Tracing the temporal trends of modifiable risk factors in dementia: insights from the English Longitudinal Study of Ageing (2004-2019).

BACKGROUND: Dementia's growing impact, especially in ageing societies such as the UK, emphasises the importance of modifiable risk factors as primary prevention targets. Despite this, the temporal progression and the population attributable fraction (PAF) of dementia attributable to these factors remain unclear. This investigation aims to examine the temporal trajectories of the modifiable risk factors for dementia in England from 2004 to 2019. METHODS: We used data from the English Longitudinal Study of Ageing collected between June, 2004, and July, 2019, covering 76 904 participants. We calculated the PAFs for 12 modifiable risk factors, as recommended by the Lancet Commission on dementia prevention, intervention, and care, and the individual weighted PAFs (IW-PAFs) for each risk factor. We analysed temporal trends to understand the changes in the overall PAF and IW-PAF over the study period. FINDINGS: The overall PAF for dementia showed a decrease from 46·31% in 2004-05 to 43·95% in 2018-19, but this trend was not significant (p=0·226). Hypertension, with an average IW-PAF of 8·67%, has been the primary modifiable determinant of dementia, trailed by obesity (6·42%), social isolation (5·84%), hearing loss (5·02%), depression (4·89%), low education (4·80%), physical inactivity (3·40%), diabetes (2·61%), smoking (2·08%), excessive alcohol consumption (1·22%), air pollution (0·44%), and traumatic brain injury (0·28%). During 2004-19, only IW-PAFs of low education (p=0·001), social isolation (p=0·034), and smoking (p=0·007) showed significant decreasing trends, whereas IW-PAFs of other factors had either stagnated with insignificant changes or, worryingly, climbed upwards. INTERPRETATION: This investigation provides valuable insights into the temporal trends of modifiable risk factors for dementia in England. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them. Notable, PAF was based on a theoretical scenario in which dementia risk can be wholly eliminated by removing risk factors, which should be explained with caution in practice. FUNDING: UK Foreign, Commonwealth and Development Office; National Institute for Health and Care Research (NIHR).

Integrating machine learning and artificial intelligence in life-course epidemiology: pathways to innovative public health solutions.

The integration of machine learning (ML) and artificial intelligence (AI) techniques in life-course epidemiology offers remarkable opportunities to advance our understanding of the complex interplay between biological, social, and environmental factors that shape health trajectories across the lifespan. This perspective summarizes the current applications, discusses future potential and challenges, and provides recommendations for harnessing ML and AI technologies to develop innovative public health solutions. ML and AI have been increasingly applied in epidemiological studies, demonstrating their ability to handle large, complex datasets, identify intricate patterns and associations, integrate multiple and multimodal data types, improve predictive accuracy, and enhance causal inference methods. In life-course epidemiology, these techniques can help identify sensitive periods and critical windows for intervention, model complex interactions between risk factors, predict individual and population-level disease risk trajectories, and strengthen causal inference in observational studies. By leveraging the five principles of life-course research proposed by Elder and Shanahan-lifespan development, agency, time and place, timing, and linked lives-we discuss a framework for applying ML and AI to uncover novel insights and inform targeted interventions. However, the successful integration of these technologies faces challenges related to data quality, model interpretability, bias, privacy, and equity. To fully realize the potential of ML and AI in life-course epidemiology, fostering interdisciplinary collaborations, developing standardized guidelines, advocating for their integration in public health decision-making, prioritizing fairness, and investing in training and capacity building are essential. By responsibly harnessing the power of ML and AI, we can take significant steps towards creating healthier and more equitable futures across the life course.

Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004-2019).

