Development of a cost of illness inventory questionnaire for children with autism spectrum disorder in South Asia.

BACKGROUND: The economic burden of autism is substantial and includes a range of costs, including healthcare, education, productivity losses, informal care and respite care, among others. In India, approximately, 2 million children aged 2-9 years have autism. Given the likely substantial burden of illness and the need to identify effective and cost-effective interventions, this research aimed to produce a comprehensive cost of illness inventory (COII) suitable for children with autism in South Asia (India) to support future research. METHODS: A structured and iterative design process was followed to create the COII, including literature reviews, interviews with caregivers, pilot testing and translation. Across the development of the COII, thirty-two families were involved in the design and piloting of the tool. The COII was forward translated (from English to Hindi) and back translated. Each stage of the process of development of the COII resulted in the further refinement of the tool. RESULTS: Domains covered in the final COII include education, childcare, relocation, healthcare contacts (outpatient, inpatient, medical emergencies, investigations and medication), religious retreats and rituals, specialist equipment, workshops and training, special diet, support and care, certification, occupational adjustments and government rebates/schemes. Administration and completion of the COII determined it to be feasible to complete in 35 minutes by qualified and trained researchers. The final COII is hosted by REDCap Cloud and is a bilingual instrument (Hindi and English). CONCLUSIONS: The COII was developed using experiences gathered from an iterative process in a metropolitan area within the context of one low- and middle-income country (LMIC) setting, India. Compared to COII tools used for children with autism in high-income country settings, additional domains were required, such as complimentary medication (e.g. religious retreats and homeopathy). The COII will allow future research to quantify the cost of illness of autism in India from a broad perspective and will support relevant economic evaluations. Understanding the process of developing the questionnaire will help researchers working in LMICs needing to adapt the current COII or developing similar questionnaires.

Why we heal: The evolution of psychological healing and implications for global mental health.

Why do humans heal one another? Evolutionary psychology has advanced our understanding of why humans suffer psychological distress and mental illness. However, to date, the evolutionary origins of what drives humans to alleviate the suffering of others has received limited attention. Therefore, we draw upon evolutionary theory to assess why humans psychologically support one another, focusing on the interpersonal regulation of emotions that shapes how humans heal and console one another when in psychosocial distress. To understand why we engage in psychological healing, we review the evolution of cooperation among social species and the roles of emotional contagion, empathy, and self-regulation. We discuss key aspects of human biocultural evolution that have contributed to healing behaviors: symbolic logic including language, complex social networks, and the long period of childhood that necessitates identifying and responding to others in distress. However, both biological and cultural evolution also have led to social context when empathy and consoling are impeded. Ultimately, by understanding the evolutionary processes shaping why humans psychologically do or do not heal one another, we can improve our current approaches in global mental health and uncover new opportunities to improve the treatment of mental illness across cultures and context around the world.

"Is there a medicine for these tensions?" Barriers to treatment-seeking for depressive symptoms in rural India: A qualitative study.

Rationale and objective Fewer than 15% of adults who meet criteria for a depression diagnosis in India seek treatment for these symptoms. It is unclear whether this reflects limited supply of mental health services or lack of demand for medical intervention for these experiences. This paper aims to identify and describe self-reported barriers that contribute to this "treatment gap" in a rural district in central India, where depression treatment had recently become available in primary care facilities. METHOD: In this qualitative study we conducted in-depth interviews with 35 adults who screened positive for depression and who had not sought treatment for their condition, and 15 of their relatives. We analysed the data using the framework approach. RESULTS: A key barrier to seeking health care for psychological symptoms was lack of perceived need for treatment for these symptoms. Low perceived need for health interventions arose because participants frequently attributed depression-like symptoms to their socio-economic circumstances, or to the stress of physical illness, which conflicted with the biomedical approach associated with health services. Despite widespread recognition of the links between psychological symptoms, social circumstances and physical health, it was believed that health care providers are equipped to treat only somatic symptoms, which were commonly reported. CONCLUSIONS: Low demand for depression treatment reflected discrepancies between the community's perceived needs and a narrow biomedical model of mental health. Meeting their needs may require a radical change in approach that acknowledges the social determinants of distress, and the interactions between mental and physical health. The capabilities approach may provide a framework for more holistically conceptualising people's needs.

The psychosis treatment gap and its consequences in rural Ethiopia.

