A cross-sectional survey of the prevalence and determinants of comorbid psychological distress in attendees at two general hospitals in Gaza.

BACKGROUND: There is an absence of mental health services within general hospitals in Gaza. As part of the Ministry of Health plan to develop mental health liaison services, a cross-sectional survey of the prevalence of and risk factors for psychological distress in attendees at two general hospitals was undertaken to estimate and highlight the need for establishing such services. METHODS: 20 volunteers aged 24-30 years with a degree in psychological or social science from a university accredited by the Palestinian Ministry of Education and Higher Education, and with experience in field data collection for studies in mental health, were selected and trained in the use of the Arabic version of the 12-item General Health Questionnaire (GHQ-12), an internationally and well validated tool for measuring psychological distress in adults. The volunteers were supervised as they screened adult attendees at emergency rooms, inpatient wards and outpatient departments, and women attending the maternity units at two of the largest general hospitals in Gaza (Nasser and Indonesian) over seven consecutive days (March 18-23, 2018). Attendees at emergency and outpatient departments were included if they were on repeat visits with medically unexplained somatic complaints, if they attended with complaints resulting from any kind of social problem, physical or sexual violence, or had a history of any kind of chronic disease. All patients from the internal medicine and inpatient departments were included. The data from the questionnaires were collated and analysed with descriptive and inferential statistics. FINDINGS: 1789 attendees (791 men and 998 women) were screened using the GHQ-12. Of these attendees, 23·8% (426 of 1789) had a GHQ-12 score of 6 or 7, indicating the presence of significant psychological distress with a high possibility of caseness (ie, meeting the diagnostic threshold for clinical depression). 36·2% (648 of 1789) scored 8 or above, indicating the presence of moderate to severe depression or anxiety disorders that require immediate clinical intervention. For all of the hospital departments surveyed, individuals with scores of 6 or greater made up a large proportion of the attendees (385 of 660 [58·3%] in emergency rooms, 197 of 306 [64·4%] in inpatient wards, 430 of 711 [60·5%] in outpatient departments, and 62 of 112 [55·4%] in maternity units), in both hospitals. In addition, a set of risk factors were found to be significantly associated with GHQ-12 scores of 6 or greater. These were being a woman (p=0·020), living in villages adjoining the most conflict prone areas (p<0·0001), no or low formal education (p<0·0001), being divorced (p<0·001) or widowed (p<0·0001), being unemployed (p<0·0001), and low family income (monthly income of <1000 ILS; p<0·0001). On further stepwise regression analysis, unemployment and low family income were found to be the most important risk factors associated with GHQ-12 scores of 6 or greater. INTERPRETATION: In general hospital attendees there was a very high rate of significant psychological distress. Given the absence of mental health services within general hospitals in Gaza, the findings indicate an urgent need to make mental health interventions routinely available through general hospital liaison units in Gaza. The risk factors that were identified indicate that psychosocial interventions and access to developmental support are key components of such clinical services, and will be required to reduce the very large, and mostly unmet, population burden of mental health problems in Gaza. FUNDING: WHO, occupied Palestinian territory, as part of the EU project "Building Palestinian resilience: improving psychosocial and mental health responses in emergency".

Alkaline air: changing perspectives on nitrogen and air pollution in an ammonia-rich world.

Ammonia and ammonium have received less attention than other forms of air pollution, with limited progress in controlling emissions at UK, European and global scales. By contrast, these compounds have been of significant past interest to science and society, the recollection of which can inform future strategies. Sal ammoniac (nushadir, nao sha) is found to have been extremely valuable in long-distance trade (ca AD 600-1150) from Egypt and China, where 6-8 kg N could purchase a human life, while air pollution associated with nushadir collection was attributed to this nitrogen form. Ammonia was one of the keys to alchemy-seen as an early experimental mesocosm to understand the world-and later became of interest as 'alkaline air' within the eighteenth century development of pneumatic chemistry. The same economic, chemical and environmental properties are found to make ammonia and ammonium of huge relevance today. Successful control of acidifying SO2 and NOx emissions leaves atmospheric NH3 in excess in many areas, contributing to particulate matter (PM2.5) formation, while leading to a new significance of alkaline air, with adverse impacts on natural ecosystems. Investigations of epiphytic lichens and bog ecosystems show how the alkalinity effect of NH3 may explain its having three to five times the adverse effect of ammonium and nitrate, respectively. It is concluded that future air pollution policy should no longer neglect ammonia. Progress is likely to be mobilized by emphasizing the lost economic value of global N emissions ($200 billion yr-1), as part of developing the circular economy for sustainable nitrogen management. This article is part of a discussion meeting issue 'Air quality, past present and future'.