BACKGROUND: Interest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies. This investigation examined the temporal trajectories of MRFs for dementia in England. METHODS: We used data from the English Longitudinal Study of Ageing, a panel study over eight waves collected between 2004 and 2019 (76,904 interviews in total). We calculated the PAFs for twelve MRFs (including six early- to mid-life factors and six late-life factors), as recommended by the Lancet Commission, and the individual weighted PAFs (IW-PAFs) for each risk factor. Temporal trends were analysed to understand the changes in the overall PAF and IW-PAF over the study period. Subgroup analyses were conducted by sex and socioeconomic status (SES). RESULTS: The overall PAF for dementia MRFs changed from 46.73% in 2004/2005 to 36.79% in 2018/2019, though this trend was not statistically significant. During 2004-2019, hypertension, with an average IW-PAF of 8.21%, was the primary modifiable determinant of dementia, followed by obesity (6.16%), social isolation (5.61%), hearing loss (4.81%), depression (4.72%), low education (4.63%), physical inactivity (3.26%), diabetes mellitus (2.49%), smoking (2.0%), excessive alcohol consumption (1.16%), air pollution (0.42%), and traumatic brain injury (TBI) (0.26%). During 2004-2019, only IW-PAFs of low education, social isolation, and smoking showed significant decreasing trends, while IW-PAFs of other factors either did not change significantly or increased (including TBI, diabetes mellitus, and air pollution). Upon sex-specific disaggregation, a higher overall PAF for MRFs was found among women, predominantly associated with later-life risk factors, most notably social isolation, depression, and physical inactivity. Additionally, hearing loss, classified as an early- to mid-life factor, played a supplementary role in the identified sex disparity. A comparable discrepancy was evident upon PAF evaluation by SES, with lower income groups experiencing a higher dementia risk, largely tied to later-life factors such as social isolation, physical inactivity, depression, and smoking. Early- to mid-life factors, in particular, low education and obesity, were also observed to contribute to the SES-associated divergence in dementia risk. Temporal PAF and IW-PAF trends, stratified by sex and SES, revealed that MRF PAF gaps across sex or SES categories have persisted or increased. CONCLUSIONS: In England, there was little change over time in the proportion of dementia attributable to known modifiable risk factors. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them.

Predicting patients with dementia most at risk of needing psychiatric in-patient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study.

BACKGROUND: Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death. AIMS: To test whether individuals who are most likely to need enhanced care later in the disease course can be identified at the point of diagnosis, thus allowing the targeted intervention. METHOD: We used clinical information collected routinely in de-identified electronic patient records from two UK National Health Service (NHS) trusts to identify at diagnosis which individuals were at increased risk of needing enhanced care (psychiatric in-patient or intensive (crisis) community care). RESULTS: We examined the records of a total of 25 326 patients with dementia. A minority (16% in the Cambridgeshire trust and 2.4% in the London trust) needed enhanced care. Patients who needed enhanced care differed from those who did not in age, cognitive test scores and Health of the Nation Outcome Scale scores. Logistic regression discriminated risk, with an area under the receiver operating characteristic curve (AUROC) of up to 0.78 after 1 year and 0.74 after 4 years. We were able to confirm the validity of the approach in two trusts that differed widely in the populations they serve. CONCLUSIONS: It is possible to identify, at the time of diagnosis of dementia, individuals most likely to need enhanced care later in the disease course. This permits the development of targeted clinical interventions for this high-risk group.

The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study.

BACKGROUND: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood. AIMS: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS). METHOD: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample. RESULTS: A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04-0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = -0.28, 95% CI -0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction. CONCLUSIONS: We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians' therapeutic decisions.

Sex-Specific Differences in the Progression of Huntington's Disease Symptoms - A National Study in China.

INTRODUCTION: Huntington's disease (HD) is a rare, inherited neurodegenerative disorder. Despite extensive research on symptom progression and sex differences in Western populations, little is known about these aspects within the Chinese context. The objective of this study was to investigate the temporal trends of symptoms in individuals with HD in China. METHODS: A nationwide cross-sectional study was conducted in Chinese individuals diagnosed with HD. Symptom progression over time, encompassing physical, psychiatric, and cognitive symptoms, was self-reported. We calculated the proportions of individuals who currently had each symptom by disease duration, and tested corresponding temporal trends by linear regression analyses. RESULTS: A total of 269 individuals diagnosed with HD were included. Specific symptoms were found to progress more significantly in males compared to females over time, including psychotic symptoms (p = 0.007), urinary incontinence (p = 0.013), reduced concentration (p = 0.005), font alteration (p = 0.029), atypical facial expression (p = 0.037), and suicidal ideation (p = 0.047). In terms of cognitive and psychiatric symptoms, no significant temporal trends were identified in females, while males demonstrated significant increasing trends, with reduced concentration (p = 0.005) and psychotic symptoms (p = 0.007) standing out. CONCLUSIONS: This study emphasizes the existence of sex-specific symptom progression in HD within the Chinese population, underscoring the importance of considering sex in clinical practice. Further research should investigate the mechanisms behind these differences and explore tailored treatment options.

