Supply-chain strategies for essential medicines in rural western Kenya during COVID-19.

PROBLEM: The coronavirus disease 2019 (COVID-19) pandemic has disrupted health systems worldwide and threatened the supply of essential medicines. Especially affected are vulnerable patients in low- and middle-income countries who can only afford access to public health systems. APPROACH: Soon after physical distancing and curfew orders began on 15 March 2020 in Kenya, we rapidly implemented three supply-chain strategies to ensure a continuous supply of essential medicines while minimizing patients' COVID-19 exposure risks. We redistributed central stocks of medicines to peripheral health facilities to ensure local availability for several months. We equipped smaller, remote health facilities with medicine tackle boxes. We also made deliveries of medicines to patients with difficulty reaching facilities. LOCAL SETTING: Τo implement these strategies we leveraged our 30-year partnership with local health authorities in rural western Kenya and the existing revolving fund pharmacy scheme serving 85 peripheral health centres. RELEVANT CHANGES: In April 2020, stocks of essential chronic and non-chronic disease medicines redistributed to peripheral health facilities increased to 835 140 units, as compared with 316 330 units in April 2019. We provided medicine tackle boxes to an additional 46 health facilities. Our team successfully delivered medications to 264 out of 311 patients (84.9%) with noncommunicable diseases whom we were able to reach. LESSONS LEARNT: Our revolving fund pharmacy model has ensured that patients' access to essential medicines has not been interrupted during the pandemic. Success was built on a community approach to extend pharmaceutical services, adapting our current supply-chain infrastructure and working quickly in partnership with local health authorities.

The Relationship Between Household Microfinance Group Participation and Vaccine Adherence Among Children in Rural Western Kenya.

INTRODUCTION: High childhood vaccine adherence is critical for disease prevention, and poverty is a key barrier to vaccine uptake. Interventions like microfinance programs that aim to lift individuals out of poverty could thus improve vaccine adherence of the children in the household. BIGPIC Family Program in rural Western Kenya provides group-based microfinance services while working to improve access to healthcare and health screenings for the local community. The aim of the present paper is to evaluate the association between household participation in BIGPIC's microfinance program and vaccine adherence among children in the household. We hypothesize that microfinance group participation will have a positive impact on vaccine adherence among children in the household. METHODS: From 2018 to 2019, we surveyed a sample of 300 participants from two rural communities in Western Kenya, some of whom were participants in the BIGPIC Family's microfinance program. The primary outcome of interest was vaccine adherence of children in the household. Log-binomial models were used to estimate the relationship between microfinance group participation and vaccine adherence, adjusted for key covariates. We also assessed whether the relationship differed by gender of the adult respondent. RESULTS: Microfinance group members were more likely to have all children in their households fully vaccinated [aPR (95% CI): 1.68 (1.20,2.35)] compared to non-microfinance group members. Further, the association was stronger when women were the microfinance members [PR (95% CI): 1.87 (1.27,2.76)] compared to men [PR (95% CI): 1.24 (0.81,1.90)]. CONCLUSIONS: Microfinance participation was associated with higher childhood vaccine adherence in rural Western Kenya. Microfinance interventions should be further explored as strategies to improve child health and well-being in low- and middle-income countries.

The relationship between a microfinance-based healthcare delivery platform, health insurance coverage, health screenings, and disease management in rural Western Kenya.

BACKGROUND: Structural barriers often prevent rural Kenyans from receiving healthcare and diagnostic testing. The Bridging Income Generation through grouP Integrated Care (BIGPIC) Family intervention facilitates microfinance groups, provides health screenings and treatment, and delivers education about health insurance coverage to address some of these barriers. This study evaluated the association between participation in BIGPIC microfinance groups and health screening/disease management outcomes. METHODS: From November 2018 to March 2019, we interviewed a sample of 300 members of two rural communities in Western Kenya, 100 of whom were BIGPIC microfinance members. We queried participants about their experiences with health screening and disease management for HIV, diabetes, hypertension, tuberculosis, and cervical cancer. We used log-binomial regression models to estimate the association between microfinance membership and each health outcome, adjusting for key covariates. RESULTS: Microfinance members were more likely to be screened for most of the health conditions we queried, including those provided by BIGPIC [e.g. diabetes: aPR (95% CI): 3.46 (2.60, 4.60)] and those not provided [e.g. cervical cancer: aPR (95% CI): 2.43 (1.21, 4.86)]. Microfinance membership was not significantly associated with health insurance uptake and disease management outcomes. CONCLUSIONS: In rural Kenya, a microfinance program integrated with healthcare delivery may be effective at increasing health screening. Interventions designed to thoughtfully and sustainably address structural barriers to healthcare will be critical to improving the health of those living in low-resource settings.