Mapping the evidence on pharmacological interventions for non-affective psychosis in humanitarian non-specialised settings: a UNHCR clinical guidance.

BACKGROUND: Populations exposed to humanitarian emergencies are particularly vulnerable to mental health problems, including new onset, relapse and deterioration of psychotic disorders. Inadequate care for this group may lead to human rights abuses and even premature death. The WHO Mental Health Gap Action Programme Intervention Guide (mhGAP-IG), and its adaptation for humanitarian settings (mhGAP-HIG), provides guidance for management of mental health conditions by non-specialised healthcare professionals. However, the pharmacological treatment of people with non-affective psychosis who do not improve with mhGAP first-line antipsychotic treatments is not addressed. In order to fill this gap, UNHCR has formulated specific guidance on the second-line pharmacological treatment of non-affective psychosis in humanitarian, non-specialised settings. METHODS: Following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a group of international experts performed an extensive search and retrieval of evidence on the basis of four scoping questions. Available data were critically appraised and summarised. Clinical guidance was produced by integrating this evidence base with context-related feasibility issues, preferences, values and resource-use considerations. RESULTS: When first-line treatments recommended by mhGAP (namely haloperidol and chlorpromazine) are not effective, no other first-generation antipsychotics are likely to provide clinically meaningful improvements. Risperidone or olanzapine may represent beneficial second-line options. However, if these second-line medications do not produce clinically significant beneficial effects, there are two possibilities. First, to switch to the alternative (olanzapine to risperidone or vice versa) or, second, to consider clozapine, provided that specialist supervision and regular laboratory monitoring are available in the long term. If clinically relevant depressive, cognitive or negative symptoms occur, the use of a selective serotonin reuptake inhibitor may be considered in addition or as an alternative to standard psychological interventions. CONCLUSIONS: Adapting scientific evidence into practical guidance for non-specialised health workers in humanitarian settings was challenging due to the paucity of relevant evidence as well as the imprecision and inconsistency of results between studies. Pragmatic outcome evaluation studies from low-resource contexts are urgently needed. Nonetheless, the UNHCR clinical guidance is based on best available evidence and can help to address the compelling issue of undertreated, non-affective psychosis in humanitarian settings.

Effectiveness of a community-based intervention for people with schizophrenia and their caregivers in India (COPSI): a randomised controlled trial.

BACKGROUND: Observational evidence suggests that community-based services for people with schizophrenia can be successfully provided by community health workers, when supervised by specialists, in low-income and middle-income countries. We did the COmmunity care for People with Schizophrenia in India (COPSI) trial to compare the effectiveness of a collaborative community-based care intervention with standard facility-based care. METHODS: We did a multicentre, parallel-group, randomised controlled trial at three sites in India between Jan 1, 2009 and Dec 31, 2010. Patients aged 16-60 years with a primary diagnosis of schizophrenia according to the tenth edition of the International Classification of Diseases, Diagnostic Criteria for Research (ICD-10-DCR) were randomly assigned (2:1), via a computer-generated randomisation list with block sizes of three, six, or nine, to receive either collaborative community-based care plus facility-based care or facility-based care alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. The primary outcome was a change in symptoms and disabilities over 12 months, as measured by the positive and negative syndrome scale (PANSS) and the Indian disability evaluation and assessment scale (IDEAS). Analysis was by modified intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 56877013. FINDINGS: 187 participants were randomised to the collaborative community-based care plus facility-based care group and 95 were randomised to the facility-based care alone group; 253 (90%) participants completed follow-up to month 12. At 12 months, total PANSS and IDEAS scores were lower in patients in the intervention group than in those in the control group (PANSS adjusted mean difference -3.75, 95% CI -7.92 to 0.42; p=0.08; IDEAS -0.95, -1.68 to -0.23; p=0.01). However, no difference was shown in the proportion of participants who had a reduction of more than 20% in overall symptoms (PANSS 85 [51%] in the intervention group vs 44 [51%] in the control group; p=0.89; IDEAS 75 [48%] vs 28 [35%]). We noted a significant reduction in symptom and disability outcomes at the rural Tamil Nadu site (-9.29, -15.41 to -3.17; p=0.003). Two patients (one in each group) died by suicide during the study, and two patients died because of complications of a road traffic accident and pre-existing cardiac disease. 18 (73%) patients (17 in the intervention group) were admitted to hospital during the course of the trial, of whom seven were admitted because of physical health problems, such as acute gastritis and vomiting, road accident, high fever, or cardiovascular disease. INTERPRETATION: The collaborative community-based care plus facility-based care intervention is modestly more effective than facility-based care, especially for reducing disability and symptoms of psychosis. Our results show that the study intervention is best implemented as an initial service in settings where services are scarce, for example in rural areas. FUNDING: Wellcome Trust.