BACKGROUND: The "treatment gap" (TG) for mental disorders, widely advocated by the WHO in low-and middle-income countries, is an important indicator of the extent to which a health system fails to meet the care needs of people with mental disorder at the population level. While there is limited research on the TG in these countries, there is even a greater paucity of studies looking at TG beyond a unidimensional understanding. This study explores several dimensions of the TG construct for people with psychosis in Sodo, a rural district in Ethiopia, and its implications for building a more holistic capacity for mental health services. METHOD: The study was a cross-sectional survey of 300 adult participants with psychosis identified through community-based case detection and confirmed through subsequent structured clinical evaluations. The Butajira Treatment Gap Questionnaire (TGQ), a new customised tool with 83 items developed by the Ethiopia research team, was administered to evaluate several TG dimensions (access, adequacy and effectiveness of treatment, and impact/consequence of the treatment gap) across a range of provider types corresponding with the WHO pyramid service framework. RESULTS: Lifetime and current access gap for biomedical care were 41.8 and 59.9% respectively while the corresponding figures for faith and traditional healing (FTH) were 15.1 and 45.2%. Of those who had received biomedical care for their current episode, 71.7% did not receive minimally adequate care. Support from the community and non-governmental organisations (NGOs) were negligible. Those with education (Adj. OR: 2.1; 95% CI: 1.2, 3.8) and history of use of FTH (Adj. OR: 3.2; 95% CI: 1.9-5.4) were more likely to use biomedical care. Inadequate biomedical care was associated with increased lifetime risk of adverse experiences, such as history of restraint, homelessness, accidents and assaults. CONCLUSION: This is the first study of its kind. Viewing TG not as a unidimensional, but as a complex, multi-dimensional construct, offers a more realistic and holistic understanding of health beliefs, help-seeking behaviors, and need for care. The reconceptualized multidimensional TG construct could assist mental health services capacity building advocacy and policy efforts and allow community and NGOs play a larger role in supporting mental healthcare.

Liver Microphysiological Systems for Predicting and Evaluating Drug Effects.

Liver plays a major role in drug metabolism and is one of the main sites of drug adverse effects. Microphysiological systems (MPS), also known as organs-on-a-chip, are a class of microfluidic platforms that recreate properties of tissue microenvironments. Among different properties, the liver microenvironment is three-dimensional, fluid flows around its cells, and different cell types regulate its function. Liver MPS aim to recreate these properties and enable drug testing and measurement of functional endpoints. Tests with these systems have demonstrated their potential for predicting clinical drug effects. Properties of liver MPS that improve the physiology of cell culture are reviewed, specifically focusing on the importance of recreating a physiological microenvironment to evaluate and model drug effects. Advances in modeling hepatic function by leveraging MPS are addressed, noting the need for standardization in the use, quality control, and interpretation of data from these systems.

Integrated care for people with long-term mental and physical health conditions in low-income and middle-income countries.

Integrated care is defined as health services that are managed and delivered such that people receive a continuum of health promotion, disease prevention, diagnosis, treatment, disease management, rehabilitation, and palliative care services, coordinated across the different levels and sites of care within and beyond the health sector and, according to their needs, throughout the life course. In this Review, we describe the most relevant concepts and models of integrated care for people with chronic (or recurring) mental illness and comorbid physical health conditions, provide a conceptual overview and a narrative review of the strength of the evidence base for these models in high-income countries and in low-income and middle-income countries, and identify opportunities to test the feasibility and effects of such integrated care models. We discuss the rationale for integrating care for people with mental disorders into chronic care; the models of integrated care; the evidence of the effects of integrating care in high-income countries and in low-income and middle-income countries; the key organisational challenges to implementing integrated chronic care in low-income and middle-income countries; and the practical steps to realising a vision of integrated care in the future.

Unchaining people with mental disorders: medication is not the solution.

Chaining of people with mental disorders, and their incarceration and abuse in prisons or mental hospitals, is an affront to psychiatry and humanity. Although mental healthcare always needs attention to cultural and social contexts, this must never be at the cost of allowing human rights violations to go unchallenged. A rights-based approach must enforce well-established international human rights conventions, and scale-up comprehensive community services around the needs and preferences of people affected by mental disorders. Declaration of interest None.

Mechanistic Model-Informed Proarrhythmic Risk Assessment of Drugs: Review of the "CiPA" Initiative and Design of a Prospective Clinical Validation Study.

