Leicestershire Partnership NHS Trust

OBJECTIVE: To quantify the risk of developing dementia in those with mild cognitive impairment (MCI). METHOD: Meta-analysis of inception cohort studies. RESULTS: Forty-one robust cohort studies were identified. To avoid heterogeneity clinical studies, population studies and clinical trials were analysed separately. Using Mayo defined MCI at baseline and adjusting for sample size, the cumulative proportion who progressed to dementia, to Alzheimer's disease (AD) and to vascular dementia (VaD) was 39.2%, 33.6% and 6.2%, respectively in specialist settings and 21.9%, 28.9% and 5.2%, respectively in population studies. The adjusted annual conversion rate (ACR) from Mayo defined MCI to dementia, AD and VaD was 9.6%, 8.1% and 1.9%, respectively in specialist clinical settings and 4.9%, 6.8% and 1.6% in community studies. Figures from non-Mayo defined MCI and clinical trials are also reported. CONCLUSION: The ACR is approximately 5-10% and most people with MCI will not progress to dementia even after 10 years of follow-up.

Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta-analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%-34.4%; N = 198; n = 52,678). Relative risk meta-analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta-analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = -3.6, p = 0.0003, r(2) = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic-naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35-1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.

The data given in the published solvent guides have been compiled. An acceptable alignment of the classifications could be met.

PURPOSE: This review summarizes the need for and process of screening for distress and assessing unmet needs of patients with cancer as well as the possible benefits of implementing screening. METHODS: Three areas of the relevant literature were reviewed and summarized using structured literature searches: psychometric properties of commonly used distress screening tools, psychometric properties of relevant unmet needs assessment tools, and implementation of distress screening programs that assessed patient-reported outcomes (PROs). RESULTS: Distress and unmet needs are common problems in cancer settings, and programs that routinely screen for and treat distress are feasible, particularly when staff are supported and links with specialist psychosocial services exist. Many distress screening and unmet need tools have been subject to preliminary validation, but few have been compared head to head in independent centers and in different stages of cancer. Research investigating the overall effectiveness of screening for distress in terms of improved recognition and treatment of distress and associated problems is not yet conclusive, but screening seems to improve communication between patients and clinicians and may enhance psychosocial referrals. Direct effects on quality of life are uncertain, but screening may help improve discussion of quality-of-life issues. CONCLUSION: Involving all stakeholders and frontline clinicians when planning screening for distress programs is recommended. Training frontline staff to deliver screening programs is crucial, and continuing to rigorously evaluate outcomes, including PROs, process of care, referrals, and economic costs and benefits is essential.

OBJECTIVE: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. METHODS: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. RESULTS: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. CONCLUSIONS: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors.

BACKGROUND: The Patient Health Questionnaire (PHQ) is the most commonly used measure to screen for depression in primary care but there is still lack of clarity about its accuracy and optimal scoring method. AIMS: To determine via meta-analysis the diagnostic accuracy of the PHQ-9-linear, PHQ-9-algorithm and PHQ-2 questions to detect major depressive disorder (MDD) among adults. METHOD: We systematically searched major electronic databases from inception until June 2015. Articles were included that reported the accuracy of PHQ-9 or PHQ-2 questions for diagnosing MDD in primary care defined according to standard classification systems. We carried out a meta-analysis, meta-regression, moderator and sensitivity analysis. RESULTS: Overall, 26 publications reporting on 40 individual studies were included representing 26 902 people (median 502, s.d.=693.7) including 14 760 unique adults of whom 14.3% had MDD. The methodological quality of the included articles was acceptable. The meta-analytic area under the receiver operating characteristic curve of the PHQ-9-linear and the PHQ-2 was significantly higher than the PHQ-9-algorithm, a difference that was maintained in head-to-head meta-analysis of studies. Our best estimates of sensitivity and specificity were 81.3% (95% CI 71.6-89.3) and 85.3% (95% CI 81.0-89.1), 56.8% (95% CI 41.2-71.8) and 93.3% (95% CI 87.5-97.3) and 89.3% (95% CI 81.5-95.1) and 75.9% (95% CI 70.1-81.3) for the PHQ-9-linear, PHQ-9-algorithm and PHQ-2 respectively. For case finding (ruling in a diagnosis), none of the methods were suitable but for screening (ruling out non-cases), all methods were encouraging with good clinical utility, although the cut-off threshold must be carefully chosen. CONCLUSIONS: The PHQ can be used as an initial first step assessment in primary care and the PHQ-2 is adequate for this purpose with good acceptability. However, neither the PHQ-2 nor the PHQ-9 can be used to confirm a clinical diagnosis (case finding). DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