Customising informed consent procedures for people with schizophrenia in India.

BACKGROUND: There is little information on how the ethical and procedural challenges involved in the informed participation of people with schizophrenia in clinical trials are addressed in low- and middle-income countries (LMICs). The informed consent procedure used in the collaborative community care for people with schizophrenia in India (COPSI) RCT was developed keeping these challenges in mind. We describe the feasibility of conducting the procedure from the trial, researcher and participants perspectives and describe the reasons for people consenting to participate in the trial or refusing to do so. METHODS: Three sources of information were used to describe the feasibility of the COPSI consent procedure: key process indicators for the trial perspective, data from a specially designed post-interview form for participant's observations and focus group discussion (FGD) with the research interviewers. Categorical data were analysed by calculating frequencies and proportions, while the qualitative data from the FGD, and the reasons for participation or refusal were analysed using a thematic content analysis approach. FINDINGS: 434 people with schizophrenia and their primary caregiver(s) were approached for participation in the trial. Consent interviews were conducted with 332, of whom 303 (91%) agreed to participate in the trial. Expectation of improvement was the most common reason for agreeing to participate in the trial, while concerns related to the potential disclosure of the illness, especially for women, were an important reason for refusing consent. CONCLUSIONS: The COPSI consent procedure demonstrates preliminary, observational information about the feasibility of customising informed consent procedures for people with schizophrenia LMIC contexts. This and other similar innovations need to be refined and rigorously tested to develop evidence-based guidelines for informed consent procedures in such settings.

Exploring the feasibility and public health impact of integrating a community-based recovery-oriented intervention for people living with schizophrenia in partnership with a tertiary care mental hospital in India.

Background: There is a priority need to make community-based care widely available for people living with schizophrenia (PLwS) in low- and middle-income countries. An innovative approach for increasing access could be to integrate clinical services available in tertiary care hospitals with community-based care through a task-sharing approach. We describe such an integrated intervention that was implemented at Tezpur in northeast India in collaboration with the Lokopriya Gopinath Bordoloi Regional Institute of Mental Health (LGBRIMH). Method: The objectives of the study were to illustrate the feasibility of integrating and implementing the intervention and to describe its individual, systemic, and public health impacts. Due to the limited resources available, we conducted a pragmatic single-arm longitudinal evaluation of the intervention cohort over 24 months. Results: Of the 239 PLwS enrolled in the intervention, 198 (83%) were followed up for 24 months, with nearly three-quarters reporting a >70% reduction in disabilities, most notably between 6 and 18 months. There was a marked reduction in unmet needs across multiple domains, and at 24 months, 62% of the cohort was engaged in individual jobs or other market-linked livelihood opportunities. There was greater uptake and retention with outpatient contacts at the LGBRIMH, and PLwS experienced a marked (82%) reduction in inpatient admissions rates, as compared to before enrolment. Over a period of 24 months, primary caregivers reported that their families experienced significantly fewer social difficulties such as unemployment, interpersonal conflicts, and social isolation. The intervention had a significant public health impact, with an estimated 51.8% effective treatment coverage rate for the integrated intervention. Conclusion: Our findings provide preliminary evidence of the feasibility of implementing the integrated intervention and its effectiveness. We believe that there is merit in further in-depth refinement and exploration of this implementation-related research and cost analysis while replicating the intervention in other tertiary care institutions.

