Seeking a better landscape for therapy development in neuromuscular disorders.

Although the neuromuscular field has seen accelerated approval of a drug for Duchenne muscular dystrophy (DMD) and full approval of one for spinal muscular atrophy, these experiences have shown that objective data and an adequate level of effect are essential for drug approval and reimbursement. The appropriateness and validity of biomarkers and clinically meaningful endpoints and an understanding of disease progression rates all played essential roles in the levels of evidence for these drugs. Such tools are best developed through integration of clinical data. The siloing of clinical data for rare neuromuscular diseases represents a considerable barrier to achieving better care and novel therapies for patients living with neuromuscular diseases. We discuss a data-sharing model implemented for DMD and urge cultural changes in the ways natural history and clinical trial data are collected and shared across all neuromuscular diseases in order to benefit the primary stakeholder, the patient. Muscle Nerve 57: 16-19, 2018.

Understanding the complex relationships among actors involved in the implementation of public-private mix (PPM) for TB control in India, using social theory.

BACKGROUND: Public Private Partnerships (PPP) are increasingly utilized as a public health strategy for strengthening health systems and have become a core component for the delivery of TB control services in India, as promoted through national policy. However, partnerships are complex systems that rely on relationships between a myriad of different actors with divergent agendas and backgrounds. Relationship is a crucial element of governance, and relationship building an important aspect of partnerships. To understand PPPs a multi-disciplinary perspective that draws on insights from social theory is needed. This paper demonstrates how social theory can aid the understanding of the complex relationships of actors involved in implementation of Public-Private Mix (PPM)-TB policy in India. METHODS: Ethnographic research was conducted within a district in a Southern state of India over a 14 month period, combining participant observations, informal interactions and in-depth interviews with a wide range of respondents across public, private and non-government organisation (NGO) sectors. RESULTS: Drawing on the theoretical insights from Bourdieu's "theory of practice" this study explores the relationships between the different actors. The study found that programme managers, frontline TB workers, NGOs, and private practitioners all had a crucial role to play in TB partnerships. They were widely regarded as valued contributors with distinct social skills and capabilities within their organizations and professions. However, their potential contributions towards programme implementation tended to be unrecognized both at the top and bottom of the policy implementation chain. These actors constantly struggled for recognition and used different mechanisms to position themselves alongside other actors within the programme that further complicated the relationships between different actors. CONCLUSION: This paper demonstrates that applying social theory can enable a better understanding of the complex relationship across public, private and NGO sectors. A closer understanding of these processes is a prerequisite for bridging the gap between field-level practices and central policy intentions, facilitating a move towards more effective partnership strategies for strengthening local health systems. The study contributes to our understanding of implementation of PPP for TB control and builds knowledge to help policy makers and programme managers strengthen and effectively implement strategies to enable stronger governance of these partnerships.

A call for transparent reporting to optimize the predictive value of preclinical research.

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.

A public health approach to palliative care in the response to drug resistant TB: an ethnographic study in Bengaluru, India.

BACKGROUND: The treatment of Multidrug-Resistant Tuberculosis represents one of the most significant challenges to global health. Despite guidance on improving treatment outcomes, there is little focus on how to support individuals in their suffering. Palliative care is therefore proposed as a necessary component in the global strategy to fight Tuberculosis. We aim to describe the informal resources and networks available to persons affected by Multidrug-Resistant Tuberculosis, how they are accessed and how they are integrated into everyday lives. METHODS: In-depth ethnographic research was conducted in Bengaluru, India. Informal interactions and observations were recorded across a range of palliative care and tuberculosis treatment providers over a month-long period. In addition, ten individuals with Multidrug-Resistant Tuberculosis were asked for in-depth interviews, and five agreed. RESULTS: Multidrug-Resistant Tuberculosis caused a dynamic chain of events that transgress through physical and psychological domains to cause human suffering. Participants utilised support from their family and friends to build a network of care that was of therapeutic benefit. Informal care networks were similar to the holistic model of care practice by specialist palliative care services and represent an underused resource with enormous potential. CONCLUSION: Patient suffering is poorly addressed in current Tuberculosis treatment programmes. A community-based palliative care approach may extend peoples' support networks, helping to alleviate suffering. Further research on existing support structures and integration of these services into Tuberculosis control programmes is required.