UNLABELLED: We aimed to discover whether metabolic complications of schizophrenia (SZ) are present in first episode (FE) and unmedicated (UM) patients, in comparison with patients established on antipsychotic medication (AP). METHOD: A systematic search, critical appraisal, and meta-analysis were conducted of studies to December 2011 using Medline, PsycINFO, Embase and experts. Twenty-six studies examined FE SZ patients (n = 2548) and 19 included UM SZ patients (n = 1325). For comparison we identified 78 publications involving 24 892 medicated patients who had chronic SZ already established on AP. RESULTS: In UM, the overall rate of metabolic syndrome (MetS) was 9.8% using any standardized criteria. Diabetes was found in only 2.1% and hyperglycaemia (>100 mg/dl) in 6.4%. In FE, the overall MetS rate was 9.9%, diabetes was found in only 1.2%, and hyperglycaemia in 8.7%. In UM and FE, the rates of overweight were 26.6%, 22%; hypertriglyceridemia 16.9%, 19.6%; low HDL 20.4%, 21.9%; high blood pressure 24.3%, 30.4%; smoking 40.2%, 46.8%, respectively. In both groups all metabolic components and risk factors were significantly less common in early SZ than in those already established on AP. Waist size, blood pressure and smoking were significantly lower in UM compared with FE. CONCLUSION: There is a significantly lower cardiovascular risk in early SZ than in chronic SZ. Both diabetes and pre-diabetes appear uncommon in the early stages, especially in UM. However, smoking does appear to be elevated early after diagnosis. Clinicians should focus on preventing initial cardiometabolic risk because subsequent reduction in this risk is more difficult to achieve, either through behavioral or pharmacologic interventions.

A meta-analysis was conducted to explore the risk for cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia and age- and gender- or cohort-matched general population controls. Our literature search generated 203 relevant studies, of which 136 were included. The final dataset comprised 185,606 unique patients with schizophrenia, and 28 studies provided data for age- and gender-matched or cohort-matched general population controls (n=3,898,739). We found that multi-episode patients with schizophrenia were at increased risk for abdominal obesity (OR=4.43; CI=2.52-7.82; p<0.001), hypertension (OR=1.36; CI=1.21-1.53; p<0.001), low high-density lipoprotein cholesterol (OR=2.35; CI=1.78-3.10; p<0.001), hypertriglyceridemia (OR=2.73; CI=1.95-3.83; p<0.001), metabolic syndrome (OR=2.35; CI=1.68-3.29; p<0.001), and diabetes (OR=1.99; CI=1.55-2.54; p<0.001), compared to controls. Multi-episode patients with schizophrenia were also at increased risk, compared to first-episode (p<0.001) and drug-naïve (p<0.001) patients, for the above abnormalities, with the exception of hypertension and diabetes. Our data provide further evidence supporting WPA recommendations on screening, follow-up, health education and lifestyle changes in people with schizophrenia.

BACKGROUND: Individuals with depression have an elevated risk of cardiovascular disease (CVD) and metabolic syndrome (MetS) is an important risk factor for CVD. We aimed to clarify the prevalence and correlates of MetS in persons with robustly defined major depressive disorder (MDD). METHOD: We searched Medline, PsycINFO, EMBASE and CINAHL up until June 2013 for studies reporting MetS prevalences in individuals with MDD. Medical subject headings 'metabolic' OR 'diabetes' or 'cardiovascular' or 'blood pressure' or 'glucose' or 'lipid' AND 'depression' OR 'depressive' were used in the title, abstract or index term fields. Manual searches were conducted using reference lists from identified articles. RESULTS: The initial electronic database search resulted in 91 valid hits. From candidate publications following exclusions, our search generated 18 studies with interview-defined depression (n = 5531, 38.9% male, mean age = 45.5 years). The overall proportion with MetS was 30.5% [95% confidence interval (CI) 26.3-35.1] using any standardized MetS criteria. Compared with age- and gender-matched control groups, individuals with MDD had a higher MetS prevalence [odds ratio (OR) 1.54, 95% CI 1.21-1.97, p = 0.001]. They also had a higher risk for hyperglycemia (OR 1.33, 95% CI 1.03-1.73, p = 0.03) and hypertriglyceridemia (OR 1.17, 95% CI 1.04-1.30, p = 0.008). Antipsychotic use (p < 0.05) significantly explained higher MetS prevalence estimates in MDD. Differences in MetS prevalences were not moderated by age, gender, geographical area, smoking, antidepressant use, presence of psychiatric co-morbidity, and median year of data collection. CONCLUSIONS: The present findings strongly indicate that persons with MDD are a high-risk group for MetS and related cardiovascular morbidity and mortality. MetS risk may be highest in those prescribed antipsychotics.

