Metro South Health

OBJECTIVE: To examine the psychological effects on clinicians of working to manage novel viral outbreaks, and successful measures to manage stress and psychological distress. DESIGN: Rapid review and meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials, PubMed/Medline, PsycInfo, Scopus, Web of Science, Embase, and Google Scholar, searched up to late March 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Any study that described the psychological reactions of healthcare staff working with patients in an outbreak of any emerging virus in any clinical setting, irrespective of any comparison with other clinicians or the general population. RESULTS: 59 papers met the inclusion criteria: 37 were of severe acute respiratory syndrome (SARS), eight of coronavirus disease 2019 (covid-19), seven of Middle East respiratory syndrome (MERS), three each of Ebola virus disease and influenza A virus subtype H1N1, and one of influenza A virus subtype H7N9. Of the 38 studies that compared psychological outcomes of healthcare workers in direct contact with affected patients, 25 contained data that could be combined in a pairwise meta-analysis comparing healthcare workers at high and low risk of exposure. Compared with lower risk controls, staff in contact with affected patients had greater levels of both acute or post-traumatic stress (odds ratio 1.71, 95% confidence interval 1.28 to 2.29) and psychological distress (1.74, 1.50 to 2.03), with similar results for continuous outcomes. These findings were the same as in the other studies not included in the meta-analysis. Risk factors for psychological distress included being younger, being more junior, being the parents of dependent children, or having an infected family member. Longer quarantine, lack of practical support, and stigma also contributed. Clear communication, access to adequate personal protection, adequate rest, and both practical and psychological support were associated with reduced morbidity. CONCLUSIONS: Effective interventions are available to help mitigate the psychological distress experienced by staff caring for patients in an emerging disease outbreak. These interventions were similar despite the wide range of settings and types of outbreaks covered in this review, and thus could be applicable to the current covid-19 outbreak.

There is increasing academic and clinical interest in how "lifestyle factors" traditionally associated with physical health may also relate to mental health and psychological well-being. In response, international and national health bodies are producing guidelines to address health behaviors in the prevention and treatment of mental illness. However, the current evidence for the causal role of lifestyle factors in the onset and prognosis of mental disorders is unclear. We performed a systematic meta-review of the top-tier evidence examining how physical activity, sleep, dietary patterns and tobacco smoking impact on the risk and treatment outcomes across a range of mental disorders. Results from 29 meta-analyses of prospective/cohort studies, 12 Mendelian randomization studies, two meta-reviews, and two meta-analyses of randomized controlled trials were synthesized to generate overviews of the evidence for targeting each of the specific lifestyle factors in the prevention and treatment of depression, anxiety and stress-related disorders, schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. Standout findings include: a) convergent evidence indicating the use of physical activity in primary prevention and clinical treatment across a spectrum of mental disorders; b) emerging evidence implicating tobacco smoking as a causal factor in onset of both common and severe mental illness; c) the need to clearly establish causal relations between dietary patterns and risk of mental illness, and how diet should be best addressed within mental health care; and d) poor sleep as a risk factor for mental illness, although with further research required to understand the complex, bidirectional relations and the benefits of non-pharmacological sleep-focused interventions. The potentially shared neurobiological pathways between multiple lifestyle factors and mental health are discussed, along with directions for future research, and recommendations for the implementation of these findings at public health and clinical service levels.