Medical pluralism among indigenous peoples in northeast India - implications for health policy.

OBJECTIVES: The government of India is promoting and increasing investment in the traditional medicine systems of Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) in the northeast region of India. But there are few empirical data that support this policy decision. This study estimates the awareness and use of the different medical systems in rural Meghalaya, a state in north-east India with a predominantly ethnic tribal population. METHOD: We conducted a cross-sectional multistage random sample household survey across all districts of Meghalaya. To enable appropriate estimates for the whole of rural Meghalaya, the data were weighted to allow for the probability of selection of households at each stage of the sampling process. RESULTS: Both local tribal medicine and biomedicine were widely accepted and used, but the majority (68.7%, 95% CI: 51.9-81.7) had not heard of AYUSH and even fewer had used it. Tribal medicine was used (79.1%, 95% CI 66.3-88.0), thought to be effective (87.5%, 95% CI: 74.2-94.1) and given in a variety of disorders, including both minor and major diseases. In the 3 months prior to the survey, 46.2% (95% CI: 30.5-62.8) had used tribal medicine. Only 10.5% (95% CI: 6.1-17.6) reported ever using any of the AYUSH systems. CONCLUSION: Our comparative estimates of the awareness and use of tribal medicine, different systems of AYUSH and of biomedicine among indigenous populations of India question the basis on which AYUSH is promoted in the northeast region of India and in the state of Meghalaya in particular.

Prevalence of clinically captured and confirmed malaria among HIV seropositve clinic attendants in five hospitals in Ghana.

BACKGROUND: Malaria is associated with an increase in HIV viral load and a fall in CD4-cell count. Conversely, HIV infection disrupts the acquired immune responses to malaria and the efficacy of antimalarial drugs. This study was carried out in five Ghanaian hospitals to estimate the prevalence of clinically confirmed malaria among HIV patients by evaluating their hospital records. METHODS: This retrospective descriptive cross sectional study reviewed and collected data on malaria, using Case Record Forms from HIV patients' folders in five hospitals in Ghana. RESULTS: There were 933 patients records made up of 272 (29.2%) males and 661 (70.8%) females. Majority of the patients were aged between 21-40 (63.6%) years and the rest were between the ages 1-20 (2.8%) years, 41-60 (31.6%) years and 61-80 (2.1%) years of age.A total of 38.1% (355/933) of the patients were clinically suspected of having clinical malaria. Of these 339 (95.5%) were referred to the laboratory for confirmation of the diagnosis of malaria. Only 4.4% (15/339) of patients tested were confirmed as cases of malaria among the patients that were clinically suspected of having malaria and subsequently confirmed. Fever, was not significantly associated with a confirmed diagnosis of malaria [OR = 3.11, 95% CI: (0.63, 15.37), P = 0.142]. CONCLUSIONS: There was a 4.4% prevalence of confirmed malaria and 38.1% of presumptively diagnosed malaria from the case records of HIV patients from the selected hospitals in Ghana.

Ethical aspects of directly observed treatment for tuberculosis: a cross-cultural comparison.

BACKGROUND: Tuberculosis is a major global public health challenge, and a majority of countries have adopted a version of the global strategy to fight Tuberculosis, Directly Observed Treatment, Short Course (DOTS). Drawing on results from research in Ethiopia and Norway, the aim of this paper is to highlight and discuss ethical aspects of the practice of Directly Observed Treatment (DOT) in a cross-cultural perspective. DISCUSSION: Research from Ethiopia and Norway demonstrates that the rigid enforcement of directly observed treatment conflicts with patient autonomy, dignity and integrity. The treatment practices, especially when imposed in its strictest forms, expose those who have Tuberculosis to extra burdens and costs. Socially disadvantaged groups, such as the homeless, those employed as day labourers and those lacking rights as employees, face the highest burdens. SUMMARY: From an ethical standpoint, we argue that a rigid practice of directly observed treatment is difficult to justify, and that responsiveness to social determinants of Tuberculosis should become an integral part of the management of Tuberculosis.