Interruptions to HIV Care Delivery During Pandemics and Natural Disasters: A Qualitative Study of Challenges and Opportunities From Frontline Healthcare Providers in Western Kenya.

During public health crises, people living with HIV (PLWH) may become disengaged from care. The goal of this study was to understand the impact of the COVID-19 pandemic and recent flooding disasters on HIV care delivery in western Kenya. We conducted ten individual in-depth interviews with HIV providers across four health facilities. We used an iterative and integrated inductive and deductive data analysis approach to generate four themes. First, increased structural interruptions created exacerbating strain on health facilities. Second, there was increased physical and psychosocial burnout among providers. Third, patient uptake of services along the HIV continuum decreased, particularly among vulnerable patients. Finally, existing community-based programs and teleconsultations could be adapted to provide differentiated HIV care. Community-centric care programs, with an emphasis on overcoming the social, economic, and structural barriers will be crucial to ensure optimal care and limit the impact of public health disruptions on HIV care globally.

Pharmacological inhibition of the ClpXP protease increases bacterial susceptibility to host cathelicidin antimicrobial peptides and cell envelope-active antibiotics.

The ClpXP protease is a critical bacterial intracellular protease that regulates protein turnover in many bacterial species. Here we identified a pharmacological inhibitor of the ClpXP protease, F2, and evaluated its action in Bacillus anthracis and Staphylococcus aureus. We found that F2 exhibited synergistic antimicrobial activity with cathelicidin antimicrobial peptides and antibiotics that target the cell well and/or cell membrane, such as penicillin and daptomycin, in B. anthracis and drug-resistant strains of S. aureus. ClpXP inhibition represents a novel therapeutic strategy to simultaneously sensitize pathogenic bacteria to host defenses and pharmaceutical antibiotics.

How health systems can adapt to a population ageing with HIV and comorbid disease.

As people age with HIV, their needs increase beyond solely managing HIV care. Ageing people with HIV, defined as people with HIV who are 50 years or older, face increased risk of both age-regulated comorbidities and ageing-related issues. Globally, health-care systems have struggled to meet these changing needs of ageing people with HIV. We argue that health systems need to rethink care strategies to meet the growing needs of this population and propose models of care that meet these needs using the WHO health system building blocks. We focus on care provision for ageing people with HIV in the three different funding mechanisms: President's Emergency Plan for AIDS Relief and Global Fund funded nations, the USA, and single-payer government health-care systems. Although our categorisation is necessarily incomplete, our efforts provide a valuable contribution to the debate on health systems strengthening as the need for integrated, people-centred, health services increase.

Strategies to Improve Women's Leadership Preparation for Early Career Global Health Professionals: Suggestions from Two Working Groups.