OBJECTIVES: This guideline provides recommendations for the clinical management of schizophrenia and related disorders for health professionals working in Australia and New Zealand. It aims to encourage all clinicians to adopt best practice principles. The recommendations represent the consensus of a group of Australian and New Zealand experts in the management of schizophrenia and related disorders. This guideline includes the management of ultra-high risk syndromes, first-episode psychoses and prolonged psychoses, including psychoses associated with substance use. It takes a holistic approach, addressing all aspects of the care of people with schizophrenia and related disorders, not only correct diagnosis and symptom relief but also optimal recovery of social function. METHODS: The writing group planned the scope and individual members drafted sections according to their area of interest and expertise, with reference to existing systematic reviews and informal literature reviews undertaken for this guideline. In addition, experts in specific areas contributed to the relevant sections. All members of the writing group reviewed the entire document. The writing group also considered relevant international clinical practice guidelines. Evidence-based recommendations were formulated when the writing group judged that there was sufficient evidence on a topic. Where evidence was weak or lacking, consensus-based recommendations were formulated. Consensus-based recommendations are based on the consensus of a group of experts in the field and are informed by their agreement as a group, according to their collective clinical and research knowledge and experience. Key considerations were selected and reviewed by the writing group. To encourage wide community participation, the Royal Australian and New Zealand College of Psychiatrists invited review by its committees and members, an expert advisory committee and key stakeholders including professional bodies and special interest groups. RESULTS: The clinical practice guideline for the management of schizophrenia and related disorders reflects an increasing emphasis on early intervention, physical health, psychosocial treatments, cultural considerations and improving vocational outcomes. The guideline uses a clinical staging model as a framework for recommendations regarding assessment, treatment and ongoing care. This guideline also refers its readers to selected published guidelines or statements directly relevant to Australian and New Zealand practice. CONCLUSIONS: This clinical practice guideline for the management of schizophrenia and related disorders aims to improve care for people with these disorders living in Australia and New Zealand. It advocates a respectful, collaborative approach; optimal evidence-based treatment; and consideration of the specific needs of those in adverse circumstances or facing additional challenges.

Neuronal dynamics display a complex spatiotemporal structure involving the precise, context-dependent coordination of activation patterns across a large number of spatially distributed regions. Functional magnetic resonance imaging (fMRI) has played a central role in demonstrating the nontrivial spatial and topological structure of these interactions, but thus far has been limited in its capacity to study their temporal evolution. Here, using high-resolution resting-state fMRI data obtained from the Human Connectome Project, we mapped time-resolved functional connectivity across the entire brain at a subsecond resolution with the aim of understanding how nonstationary fluctuations in pairwise interactions between regions relate to large-scale topological properties of the human brain. We report evidence for a consistent set of functional connections that show pronounced fluctuations in their strength over time. The most dynamic connections are intermodular, linking elements from topologically separable subsystems, and localize to known hubs of default mode and fronto-parietal systems. We found that spatially distributed regions spontaneously increased, for brief intervals, the efficiency with which they can transfer information, producing temporary, globally efficient network states. Our findings suggest that brain dynamics give rise to variations in complex network properties over time, possibly achieving a balance between efficient information-processing and metabolic expenditure.

BACKGROUND: Although clozapine is the 'gold standard' for treatment-refractory schizophrenia, meta-analyses of clozapine for this condition are lacking. AIMS: We conducted a systematic review and meta-analysis of clozapine treatment for people with treatment-refractory schizophrenia. METHOD: We searched the Cochrane Schizophrenia Group's trial register, PubMed and EMBASE and hand-searched key papers for randomised controlled trials of clozapine for treatment-refractory schizophrenia. RESULTS: Twenty-one papers with 25 comparisons were included. The number needed to treat was 9. Clozapine was superior for positive symptoms in both the short and long term. In the short term only clozapine was superior for total and negative symptoms, with higher response rates. Both funding source and dosage affected results. Higher baseline psychosis scores predicted better outcomes for clozapine in a meta-regression. CONCLUSIONS: Clozapine is superior for treatment-refractory disorder but if there is no response by 6 months medications with lower adverse reactions should be considered.