Adding more muscle and nerve to clinical trials.

In this review we illustrate both the fundamentals and challenges of randomized clinical trials in neuromuscular disorders and suggest directions for prospective efforts to improve the design, conduct, rigor, and objectivity of these trials. Current research in clinical trials for neuromuscular disorders and key issues affecting these trials are reviewed. This perspective addresses the planning of clinical research, level of preclinical data needed to justify trials, patient recruitment and retention, and opportunities to access federal funding and infrastructure in support of clinical trials. The need for innovation in trial design and conduct, rigorous standards for the preclinical efficacy and safety data that support trial rationale, novel collaborative paradigms, objective interpretations of outcomes, and sharing of the lessons learned from trials in any one disorder among all neuromuscular trialists are imperative to improving the heretofore limited success in delivering novel, safe, and effective therapies to patients burdened by neuromuscular disorders.

The social determinants of tuberculosis: from evidence to action.

Growing consensus indicates that progress in tuberculosis control in the low- and middle-income world will require not only investment in strengthening tuberculosis control programs, diagnostics, and treatment but also action on the social determinants of tuberculosis. However, practical ideas for action are scarcer than is notional support for this idea. We developed a framework based on the recent World Health Organization Commission on Social Determinants of Health and on current understanding of the social determinants of tuberculosis. Interventions from outside the health sector-specifically, in social protection and urban planning-have the potential to strengthen tuberculosis control.

Promoting critical consciousness and social mobilization in HIV/AIDS programmes: lessons and curricular tools from a South African intervention.

The development of critical consciousness is seen as a key stage in communities increasing levels of dialogue about priority problems and effecting structural change for health. However, relatively little research identifies concrete methods for programmes to build critical consciousness. We examined how a South African structural intervention used critical consciousness as a tool for prevention of intimate partner violence and HIV infection. We collected qualitative data in the form of in-depth interviews with managers, trainers, and participants of the Intervention with Microfinance for AIDS and Gender Equity intervention (IMAGE) in rural South Africa. The data were analysed through a coding structure developed in QSR NVivo. We draw practical lessons from IMAGE to guide other HIV programmes aiming to promoting critical consciousness and social mobilization. This research suggests that specific curricular tools can work towards critical consciousness and that mobilization efforts in future programmes can be strengthened by including individual and collective efforts by participants.

New public health approaches to palliative care, a brave new horizon or an impractical ideal? An Integrative literature review with thematic synthesis.

Access to palliative care for marginalized communities is frequently problematized as a major challenge facing palliative care services. The traditional response of asking what services can do for the disadvantaged has been invigorated by a new wave of public health measures that embrace death and dying as social processes and ask, what can be done together with such communities as partners working in palliative care. Such work has generated a significant amount of academic, social and political interests over the last 20 years; however, we are yet to see a consistent and sustained change in approach from providers. We argue that this is due to inherent tensions that arise when modelling death, dying and loss as a unified and shared social process. Unresolved tensions destabilize the theoretical foundations and risk misrepresentation of core philosophies. In this integrative review of 75 articles, we present previously undiscussed areas of contention drawing from a pan-disciplinary field of theoretical and empirical evidence. We conclude that new public health approaches lack a consistent and unified theoretical approach. From philosophical, ontological and existential ideas relating to how different stakeholders conceptualize death, to the processes by which communities are motivated and their constituent members empowered through responsibilized notions of duty and reciprocity, there is little acknowledgement of the complex tensions at hand. Increasing academic and political initiative alone is not enough to progress this movement in a manner that achieves its full potential. Instead, we must pay greater attention to the tensions described. This article aims to work with such tensions to better define the landscape of collective moral responsibility in end-of-life care. We believe that this is crucial if palliative care is to avoid becoming a technical speciality with community and communitization reduced to a mere technical solution to more profound questions.