Economic Burden of Huntington's Disease in China: Results from a National-Wide Cross-Sectional Study.

BACKGROUND: Huntington's disease (HD) poses a significant socio-economic burden globally. Existing research on HD's economic burden predominantly comes from Western settings, leaving a gap in data from Asian countries. This study aimed to assess the economic burden of HD in China and identify cost-driving factors. METHODS: This study used data from a 2019 nationwide cross-sectional survey of individuals affected by rare diseases in China. Data included socio-demographic characteristics, income, disease stage, health and social insurance coverage status, treatment-seeking behaviour, and costs. Logistic regression and linear regression were used to explore potential contributors to treatment-seeking behaviour and associated costs. RESULTS: Of the 269 individuals with HD included in this study, 80.6% were actively seeking treatment. The average annual direct medical cost, direct non-medical cost, and indirect cost were 3,265.65, 805.82, and 801.97 Euros, respectively. Compared to participants with early-stage HD, those with middle- or advanced-stage HD reported higher direct medical costs (coefficient 1,612.70, 95% confidence interval [CI]: [141.92, 3,083.48] and 2,398.58, 95% CI: [791.16, 4,006.00], respectively). However, the disease stage was not significantly associated with direct non-medical costs or indirect costs. CONCLUSIONS: This study provides crucial insights into the economic burden of HD in China. It emphasises a need for targeted policies that better cater to the financial needs of HD patients.

Longitudinal effect of clozapine-associated sedation on motivation in schizophrenia: naturalistic longitudinal study.

Negative symptoms of schizophrenia manifest as reduced motivation and pleasure (MAP) and impaired emotional expressivity (EXP). These can occur as primary phenomena, but have also been suggested to occur secondary to other clinical factors, including antipsychotic-induced sedation. However, this relationship has not been established formally. Here, we examined the effect of antipsychotic-induced sedation (assessed via the proxy of total daily sleep duration) on MAP and EXP in a cohort of 187 clozapine-treated patients with schizophrenia followed for over 2 years on average, using multilevel regression and mediation models. MAP, but not EXP, was adversely influenced by sedation, independently of the severity of psychosis or depression. Moreover, clozapine impaired MAP indirectly by worsening sedation, but after accounting for clozapine-induced sedation, clozapine improved MAP. Our results highlight the importance of addressing sedative side-effects of antipsychotics to improve clinical outcomes.

Clozapine-related obsessive-compulsive symptoms and their impact on wellbeing: a naturalistic longitudinal study.

BACKGROUND: Obsessive-compulsive symptoms (OCS) are commonly associated with clozapine treatment but are frequently overlooked by clinicians despite their potential impact on patients' quality of life. In this study, we explored whether OCS severity impacted subjective wellbeing and general functioning, independently of depressive and psychotic symptoms. METHODS: We used anonymised electronic healthcare records from a large cohort of patients who were treated with clozapine and assessed annually for OCS, wellbeing, general functioning, and psychopathology using standardised scales as part of routine clinical practice. We used statistical mixed linear model techniques to evaluate the longitudinal influence of OCS severity on wellbeing and general functioning. RESULTS: A total of 184 patients were included, with 527 face-to-face assessments and 64.7% evaluated three or more times. Different linear mixed models demonstrated that OCS in patients treated with clozapine were associated with significantly worse wellbeing scores, independently of depression and psychotic symptoms, but OCS did not impair general functioning. Obsessional thinking and hoarding behaviour, but not compulsions, were significantly associated with the impact on wellbeing, which may be attributable to the ego-syntonic nature of the compulsions. CONCLUSIONS: Given the frequent occurrence of OCS and their negative impact on wellbeing, we encourage clinicians to routinely assess and treat OCS in patients who are taking clozapine.