In low- and middle-income countries such as India, integrating clinical services available at tertiary mental health hospitals with community-based care through a task-sharing approach is an innovative way to make community-based care widely available for people living with schizophrenia (PLwS). The purpose of our study was to investigate the feasibility of implementing such an intervention in a community in Tezpur, northeastern India, in collaboration with a Lokopriya Gopinath Bordoloi Regional Institute of Mental Health (LGBRIMH), and to describe the individual, systemic, and public health effects of the intervention. Our findings suggest that integrating the intervention is feasible, has significant impacts on individuals and public health, and is an effective way to expand access to community-based care for PLwS through partnerships with existing tertiary care institutions.

Updating the WHO Model Lists of Essential Medicines to promote global access to the most cost-effective and safe medicines for mental disorders.

Since 1977, the WHO Model Lists of Essential Medicines (EML) have been a benchmark to guide the procurement of medicines at the national level, especially in low-income and middle-income countries. Aiming to include the most effective, safe, and cost-effective medicines for priority conditions, WHO updates the EML for adults and the EML for children every 2 years. Over the past 45 years, updates to the EML mental health section have been infrequent, in most cases with additions of individual medicines. A comprehensive revision of the entire section has never been attempted. With the aim of increasing the use of the WHO EML to expand the selection of the most effective and safe medicines for mental disorders, a series of evidence-based applications were submitted to the WHO Expert Committee on the Selection and Use of Essential Medicines in 2022, recommending a substantial revision of the entire mental health section. In this Health Policy, we summarise the recommended update and the evidence justifying it. We also discuss challenges in the update process, suggesting possible solutions. The requested comprehensive revision of the WHO EML mental health section aligns the list with the latest evidence. The revision offers an opportunity for countries to promote access to the most effective, safe, and cost-effective medicines for mental disorders, contributing to universal health coverage and global mental health equity.

Lichens as spatially transferable bioindicators for monitoring nitrogen pollution.

Excess nitrogen is a pollutant and global problem that harms ecosystems and can severely affect human health. Pollutant nitrogen is becoming more widespread and intensifying in the tropics. There is thus a requirement to develop nitrogen biomonitoring for spatial mapping and trend analysis of tropical biodiversity and ecosystems. In temperate and boreal zones, multiple bioindicators for nitrogen pollution have been developed, with lichen epiphytes among the most sensitive and widely applied. However, the state of our current knowledge on bioindicators is geographically biased, with extensive research effort focused on bioindicators in the temperate and boreal zones. The development of lichen bioindicators in the tropics is further weakened by incomplete taxonomic and ecological knowledge. In this study we performed a literature review and meta-analysis, attempting to identify characteristics of lichens that offer transferability of bioindication into tropical regions. This transferability must overcome the different species pools between source information - drawing on extensive research effort in the temperate and boreal zone - and tropical ecosystems. Focussing on ammonia concentration as the nitrogen pollutant, we identify a set of morphological traits and taxonomic relationships that cause lichen epiphytes to be more sensitive, or more resistant to this excess nitrogen. We perform an independent test of our bioindicator scheme and offer recommendations for its application and future research in the tropics.

Scale up of services for mental health in low-income and middle-income countries.

Mental disorders constitute a huge global burden of disease, and there is a large treatment gap, particularly in low-income and middle-income countries. One response to this issue has been the call to scale up mental health services. We assess progress in scaling up such services worldwide using a systematic review of literature and a survey of key national stakeholders in mental health. The large number of programmes identified suggested that successful strategies can be adopted to overcome barriers to scaling up, such as the low priority accorded to mental health, scarcity of human and financial resources, and difficulties in changing poorly organised services. However, there was a lack of well documented examples of services that had been taken to scale that could guide how to replicate successful scaling up in other settings. Recommendations are made on the basis of available evidence for how to take forward the process of scaling up services globally.

The development of a lay health worker delivered collaborative community based intervention for people with schizophrenia in India.