Background: Despite advances in gender equality, women still experience inequitable gaps in global health leadership, and barriers to women's advancement as leaders in global health have been well described in the literature. In 2021, the Johns Hopkins Center for Global Health conducted two virtual working groups for emerging women leaders to share challenges and suggest solutions to advance women's leadership in global health. In this paper, we present emerging themes from the working groups, provide a framework for the results, and discuss strategies for advancing women's leadership in global health. Objectives: The objective of this paper is to synthesize and share the themes of the two working group sessions to provide strategies for improving women's leadership training and opportunities in the field of global health. Methods: Approximately 182 women in the global health field participated in two virtual working group sessions hosted by the Johns Hopkins Center for Global Health using the Zoom platform. Participants were divided into virtual breakout rooms and discussed pre-assigned topics related to women's leadership in global health. The participants then returned to share their ideas in a plenary session. Notes from the breakout rooms and transcripts from the plenary session were analyzed through a participatory and iterative thematic analysis approach. Findings: We found that the working group participants identified two overarching themes that were critical for emerging women leaders to find success in global health leadership. First, the acquisition of individual essential skills is necessary to advance in their careers. Second, the institutional environments should be setup to encourage and enable women to enter and succeed in leadership roles. The participants also shared suggestions for improving women's leadership opportunities such as including the use of virtual technologies to increase training and networking opportunities, intersectionality in mentorship and sponsorship, combatting impostor syndrome, and the importance of work-life balance. Conclusions: Investing in women and their leadership potential has the promise to improve health and wealth at the individual, institutional, and community levels. This manuscript offers lessons and proposes solutions for increasing women's leadership through improving individual level essential skills and fostering environments in which women leaders can emerge and thrive.

Incorporating respondent-driven sampling into web-based discrete choice experiments: preferences for COVID-19 mitigation measures.

To slow the spread of COVID-19, most countries implemented stay-at-home orders, social distancing, and other nonpharmaceutical mitigation strategies. To understand individual preferences for mitigation strategies, we piloted a web-based Respondent Driven Sampling (RDS) approach to recruit participants from four universities in three countries to complete a computer-based Discrete Choice Experiment (DCE). Use of these methods, in combination, can serve to increase the external validity of a study by enabling recruitment of populations underrepresented in sampling frames, thus allowing preference results to be more generalizable to targeted subpopulations. A total of 99 students or staff members were invited to complete the survey, of which 72% started the survey (n = 71). Sixty-three participants (89% of starters) completed all tasks in the DCE. A rank-ordered mixed logit model was used to estimate preferences for COVID-19 nonpharmaceutical mitigation strategies. The model estimates indicated that participants preferred mitigation strategies that resulted in lower COVID-19 risk (i.e. sheltering-in-place more days a week), financial compensation from the government, fewer health (mental and physical) problems, and fewer financial problems. The high response rate and survey engagement provide proof of concept that RDS and DCE can be implemented as web-based applications, with the potential for scale up to produce nationally-representative preference estimates.

Integrating community-based HIV and non-communicable disease care with microfinance groups: a feasibility study in Western Kenya.

BACKGROUND: The Harambee study is a cluster randomized trial in Western Kenya that tests the effect, mechanisms, and cost-effectiveness of integrating community-based HIV and non-communicable disease care within microfinance groups on chronic disease treatment outcomes. This paper documents the stages of our feasibility study conducted in preparation for the Harambee trial, which include (1) characterizing the target population and gauging recruitment capacity, (2) determining community acceptability of the integrated intervention and study procedures, and (3) identifying key implementation considerations prior to study start. METHODS: Feasibility research took place between November 2019 and February 2020 in Western Kenya. Mixed methods data collection included surveys administered to 115 leaders of 105 community-based microfinance groups, 7 in-person meetings and two workshops with stakeholders from multiple sectors of the health system, and ascertainment of field notes and geographic coordinates for group meeting locations and HIV healthcare facilities. Quantitative survey data were analyzed using STATA IC/13. Longitude and latitude coordinates were mapped to county boundaries using Esri ArcMap. Qualitative data obtained from stakeholder meetings and field notes were analyzed thematically. RESULTS: Of the 105 surveyed microfinance groups, 77 met eligibility criteria. Eligible groups had been in existence from 6 months to 18 years and had an average of 22 members. The majority (64%) of groups had at least one member who owned a smartphone. The definition of "active" membership and model of saving and lending differed across groups. Stakeholders perceived the community-based intervention and trial procedures to be acceptable given the minimal risks to participants and the potential to improve HIV treatment outcomes while facilitating care integration. Potential challenges identified by stakeholders included possible conflicts between the trial and existing community-based interventions, fear of group disintegration prior to trial end, clinicians' inability to draw blood for viral load testing in the community, and deviations from standard care protocols. CONCLUSIONS: This study revealed that it was feasible to recruit the number of microfinance groups necessary to ensure that our clinical trial was sufficient powered. Elicitation of stakeholder feedback confirmed that the planned intervention was largely acceptable and was critical to identifying challenges prior to implementation. TRIAL REGISTRATION: The original trial was prospectively registered with ClinicalTrials.gov (NCT04417127) on 4 June 2020.