The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a mechanistic-based assessment of the proarrhythmic risk of drugs. CiPA proposes to assess a drug's effect on multiple ion channels and integrate the effects in a computer model of the human cardiomyocyte to predict proarrhythmic risk. Unanticipated or missed effects will be assessed with human stem cell-derived cardiomyocytes and electrocardiogram (ECG) analysis in early phase I clinical trials. This article provides an overview of CiPA and the rationale and design of the CiPA phase I ECG validation clinical trial, which involves assessing an additional ECG biomarker (J-Tpeak) for QT prolonging drugs. If successful, CiPA will 1) create a pathway for drugs with hERG block / QT prolongation to advance without intensive ECG monitoring in phase III trials if they have low proarrhythmic risk; and 2) enable updating drug labels to be more informative about proarrhythmic risk, not just QT prolongation.

District mental healthcare plans for five low- and middle-income countries: commonalities, variations and evidence gaps.

BACKGROUND: Little is known about the service and system interventions required for successful integration of mental healthcare into primary care across diverse low- and middle-income countries (LMIC). AIMS: To examine the commonalities, variations and evidence gaps in district-level mental healthcare plans (MHCPs) developed in Ethiopia, India, Nepal, Uganda and South Africa for the PRogramme for Improving Mental health carE (PRIME). METHOD: A comparative analysis of MHCP components and human resource requirements. RESULTS: A core set of MHCP goals was seen across all countries. The MHCPs components to achieve those goals varied, with most similarity in countries within the same resource bracket (low income v. middle income). Human resources for advanced psychosocial interventions were only available in the existing health service in the best-resourced PRIME country. CONCLUSIONS: Application of a standardised methodological approach to MHCP across five LMIC allowed identification of core and site-specific interventions needed for implementation.

Development and piloting of a plan for integrating mental health in primary care in Sehore district, Madhya Pradesh, India.

BACKGROUND: The large treatment gap for mental disorders in India underlines the need for integration of mental health in primary care. AIMS: To operationalise the delivery of the World Health Organization Mental Health Gap Action Plan interventions for priority mental disorders and to design an integrated mental healthcare plan (MHCP) comprising packages of care for primary healthcare in one district. METHOD: Mixed methods were used including theory of change workshops, qualitative research to develop the MHCP and piloting of specific packages of care in a single facility. RESULTS: The MHCP comprises three enabling packages: programme management, capacity building and community mobilisation; and four service delivery packages: awareness for mental disorders, identification, treatment and recovery. Challenges were encountered in training primary care workers to improve identification and treatment. CONCLUSIONS: There are a number of challenges to integrating mental health into primary care, which can be addressed through the injection of new resources and collaborative care models.

Integrating mental health into chronic care in South Africa: the development of a district mental healthcare plan.

BACKGROUND: In South Africa, the escalating prevalence of chronic illness and its high comorbidity with mental disorders bring to the fore the need for integrating mental health into chronic care at district level. AIMS: To develop a district mental healthcare plan (MHCP) in South Africa that integrates mental healthcare for depression, alcohol use disorders and schizophrenia into chronic care. METHOD: Mixed methods using a situation analysis, qualitative key informant interviews, theory of change workshops and piloting of the plan in one health facility informed the development of the MHCP. RESULTS: Collaborative care packages for the three conditions were developed to enable integration at the organisational, facility and community levels, supported by a human resource mix and implementation tools. Potential barriers to the feasibility of implementation at scale were identified. CONCLUSIONS: The plan leverages resources and systems availed by the emerging chronic care service delivery platform for the integration of mental health. This strengthens the potential for future scale up.

Integration of mental health into primary care in low- and middle-income countries: the PRIME mental healthcare plans.

This supplement outlines the development and piloting of district mental healthcare plans from five low- and middle-income countries, together with the methods for their design, evaluation and costing. In this editorial we consider the challenges that these programmes face, highlight their innovations and draw conclusions.

Interventional Therapies for Chronic Low Back Pain: A Focused Review (Efficacy and Outcomes).

CONTEXT: Lower back pain is considered to be one of the most common complaints that brings a patient to a pain specialist. Several modalities in interventional pain management are known to be helpful to a patient with chronic low back pain. Proper diagnosis is required for appropriate intervention to provide optimal benefits. From simple trigger point injections for muscular pain to a highly complex intervention such as a spinal cord stimulator are very effective if chosen properly. The aim of this article is to provide the reader with a comprehensive reading for treatment of lower back pain using interventional modalities. EVIDENCE ACQUISITION: Extensive search for published literature was carried out online using PubMed, Cochrane database and Embase for the material used in this manuscript. This article describes the most common modalities available to an interventional pain physician along with the most relevant current and past references for the treatment of lower back pain. All the graphics and images were prepared by and belong to the author. RESULTS: This review article describes the most common modalities available to an interventional pain physician along with the most relevant current and past references for the treatment of lower back pain. All the graphics and images belong to the author. Although it is beyond the scope of this review article to include a very detailed description of each procedure along with complete references, a sincere attempt has been made to comprehensively cover this very complex and perplexing topic. CONCLUSION: Lower back pain is a major healthcare issue and this review article will help educate the pain practitioners about the current evidence based treatment options.