BACKGROUND: Care for schizophrenia in low and middle income countries is predominantly facility based and led by specialists, with limited use of non-pharmacological treatments. Although community based psychosocial interventions are emphasised, there is little evidence about their acceptability and feasibility. Furthermore, the shortage of skilled manpower is a major barrier to improving access to these interventions. Our study aimed to develop a lay health worker delivered community based intervention in three sites in India. This paper describes how the intervention was developed systematically, following the MRC framework for the development of complex interventions. METHODS: We reviewed the lierature on the burden of schizophrenia and the treatment gap in low and middle income countries and the evidence for community based treatments, and identified intervention components. We then evaluated the acceptability and feasibility of this package of care through formative case studies with individuals with schizophrenia and their primary caregivers and piloted its delivery with 30 families. RESULTS: Based on the reviews, our intervention comprised five components (psycho-education; adherence management; rehabilitation; referral to community agencies; and health promotion) to be delivered by trained lay health workers supervised by specialists. The intervention underwent a number of changes as a result of formative and pilot work. While all the components were acceptable and most were feasible, experiences of stigma and discrimination were inadequately addressed; some participants feared that delivery of care at home would lead to illness disclosure; some participants and providers did not understand how the intervention related to usual care; some families were unwilling to participate; and there were delivery problems, for example, in meeting the targeted number of sessions. Participants found delivery by health workers acceptable, and expected them to have knowledge about the subject matter. Some had expectations regarding their demographic and personal characteristics, for example, preferring only females or those who are understanding/friendly. New components to address stigma were then added to the intervention, the collaborative nature of service provision was strengthened, a multi-level supervision system was developed, and delivery of components was made more flexible. Criteria were evolved for the selection and training of the health workers based on participants' expectations. CONCLUSIONS: A multi-component community based intervention, targeting multiple outcomes, and delivered by trained lay health workers, supervised by mental health specialists, is an acceptable and feasible intervention for treating schizophrenia in India.

Effectiveness of an intervention led by lay health counsellors for depressive and anxiety disorders in primary care in Goa, India (MANAS): a cluster randomised controlled trial.

BACKGROUND: Depression and anxiety disorders are common mental disorders worldwide. The MANAS trial aimed to test the effectiveness of an intervention led by lay health counsellors in primary care settings to improve outcomes of people with these disorders. METHODS: In this cluster randomised trial, primary care facilities in Goa, India, were assigned (1:1) by computer-generated randomised sequence to intervention or control (enhanced usual care) groups. All adults who screened positive for common mental disorders were eligible. The collaborative stepped-care intervention offered case management and psychosocial interventions, provided by a trained lay health counsellor, supplemented by antidepressant drugs by the primary care physician and supervision by a mental health specialist. The research assessor was masked. The primary outcome was recovery from common mental disorders as defined by the International Statistical Classification of Diseases and Related Health Problems-10th revision (ICD-10) at 6 months. This study is registered with ClinicalTrials.gov, number NCT00446407. FINDINGS: 24 study clusters, with an equal proportion of public and private facilities, were randomised equally between groups. 1160 of 1360 (85%) patients in the intervention group and 1269 of 1436 (88%) in the control group completed the outcome assessment. Patients with ICD-10-confirmed common mental disorders in the intervention group were more likely to have recovered at 6 months than were those in the control group (n=620 [65·0%] vs 553 [52·9%]; risk ratio 1·22, 95% CI 1·00-1·47; risk difference=12·1%, 95% CI 1·6%-22·5%). The intervention had strong evidence of an effect in public facility attenders (369 [65·9%] vs 267 [42·5%], risk ratio 1·55, 95% CI 1·02-2·35) but no evidence for an effect in private facility attenders (251 [64·1%] vs 286 [65·9%], risk ratio 0·95, 0·74-1·22). There were three deaths and four suicide attempts in the collaborative stepped-care group and six deaths and six suicide attempts in the enhanced usual care group. None of the deaths were from suicide. INTERPRETATION: A trained lay counsellor-led collaborative care intervention can lead to an improvement in recovery from CMD among patients attending public primary care facilities. FUNDING: The Wellcome Trust.

Lay health worker led intervention for depressive and anxiety disorders in India: impact on clinical and disability outcomes over 12 months.