Community-based medication delivery program for antihypertensive medications improves adherence and reduces blood pressure.

Non-adherence to antihypertensive medications is a major cause of uncontrolled hypertension, leading to cardiovascular morbidity and mortality. Ensuring consistent medication possession is crucial in addressing non-adherence. Community-based medication delivery is a strategy that may improve medication possession, adherence, and blood pressure (BP) reduction. Our program in Kenya piloted a community medication delivery program, coupled with blood pressure monitoring and adherence evaluation. Between September 2019 and March 2020, patients who received hypertension care from our chronic disease management program also received community-based delivery of antihypertensive medications. We calculated number of days during which each patient had possession of medications and analyzed the relationship between successful medication delivery and self-reported medication adherence and BP. A total of 128 patient records (80.5% female) were reviewed. At baseline, mean systolic blood pressure (SBP) was 155.7 mmHg and mean self-reported adherence score was 2.7. Sixty-eight (53.1%) patients received at least 1 successful medication delivery. Our pharmacy dispensing records demonstrated that medication possession was greater among patients receiving medication deliveries. Change in self-reported medication adherence from baseline worsened in patients who did not receive any medication delivery (+0.5), but improved in patients receiving 1 delivery (-0.3) and 2 or more deliveries (-0.8). There was an SBP reduction of 1.9, 6.1, and 15.5 mmHg among patients who did not receive any deliveries, those who received 1 delivery, and those who received 2 or more medication deliveries, respectively. Adjusted mixed-effect model estimates revealed that mean SBP reduction and self-reported medication adherence were improved among individuals who successfully received medication deliveries, compared to those who did not. A community medication delivery program in western Kenya was shown to be implementable and enhanced medication possession, reduced SBP, and significantly improved self-reported adherence. This is a promising strategy to improve health outcomes for patients with uncontrolled hypertension that warrants further investigation.

Pharmacological properties of the marine natural product marinopyrrole A against methicillin-resistant Staphylococcus aureus.

The ongoing spread of methicillin-resistant Staphylococcus aureus (MRSA) strains in hospital and community settings presents a great challenge to public health and illustrates the urgency of discovering new antibiotics. Marinopyrrole A is a member of a structurally novel class of compounds identified from a species of marine-derived streptomycetes with evidence of antistaphylococcal activity. We show that marinopyrrole A has potent concentration-dependent bactericidal activity against clinically relevant hospital- and community-acquired MRSA strains, a prolonged postantibiotic effect superior to that of the current first-line agents vancomycin and linezolid, and a favorable resistance profile. Marinopyrrole A showed limited toxicity to mammalian cell lines (at >20× MIC). However, its antibiotic activity against MRSA was effectively neutralized by 20% human serum. A variety of marinopyrrole analogs were isolated from culture or synthetically produced to try to overcome the inhibitory effect of serum. While many of these compounds retained potent bactericidal effect against MRSA, their activities were also inhibited by serum. Marinopyrrole A has significant affinity for plastic and may therefore have potential as a potent anti-MRSA agent in cutaneous, intracatheter, or antibiotic-lock applications.

Microfinance, retention in care, and mortality among patients enrolled in HIV care in East Africa.