Mortality rates and proximal causes of death in patients with Lewy body dementia versus Alzheimer's disease: A longitudinal study using secondary care mental health records.

BACKGROUND: Previous studies have shown reduced survival in Lewy body dementia (LBD) compared to Alzheimer's disease (AD), but the reasons for this are not known. We identified cause of death categories accounting for the reduced survival in LBD. METHODS: We linked cohorts of patients with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and AD, with proximal cause of death data. We examined mortality by dementia group and hazard ratios for each death category by dementia group in males and females separately. In a specific focus on the dementia group with the highest mortality rate versus reference, we examined cumulative incidence to identify the main causes of death accounting for the excess deaths. RESULTS: Hazard ratios for death were higher in PDD and DLB compared to AD, for both males and females. PDD males had the highest hazard ratio for death across the dementia comparison groups (HR 2.7, 95% CI 2.2-3.3). Compared with AD, hazard ratios for "nervous system" causes of death were significantly elevated in all LBD groups. Additional significant cause-of-death categories included aspiration pneumonia, genitourinary causes, other respiratory causes, circulatory and a "symptoms and signs" category in PDD males; other respiratory causes in DLB males; mental disorders in PDD females; and aspiration pneumonia, genitourinary and other respiratory causes in DLB females. CONCLUSION: Further research and cohort development is required to investigate differences by age group, to extend cohort follow-up to the whole population and to investigate the risk-balance of interventions which may differ by dementia group.

Prevalence and gender disparity of those who screen positive for depression in China by the classification of the employer and industry: a cross-sectional, population-based study.

BACKGROUND: The important role of mental health in sustainable economic development is gradually being recognized. This study aimed to evaluate the prevalence and gender disparity of those who screen positive for depression in China by the employer and industrial classification. METHODS: We used data from a nationally representative survey, the China Family Panel Studies. Depression was judged by the Centre for Epidemiologic Studies Depression Scale. Employer classifications were categorized according to the local characteristics of Mainland China. Industrial classifications were defined using level-1 of the China version of the International Standard Industrial Classification of All Economic Activities. Weighted logistic regressions were fitted to estimate the gender disparities, controlling for confounders. RESULTS: Forty eight thousand six hundred twenty eight adults were included. 18.7% (95%CI 18.1-19.4) of sampled adults were screened positive for depression symptoms, with 16.6% (95%CI 15.8-17.5) in males vs 21.0% (95%CI 20.1-22.0) in females. By classification of the employer, the prevalence was lowest among those employed by Government/party organisations (11.8%, 95%CI 8.9-15.4), and highest in those self-employed (21.8%, 95%CI 20.8-22.9); the gender disparity was mainly found in those employed by Sole proprietorship (Adjusted odds ratio [AOR] = 1.95, 95%CI 1.19-3.19) and Private enterprise (AOR = 1.34, 95%CI 1.13-1.59), as well as those self-employed (AOR = 1.49, 95%CI 1.3-1.17). By industrial classification, the prevalence was lowest among those who worked in the industry of Real estate (7.2%, 95%CI 4.8-10.6), and highest among those who worked in the industry of Agriculture, forestry, animal husbandry and fishing (22.9%, 95%CI 15.5-32.4); the gender disparity was mainly found in those who worked in the industry of Agriculture, forestry, animal husbandry and fishing (AOR = 3.29, 95%CI 1.18-9.15), Manufacturing (AOR = 1.41, 95% CI 1.09-1.82), Wholesale and retail trade (AOR = 1.48, 95% CI 1.07-2.06), and Accommodation and food service (AOR = 1.91, 95% CI 1.15-3.18). CONCLUSION: The prevalence of depression in China had a wide variation by classifications of the employer and industry. Gender disparities were identified among workers from Sole proprietorship, Private enterprise, and self-employed, or workers from the industry of Agriculture, forestry, animal husbandry and fishing, Manufacturing, Wholesale and retail trade, and Accommodation and food service.

Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study.

