Prior diagnosis was associated with greater clinical dementia rating (CDR), from 26% (CDR = 1) to 83% (CDR = 5). In multivariate analysis, those aged 90 years or older were less likely to be diagnosed (P = 0.008), but prior diagnosis was more common among married women (P = 0.038) and those who had spent more than 9 years in full-time education (P = 0.043). CONCLUSIONS: people with dementia who are undiagnosed are older, have fewer years in education, are more likely to be unmarried, male and have less severe dementia than those with a diagnosis. Policymakers and clinicians should be mindful of the variation in diagnosis rates among subgroups of the population with dementia.

Changing non-participation in epidemiological studies of older people: evidence from the Cognitive Function and Ageing Study I and II.

BACKGROUND: non-participation in epidemiological studies threatens the generalisability of findings. OBJECTIVE: to investigate the change in non-participation between the Medical Research Council Cognitive Function and Ageing Study (CFAS) I and II. DESIGN: a comparison of two epidemiological studies of older people using identical methods. SETTING: three geographical areas of the United Kingdom. SUBJECTS: older people aged 65 years and over. METHODS: the two studies were conducted approximately two decades apart between 1989 and 1994 (CFAS I) and between 2008 and 2011 (CFAS II). Random samples were drawn from primary care lists. We compared demographic factors associated with non-participation. RESULTS: non-participation in CFAS II was higher than in CFAS I (45.3 versus 18.3%). After adjustment for confounders, in both CFAS I and CFAS II, women were more likely to decline to take part (CFAS I: odds ratio (OR) 1.3 95% confidence interval (CI) 1.2 to 1.4; CFAS II: 1.1 95% CI 1.1 to 1.2). Deprivation was associated with non-participation in both studies (highest versus lowest Townsend deprivation quintile, CFAS I: OR 1.4 95% CI 1.2 to 1.6; CFAS II: 2.0 95% CI 1.8 to 2.2). Age was not associated with non-participation in either study (CFAS I, P = 0.21; CFAS II, P = 0.47). CONCLUSIONS: non-participation in epidemiological studies of older people has increased substantially in the past two decades and public willingness to take part in studies of this kind would appear to be declining. As communities become more diverse and older people have increasing commitments on their time, new ways to engage prospective participants are urgently needed.

Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64 years: cohort study using a primary care database.

BACKGROUND: Epilepsy is a serious condition which can profoundly affect an individual's life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years. METHODS: Data on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox's proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables. RESULTS: In the first 5 years of follow-up, 878 (0.37 %) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95 % confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95 % CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95 % CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95 % CI 1.52 to 4.91, NNH 166). CONCLUSIONS: Risk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies.

A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II.

BACKGROUND: The prevalence of dementia is of interest worldwide. Contemporary estimates are needed to plan for future care provision, but much evidence is decades old. We aimed to investigate whether the prevalence of dementia had changed in the past two decades by repeating the same approach and diagnostic methods as used in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) in three of the original study areas in England. METHODS: Between 1989 and 1994, MRC CFAS investigators did baseline interviews in populations aged 65 years and older in six geographically defined areas in England and Wales. A two stage process, with screening followed by diagnostic assessment, was used to obtain data for algorithmic diagnoses (geriatric mental state-automated geriatric examination for computer assisted taxonomy), which were then used to estimate dementia prevalence. Data from three of these areas--Cambridgeshire, Newcastle, and Nottingham--were selected for CFAS I. Between 2008 and 2011, new fieldwork was done in the same three areas for the CFAS II study. For both CFAS I and II, each area needed to include 2500 individuals aged 65 years and older to provide power for geographical and generational comparison. Sampling was stratified according to age group (65-74 years vs ≥75 years). CFAS II used identical sampling, approach, and diagnostic methods to CFAS I, except that screening and assessement were combined into one stage. Prevalence estimates were calculated using inverse probability weighting methods to adjust for sampling design and non-response. Full likelihood Bayesian models were used to investigate informative non-response. FINDINGS: 7635 people aged 65 years or older were interviewed in CFAS I (9602 approached, 80% response) in Cambridgeshire, Newcastle, and Nottingham, with 1457 being diagnostically assessed. In the same geographical areas, the CFAS II investigators interviewed 7796 individuals (14,242 approached, 242 with limited frailty information, 56% response). Using CFAS I age and sex specific estimates of prevalence in individuals aged 65 years or older, standardised to the 2011 population, 8·3% (884,000) of this population would be expected to have dementia in 2011. However, CFAS II shows that the prevalence is lower (6·5%; 670,000), a decrease of 1·8% (odds ratio for CFAS II vs CFAS I 0·7, 95% CI 0·6-0·9, p=0·003). Sensitivity analyses suggest that these estimates are robust to the change in response. INTERPRETATION: This study provides further evidence that a cohort effect exists in dementia prevalence. Later-born populations have a lower risk of prevalent dementia than those born earlier in the past century. FUNDING: UK Medical Research Council.