BACKGROUND: Depressive and anxiety disorders (common mental disorders) are the most common psychiatric condition encountered in primary healthcare. AIMS: To test the effectiveness of an intervention led by lay health counsellors in primary care settings (the MANAS intervention) to improve the outcomes of people with common mental disorders. METHOD: Twenty-four primary care facilities (12 public, 12 private) in Goa (India) were randomised to provide either collaborative stepped care or enhanced usual care to adults who screened positive for common mental disorders. Participants were assessed at 2, 6 and 12 months for presence of ICD-10 common mental disorders, the severity of symptoms of depression and anxiety, suicidal behaviour and disability levels. All analyses were intention to treat and carried out separately for private and public facilities and adjusted for the design. The trial has been registered with clinical trials.gov (NCT00446407). RESULTS: A total of 2796 participants were recruited. In public facilities, the intervention was consistently associated with strong beneficial effects over the 12 months on all outcomes. There was a 30% decrease in the prevalence of common mental disorders among those with baseline ICD-10 diagnoses (risk ratio (RR) = 0.70, 95% CI 0.53-0.92); and a similar effect among the subgroup of participants with depression (RR = 0.76, 95% CI 0.59-0.98). Suicide attempts/plans showed a 36% reduction over 12 months (RR=0.64, 95% CI0.42­0.98) among baseline ICD-10 cases. Strong effects were observed on days out of work and psychological morbidity, and modest effects on overall disability [corrected]. In contrast, there was little evidence of impact of the intervention on any outcome among participants attending private facilities. CONCLUSIONS: Trained lay counsellors working within a collaborative-care model can reduce prevalence of common mental disorders, suicidal behaviour, psychological morbidity and disability days among those attending public primary care facilities.

Important Steps to Control COVID-19/SARS-CoV-2 Infection.

Elderly patients are having high mortality rates from COVID-19/SARS-CoV-2 infection compared to younger patients. The SARS-CoV-2 virus uses the ACE2 receptor as the entry point to the host cells. ARBs/ACEIs which are widely used in elderly patients, have been found to be associated with overexpression of ACE2.To decrease the severity of COVID-19 infection, ARB/ACEI should be switched to another class drug not known to cause a rise in ACE2 until the COVID-19 infection subsides. Specific human immunoglobulin can be tried for COVID-19 patients with critical conditions under supervision.

Outcomes of people with psychotic disorders in a community-based rehabilitation programme in rural India.

BACKGROUND: There is little evidence of the feasibility, acceptability and impact of services for the care of people with psychotic disorders in low- and middle-income countries. AIMS: To describe the scaling up and impact of a community-based rehabilitation programme for people with psychotic disorders in a very-low-resource setting. METHODS: Longitudinal study of people with psychotic disorders who had been ill for an average of 8 years in a rural Indian community. All individuals received a community-based intervention package comprising psychotropic medications, psychoeducation, adherence management, psychosocial rehabilitation and support for livelihoods. The primary outcome was change in disability scores. RESULTS: The cohort consisted of 256 people with psychotic disorders (schizophrenia, bipolar affective disorder and other psychosis) of whom 236 people completed the end-point assessments (92%), with a median follow-up of 46 months. There were significant reductions (P<0.05) in the levels of disability for the cohort, the vast majority (83.5%) of whom engaged with the programme. On multivariate analyses, lower baseline disability scores, family engagement with the programme, medication adherence and being a member of a self-help group were independent determinants of good outcomes. Lack of formal education, a diagnosis of schizophrenia and dropping out of the programme were independent determinants of poor outcomes. CONCLUSIONS: Community-based rehabilitation is a feasible and acceptable intervention with a beneficial impact on disability for the majority of people with psychotic disorders in low-resource settings. The impact on disability is influenced by a combination of clinical, programme and social determinants.

Treatment and prevention of mental disorders in low-income and middle-income countries.