What 'outliers' tell us about missed opportunities for tuberculosis control: a cross-sectional study of patients in Mumbai, India.

BACKGROUND: India's Revised National Tuberculosis Control Programme (RNTCP) is deemed highly successful in terms of detection and cure rates. However, some patients experience delays in accessing diagnosis and treatment. Patients falling between the 96th and 100th percentiles for these access indicators are often ignored as atypical 'outliers' when assessing programme performance. They may, however, provide clues to understanding why some patients never reach the programme. This paper examines the underlying vulnerabilities of patients with extreme values for delays in accessing the RNTCP in Mumbai city, India. METHODS: We conducted a cross-sectional study with 266 new sputum positive patients registered with the RNTCP in Mumbai. Patients were classified as 'outliers' if patient, provider and system delays were beyond the 95th percentile for the respective variable. Case profiles of 'outliers' for patient, provider and system delays were examined and compared with the rest of the sample to identify key factors responsible for delays. RESULTS: Forty-two patients were 'outliers' on one or more of the delay variables. All 'outliers' had a significantly lower per capita income than the remaining sample. The lack of economic resources was compounded by social, structural and environmental vulnerabilities. Longer patient delays were related to patients' perception of symptoms as non-serious. Provider delays were incurred as a result of private providers' failure to respond to tuberculosis in a timely manner. Diagnostic and treatment delays were minimal, however, analysis of the 'outliers' revealed the importance of social support in enabling access to the programme. CONCLUSION: A proxy for those who fail to reach the programme, these case profiles highlight unique vulnerabilities that need innovative approaches by the RNTCP. The focus on 'outliers' provides a less resource- and time-intensive alternative to community-based studies for understanding the barriers to reaching public health programmes.

Ayurveda and medicalisation today: The loss of important knowledge and practice in health?

Ayurveda translates as 'life science'. Its knowledge is not limited to medicine, cure or therapy and is for laypersons, households, communities, as well as for physicians. Throughout its evolutionary history, Ayurveda and Local Health Traditions have reciprocally influenced each other. In modern times, the influence of biomedicine on Ayurveda is leading to its medicalisation. Over the past century, the introduction and perspective of biomedicine into India has made the human being an object for positive knowledge, a being who can be understood with scientific reason and can be governed and controlled through medical knowledge. This paper explores how this shift towards medicalisation is affecting the knowledge, teaching, and practice of Ayurveda. It examines the impact and contribution of processes like standardisation, professionalisation, bio-medicalisation and pharmaceuticalisation on Ayurveda education, knowledge, practice and policies. To maintain health and wellbeing Ayurveda's ancient knowledge and practice needs to be applied at individual, community and health care provider levels and not be limited to the medical system. The current over medicalisation of society is a potential threat to human health and well-being. Ayurveda and LHT knowledge can provide essential teachings and practices to counter-balance this current trend through encouraging a population's self-reliance in its health.

Characteristics of sexual partnerships, not just of individuals, are associated with condom use and recent HIV infection in rural South Africa.