BACKGROUND: Gait speed is a quick, inexpensive, reliable measure of functional capacity with well-documented predictive value for major health-related outcomes. Numerous epidemiological studies have documented gait speed in healthy, community-dwelling older people. The purpose of this study is to undertake a systematic review and meta-analysis of gait speed in a specific group with mobility limitations-geriatric patients in clinical settings. METHODS: Relevant databases were searched systematically for original research articles published in February 2011 measuring gait speed in persons aged 70 or older in hospital inpatient or outpatients settings. Meta-analysis determined gait speed data for each setting adjusting for covariates. RESULTS: The review included 48 studies providing data from 7,000 participants. Across the hospital settings, the gait speed estimate for usual pace was 0.58 m/s (95% confidence interval [CI]: 0.49-0.67) and for maximal pace was 0.89 m/s (95% CI: 0.75-1.02). These estimates were based on most recent year of publication (2011) and median percentage of female participants (63%). Gait speed at usual pace in acute care settings was 0.46 m/s (95% CI: 0.34-0.57), which was significantly slower than the gait speed of 0.74 m/s (95% CI: 0.65-0.83) recorded in outpatient settings. CONCLUSIONS: Gait speed is an important measure in comprehensive geriatric assessment. The consolidation of data from multiple studies reported in this meta-analysis highlights the mobility limitations experienced by older people in clinical settings and the need for ongoing rehabilitation to attain levels sufficient for reintegration in the community.

Effective and resource-efficient long-term management of multimorbidity is one of the greatest health-related challenges facing patients, health professionals, and society more broadly. The purpose of this review was to provide a synthesis of literature examining multimorbidity and resource utilization, including implications for cost-effectiveness estimates and resource allocation decision making. In summary, previous literature has reported substantially greater, near exponential, increases in health care costs and resource utilization when additional chronic comorbid conditions are present. Increased health care costs have been linked to elevated rates of primary care and specialist physician occasions of service, medication use, emergency department presentations, and hospital admissions (both frequency of admissions and bed days occupied). There is currently a paucity of cost-effectiveness information for chronic disease interventions originating from patient samples with multimorbidity. The scarcity of robust economic evaluations in the field represents a considerable challenge for resource allocation decision making intended to reduce the burden of multimorbidity in resource-constrained health care systems. Nonetheless, the few cost-effectiveness studies that are available provide valuable insight into the potential positive and cost-effective impact that interventions may have among patients with multiple comorbidities. These studies also highlight some of the pragmatic and methodological challenges underlying the conduct of economic evaluations among people who may have advanced age, frailty, and disadvantageous socioeconomic circumstances, and where long-term follow-up may be required to directly observe sustained and measurable health and quality of life benefits. Research in the field has indicated that the impact of multimorbidity on health care costs and resources will likely differ across health systems, regions, disease combinations, and person-specific factors (including social disadvantage and age), which represent important considerations for health service planning. Important priorities for research include economic evaluations of interventions, services, or health system approaches that can remediate the burden of multimorbidity in safe and cost-effective ways.

OBJECTIVE: No study has reported global disability burden estimates for individual diabetes-related lower-extremity complications (DRLECs). The Global Burden of Disease (GBD) study presents a robust opportunity to address this gap. RESEARCH DESIGN AND METHODS: GBD 2016 data, including prevalence and years lived with disability (YLDs), for the DRLECs of diabetic neuropathy, foot ulcer, and amputation with and without prosthesis were used. The GBD estimated prevalence using data from systematic reviews and DisMod-MR 2.1, a Bayesian meta-regression tool. YLDs were estimated as the product of prevalence estimates and disability weights for each DRLEC. We reported global and sex-, age-, region-, and country-specific estimates for each DRLEC for 1990 and 2016. RESULTS: In 2016, an estimated 131 million people (1.8% of the global population) had DRLECs. An estimated 16.8 million YLDs (2.1% global YLDs) were caused by DRLECs, including 12.9 million (95% uncertainty interval 8.30-18.8) from neuropathy only, 2.5 million (1.7-3.6) from foot ulcers, 1.1 million (0.7-1.4) from amputation without prosthesis, and 0.4 million (0.3-0.5) from amputation with prosthesis. Age-standardized YLD rates of all DRLECs increased by between 14.6% and 31.0% from 1990 estimates. Male-to-female YLD ratios ranged from 0.96 for neuropathy only to 1.93 for foot ulcers. The 50- to 69-year-old age-group accounted for 47.8% of all YLDs from DRLECs. CONCLUSIONS: These first-ever global estimates suggest that DRLECs are a large and growing contributor to the disability burden worldwide and disproportionately affect males and middle- to older-aged populations. These findings should facilitate policy makers worldwide to target strategies at populations disproportionately affected by DRLECs.