OBJECTIVE: To measure associations between participation in community-based microfinance groups, retention in HIV care, and death among people with HIV (PWH) in low-resource settings. DESIGN AND METHODS: We prospectively analyzed data from 3609 patients enrolled in an HIV care program in western Kenya. HIV patients who were eligible and chose to participate in a Group Integrated Savings for Health Empowerment (GISHE) microfinance group were matched 1 : 2 on age, sex, year of enrollment in HIV care, and location of initial HIV clinic visit to patients not participating in GISHE. Follow-up data were abstracted from medical records from January 2018 through February 2020. Logistic regression analysis examined associations between GISHE participation and two outcomes: retention in HIV care (i.e. >1 HIV care visit attended within 6 months prior to the end of follow-up) and death. Socioeconomic factors associated with HIV outcomes were included in adjusted models. RESULTS: The study population was majority women (78.3%) with a median age of 37.4 years. Microfinance group participants were more likely to be retained in care relative to HIV patients not participating in a microfinance group [adjusted odds ratio (aOR) = 1.31, 95% confidence interval (CI) 1.01-1.71; P = 0.046]. Participation in group microfinance was associated with a reduced odds of death during the follow-up period (aOR = 0.57, 95% CI 0.28-1.09; P = 0.105). CONCLUSION: Participation in group-based microfinance appears to be associated with better HIV treatment outcomes. A randomized trial is needed to assess whether microfinance groups can improve clinical and socioeconomic outcomes among PWH in similar settings.

Integrated community-based HIV and non-communicable disease care within microfinance groups in Kenya: study protocol for the Harambee cluster randomised trial.

INTRODUCTION: In Kenya, distance to health facilities, inefficient vertical care delivery and limited financial means are barriers to retention in HIV care. Furthermore, the increasing burden of non-communicable diseases (NCDs) among people living with HIV complicates chronic disease treatment and strains traditional care delivery models. Potential strategies for improving HIV/NCD treatment outcomes are differentiated care, community-based care and microfinance (MF). METHODS AND ANALYSIS: We will use a cluster randomised trial to evaluate integrated community-based (ICB) care incorporated into MF groups in medium and high HIV prevalence areas in western Kenya. We will conduct baseline assessments with n=900 HIV positive members of 40 existing MF groups. Group clusters will be randomised to receive either (1) ICB or (2) standard of care (SOC). The ICB intervention will include: (1) clinical care visits during MF group meetings inclusive of medical consultations, NCD management, distribution of antiretroviral therapy (ART) and NCD medications, and point-of-care laboratory testing; (2) peer support for ART adherence and (3) facility referrals as needed. MF groups randomised to SOC will receive regularly scheduled care at a health facility. Findings from the two trial arms will be compared with follow-up data from n=300 matched controls. The primary outcome will be VS at 18 months. Secondary outcomes will be retention in care, absolute mean change in systolic blood pressure and absolute mean change in HbA1c level at 18 months. We will use mediation analysis to evaluate mechanisms through which MF and ICB care impact outcomes and analyse incremental cost-effectiveness of the intervention in terms of cost per HIV suppressed person-time, cost per patient retained in care and cost per disability-adjusted life-year saved. ETHICS AND DISSEMINATION: The Moi University Institutional Research and Ethics Committee approved this study (IREC#0003054). We will share data via the Brown University Digital Repository and disseminate findings via publication. TRIAL REGISTRATION NUMBER: NCT04417127.

Interprofessional peer teaching: The value of a pharmacy student-led pharmacology course for physical therapy students.

BACKGROUND: This report describes the creation, implementation, and evaluation of an interprofessional pharmacy student-led pharmacology course for physical therapy students. The course was designed using a flipped classroom model and a peer-assisted learning framework. INTERPROFESSIONAL EDUCATION ACTIVITY: We describe the development, design, assessment, and evaluation of a pharmacy student-led pharmacology course for physical therapy students. This report focuses specifically on the interprofessional aspect of the course, which was measured using the student perceptions of physician-pharmacist interprofessional clinical education (SPICE) instrument. DISCUSSION: The SPICE instrument was measured across two cohorts in 2015 and 2016. Each cohort consisted of approximately 50 physical therapy students. After implementation of the course, there were significant improvements across all three domains of the SPICE instrument: interprofessional teamwork, roles/responsibilities for collaborative practice, and patient outcomes from collaborative practice (P < .01). Qualitative feedback from the physical therapy students and pharmacy student teaching assistants was positive and emphasized the benefits of interprofessional peer teaching. IMPLICATIONS: Overall, this interprofessional peer teaching model effectively improved interprofessional attitudes while accomplishing didactic needs. This innovative course may serve as a model for interprofessional education in different subject areas or across other health professions programs.