Dying at home: a qualitative study of the perspectives of older South Asians living in the United Kingdom.

BACKGROUND: South Asians constitute the single largest ethnic minority group in the United Kingdom, yet little is known about their perspectives on, and experiences of, end-of-life care. AIM: To explore beliefs, attitudes and expectations expressed by older South Asians living in East London about dying at home. DESIGN: A qualitative study using focus groups and semi-structured interviews. Data were analysed using a constructivist grounded theory approach. SETTING/PARTICIPANTS: Five focus groups and 29 in-depth semi-structured interviews were conducted with a total of 55 older adults (24 men and 31 women) aged between 52 and 78 years. Participants from six South Asian ethnic groups were recruited via 11 local community organisations. RESULTS: Two key themes were identified. The theme of 'reconsidering the homeland' draws on the notion of 'diaspora' to help understand why for many participants, the physical place of death was perceived as less important than the opportunity to carry out cultural and religious practices surrounding death. The second theme 'home as a haven' describes participants' accounts of how their home is a place in which it is possible to perform various cultural and religious rituals. Cultural and religious practices were often seen as essential to achieving a peaceful death and honouring religious and filial duties. CONCLUSIONS: Older people of South Asian ethnicity living in East London perceive home as more than a physical location for dying relatives. They make efforts to adhere, and also adapt, to important social and cultural values relating to death and dying as part of the wider challenge of living in an emigrant society.

The use of botulinum toxin injections to manage drooling in amyotrophic lateral sclerosis/motor neurone disease: a systematic review.

Difficulty in managing oral secretions is commonly experienced by patients with amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) and associated bulbar weakness including dysphagia. There are no definitive evidence-based treatment guidelines to manage the distressing symptom of drooling. We reviewed the evidence for the effectiveness of botulinum toxin injections to reduce saliva in ALS/MND. The search strategy was conducted in four stages: (1) electronic search of relevant databases, (2) hand searches of all international ALS/MND symposium journals, (3) email request to MND care centres in the UK and Ireland, and (4) hand searching of reference lists. All studies were critically appraised and relevant data extracted. Botulinum toxin type A and type B were analysed separately. Due to heterogeneity, it was not possible to calculate a pooled estimate of effect. Twelve studies met the inclusion criteria (9 for type A and 3 for type B). Only two randomised controlled trials were identified. Study sample sizes were small with a mean of 12.5 subjects. The most frequently reported outcomes were weight of cotton rolls and number of tissues used. All studies claimed the intervention tested was effective, but only seven studies (4 for type A and 3 for type B) reported statistically significant differences. Although there is evidence to suggest that botulinum toxin B can reduce drooling, the evidence base is limited by a lack of randomized controlled trials. Evidence to support the use of botulinum toxin A is weaker. Larger trials will help remove the uncertainty practitioners face in treating this disabling symptom.

Proactive review for people with diabetes in hospital: a cluster randomised feasibility trial with process evaluation, protocol V3.1.