We review the evidence on effectiveness of interventions for the treatment and prevention of selected mental disorders in low-income and middle-income countries. Depression can be treated effectively in such countries with low-cost antidepressants or with psychological interventions (such as cognitive-behaviour therapy and interpersonal therapies). Stepped-care and collaborative models provide a framework for integration of drug and psychological treatments and help to improve rates of adherence to treatment. First-generation antipsychotic drugs are effective and cost effective for the treatment of schizophrenia; their benefits can be enhanced by psychosocial treatments, such as community-based models of care. Brief interventions delivered by primary-care professionals are effective for management of hazardous alcohol use, and pharmacological and psychosocial interventions have some benefits for people with alcohol dependence. Policies designed to reduce consumption, such as increased taxes and other control strategies, can reduce the population burden of alcohol abuse. Evidence about the efficacy of interventions for developmental disabilities is inadequate, but community-based rehabilitation models provide a low-cost, integrative framework for care of children and adults with chronic mental disabilities. Evidence for mental health interventions for people who are exposed to conflict and other disasters is still weak-especially for interventions in the midst of emergencies. Some trials of interventions for prevention of depression and developmental delays in low-income and middle-income countries show beneficial effects. Interventions for depression, delivered in primary care, are as cost effective as antiretroviral drugs for HIV/AIDS. The process and effectiveness of scaling up mental health interventions has not been adequately assessed. Such research is needed to inform the continuing process of service reform and innovation. However, we recommend that policymakers should act on the available evidence to scale up effective and cost-effective treatments and preventive interventions for mental disorders.

Experiences of stigma and discrimination faced by family caregivers of people with schizophrenia in India.

Stigma associated with schizophrenia significantly affects family caregivers, yet few studies have examined the nature and determinants of family stigma and its relationship to their knowledge about the condition. This paper describes the experiences and determinants of stigma reported by the primary caregivers of people living with schizophrenia (PLS) in India. The study used mixed methods and was nested in a randomised controlled trial of community care for people with schizophrenia. Between November 2009 and October 2010, data on caregiver stigma and functional outcomes were collected from a sample of 282 PLS-caregiver dyads. In addition, 36 in-depth-interviews were conducted with caregivers. Quantitative findings indicate that 'high caregiver stigma' was reported by a significant minority of caregivers (21%) and that many felt uncomfortable to disclose their family member's condition (45%). Caregiver stigma was independently associated with higher levels of positive symptoms of schizophrenia, higher levels of disability, younger PLS age, household education at secondary school level and research site. Knowledge about schizophrenia was not associated with caregiver stigma. Qualitative data illustrate the various ways in which stigma affected the lives of family caregivers and reveal relevant links between caregiver-stigma related themes ('others finding out', 'negative reactions' and 'negative feelings and views about the self') and other themes in the data. Findings highlight the need for interventions that address both the needs of PLS and their family caregivers. Qualitative data also illustrate the complexities surrounding the relationship between knowledge and stigma and suggest that providing 'knowledge about schizophrenia' may influence the process of stigmatisation in both positive and negative ways. We posit that educational interventions need to consider context-specific factors when choosing anti-stigma-messages to be conveyed. Our findings suggest that messages such as 'recovery is possible' and 'no-one is to blame' may be more helpful than focusing on bio-medical knowledge alone.

Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study.

BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.

Experiences of stigma and discrimination of people with schizophrenia in India.

Stigma contributes greatly to the burden of schizophrenia and is a major obstacle to recovery, yet, little is known about the subjective experiences of those directly affected in low and middle income countries. This paper aims to describe the experiences of stigma and discrimination of people living with schizophrenia (PLS) in three sites in India and to identify factors influencing negative discrimination. The study used mixed methods and was nested in a randomised controlled trial of community care for schizophrenia. Between November 2009 and October 2010, data on four aspects of stigma experienced by PLS and several clinical variables were collected from 282 PLS and 282 caregivers and analysed using multivariate regression. In addition, in-depth-interviews with PLS and caregivers (36 each) were carried out and analysed using thematic analysis. Quantitative findings indicate that experiences of negative discrimination were reported less commonly (42%) than more internalised forms of stigma experience such as a sense of alienation (79%) and significantly less often than in studies carried out elsewhere. Experiences of negative discrimination were independently predicted by higher levels of positive symptoms of schizophrenia, lower levels of negative symptoms of schizophrenia, higher caregiver knowledge about symptomatology, lower PLS age and not having a source of drinking water in the home. Qualitative findings illustrate the major impact of stigma on 'what matters most' in the lives of PLS and highlight three key domains influencing the themes of 'negative reactions' and 'negative views and feelings about the self', i.e., 'others finding out', 'behaviours and manifestations of the illness' and 'reduced ability to meet role expectations'. Findings have implications for conceptualising and measuring stigma and add to the rationale for enhancing psycho-social interventions to support those facing discrimination. Findings also highlight the importance of addressing public stigma and achieving higher level social and political structural change.