Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data.

UNLABELLED: Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%. PERSPECTIVE: This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long-term benefits and risks of this treatment.

Micronutrients in HIV: a Bayesian meta-analysis.

BACKGROUND: Approximately 28.5 million people living with HIV are eligible for treatment (CD4<500), but currently have no access to antiretroviral therapy. Reduced serum level of micronutrients is common in HIV disease. Micronutrient supplementation (MNS) may mitigate disease progression and mortality. OBJECTIVES: We synthesized evidence on the effect of micronutrient supplementation on mortality and rate of disease progression in HIV disease. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central, AMED and CINAHL databases through December 2014, without language restriction, for studies of greater than 3 micronutrients versus any or no comparator. We built a hierarchical Bayesian random effects model to synthesize results. Inferences are based on the posterior distribution of the population effects; posterior distributions were approximated by Markov chain Monte Carlo in OpenBugs. PRINCIPAL FINDINGS: From 2166 initial references, we selected 49 studies for full review and identified eight reporting on disease progression and/or mortality. Bayesian synthesis of data from 2,249 adults in three studies estimated the relative risk of disease progression in subjects on MNS vs. control as 0.62 (95% credible interval, 0.37, 0.96). Median number needed to treat is 8.4 (4.8, 29.9) and the Bayes Factor 53.4. Based on data reporting on 4,095 adults reporting mortality in 7 randomized controlled studies, the RR was 0.84 (0.38, 1.85), NNT is 25 (4.3, ∞). CONCLUSIONS: MNS significantly and substantially slows disease progression in HIV+ adults not on ARV, and possibly reduces mortality. Micronutrient supplements are effective in reducing progression with a posterior probability of 97.9%. Considering MNS low cost and lack of adverse effects, MNS should be standard of care for HIV+ adults not yet on ARV.

Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina.

OBJECTIVE: Our objective was to estimate primary resistance in an urban setting in a developing country characterized by high antiretroviral (ARV) coverage over the diagnosed population and also by an important proportion of undiagnosed individuals, in order to determine whether any change in primary resistance occurred in the past five years. DESIGN: We carried out a multi-site resistance surveillance study according to WHO HIV resistance guidelines, using a weighted sampling technique based on annual HIV case reports per site. METHODS: Blood samples were collected from 197 drug-naive HIV-1-infected individuals diagnosed between March 2010 and August 2011 at 20 HIV voluntary counselling and testing centres in Buenos Aires. Clinical records of enrolled patients at the time of diagnosis were compiled. Viral load and CD4 counts were performed on all samples. The pol gene was sequenced and the resistance profile determined. Phylogenetic analysis was performed by neighbour-joining (NJ) trees and bootscanning analysis. RESULTS: We found that 12 (7.9%) of the 152 successfully sequenced samples harboured primary resistance mutations, of which K103N and G190A were the most prevalent. Non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance mutations were largely the most prevalent (5.9%), accounting for 75% of all primary resistance and exhibiting a significant increase (p=0.0072) in prevalence during the past 10 years as compared to our previous study performed in 1997-2000 and in 2003-2005. Nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor primary resistance were low and similar to the one previously reported. CONCLUSIONS: Levels of primary NNRTI resistance in Buenos Aires appear to be increasing in the context of a sustained ARV coverage and a high proportion of undiagnosed HIV-positive individuals.

The rationale of interorganizational linkages to connect multiple sites of expertise, knowledge production, and knowledge transfer: an example from HIV/AIDS services for the inner city.

This paper presents the rationale for a long-running project in which various community-based and tertiary-based providers are being linked to each other in order to understand, reach, and engage high-risk, hard-to-reach inner-city residents for prevention, treatment, and management of HIV/AIDS. Not simply a program to link disparate actors, the work has developed into a more fundamental approach through which to build and maintain the infrastructure required to generate and sustain knowledge development and integration within and between systems. This work is grounded in the recognition that each type of provider, as well as patients and clients themselves, has a particular type of expertise. All forms of expertise are necessary to fight HIV/ AIDS. Different forms of expertise are necessary to diagnose, treat, prevent, and cure HIV/AIDS and its sequelae. This work suggests revisions in traditional approaches to expertise and to the content and geometry of dissemination networks, and ultimately challenges the very concepts of dissemination and the lay/scientific boundary.

Wiring the HIV/AIDS system: building interorganizational infrastructure to link people, sites, and networks.

This paper presents a case example of the new "geometry of care" (Rier and Indyk, this volume), by examining selected examples from five facets of a program developed by the lead author and in operation since 1989. This program is designed to understand, build, revise, and maintain the organizational infrastructure with which to link diverse players and sites, and combine these into a web for producing, assessing, and exchanging the information needed to combat HIV/AIDS. Each example demonstrates how opportunities were exploited for developing and linking resources within and between systems of care and prevention. The program began as an iterative and systems approach to improve access of high-risk, hard-to-reach inner city New York populations to HIV/AIDS services, treatment, and research. The approach is also currently being further elaborated and applied in Argentina and India (see Boylan et al., this volume), and is adaptable to other local and global public health challenges (see Indyk & Rier, this volume).