BACKGROUND: Diabetes inpatient specialist services vary across the country, with limited evidence to guide service delivery. Currently, referrals to diabetes inpatient specialists are usually 'reactive' after diabetes-related events have taken place, which are associated with an increased risk of morbidity/mortality and increased length of hospital stay. We propose that a proactive diabetes review model of care, delivered by diabetes inpatient specialist nurses, may contribute to the prevention of such diabetes-related events and result in a reduction in the risk of harm. METHOD: We will conduct a cluster randomised feasibility study with process evaluation. The proactive diabetes review model (PDRM) is a complex intervention that focuses on the prevention of potentially modifiable diabetes-related harms. All eligible patients will receive a comprehensive, structured diabetes review that aims to identify and prevent potentially modifiable diabetes-related harms through utilising a standardised review structure. Reviews are undertaken by a diabetes inpatient specialist nurse within one working day of admission. This differs from usual care where patients are often only seen after diabetes-related harms have taken place. The trial duration will be approximately 32 weeks, with intervention delivery throughout. There will be an initial 8-week run-in phase, followed by a 24-week data collection phase. Eight wards will be equally randomised to either PDRM or usual care. Adult patients with a known diagnosis of diabetes admitted to an included ward will be eligible. Data collection will be limited to that typically collected as part of usual care. Data collected will include descriptive data at both the ward and patient level and glucose measures, such as frequency and results of capillary glucose testing, ketonaemia and hypoglycaemic events. The analysis aims to determine the fidelity and acceptability of the intervention and the feasibility of a future definitive trial. Whilst this study is primarily about trial feasibility, the findings of the process evaluation may lead to changes to both trial processes and modifications to the intervention. A qualitative process evaluation will be conducted in parallel to the trial. A minimum of 22 patients, nurses, doctors, and managers will be recruited with methods including direct non-participant observation and semi-structured interviews. The feasibility of a future definitive trial will be assessed by evaluating recruitment and randomisation processes, staffing resources and quality of available data. DISCUSSION: The aim of this cluster randomised feasibility trial with a process evaluation is to explore the feasibility of a definitive trial and identify appropriate outcome measures. If a trial is feasible and the effectiveness of PDRM can be evaluated, this could inform the future development of inpatient diabetes services nationally. TRIAL REGISTRATION: UK Clinical Research Network, 51,167. ISRCTN, ISRCTN70402110. Registered on 21 February 2022.

Relationship between staff and quality of care in care homes: StaRQ mixed methods study.

Background: Quality of life and care varies between and within the care homes in which almost half a million older people live and over half a million direct care staff (registered nurses and care assistants) work. The reasons are complex, understudied and sometimes oversimplified, but staff and their work are a significant influence. Objective(s): To explore variations in the care home nursing and support workforce; how resident and relatives' needs in care homes are linked to care home staffing; how different staffing models impact on care quality, outcomes and costs; how workforce numbers, skill mix and stability meet residents' needs; the contributions of the care home workforce to enhancing quality of care; staff relationships as a platform for implementation by providers. Design: Mixed-method (QUAL-QUANT) parallel design with five work packages. WP1 - two evidence syntheses (one realist); WP2 - cross-sectional survey of routine staffing and rated quality from care home regulator; WP3 - analysis of longitudinal data from a corporate provider of staffing characteristics and quality indicators, including safety; WP4 - secondary analysis of care home regulator reports; WP5 - social network analysis of networks likely to influence quality innovation. We expressed our synthesised findings as a logic model. Setting: English care homes, with and without nursing, with various ownership structures, size and location, with varying quality ratings. Participants: Managers, residents, families and care home staff. Findings: Staffing's contribution to quality and personalised care requires: managerial and staff stability and consistency; sufficient staff to develop 'familial' relationships between staff and residents, and staff-staff reciprocity, 'knowing' residents, and skills and competence training beyond induction; supported, well-led staff seeing modelled behaviours from supervisors; autonomy to act. Outcome measures that capture the relationship between staffing and quality include: the extent to which resident needs and preferences are met and culturally appropriate; resident and family satisfaction; extent of residents living with purpose; safe care (including clinical outcomes); staff well-being and job satisfaction were important, but underacknowledged. Limitations: Many of our findings stem from self-reported and routine data with known biases - such as under reporting of adverse incidents; our analysis may reflect these biases. COVID-19 required adapting our original protocol to make it feasible. Consequently, the effects of the pandemic are reflected in our research methods and findings. Our findings are based on data from a single care home operator and so may not be generalised to the wider population of care homes. Conclusions: Innovative and multiple methods and theory can successfully highlight the nuanced relationship between staffing and quality in care homes. Modifiable characteristics such as visible philosophies of care and high-quality training, reinforced by behavioural and relational role modelling by leaders can make the difference when sufficient amounts of consistent staff are employed. Greater staffing capacity alone is unlikely to enhance quality in a cost-effective manner. Social network analysis can help identify the right people to aid adoption and spread of quality and innovation. Future research should focus on richer, iterative, evaluative testing and development of our logic model using theoretically and empirically defensible - rather than available - inputs and outcomes. Study registration: This study is registered as PROSPERO CRD42021241066 and Research Registry registration: 1062. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/144/29) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 8. See the NIHR Funding and Awards website for further award information.