The prevalence of psoriasis in a defined semi-urban general practice population of 5395 was estimated by means of a postal questionnaire, describing the features of psoriasis followed by physical examination of positive responders, and by a practice disease register, which directly identified psoriatic patients. A point prevalence of 1.48% was found based on examination at the time of study with an equal sex distribution. The mean age of development of the disease was 33 years. At the time of examination, the disease was mild in most patients (mean PASI 2.87). However, there was evidence of marked variability in severity within individuals with time. At some stage, 60% of individuals had required referral to a consultant dermatologist, and approximately 50% of these had received second-line, i.e. non-topical, treatments. Approximately 25% of patients had been in remission at some stage. Forty-one per cent of patients were aware that psoriasis was a genetically determined disease and 37% thought that stress was an exacerbating factor. Seventy per cent of patients were aware that the condition was not curable, but 63% thought that treatment was worthwhile. Fifty-three per cent described themselves as 'bothered' by the appearance of the condition. This concern was positively (and inversely) related to current age, and to stress as an exacerbating factor, but not to sex, PASI, duration of psoriasis, previous hospital referral, or the presence of pruritus. In this study of psoriasis in the community, the findings, particularly in relation to patients' attitude to the disease, disease severity, fluctuation in severity and referral requirements, are of potential interest in health care planning.

OBJECTIVE: To conduct a meta-analysis investigating the prevalence of type two diabetes mellitus (T2DM) in people with schizophrenia compared to controls. METHOD: Systematic review of electronic databases from inception till November 2014. Articles reporting the prevalence of T2DM in people with schizophrenia and healthy controls (without mental illness) were included. Two independent authors conducted searches and extracted data. A random effects relative risks (RR) meta-analysis was conducted. RESULTS: Twenty-five studies including 145,718 individuals with schizophrenia (22.5-54.4 years) and 4,343,407 controls were included. The prevalence of T2DM in people with schizophrenia was 9.5% (95% CI = 7.0-12.8, n = 145,718) and 10.75% (95% CI 7.44-14.5%, n = 2698) in studies capturing T2DM according to recognized criteria. The pooled RR across all studies was 1.82 (95% CI = 1.56-2.13; = 4,489,125). Subgroup analyses found a RR of 2.53 (95% CI = 1.68-3.799, n = 17,727) in studies ascertaining T2DM according to recognized criteria and RR 1.65 (95% CI = 1.34-2.03, n = 4,243,389) in studies relying on T2DM determined through medical records. CONCLUSION: People with schizophrenia are at least double the risk of developing T2DM according to recognized T2DM criteria. Proactive lifestyle and screening programmes should be given clinical priority.

BACKGROUND: As the population ages, it is increasingly important to use effective short cognitive tests for suspected dementia. We aimed to review systematically brief cognitive tests for suspected dementia and report on their validation in different settings, to help clinicians choose rapid and appropriate tests. METHODS: Electronic search for face-to-face sensitive and specific cognitive tests for people with suspected dementia, taking ≤ 20 minutes, providing quantitative psychometric data. RESULTS: 22 tests fitted criteria. Mini-Mental State Examination (MMSE) and Hopkins Verbal Learning Test (HVLT) had good psychometric properties in primary care. In the secondary care settings, MMSE has considerable data but lacks sensitivity. 6-Item Cognitive Impairment Test (6CIT), Brief Alzheimer's Screen, HVLT, and 7 Minute Screen have good properties for detecting dementia but need further validation. Addenbrooke's Cognitive Examination (ACE) and Montreal Cognitive Assessment are effective to detect dementia with Parkinson's disease and Addenbrooke's Cognitive Examination-Revised (ACE-R) is useful for all dementias when shorter tests are inconclusive. Rowland Universal Dementia Assessment scale (RUDAS) is useful when literacy is low. Tests such as Test for Early Detection of Dementia, Test Your Memory, Cognitive Assessment Screening Test (CAST) and the recently developed ACE-III show promise but need validation in different settings, populations, and dementia subtypes. Validation of tests such as 6CIT, Abbreviated Mental Test is also needed for dementia screening in acute hospital settings. CONCLUSIONS: Practitioners should use tests as appropriate to the setting and individual patient. More validation of available tests is needed rather than development of new ones.