Integrating Mental Health In Care For Noncommunicable Diseases: An Imperative For Person-Centered Care.

Mental disorders such as depression and alcohol use disorders often co-occur with other common noncommunicable diseases such as diabetes and heart disease. Furthermore, noncommunicable diseases are frequently encountered in patients with severe mental disorders such as schizophrenia. The pathways underlying the comorbidity of mental disorders and noncommunicable diseases are complex. For example, mental and physical noncommunicable diseases may have common environmental risk factors such as unhealthy lifestyles, and treatments for one condition may have side effects that increase the risk of another condition. Building on the robust evidence base for effective treatments for a range of mental disorders, there is now a growing evidence base for how such treatments can be integrated into the care of people with noncommunicable diseases. The best-established delivery model is a team approach that features a nonspecialist case manager who coordinates care with primary care physicians and specialists. This approach maximizes efficiencies in person-centered care, which are essential for achieving universal health coverage for both noncommunicable diseases and mental disorders. A number of research gaps remain, but there is sufficient evidence for policy makers to immediately implement measures to integrate mental health and noncommunicable disease care in primary care platforms.

Searching for psychosis: INTREPID (1): systems for detecting untreated and first-episode cases of psychosis in diverse settings.

PURPOSE: Our understanding of psychotic disorders is largely based on studies conducted in North America, Europe and Australasia. Few methodologically robust and comparable studies have been carried out in other settings. INTREPID is a programme of research on psychoses in India, Nigeria, and Trinidad. As a platform for INTREPID, we sought to establish comprehensive systems for detecting representative samples of cases of psychosis by mapping and seeking to engage all professional and folk (traditional) providers and potential key informants in defined catchment areas. METHOD: We used a combination of official sources, local knowledge of principal investigators, and snowballing techniques. RESULTS: The structure of the mental health systems in each catchment area was similar, but the content (i.e., type, extent, and nature) differed. Tunapuna-Piarco (Trinidad), for example, has the most comprehensive and accessible professional services. By contrast, Ibadan (Nigeria) has the most extensive folk (traditional) sector. We identified and engaged in our detection system-(a) all professional mental health services in each site (in- and outpatient services-Chengalpet, 6; Ibadan, 3; Trinidad, 5); (b) a wide range of folk providers (Chengalpet, 3 major healing sites; Ibadan, 19 healers; Trinidad: 12 healers); and c) a number of key informants, depending on need (Chengalpet, 361; Ibadan, 54; Trinidad, 1). CONCLUSIONS: Marked differences in mental health systems in each catchment area illustrate the necessity of developing tailored systems for the detection of representative samples of cases with untreated and first-episode psychosis as a basis for robust, comparative epidemiological studies.

Pharmacodynamic evaluation of the activities of six parenteral vancomycin products available in the United States.

A recent report found that generic parenteral vancomycin products may not have in vivo efficacies equivalent to those of the innovator in a neutropenic murine thigh infection model despite having similar in vitro microbiological activities and murine serum pharmacokinetics. We compared the in vitro and in vivo activities of six of the parenteral vancomycin products available in the United States. The in vitro assessments for the potencies of the vancomycin products included MIC/minimal bactericidal concentration (MBC) determinations, quantifying the impact of human and murine serum on the MIC values, and time-kill studies. Also, the potencies of the vancomycin products were quantified with a biological assay, and the human and mouse serum protein binding rates for the vancomycin products were measured. The in vivo studies included dose-ranging experiments with the 6 vancomycin products for three isolates of Staphylococcus aureus in a neutropenic mouse thigh infection model. The pharmacokinetics of the vancomycin products were assessed in infected mice by population pharmacokinetic modeling. No differences were seen across the vancomycin products with regard to any in vitro evaluation. Inhibitory sigmoid maximal bacterial kill (Emax) modeling of the relationship between vancomycin dosage and the killing of the bacteria in mice in vivo yielded similar Emax and EC50 (drug exposure driving one-half Emax) values for bacterial killing. Further, there were no differences in the pharmacokinetic clearances of the 6 vancomycin products from infected mice. There were no important pharmacodynamic differences in the in vitro or in vivo activities among the six vancomycin products evaluated.