BACKGROUND: Dementia is the leading cause of death in elderly Western populations. Preventative interventions that could delay dementia onset even modestly would provide a major public health impact. There are no disease-modifying treatments currently available. Lithium has been proposed as a potential treatment. We assessed the association between lithium use and the incidence of dementia and its subtypes. METHODS AND FINDINGS: We conducted a retrospective cohort study comparing patients treated between January 1, 2005 and December 31, 2019, using data from electronic clinical records of secondary care mental health (MH) services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million). Eligible patients were those aged 50 years or over at baseline and who had at least 1 year follow-up, excluding patients with a diagnosis of mild cognitive impairment (MCI) or dementia before, or less than 1 year after, their start date. The intervention was the use of lithium. The main outcomes were dementia and its subtypes, diagnosed and classified according to the International Classification of Diseases-10th Revision (ICD-10). In this cohort, 29,618 patients (of whom 548 were exposed to lithium) were included. Their mean age was 73.9 years. A total of 40.2% were male, 33.3% were married or in a civil partnership, and 71.0% were of white ethnicity. Lithium-exposed patients were more likely to be married, cohabiting or in a civil partnership, to be a current/former smoker, to have used antipsychotics, and to have comorbid depression, mania/bipolar affective disorder (BPAD), hypertension, central vascular disease, diabetes mellitus, or hyperlipidemias. No significant difference between the 2 groups was observed for other characteristics, including age, sex, and alcohol-related disorders. In the exposed cohort, 53 (9.7%) patients were diagnosed with dementia, including 36 (6.8%) with Alzheimer disease (AD) and 13 (2.6%) with vascular dementia (VD). In the unexposed cohort, corresponding numbers were the following: dementia 3,244 (11.2%), AD 2,276 (8.1%), and VD 698 (2.6%). After controlling for sociodemographic factors, smoking status, other medications, other mental comorbidities, and physical comorbidities, lithium use was associated with a lower risk of dementia (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.40 to 0.78), including AD (HR 0.55, 95% CI 0.37 to 0.82) and VD (HR 0.36, 95% CI 0.19 to 0.69). Lithium appeared protective in short-term (≤1-year exposure) and long-term lithium users (>5-year exposure); a lack of difference for intermediate durations was likely due to lack of power, but there was some evidence for additional benefit with longer exposure durations. The main limitation was the handling of BPAD, the most common reason for lithium prescription but also a risk factor for dementia. This potential confounder would most likely cause an increase in dementia in the exposed group, whereas we found the opposite, and the sensitivity analysis confirmed the primary results. However, the specific nature of the group of patients exposed to lithium means that caution is needed in extending these findings to the general population. Another limitation is that our sample size of patients using lithium was small, reflected in the wide CIs for results relating to some durations of lithium exposure, although again sensitivity analyses remained consistent with our primary findings. CONCLUSIONS: We observed an association between lithium use and a decreased risk of developing dementia. This lends further support to the idea that lithium may be a disease-modifying treatment for dementia and that this is a promising treatment to take forwards to larger randomised controlled trials (RCTs) for this indication.

Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study.

BACKGROUND: Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality. METHODS AND FINDINGS: We performed a retrospective cohort study of those diagnosed with DLB between 1 January 2005 and 31 December 2019, using data from electronic clinical records of secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as linked records from national Hospital Episode Statistics (HES) data. Eligible patients were those who started AChEIs or memantine within 3 months of their diagnosis (cases) and those who never used AChEIs or memantine (controls). Outcomes included admission, length of stay, and mortality. Cox proportional hazard and linear regression models were used. Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only, and 273 took both AChEIs and memantine. The cohorts were followed up for an average of 896 days, 981 days, and 1,004 days, respectively. There were no significant differences in the cohorts' baseline characteristics, except for socioeconomic status that was lower in patients who never took AChEIs or memantine (χ2 = 23.34, P = 0.003). After controlling for confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity, anticholinergic burden, and global health performance, compared with patients who never took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02; adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs or both AChEIs and memantine had significantly shorter periods of unplanned hospital admission for physical disorders (adjusted coefficient -13.48, 95% CI = [-26.87, -0.09], P = 0.049; adjusted coefficient -14.21, 95% CI = [-24.58, -3.85], P = 0.007, respectively), but no difference in length of stay for planned admissions for physical disorders, or for admissions for mental health disorders. No significant additional associations of memantine on admission, length of stay, and mortality were found (all P > 0.05). The main limitation was that this was a naturalistic study and possible confounds cannot be fully controlled, and there may be selection bias resulting from nonrandom prescription behaviour in clinical practice. However, we mimicked the intention-to-treat design of clinical trials, and the majority of baseline characters were balanced between cohorts. In addition, our series of sensitivity analyses confirmed the consistency of our results. CONCLUSION: In this study, we observed that use of AChEIs with or without memantine in DLB was associated with shorter duration of hospital admissions and decreased risk of mortality. Although our study was naturalistic, it supports further the use of AChEIs in DLB.