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

The pheromone N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) regulates expression of bioluminescence in the marine bacterium Vibrio fischeri, the production of carbapenem antibiotic in Erwinia carotovora and exoenzymes in both E. carotovora and Pseudomonas aeruginosa. A characteristic feature of this regulatory mechanism in V. fischeri is that it is cell density-dependent, reflecting the need to accumulate sufficient pheromone to trigger the induction of gene expression. Using a lux plasmid-based bioluminescent sensor for OHHL, pheromone production by E. carotovora, Enterobacter agglomerans, Hafnia alvei, Rahnella aquatilis and Serratia marcescens has been demonstrated and shown also to be cell density-dependent. Production of OHHL implies the presence in these bacteria of a gene equivalent to luxI. Chromosomal banks from all five enteric bacteria have yielded clones capable of eliciting OHHL production when expressed in Escherichia coli. The luxI homologue from both E. carotovora (carI) and E. agglomerans (eagI) were characterized at the DNA sequence level and the deduced protein sequences have only 25% identity with the V. fischeri LuxI. Despite this, carI, eagI and luxI are shown to be biologically equivalent. An insertion mutant of eagI demonstrates that this gene is essential for OHHL production in E. agglomerans.

BACKGROUND: Although depression and mood-related disorders are common in persons with cancer, these conditions remain frequently overlooked in clinical practice. Negative consequences of depressive disorder spectrum have been reported (e.g. suicidal ideation, increase physical complications and somatic symptoms, negative influence on prognosis), indicating the need for routine screening, assessment and management. METHODS: A search of the major databases (Medline, Embase, PsycLIT, PsycINFO, and the Cochrane Library) was conducted on the reviews and meta-analyses available in order to summarize relevant data concerning depressive disorders spectrum in terms of prevalence, risk factors, and screening and assessment among patients with cancer across the trajectory of the disease. RESULTS: The data show a prevalence of depression and depressive disorders between 5% and 60% according to the different diagnostic criteria, the tools used in the studies (e.g. semi-structured psychiatric interview and psychometric questionnaires), as well as the stage and type of cancer. Furthermore, despite the significant health care resources devoted to cancer care and the importance of addressing depressive symptoms, assessment and management of depressive spectrum disorders in cancer patients remains suboptimal. CONCLUSIONS: Routine screening and adequate assessment of depressive spectrum disorders is necessary in patients with cancer in order to effectively manage the multifaceted and complex consequences on cancer care.

Objective. Screening for distress is controversial with many advocates and detractors. Previously it was reasonable to assert that there was a lack of evidence but this position is no longer tenable. The question is now: what does the evidence show and, in particular, when is screening successful and when is screening unsuccessful? The aim of this paper is to review the most up-to-date recent findings from randomized and non-randomized trials regarding the merits of screening for distress in cancer settings. Methods. A search was made of the Embase/Medline and Web of knowledge abstract databases from inception to December 2012. Online theses and experts were contacted. Inclusion criteria were interventional (randomized and non-randomized) trials concerning screening for psychological distress and related disorders. Studies screening for quality of life were included. Results. Twenty-four valid interventional studies of distress/QoL screening were identified, 14 being randomized controlled trials (RCTs). Six of 14 screening RCTs reported benefits on patient well-being and an additional three showed benefits on secondary outcomes such as communication between clinicians and patients. Five randomized screening trials failed to show any benefits. Only two of 10 non-randomized sequential cohort screening studies reported benefits on patient well-being but an additional six showed secondary benefits on quality of care (such as receipt of psychosocial referral). Two non-randomized screening trials failed to show benefits. Of 24 studies, there were 17 that reported some significant benefits of screening on primary or secondary outcomes, six that reported no effect and one that reported a non-significantly deleterious effect upon communication. Across all studies, barriers to screening success were significant. The most significant barrier was receipt of appropriate aftercare. The proportion of cancer patients who received psychosocial care after a positive distress screen was only one in three. Screening was more effective when it was linked with mandatory intervention or referral. Conclusions. Screening for distress/QoL is likely to benefit communication and referral for psychosocial help. Screening for distress has the potential to influence patient well-being but only if barriers are addressed. Quality of care barriers often act as a rate limiting step. Key barriers are lack of training and support, low acceptability and failure to link treatment to the screening results.