Characteristics of sexual partnerships, as well as those of the individuals involved, might influence the use of condoms and risk of HIV transmission. We set out to identify characteristics of non-spousal sexual partnerships associated with condom use at last sex in the previous year and HIV infection in the previous three years among sexually active young people in rural South Africa. We conducted an analysis of follow-up data (collected in 2004) from a cohort of 14-35-year old men and women recruited to a cluster-randomised trial. Data on 1647 non-spousal sexual partnerships during the previous year were reported in 2004 and analysed alongside new HIV infections over the previous three years among 762 individuals who were HIV-negative in 2001. Structured interviews elicited information on sexual behaviour. HIV serostatus was assessed through oral-fluid ELISA. Condom use at last sex was reported for 615/1647 non-spousal sexual partnerships (37.3%) and was more commonly reported by individuals who were younger, more educated and aware of their HIV status. Condom use was more common in casual partnerships, those where the male partner was younger, where sex was less frequent and where the respondent believed the partner to have other sexual contacts. New HIV infection in the last three years was identified for 87/762 individuals (11.4%) and was more common among females and those out of school. Infection risk was associated with the age of the partners and was less common among individuals reporting less frequent intercourse in the previous year. Characteristics of sexual partnerships, as well as those of individuals, are important determinants of condom use and risk of HIV infection. Male characteristics may be particularly important because of their greater capacity to make decisions about HIV prevention. Established non-spousal sexual partnerships are an increasingly important context for HIV transmission in this setting.

Is social capital associated with HIV risk in rural South Africa?

The role of social capital in promoting health is now widely debated within international public health. In relation to HIV, the results of previous observational and cross-sectional studies have been mixed. In some settings it has been suggested that high levels of social capital and community cohesion might be protective and facilitate more effective collective responses to the epidemic. In others, group membership has been a risk factor for HIV infection. There have been few attempts to strengthen social capital, particularly in developing countries, and examine its effect on vulnerability to HIV. Employing data from an intervention study, we examined associations between social capital and HIV risk among 1063 14 to 35-year-old male and female residents of 750 poor households from 8 villages in rural Limpopo province, South Africa. We assessed cognitive social capital (CSC) and structural social capital (SSC) separately, and examined associations with numerous aspects of HIV-related psycho-social attributes, risk behavior, prevalence and incidence. Among males, after adjusting for potential confounders, residing in households with greater levels of CSC was linked to lower HIV prevalence and higher levels of condom use. Among females, similar patterns of relationships with CSC were observed. However, while greater SSC was associated with protective psychosocial attributes and risk behavior, it was also associated with higher rates of HIV infection. This work underscores the complex and nuanced relationship between social capital and HIV risk in a rural African context. We suggest that not all social capital is protective or health promotive, and that getting the balance right is critical to informing HIV prevention efforts.

Can social capital be intentionally generated? a randomized trial from rural South Africa.

While much descriptive research has documented positive associations between social capital and a range of economic, social and health outcomes, there have been few intervention studies to assess whether social capital can be intentionally generated. We conducted an intervention in rural South Africa that combined group-based microfinance with participatory gender and HIV training in an attempt to catalyze changes in solidarity, reciprocity and social group membership as a means to reduce women's vulnerability to intimate partner violence and HIV. A cluster randomized trial was used to assess intervention effects among eight study villages. In this paper, we examined effects on structural and cognitive social capital among 845 participants and age and wealth matched women from households in comparison villages. This was supported by a diverse portfolio of qualitative research. After two years, adjusted effect estimates indicated higher levels of structural and cognitive social capital in the intervention group than the comparison group, although confidence intervals were wide. Qualitative research illustrated the ways in which economic and social gains enhanced participation in social groups, and the positive and negative dynamics that emerged within the program. There were numerous instances where individuals and village loan centres worked to address community concerns, both working through existing social networks, and through the establishment of new partnerships with local leadership structures, police, the health sector and NGOs. This is among the first experimental trials suggesting that social capital can be exogenously strengthened. The implications for community interventions in public health are further explored.

HIV progression and predictors of mortality in a community-based cohort of Zambian adults.