Difficulty and help with activities of daily living among older adults living alone during the COVID-19 pandemic: a multi-country population-based study.

BACKGROUND: Older adults who live alone and have difficulties in activities of daily living (ADLs) may have been more vulnerable during the COVID-19 pandemic. However, little is known about pandemic-related changes in ADL assistance (such as home care, domiciliary care) and its international variation. We examined international patterns and changes in provision of ADL assistance, and related these to country-level measures including national income and health service expenditure. METHODS: We analysed data covering 29 countries from three longitudinal cohort studies (Health and Retirement Study, English Longitudinal Study of Aging, and Survey of Health, Ageing and Retirement in Europe). Eligible people were aged ≥50 years and living alone. Outcomes included ADL difficulty status (assessed via six basic ADLs and five instrumental ADLs) and receipt of ADL assistance. Wealth-related inequality and need-related inequity in ADL assistance were measured using Erreygers' corrected concentration index (ECI). Correlations were estimated between prevalence/inequality/inequity in ADL assistance and national health-related indicators. We hypothesized these measures would be associated with health system factors such as affordability and availability of ADL assistance, as well as active ageing awareness. RESULTS: During COVID-19, 18.4% of older adults living alone reported ADL difficulties (ranging from 8.8% in Switzerland to 29.2% in the USA) and 56.8% of those reporting difficulties received ADL assistance (ranging from 38.7% in the UK to 79.8% in Lithuania). Females were more likely to receive ADL assistance than males in 16/29 countries; the sex gap increased further during the pandemic. Wealth-related ECIs indicated socioeconomic equality in ADL assistance within 24/39 countries before the pandemic, and significant favouring of the less wealthy in 18/29 countries during the pandemic. Needs-related ECIs indicated less equity in assistance with ADLs during the pandemic than before. Our hypotheses on the association between ADL provision measures and health system factors were confirmed before COVID-19, but unexpectedly disconfirmed during COVID-19. CONCLUSION: This study revealed an unequal (and in some countries, partly needs-mismatched) response from countries to older adults living alone during the COVID-19 pandemic. The findings might inform future research about, and policies for, older adults living alone, particularly regarding social protection responses during crises.

Factors associated with the psychological quality of life among adolescents with rare diseases in China: a national repetitive cross-sectional study.

OBJECTIVE: To explore the factors associated with the psychosocial quality of life (QoL) among adolescents with rare diseases (RDs). METHODS: We used cross-sectional design to collect data in February 2016 and February 2018, respectively, in China through a structured questionnaire. Those included in the study were adolescents aged between 10 and 18 who had a doctor-diagnosed RD. Multivariable linear regression was used to identify the predictors associated with psychosocial QoL among adolescents with RDs. RESULTS: The study included 737 adolescents (28.4% girls). The mean score of their psychological QoL was 43.79 (SD = 20.44). Multivariable linear regression analysis suggests that girls had a lower psychological QoL than boys (adjusted coefficient = -1.87, 95% CI = [-3.53, -0.21]); and receiving an education (adjusted coefficient = 6.53, 95% CI = [4.47, 8.33]), living with parents (adjusted coefficient = 6.45, 95% CI = [3.94, 8.97]), and physical function (adjusted coefficient = 0.53, 95% CI = [0.49, 0.56]) were positively associated with psychological QoL. CONCLUSION: This study reveals the status of psychological QoL among adolescents with RDs. The evidence provided can increase our understanding of the factors associated with psychological QoL among adolescents with RDs and can help formulate policies and put concrete actions into practice.