This study was about the relationship between staffing and quality in care homes. Almost half a million older people live in care homes in England. Why quality of care and quality of life for residents vary so much between and within homes is unknown, but staff and the ways they work are likely to be important. Researching staffing and quality is difficult: quality means different things to different people and a lot of things shape how quality feels to residents, families and staff. In the past, researchers have oversimplified the problem to study it and may have missed important influences. We took a more complex view. In five interlinked work packages, we collected and analysed: (1) research journal articles; (2) national data from different care homes; (3) data from a large care organisation to look at what it is about staffing that influences quality; (4) reports and ratings of homes from the Care Quality Commission; and (5) we looked at the networks between staff in homes that shape how quality improvement techniques might spread. We used theories about how our findings might be linked to plan for this data collection and analysis. The results were combined into something called a 'logic model' ­ a diagram and explanation that make it easier for managers, researchers and people interested in care homes to see how staffing influences quality. Staffing considerations that might improve quality include: not swapping managers too much; having sufficient and consistent staff for family-like relationships in homes and putting residents' needs first; supporting staff and giving them freedom to act; and key staff leading by example. Research examining care home quality should capture those aspects that mean the most to residents, their families and staff.

Safety of antidepressants in adults aged under 65: protocol for a cohort study using a large primary care database.

BACKGROUND: Antidepressants are among the most commonly prescribed drugs in primary care in England and their use is increasing. This is largely due to longer durations of treatment of depression. Observational studies have shown some differences in adverse outcomes associated with different antidepressant drugs but relatively little is known about their relative safety particularly with long term use. The primary aim of this study is to determine the relative and absolute risks of pre-defined adverse events comparing different classes of antidepressant drugs in adults aged under 65 years and diagnosed with depression. METHODS/DESIGN: The study will identify a cohort of patients with a first recorded diagnosis of depression between 1/1/2000 and 31/07/2011, and made between the ages of 20 to 64 years using a large primary care database (QResearch). Patients will be followed up until 1/08/2012. Details of all prescriptions for antidepressants in patients in the cohort will be extracted, including the date of each prescription, the type of antidepressant drug, the dose and total quantity prescribed. Prospectively recorded data will be used to ascertain information on adverse outcomes that occurred during follow-up and after entry into the cohort. These are: all-cause mortality, suicide, attempted suicide/self-harm, sudden death, antidepressant overdose/poisoning, myocardial infarction, stroke/transient ischaemic attack, cardiac arrhythmia, epilepsy/seizures, upper gastrointestinal bleeding, falls, fractures, adverse drug reactions and motor vehicle crashes. Cox proportional hazard models will be used to estimate the association of the outcomes with class of antidepressant drug adjusting for potential confounding variables. The analyses will also examine associations by duration and dose and with the most frequently prescribed individual antidepressant drugs. Self-controlled case series analyses will be used to estimate the relative incidence of the outcomes of interest for defined time periods of antidepressant use. DISCUSSION: The results of this study will help to establish the relative safety and balance of risks for different antidepressant drugs in people aged under 65.