BACKGROUND: Previous studies of weight problems in adults with intellectual disability (ID) have generally been small or selective and given conflicting results. The objectives of our large-scale study were to identify inequalities in weight problems between adults with ID and the general adult population, and to investigate factors associated with obesity and underweight within the ID population. METHODS: We undertook a population-based prevalence study of 1119 adults with ID aged 20 and over on the Leicestershire Learning Disability Register who participated in a programme of universal health checks and home interviews with their carers. We performed a cross-sectional analysis of the register data and compared the observed and expected prevalences of body mass index categories in the ID and general populations using indirect standardisation for age. We used logistic regression to evaluate the association of a range of probable demographic, physical, mental and skills attributes with obesity and underweight. RESULTS: In those aged 25 and over, the standardised morbidity ratio (SMR) for obesity was 0.80 (95% CI 0.64-1.00) in men and 1.48 (95% CI 1.23-1.77) in women. The SMR for underweight was 8.44 (95% CI 6.52-10.82) in men and 2.35 (95% CI 1.72-3.19) in women. Among those aged 20 and over, crude prevalences were 20.7% for obesity, 28.0% for overweight, 32.7% for normal weight and 18.6% for underweight. Obesity was associated with living independently/with family, ability to feed/drink unaided, being female, hypertension, Down syndrome and the absence of cerebral palsy. Underweight was associated with younger age, absence of Down syndrome and not taking medication. CONCLUSION: Obesity in women and underweight in both men and women was more common in adults with ID than in the general population after controlling for differences in the age distributions between the two populations. The associated factors suggest opportunities for targeting high-risk groups within the ID population for lifestyle and behaviour modification.

Eating disorders in dancers are thought to be common, but the exact rates remain to be clarified. The aim of this study is to systematically compile and analyse the rates of eating disorders in dancers. A literature search, appraisal and meta-analysis were conducted. Thirty-three relevant studies were published between 1966 and 2013 with sufficient data for extraction. Primary data were extracted as raw numbers or confidence intervals. Risk ratios and 95% confidence intervals were calculated for controlled studies. The overall prevalence of eating disorders was 12.0% (16.4% for ballet dancers), 2.0% (4% for ballet dancers) for anorexia, 4.4% (2% for ballet dancers) for bulimia and 9.5% (14.9% for ballet dancers) for eating disorders not otherwise specified (EDNOS). The dancer group had higher mean scores on the EAT-26 and the Eating Disorder Inventory subscales. Dancers, in general, had a higher risk of suffering from eating disorders in general, anorexia nervosa and EDNOS, but no higher risk of suffering from bulimia nervosa. The study concluded that as dancers had a three times higher risk of suffering from eating disorders, particularly anorexia nervosa and EDNOS, specifically designed services for this population should be considered.

OBJECTIVE: Many patients who experience distress do not seek help, and little is known about the reasons for this. We explored the reasons for declining help among patients who had significant emotional distress. METHODS: Data were collected through QUICATOUCH screening at an Australian hospital. Oncology outpatients scoring 4 or more on the Distress Thermometer were asked if they would 'like help' with their distress. Those who declined help were asked their reasons. Demographic variables and a clinical measure of anxiety and depression (PSYCH-6) were used to identify factors associated with reasons for declining help. RESULTS: Of 311 patients with significant distress, 221 (71%) declined help. The most common reasons were 'I prefer to manage myself' (n = 99, 46%); 'already receiving help' (n = 52, 24%) and 'my distress is not severe enough' (n = 50, 23%). Younger patients and women were more likely to decline help and were more likely to already be receiving help. Distress score and PSYCH-6 scores were significantly lower among patients who rated their distress as not severe enough to require help. Nevertheless, there were patients who had maximal scores on distress and PSYCH in each group. CONCLUSIONS: Two common patient barriers to help with distress are a preference for self-help and a belief that distress is not sufficiently severe to warrant intervention. These beliefs were held by a sizeable proportion of individuals who reported very high levels of distress. Qualitative research and subsequent interventions for overcoming these barriers are required to obtain the most benefit from distress screening programs.