Collecting data along the continuum of prevention and care: a Continuous Quality Improvement approach.

For the past 14 years, a team of applied social scientists and system analysts has worked with a wide variety of Community- Based Organizations (CBO's), other grassroots agencies and networks, and Medical Center departments to support resource, program, staff and data development and evaluation for hospital- and community-based programs and agencies serving HIV at-risk and affected populations. A by-product of this work has been the development, elaboration and refinement of an approach to Continuous Quality Improvement (CQI) which is appropriate for diverse community-based providers and agencies. A key component of our CQI system involves the installation of a sophisticated relational database management and reporting system (DBMS) which is used to collect, analyze, and report data in an iterative process to provide feedback among the evaluators, agency administration and staff. The database system is designed for two purposes: (1) to support the agency's administrative internal and external reporting requirements; (2) to support the development of practice driven health services and early intervention research. The body of work has fostered a unique opportunity for the development of exploratory service-driven research which serves both administrative and research needs.

Culture, community networks, and HIV/AIDS outreach opportunities in a south Indian Siddha organization.

BACKGROUND: Gandeepam is an NGO in rural south India, with an HIV prevalence rate estimated at 2-7 times the national average. Aside from several outreach programs, Gandeepam practices Siddha medicine. OBJECTIVE: Evaluate Gandeepam's strengths and opportunities to promote HIV education. DESIGN: Three weeks of observing clinic practice, meeting patients, and discussing organizational structure. A survey of attitudes toward HIV was completed. RESULTS: Gandeepam reaches a broad cross-section of its community, and effectively disseminates information. No primary HIV prevention efforts were observed. CONCLUSION: Current strengths include an established network for information dissemination, and a strong community reputation. Tremendous social obstacles for disseminating effective HIV prevention messages remain.

Requisites, benefits, and challenges of sustainable HIV/AIDS system-building: where theory meets practice.

This paper is the third and final of a series that has previously presented the rationale (Rier and Indyk, this volume) and major program elements (Indyk and Rier, this volume) of an approach to link community and tertiary sociomedical providers, clients/patients, sites, and systems into an integrated response to HIV/AIDS. The primary goal has been to improve sociomedical HIV/AIDS services for a hard-to-reach inner city population. The current paper first summarizes the main advantages (e.g., greater efficiency; more realistic, effective programs with greater credibility among the community; stimulation of knowledge production and dissemination amongst players rarely formally engaged in such activities; creation of a platform useful for other applications) of this work. It then examines some of the main organizational challenges in conducting the work (involving issues such as personnel, coordination, funding, turf conflicts, sustainability). From this discussion emerge organizational requisites to conducting this work (e.g., development of key boundary-spanning figures; attention to the specific interests of potential linkage partners; translation efforts to demonstrate the value of participation; a continuous quality improvement approach featuring wide distribution of feedback in user-friendly form; flexibility, tact and patience), so that others can adapt and apply the linkage approach to manage HIV/AIDS or other problems. Finally, we explain how theory and practice have driven one another in this work.

Flexible rigidity: supporting HIV treatment adherence in a rapidly-changing treatment environment.

This paper examines adherence to AIDS treatment, focusing on the challenges posed by rapidly changing treatment protocols. We examine the evolving views of treatment adherence, and endorse the "concordance" approach. This emphasizes collaboration and negotiation between provider and patient to formulate and maintain a manageable treatment regimen tailored to what the patient is ready, willing, and able to tolerate. Given the extreme rapidity with which treatment guidelines are revised or even reversed, the persistent uncertainty surrounding treatment risks and benefits, and the great variability in individuals' ability to tolerate a given regimen, we propose the term "flexible rigidity" to describe the type of adherence best suited to AIDS treatment. We present an organizational approach to supporting the type of provider-patient relationships needed to improve treatment adherence that features treatment- readiness assessment and custom-tailoring of treatment for those at all stages of the treatment-readiness continuum. We note that this model could be applied as well to prevention and management of other chronic diseases.

HIV-infected individuals as partners in prevention: a redefinition of the partner notification process.

Over the past ten years, the advances that have turned HIV into a chronic illness have also highlighted the importance of integrating prevention and care in the fight against the epidemic. This integration involves not only the creation of new programs, but also a reexamination of the process through which services and supports are provided. In this article, HIV partner notification is used as a case example; the discussion includes: the shifting time frame within which partner notification occurs; the expanding role of HIV-positive individuals in effecting both disease management and prevention goals; the connection between partner-notification and behaviorally-based risk reduction; and the ethical implications of advances on the partner notification process. The authors argue that partner notification services must be located in the context of overall treatment for infected individuals, and demonstrate how a redefinition of the partner notification process can serve as a spring-board for ongoing prevention counseling and support.