Multimorbidity: What do we know? What should we do?

Multimorbidity, which is defined as the co-occurrence of two or more chronic conditions, has moved onto the priority agenda for many health policymakers and healthcare providers. Patients with multimorbidity are high utilizers of healthcare resources and are some of the most costly and difficult-to-treat patients in Europe. Preventing and improving the way multimorbidity is managed is now a key priority for many countries, and work is at last underway to develop more sustainable models of care. Unfortunately, this effort is being hampered by a lack of basic knowledge about the aetiology, epidemiology, and risk factors for multimorbidity, and the efficacy and cost-effectiveness of different interventions. The European Commission recognizes the need for reform in this area and has committed to raising awareness of multimorbidity, encouraging innovation, optimizing the use of existing resources, and coordinating the efforts of different stakeholders across the European Union. Many countries have now incorporated multimorbidity into their own healthcare strategies and are working to strengthen their prevention efforts and develop more integrated models of care. Although there is some evidence that integrated care for people with multimorbidity can create efficiency gains and improve health outcomes, the evidence is limited, and may only be applicable to high-income countries with relatively strong and well-resourced health systems. In low- to middle-income countries, which are facing the double burden of infectious and chronic diseases, integration of care will require capacity building, better quality services, and a stronger evidence base. Journal of Comorbidity 2016;6(1):4–1

Catalytic cleavage of HEAT and subsequent covalent binding of the tetralone moiety by the SARS-CoV-2 main protease

Here we present the crystal structure of SARS-CoV-2 main protease (Mpro) covalently bound to 2-methyl-1-tetralone. This complex was obtained by co-crystallization of Mpro with HEAT (2-(((4-hydroxyphenethyl)amino)methyl)-3,4-dihydronaphthalen-1(2H)-one) in the framework of a large X-ray crystallographic screening project of Mpro against a drug repurposing library, consisting of 5632 approved drugs or compounds in clinical phase trials. Further investigations showed that HEAT is cleaved by Mpro in an E1cB-like reaction mechanism into 2-methylene-1-tetralone and tyramine. The catalytic Cys145 subsequently binds covalently in a Michael addition to the methylene carbon atom of 2-methylene-1-tetralone. According to this postulated model HEAT is acting in a pro-drug-like fashion. It is metabolized by Mpro, followed by covalent binding of one metabolite to the active site. The structure of the covalent adduct elucidated in this study opens up a new path for developing non-peptidic inhibitors

X ray screening identifies active site and allosteric inhibitors of SARS CoV 2 main protease

The coronavirus disease COVID 19 caused by SARS CoV 2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID 19, we have performed a high throughput x ray crystallographic screen of two repurposing drug libraries against the SARS CoV 2 main protease Mpro , which is essential for viral replication. In contrast to commonly applied x ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS CoV

Factorial structure and preliminary validation of the Schema Mode Inventory for Eating Disorders (SMI-ED)

Objective: The aim of this study was to examine the psychometric properties and factorial structure of the Schema Mode Inventory for Eating Disorders (SMI-ED) in a disordered eating population. Method: 573 participants with disordered eating patterns as measured by the Eating Disorder Examination Questionnaire (EDE-Q) completed the 190-item adapted version of the Schema Mode Inventory (SMI). The new SMI-ED was developed by clinicians/researchers specializing in the treatment of eating disorders, through combining items from the original SMI with a set of additional questions specifically representative of the eating disorder population. Psychometric testing included Confirmatory Factor Analysis (CFA) and internal consistency (Cronbach's a). Multivariate Analyses of Covariance (MANCOVA) was also run to test statistical differences between the EDE-Q subscales on the SMI-ED modes, while controlling for possible confounding variables. Results: Factorial analysis confirmed an acceptable 16-related-factors solution for the SMI-ED, thus providing preliminary evidence for the adequate validity of the new measure based on internal structure. Concurrent validity was also established through moderate to high correlations on the modes most relevant to eating disorders with EDE-Q subscales. This study represents the first step in creating a psychometrically sound instrument for measuring schema modes in eating disorders, and provides greater insight into the relevant schema modes within this population. Conclusion: This research represents an important preliminary step toward understanding and labeling the schema mode model for this clinical group. Findings from the psychometric evaluation of SMI-ED suggest that this is a useful tool which may further assist in the measurement and conceptualization of schema modes in this population

