Comorbid physical health burden of serious mental health disorders in 32 European countries.

BACKGROUND: Mental health disorders (MHDs) are associated with physical health disparities, but underlying excess risk and health burden have not yet been comprehensively assessed. OBJECTIVE: To assess the burden of comorbid physical health conditions (PHCs) across serious MHDs in Europe. METHODS: We estimated the relative prevalence risk of PHCs associated with alcohol use disorders (AUD), bipolar disorder (BD), depressive disorders (DD) and schizophrenia (SZ) across working-age populations of 32 European countries in 2019 based on a targeted literature review. Excess physical health burden was modelled using population-attributable fractions and country-level prevalence data. FINDINGS: We screened 10 960 studies, of which 41 were deemed eligible, with a total sample size of over 18 million persons. Relative prevalence of PHCs was reported in 54%, 20%, 15%, 5% and 7% of studies, respectively, for SZ, DD, BD, AUD or mixed. Significant relative risk estimates ranged from 1.44 to 3.66 for BD, from 1.43 to 2.21 for DD, from 0.81 to 1.97 for SZ and 3.31 for AUD. Excess physical health burden ranged between 27% and 67% of the total, corresponding to 84 million (AUD), 67 million (BD), 66 million (DD) and 5 million (SZ) PHC diagnoses in Europe. A 1% reduction in excess risk assuming causal inference could result in two million fewer PHCs across investigated MHDs. CONCLUSIONS: This is the first comprehensive study of the physical health burden of serious MHDs in Europe. The methods allow for updates, refinement and extension to other MHDs or geographical areas. CLINICAL IMPLICATIONS: The results indicate potential population health benefits achievable through more integrated mental and physical healthcare and prevention approaches.

Analysis of the limited M. tuberculosis accessory genome reveals potential pitfalls of pan-genome analysis approaches.

Pan-genome analysis is a fundamental tool in the study of bacterial genome evolution. Benchmarking the accuracy of pan-genome analysis methods is challenging, because it can be significantly influenced by both the methodology used to compare genomes, as well as differences in the accuracy and representativeness of the genomes analyzed. In this work, we curated a collection of 151 Mycobacterium tuberculosis (Mtb) isolates to evaluate sources of variability in pan-genome analysis. Mtb is characterized by its clonal evolution, absence of horizontal gene transfer, and limited accessory genome, making it an ideal test case for this study. Using a state-of-the-art graph-genome approach, we found that a majority of the structural variation observed in Mtb originates from rearrangement, deletion, and duplication of redundant nucleotide sequences. In contrast, we found that pan-genome analyses that focus on comparison of coding sequences (at the amino acid level) can yield surprisingly variable results, driven by differences in assembly quality and the softwares used. Upon closer inspection, we found that coding sequence annotation discrepancies were a major contributor to inflated Mtb accessory genome estimates. To address this, we developed panqc, a software that detects annotation discrepancies and collapses nucleotide redundancy in pan-genome estimates. We characterized the effect of the panqc adjustment on both pan-genome analysis of Mtb and E. coli genomes, and highlight how different levels of genomic diversity are prone to unique biases. Overall, this study illustrates the need for careful methodological selection and quality control to accurately map the evolutionary dynamics of a bacterial species.

Exploring the role of the private sector in tuberculosis detection and management in Lima, Peru: a mixed-methods patient pathway analysis.

In Latin America, little is known about the involvement of private healthcare providers in TB detection and management. We sought to gain a better understanding of current and potential roles of the private sector in delivering TB services in Peru. We conducted a mixed-methods study in Lima, Peru. The quantitative component comprised a patient pathway analysis assessing the alignment of TB services with patient care-seeking behavior. The qualitative component comprised in-depth interviews with 18 private healthcare providers and 5 key informants. We estimated that 77% of patients initially sought care at a facility with TB diagnostic capacity and 59% at a facility with TB treatment capacity. The lack of TB services at initial care-seeking location was driven by the 41% of patients estimated to seek care first at a private facility. Among private facilities, 43% offered smear microscopy, 13% offered radiography, and none provided TB treatment. Among public sector facilities, 100% offered smear microscopy, 26% offered radiography, and 99% provided TB treatment. Interviews revealed that private providers believed that they offered shorter wait times and a quicker diagnosis, but they struggled with a lack of follow-up systems and communication barriers with the public sector. While expressing willingness to collaborate with public sector programs for diagnosis and referral, private providers had limited interest in treating TB. This study highlights the role of private providers in Peru as an entry point for TB care. Public-private collaboration is necessary to harness the potential of the private sector as an ally for early diagnosis.

Excess resource use and costs of physical comorbidities in individuals with mental health disorders: A systematic literature review and meta-analysis.