This article describes immunological HIV progression, mortality, and its predictors in 974 Zambian adults. During 3138 person-years of follow-up, 281 deaths occurred, and the overall mortality rate was 9.0 per 100 person-years. Thirty-six percent of patients were dead within 5 years of enrollment. The median survival in patients with baseline CD4 count ≥500 cells/mm³ was 5.62 years, with CD4 count between 200 and 499 cells/mm³ 5.46 years, and with CD4 count <200 cells/mm³ 3.89 years. The mortality rate increased significantly with older age (6.9 in patients <25 years, 9.3 in individuals aged 25-39 years, 10.2 in patients ≥40 years) and was higher in women (rate ratio 1.29). The median annual change of progression markers was -29.6 cells/mm³ for CD4 count, -3.0% for CD4 count percentage, 1.2 nmol/L for neopterin, -1.9 g/L for hemoglobin, and -70 cells/mm³ for total lymphocyte count. Hemoglobin and neopterin were as accurate as CD4 count to predict mortality.

Effect of a structural intervention for the prevention of intimate-partner violence and HIV in rural South Africa: a cluster randomised trial.

BACKGROUND: HIV infection and intimate-partner violence share a common risk environment in much of southern Africa. The aim of the Intervention with Microfinance for AIDS and Gender Equity (IMAGE) study was to assess a structural intervention that combined a microfinance programme with a gender and HIV training curriculum. METHODS: Villages in the rural Limpopo province of South Africa were pair-matched and randomly allocated to receive the intervention at study onset (intervention group, n=4) or 3 years later (comparison group, n=4). Loans were provided to poor women who enrolled in the intervention group. A participatory learning and action curriculum was integrated into loan meetings, which took place every 2 weeks. Both arms of the trial were divided into three groups: direct programme participants or matched controls (cohort one), randomly selected 14-35-year-old household co-residents (cohort two), and randomly selected community members (cohort three). Primary outcomes were experience of intimate-partner violence--either physical or sexual--in the past 12 months by a spouse or other sexual intimate (cohort one), unprotected sexual intercourse at last occurrence with a non-spousal partner in the past 12 months (cohorts two and three), and HIV incidence (cohort three). Analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT00242957. FINDINGS: In cohort one, experience of intimate-partner violence was reduced by 55% (adjusted risk ratio [aRR] 0.45, 95% CI 0.23-0.91; adjusted risk difference -7.3%, -16.2 to 1.5). The intervention did not affect the rate of unprotected sexual intercourse with a non-spousal partner in cohort two (aRR 1.02, 0.85-1.23), and there was no effect on the rate of unprotected sexual intercourse at last occurrence with a non-spousal partner (0.89, 0.66-1.19) or HIV incidence (1.06, 0.66-1.69) in cohort three. INTERPRETATION: A combined microfinance and training intervention can lead to reductions in levels of intimate-partner violence in programme participants. Social and economic development interventions have the potential to alter risk environments for HIV and intimate-partner violence in southern Africa.

Understanding the impact of a microfinance-based intervention on women's empowerment and the reduction of intimate partner violence in South Africa.

OBJECTIVES: We sought to obtain evidence about the scope of women's empowerment and the mechanisms underlying the significant reduction in intimate partner violence documented by the Intervention With Microfinance for AIDS and Gender Equity (IMAGE) cluster-randomized trial in rural South Africa. METHODS: The IMAGE intervention combined a microfinance program with participatory training on understanding HIV infection, gender norms, domestic violence, and sexuality. Outcome measures included past year's experience of intimate partner violence and 9 indicators of women's empowerment. Qualitative data about changes occurring within intimate relationships, loan groups, and the community were also collected. RESULTS: After 2 years, the risk of past-year physical or sexual violence by an intimate partner was reduced by more than half (adjusted risk ratio=0.45; 95% confidence interval=0.23, 0.91). Improvements in all 9 indicators of empowerment were observed. Reductions in violence resulted from a range of responses enabling women to challenge the acceptability of violence, expect and receive better treatment from partners, leave abusive relationships, and raise public awareness about intimate partner violence. CONCLUSIONS: Our findings, both qualitative and quantitative, indicate that economic and social empowerment of women can contribute to reductions in intimate partner violence.