Factorial Structure and Preliminary Validation of the Schema Mode Inventory for Eating Disorders (SMI-ED)

Objective: The aim of this study was to examine the psychometric properties and factorial structure of the Schema Mode Inventory for Eating Disorders (SMI-ED) in a disordered eating population.Method: 573 participants with disordered eating patterns as measured by the Eating Disorder Examination Questionnaire (EDE-Q) completed the 190-item adapted version of the Schema Mode Inventory (SMI). The new SMI-ED was developed by clinicians/researchers specializing in the treatment of eating disorders, through combining items from the original SMI with a set of additional questions specifically representative of the eating disorder population. Psychometric testing included Confirmatory Factor Analysis (CFA) and internal consistency (Cronbach's α). Multivariate Analyses of Covariance (MANCOVA) was also run to test statistical differences between the EDE-Q subscales on the SMI-ED modes, while controlling for possible confounding variables.Results: Factorial analysis confirmed an acceptable 16-related-factors solution for the SMI-ED, thus providing preliminary evidence for the adequate validity of the new measure based on internal structure. Concurrent validity was also established through moderate to high correlations on the modes most relevant to eating disorders with EDE-Q subscales. This study represents the first step in creating a psychometrically sound instrument for measuring schema modes in eating disorders, and provides greater insight into the relevant schema modes within this population.Conclusion: This research represents an important preliminary step toward understanding and labeling the schema mode model for this clinical group. Findings from the psychometric evaluation of SMI-ED suggest that this is a useful tool which may further assist in the measurement and conceptualization of schema modes in this population

The PRESIDE (PhaRmacogEnomicS In DEpression) Trial: a double-blind randomised controlled trial of pharmacogenomic-informed prescribing of antidepressants on depression outcomes in patients with major depressive disorder in primary care

Abstract Background The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs. Methods The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention. Discussion This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021

Headline indicators for monitoring the performance of health systems: findings from the european Health Systems_Indicator (euHS_I) survey

Abstract Background Cross-country comparisons of health system performance have become increasingly important. Clear evidence is needed on the prioritization of health system performance assessment (HSPA) indicators. Selected “leading” or “headline” HSPA indicators may provide early warnings of policy impacts. The goal of this paper is to propose a set of headline indicators to frame and describe health system performance. Methods We identified overlaps and gaps in the availability of reported indicators by looking at HSPA initiatives in Member States (MSs) of the European Union (EU), the European Commission as well as international institutions (e.g. OECD, WHO-EUR). On that basis, we conducted a two-stage online survey, the european Health System_Indicator (euHS_I) survey. The survey sought to elicit preferences from a wide range of HSPA experts on i) the most relevant HSPA domain(s), i.e. access, efficiency, quality of care, equity, for a specific indicator, and ii) the importance of indicators regarding their information content, i.e. headline, operational, explanatory. Frequency analysis was performed. Results We identified 2168 health and health system indicators listed in 43 relevant initiatives. After adjusting for overlaps, a total of 361 indicators were assessed by 28 experts in the 1st stage of the survey. In the 2nd stage, a more balanced set of 95 indicators was constructed and assessed by 72 experts from 22 EU MSs and 3 non-EU countries. In the domain access experts assessed share of population covered by health insurance as the top headline indicator. In the domain efficiency, the highest rank was given to Total health care expenditure by all financing agents, and in the domain quality of care to rate of hospital-acquired infections. Percentage of households experiencing high levels/catastrophic of out-of-pocket health expenditures results as the top headline indicator for domain equity. Conclusions HSPA indicators from different initiatives largely overlap and public health indicators dominate over health systems aspects. The survey allowed to quantify overlaps and gaps in HSPA indicators, their expert allocation to domain areas and establishment of an informed hierarchy structure. Yet, results show that more multidisciplinary work is needed to ensure the availability of accurate efficiency indicators which are comparable across countries