Individuals with mental health disorders (MHDs) have worse physical health than the general population, utilise healthcare resources more frequently and intensively, incurring higher costs. We provide a first comprehensive overview and quantitative synthesis of literature on the magnitude of excess resource use and costs for those with MHDs and comorbid physical health conditions (PHCs). This systematic review (PROSPERO CRD42017075319) searched studies comparing resource use or costs of individuals with MHDs and comorbid PHCs versus individuals without comorbid conditions published between 2007 and 2021. We conducted narrative and quantitative syntheses, using random-effects meta-analyses to explore ranges of excess resource use and costs across care segments, comparing to MHD only, PHC only, or general population controls (GPC). Of 20,075 records, 228 and 100 were eligible for narrative and quantitative syntheses, respectively. Most studies were from the US, covered depression or schizophrenia, reporting endocrine/metabolic or circulatory comorbidities. Frequently investigated healthcare segments were inpatient, outpatient, emergency care and medications. Evidence on lost productivity, long-term and informal care was rare. Substantial differences exist between MHDs, with depressive disorder tending towards lower average excess resource use and cost estimates, while excess resource use ranges between +6% to +320% and excess costs between +14% to +614%. PHCs are major drivers of resource use and costs for individuals with MHDs, affecting care segments differently. Significant physical health gains and cost savings are potentially achievable through prevention, earlier identification, management and treatment, using more integrated care approaches. Current international evidence, however, is heterogeneous with limited geographical representativeness and comparability.

Hypothyroidism correlates with favourable survival prognosis in patients with brain metastatic cancer.

BACKGROUND: Several preclinical and epidemiologic studies have indicated tumour-promoting effects of thyroid hormones (THs). However, very limited knowledge exists on the prognostic impact of thyroid function in metastatic cancer. METHODS: We compiled a discovery cohort of 1692 patients with newly diagnosed brain metastases (BMs) of solid cancers treated at the Medical University of Vienna and an independent validation cohort of 191 patients with newly diagnosed BMs treated at the University Hospital Zurich. RESULTS: Hypothyroidism before diagnosis of cancer was evident in 133 of 1692 (7.9%) patients of the discovery, and in 18 of 191 (9.4%) patients of the validation cohort. In the discovery cohort, hypothyroidism was statistically significantly associated with favourable survival prognosis from diagnosis of cancer (31 vs. 21 months; p = 0.0026) and with survival prognosis from diagnosis of BMs (12 vs. 7 months; p = 0.0079). In multivariate analysis including the diagnosis-specific graded prognostic assessment score, primary tumour type and sex, hypothyroidism was an independent factor associated with survival after diagnosis of BMs (hazard ratio: 0.76; 95% confidence interval [CI]: (0.63; 0.91; p = 0.0034). In the validation cohort, the association of hypothyroidism and favourable survival prognosis from diagnosis of cancer (55 vs. 11 months; p = 0.00058), as well as from diagnosis of BMs (40 vs. 10 months; p = 0.0036) was confirmed. CONCLUSION: Pre-existing hypothyroidism was strongly and independently associated with prognosis in patients with newly diagnosed BMs, supporting the evidence from preclinical data that THs may indeed have a tumour-promoting effect. Further investigation of the underlying pathobiological mechanism and potential therapeutic implications are required.

Health and well-being for all: an approach to accelerating progress to achieve the Sustainable Development Goals (SDGs) in countries in the WHO European Region.

BACKGROUND: Forty-three out of 53 of the WHO European Member States have set up political and institutional mechanisms to implement the United Nations (UN) 2030 Agenda for Sustainable Development. This includes governance and institutional mechanisms, engaging stakeholders, identifying targets and indicators, setting governmental and sectoral priorities for action and reporting progress regularly. Still, growing evidence suggests that there is room for advancing implementation of some of the Sustainable Development Goals (SDGs) and targets at a higher pace in the WHO European Region. This article proposes the E4A approach to support WHO European Member States in their efforts to achieve the health-related SDG targets. METHODS: The E4A approach was developed through a 2-year, multi-stage process, starting with the endorsement of the SDG Roadmap by all WHO European Member States in 2017. This approach resulted from a mix of qualitative methods: a semi-structured desk review of existing committal documents and tools; in-country policy dialogs, interviews and reports; joint UN missions and discussion among multi-lateral organizations; consultation with an advisory group of academics and health policy experts across countries. RESULTS: The E-engage-functions as the driver and pace-maker; the 4 As-assess, align, accelerate and account-serve as building blocks composed of policies, processes, activities and interventions operating in continuous and synchronized action. Each of the building blocks is an essential part of the approach that can be applied across geographic and institutional levels. CONCLUSION: While the E4A approach is being finalized, this article aims to generate debate and input to further refine and test this approach from a public health and user perspective.