Interrupted Time-Series Analysis to Evaluate the Impact of a National Antimicrobial Stewardship Campaign on Antibiotic Prescribing: A Typical Practice in China's Primary Care.

BACKGROUND: After implementing the 2011 national antimicrobial stewardship campaign, few studies focused on evaluating its effect in China's primary care facilities. METHODS: We randomly selected 11 community health centers in Shenzhen, China, and collected all outpatient prescriptions of these centers from 2010 to 2015. To evaluate the impact of local interventions on antibiotic prescribing, we used a segmented regression model of interrupted time series to analyze 7 outcomes (ie, percentage of prescriptions with antibiotics, and percentages of prescriptions with broad-spectrum antibiotics, with parenteral antibiotics, and with 2 or more antibiotics in all prescriptions or antibiotic-containing prescriptions). RESULTS: Overall, 1 482 223 outpatient prescriptions were obtained. The intervention was associated with a significant immediate change (-5.2%, P = .04) and change in slope (-3.1% per month, P < .01) for the percentage of prescriptions with antibiotics, and its relative cumulative effect at the end of the study was -74.0% (95% confidence interval, -79.0 to -69.1). After the intervention, the percentage of prescriptions with broad-spectrum and with parenteral antibiotics decreased dramatically by 36.7% and 77.3%, respectively, but their percentages in antibiotic-containing prescriptions decreased insignificantly. Percentage of prescriptions with two or more antibiotics in all prescriptions or antibiotic-containing prescriptions only showed immediate changes, but significant changes in slope were not observed. CONCLUSIONS: A typical practice in Shenzhen, China, showed that strict enforcement of the antimicrobial stewardship campaign could effectively reduce antibiotic prescribing in primary care with a stable long-term effect. However, prescribing of broad-spectrum and parenteral antibiotics was still prevalent. More targeted interventions are required to promote appropriate antibiotic use.

Accessibility and efficiency of mental health services, United Kingdom of Great Britain and Northern Ireland.

PROBLEM: Mental ill health in the United Kingdom of Great Britain and Northern Ireland has been a major driver of labour market exclusion through sickness absence, reduced productivity and job loss. APPROACH: A government-supported programme for improving access to psychological therapies was launched in 2008 and expanded across England in 2010. The aim was to provide evidence-based treatments for people with common mental disorders through three principal strategies: (i) routine session-by-session outcome monitoring; (ii) integration with the wider care system; and (iii) delivery of psychological therapies as part of a stepped-care approach. LOCAL SETTING: Access to effective psychological therapies was previously low in the United Kingdom. In 2010, only about 35% of people with moderately severe mental disorders were in specialist or non-specialist treatment. RELEVANT CHANGES: The accessibility of quality mental health services has increased, as has the efficiency of the country's mental health system. The numbers of people entering treatment have increased steadily from 0.43 million in 2012-2013 to 1.09 million in 2018-2019. The recovery rate of patients in treatment increased from 42.8% to 52.1% during 2012-2018. The number of people moved off sick pay and benefits rose from 3683 to 18 039 over the same period. LESSONS LEARNT: A clinical guideline on psychological therapies is a prerequisite for increasing the accessibility and efficiency of mental health services. An integrated approach allows mental health services to have better reach. Routine collection of patient-level outcome data plays an important role in the value and function of the mental health care system.

The Effect of Clozapine on Self-reported Duration of Sleep and Its Interaction With 23 Other Medications: A 5-Year Naturalistic Study.