Framework and case study for establishing impactful global health programs through academia - biopharmaceutical industry partnerships.

BACKGROUND: The field of global health has grown with multiple different public and private stakeholders engaging in the effort to improve health outcomes for underserved populations around the world. There is, however, only limited published guidance on how to promote successful partnerships between academia and the biopharmaceutical industry. OBJECTIVE: This analysis will provide a framework for developing successful partnerships around five central principles. This framework will then be applied to two representative pharmacy collaboration case studies focused on training and donations. FRAMEWORK DESCRIPTION AND CASE STUDY FINDINGS: Within the Academic Model Providing Access to Healthcare (AMPATH), successful collaborations between the biopharmaceutical industry philanthropic entities and academic partners have consistently prioritized 1) contextualization, 2) collaboration, 3) local priorities, 4) institutional commitment, and 5) integration. In the first case study, the application of this framework to clinical pharmacy training activities sponsored by Celgene and implemented by the Purdue Kenya Partnership has helped the program transition from an entirely donor dependent training program to a revenue generating, locally administered program which is now recognized and accredited by the Kenyan government. In the second case study, medication donations from Eli Lilly and Company have been converted from a traditional donation program in one Kenyan health facility to a replicable and sustainable supply chain model which has been expanded to more than 70 public sector facilities across western Kenya. CONCLUSION: Adherence to the five core principles of the proposed framework can help guide partnerships between academic institutions and the biopharmaceutical industry to advance healthcare services for underserved populations around the world. As large-scale government-based development agencies continue to primarily focus on specific disease states, biopharmaceutical industry-based collaborations can help initiate activities in underfunded therapeutic areas such as non-communicable diseases.

Solving the problem of access to cardiovascular medicines: revolving fund pharmacy models in rural western Kenya.

Availability of medicines for treatment of cardiovascular disease (CVD) is low in low-income and middle-income countries (LMIC). Supply chain models to improve the availability of quality CVD medicines in LMIC communities are urgently required. Our team established contextualised revolving fund pharmacies (RFPs) in rural western Kenya, whereby an initial stock of essential medicines was obtained through donations or purchase and then sold at a small mark-up price sufficient to replenish drug stock and ensure sustainability. In response to different contexts and levels of the public health system in Kenya (eg, primary versus tertiary), we developed and implemented three contextualised models of RFPs over the past decade, creating a network of 72 RFPs across western Kenya, that supplied 22 categories of CVD medicines and increased availability of essential CVD medications from <30% to 90% or higher. In one representative year, we were able to successfully supply 5 793 981 units of CVD and diabetes medicines to patients in western Kenya. The estimated programme running cost was US$6.5-25 per patient, serving as a useful benchmark for public governments to invest in medication supply chain systems in LMICs going forward. One important lesson that we have learnt from implementing three different RFP models over the past 10 years has been that each model has its own advantages and disadvantages, and we must continue to stay nimble and modify as needed to determine the optimal supply chain model while ensuring consistent access to essential CVD medications for patients living in these settings.

Therapeutic turnaround times for common laboratory tests in a tertiary hospital in Kenya.

METHODS: We evaluated therapeutic TAT for a tertiary hospital in Western Kenya, using a time-motion study focusing specifically on common hematology and biochemistry orders. The aim was to determine significant bottlenecks in diagnostic testing processes at the institution. RESULTS: A total of 356 (155 hematology and 201 biochemistry) laboratory tests were fully tracked from the time of ordering to availability of results to care providers. The total therapeutic TAT for all tests was 21.5 ± 0.249 hours (95% CI). The therapeutic TAT for hematology was 20.3 ± 0.331 hours (95% CI) while that for biochemistry tests was 22.2 ± 0.346 hours (95% CI). Printing, sorting and dispatch of the printed results emerged as the most significant bottlenecks, accounting for up to 8 hours of delay (Hematology-8.3 ± 1.29 hours (95% CI), Biochemistry-8.5 ± 1.18 hours (95% CI)). Time of test orders affected TAT, with orders made early in the morning and those in the afternoon experiencing the most delays in TAT. CONCLUSION: Significant inefficiencies exist at multiple steps in the turnaround times for routine laboratory tests at a large referral hospital within an LMIC setting. Multiple opportunities exist to improve TAT and streamline processes around diagnostic testing in this and other similar settings.