Cognitive function requires the coordination of neural activity across many scales, from neurons and circuits to large-scale networks. As such, it is unlikely that an explanatory framework focused upon any single scale will yield a comprehensive theory of brain activity and cognitive function. Modelling and analysis methods for neuroscience should aim to accommodate multiscale phenomena. Emerging research now suggests that multi-scale processes in the brain arise from so-called critical phenomena that occur very broadly in the natural world. Criticality arises in complex systems perched between order and disorder, and is marked by fluctuations that do not have any privileged spatial or temporal scale. We review the core nature of criticality, the evidence supporting its role in neural systems and its explanatory potential in brain health and disease.

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.

OBJECTIVE: The 2010 Survey of High Impact Psychosis (SHIP) is Australia's second national psychosis survey. This paper provides an overview of its findings, including comparisons with the first psychosis survey and general population data. METHODS: The survey covered 1.5 million people aged 18-64 years, approximately 10% of Australians in this age group. A two-phase design was used. In phase 1, screening for psychosis took place in public mental health services and non-government organizations supporting people with mental illness. In phase 2, 1825 of those screen-positive for psychosis were randomly selected and interviewed. Data collected included symptomatology, substance use, functioning, service utilization, medication use, education, employment, housing, and physical health including fasting blood samples. RESULTS: The estimated 1-month treated prevalence of psychotic disorders in public treatment services was 3.1 people per 1000 population; the 12-month treated prevalence was 4.5 people per 1000. The majority (63.0%) of participants met ICD-10 criteria for schizophrenia/schizoaffective disorder. One-half (49.5%) reported attempting suicide in their lifetime and two-thirds (63.2%) were rated as impaired in their ability to socialize. Over half (54.8%) had metabolic syndrome. The proportion currently smoking was 66.1%. Educational achievement was low. Only 21.5% were currently employed. Key changes in the 12 years since the first survey included: a marked drop in psychiatric inpatient admissions; a large increase in the proportion attending community mental health clinics; increased use of rehabilitation services and non-government organizations supporting people with mental illness; a major shift from typical to atypical antipsychotics; and large increases in the proportions with lifetime alcohol or drug abuse/dependence. CONCLUSION: People with psychotic illness face multiple challenges. An integrated approach to service provision is needed to ensure that their living requirements and needs for social participation are met, in addition to their very considerable mental and physical health needs.

Climate change is negatively impacting the mental health of populations. This scoping review aims to assess the available literature related to climate change and mental health across the World Health Organisation’s (WHO) five global research priorities for protecting human health from climate change. We conducted a scoping review to identify original research studies related to mental health and climate change using online academic databases. We assessed the quality of studies where appropriate assessment tools were available. We identified 120 original studies published between 2001 and 2020. Most studies were quantitative (n = 67), cross-sectional (n = 42), conducted in high-income countries (n = 87), and concerned with the first of the WHO global research priorities—assessing the mental health risks associated with climate change (n = 101). Several climate-related exposures, including heat, humidity, rainfall, drought, wildfires, and floods were associated with psychological distress, worsened mental health, and higher mortality among people with pre-existing mental health conditions, increased psychiatric hospitalisations, and heightened suicide rates. Few studies (n = 19) addressed the other four global research priorities of protecting health from climate change (effective interventions (n = 8); mitigation and adaptation (n = 7); improving decision-support (n = 3); and cost estimations (n = 1)). While climate change and mental health represents a rapidly growing area of research, it needs to accelerate and broaden in scope to respond with evidence-based mitigation and adaptation strategies.