BACKGROUND: Sedation is a common and incapacitating clozapine adverse effect, but the factors associated with sedation and its pharmacological management remain poorly studied. METHODS: We conducted a retrospective cohort study based on deidentified electronic clinical records of clozapine-treated patients from the secondary mental health care provider for Cambridgeshire and Peterborough, United Kingdom. We first evaluated cross-sectionally the influence of clozapine dose, clozapine, and norclozapine plasma levels on self-reported hours slept, as a proxy for sedation, using bivariate correlation and then the longitudinal effect of changes in clozapine dose and other 23 medications using linear mixed effect models. We followed 241 clozapine-treated patients for 56 months on average, with 2237 face-to-face assessments in total. RESULTS: Patients slept for a mean of 9.35 h/d, with 46% reporting 10 h/d or more. Cross-sectionally, sleep duration did not correlate with clozapine dose (r = 0.14, P = 0.106), but with clozapine plasma levels (r = 0.38, P < 0.0001) and norclozapine plasma levels (r = 0.25, P = 0.005). Longitudinally, the final mixed-effects model revealed 4 pharmacological variables that had a significant impact on hours slept: clozapine, risperidone augmentation, and atenolol were associated with increased sleep, whereas aripiprazole augmentation was associated with decreased sleep. We found that 20 other psychotropic medications measured were not associated with changes in sleep when added to clozapine. Excess sleep is a clozapine level-dependent adverse effect. CONCLUSIONS: The impact of different augmentation strategies might help clinicians decide on the most adequate strategy, albeit further studies should confirm our results.

Risk factors for excess deaths during lockdown among older users of secondary care mental health services without confirmed COVID-19: A retrospective cohort study.

OBJECTIVE: To investigate factors contributing to excess deaths of older patients during the initial 2020 lockdown beyond those attributable to confirmed COVID-19. METHODS: Retrospective cohort study comparing patients treated between 23 March 2020 and 14 June 2020, deemed exposed to the pandemic/lockdown, to patients treated between 18 December 2019 and 10 March 2020, deemed to be unexposed. Data came from electronic clinical records from secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK (catchment area population ∼0.86 million). Eligible patients were aged 65 years or over at baseline with at least 14 days' follow-up, excluding patients diagnosed with confirmed or suspected SARS-CoV-2 infection. The primary outcome was all-cause mortality. FINDINGS: In the two cohorts, 3,073 subjects were exposed to lockdown and 4,372 subjects were unexposed; the cohorts were followed up for an average of 74 and 78 days, respectively. After controlling for confounding by sociodemographic factors, smoking status, mental comorbidities, and physical comorbidities, patients with dementia suffered an additional 53% risk of death (HR = 1.53, 95% CI = 1.02-2.31), and patients with severe mental illness suffered an additional 123% risk of death (HR = 2.23, 95% CI = 1.42-3.49). No significant additional mortality risks were identified from physical comorbidities, potentially due to low statistical power in that respect. CONCLUSION: During lockdown people with dementia or severe mental illness had a higher risk of death without confirmed COVID-19. These data could inform future health service responses and policymaking to help prevent avoidable excess death during future outbreaks of this or a similar infectious disease.

Investigation of risk of dementia diagnosis and death in patients in older people's secondary care mental health services.

OBJECTIVES: Previous studies have shown increased rates of death and dementia in older people in specific serious mental illnesses (SMI) such as bipolar disorder or depression. We examined the rates of death and dementia in older people referred into a secondary care psychiatric service across a range of SMIs. METHODS: We used an anonymised dataset across 6 consecutive years with 28,340 patients aged 65 years and older from a single secondary care psychiatric trust in the United Kingdom. We identified deaths and incident dementia in patients with bipolar disorder/mania, schizophrenia, recurrent depression and anxiety disorders. We compared mortality and dementia rates between these diagnostic groups and in different treatment settings. We also examined mortality rates and dementia rates compared with general population rates. RESULTS: Patients with schizophrenia showed the highest hazard rate for death compared to other groups with SMIs (hazard ratio, 1.58; 95% confidence interval (CI), 1.18-2.1, with anxiety group the reference). Survival was reduced in patients referred to liaison psychiatry services. There were no significant differences between the SMI groups in terms of rates of dementia. However, risks of death and dementia were significantly increased compared to the general population (standardized mortality rates with 95% CI, 2.6(2.0-3.3), 3.5(2.6-4.5), 2.5(2.0-3.0) and 1.8 (1.4-2.2) and standardized dementia incidence rates with 95% CI, 2.7(1.5-4.1), 2.9(1.5-4.7), 3.8(2.6-5.2) and 4.3 (3.0-5.7) for bipolar disorder/mania, schizophrenia, recurrent depression and anxiety disorders respectively. CONCLUSIONS: Older adults referred into an old age psychiatry service show higher rates of dementia and death than those reported for the general population.