BACKGROUND: The objective of this review was to merge current treatment guidelines and best practice recommendations for management of neuropathic pain into a comprehensive algorithm for primary physicians. The algorithm covers assessment, multidisciplinary conservative care, nonopioid pharmacological management, interventional therapies, neurostimulation, low-dose opioid treatment, and targeted drug delivery therapy. METHODS: Available literature was identified through a search of the US National Library of Medicine's Medline database, PubMed.gov. References from identified published articles also were reviewed for relevant citations. RESULTS: The algorithm provides a comprehensive treatment pathway from assessment to the provision of first- through sixth-line therapies for primary care physicians. Clear indicators for progression of therapy from firstline to sixth-line are provided. Multidisciplinary conservative care and nonopioid medications (tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, gabapentanoids, topicals, and transdermal substances) are recommended as firstline therapy; combination therapy (firstline medications) and tramadol and tapentadol are recommended as secondline; serotonin-specific reuptake inhibitors/anticonvulsants/NMDA antagonists and interventional therapies as third-line; neurostimulation as a fourth-line treatment; low-dose opioids (no greater than 90 morphine equivalent units) are fifth-line; and finally, targeted drug delivery is the last-line therapy for patients with refractory pain. CONCLUSIONS: The presented treatment algorithm provides clear-cut tools for the assessment and treatment of neuropathic pain based on international guidelines, published data, and best practice recommendations. It defines the benefits and limitations of the current treatments at our disposal. Additionally, it provides an easy-to-follow visual guide of the recommended steps in the algorithm for primary care and family practitioners to utilize.

Clozapine is the most effective antipsychotic for the 25% to 33% of people with schizophrenia who are treatment resistant, but not all people achieve response. Using data from a previously published clozapine systematic review and meta-analysis, we explored the proportion of people who achieved response and examined the absolute and percentage change in Positive and Negative Syndrome Scale (PANSS) scores. Overall, 40.1% (95% confidence interval [CI], 36.8%-43.4%) responded, with a mean reduction in PANSS of 22.0 points (95% CI, 20.9-23.1), a reduction of 25.8% (95% CI, 24.7%-26.9%) from baseline. These reductions are clinically meaningful. A 40% response rate to clozapine suggests that 12% to 20% of people with schizophrenia will be ultra-resistant.

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.

Populations with common physical diseases - such as cardiovascular diseases, cancer and neurodegenerative disorders - experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug-drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic-pituitary-adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio-environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases.

BACKGROUND: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies. METHODS: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions. FINDINGS: ). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died. INTERPRETATION: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma. FUNDING: None.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

BACKGROUND: Falls remain a common and debilitating problem in hospitals worldwide. The aim of this study was to investigate the effects of falls prevention interventions on falls rates and the risk of falling in hospital. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Hospitalised adults. INTERVENTION: Prevention methods included staff and patient education, environmental modifications, assistive devices, policies and systems, rehabilitation, medication management and management of cognitive impairment. We evaluated single and multi-factorial approaches. OUTCOME MEASURES: Falls rate ratios (rate ratio: RaR) and falls risk, as defined by the odds of being a faller in the intervention compared to control group (odds ratio: OR). RESULTS: There were 43 studies that satisfied the systematic review criteria and 23 were included in meta-analyses. There was marked heterogeneity in intervention methods and study designs. The only intervention that yielded a significant result in the meta-analysis was education, with a reduction in falls rates (RaR = 0.70 [0.51-0.96], P = 0.03) and the odds of falling (OR = 0.62 [0.47-0.83], P = 0.001). The patient and staff education studies in the meta-analysis were of high quality on the GRADE tool. Individual trials in the systematic review showed evidence for clinician education, some multi-factorial interventions, select rehabilitation therapies, and systems, with low to moderate risk of bias. CONCLUSION: Patient and staff education can reduce hospital falls. Multi-factorial interventions had a tendency towards producing a positive impact. Chair alarms, bed alarms, wearable sensors and use of scored risk assessment tools were not associated with significant fall reductions.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.