Mitigating The Burden Of Diabetes In Sub-Saharan Africa Through An Integrated Diagonal Health Systems Approach.

Diabetes is a chronic non-communicable disease (NCD) presenting growing health and economic burdens in sub-Saharan Africa (SSA). Diabetes is unique due to its cross-cutting nature, impacting multiple organ systems and increasing the risk for other communicable and non-communicable diseases. Unfortunately, the quality of care for diabetes in SSA is poor, largely due to a weak disease management framework and fragmented health systems in most sub-Saharan African countries. We argue that by synergizing disease-specific vertical programs with system-specific horizontal programs through an integrated disease-system diagonal approach, we can improve access, quality, and safety of diabetes care programs while also supporting other chronic diseases. We recommend utilizing the six World Health Organization (WHO) health system building blocks - 1) leadership and governance, 2) financing, 3) health workforce, 4) health information systems, 5) supply chains, and 6) service delivery - as a framework to design a diagonal approach with a focus on health system strengthening and integration to implement and scale quality diabetes care. We discuss the successes and challenges of this approach, outline opportunities for future care programming and research, and highlight how this approach can lead to the improvement in the quality of care for diabetes and other chronic diseases across SSA.

The reversal of amphetamine-induced locomotor activation by a selective neurotensin-1 receptor agonist does not exhibit tolerance.

RATIONALE: Neurotensin-1 (NT1) receptor agonists have been proposed as putative antipsychotic drugs. Recently, brain-penetrating NT analogs produced by stability-enhancing modification of the smallest NT fragment, NT(8-13), have demonstrated antipsychotic-like efficacy after acute systemic injection in several preclinical animal tests predictive for antipsychotic efficacy. However, the evidence regarding the persistence versus tolerance of these effects after repeated administration is ambiguous. Previous studies have used compounds that nonselectively activated both NT1 and NT2 receptors or used continuous slow, central infusion of doses rather than daily acute administration, both factors which may have contributed to the ambiguity in the literature regarding the emergence of tolerance. OBJECTIVES: To determine if tolerance develops to the antipsychotic-like effects of NT1 receptor agonists, we investigated the effects of subchronic daily systemic administration of PD149163, a brain-penetrating NT analog with selectivity for the NT1 receptor, on amphetamine-induced locomotor activation, a classic preclinical test of antipsychotic efficacy. MATERIALS AND METHODS: Sprague-Dawley rats were pretreated with eight consecutive daily subcutaneous (SC) injections of PD149163 or saline. On the ninth day, rats received a pair of SC injections consisting of PD149163 or saline, followed by amphetamine (0.5 mg/kg) or saline. Locomotor activity was then measured in photobeam-equipped cages. RESULTS: The results indicated that repeated daily administration of PD149163 was able to antagonize amphetamine's locomotor-activating effect comparable to that of the first dose, despite that repeated administration of PD149163 produced an increase in baseline locomotor activity not seen after the first dose. CONCLUSIONS: The results do not support the development of tolerance for the acute antipsychotic-like effect of NT1 agonists and thus lend support to the contention that NT1 agonists are viable candidates as putative novel antipsychotic drugs.

Building reliable supply chains for noncommunicable disease commodities: lessons learned from HIV and evidence needs.

OBJECTIVE: Successful noncommunicable disease (NCD) management requires a reliable supply chain. The objectives of this article are to examine lessons learned from HIV supply chain initiatives, describe opportunities to advance supply chain systems for NCD health commodities based on HIV supply chain successes and identify areas where additional research is still needed for reliable NCD supply chains in LMICs. DESIGN: We describe practical experiences gained from developing HIV supply chain systems and how those lessons can be used to inform NCD supply chain systems. METHODS: Supply chain challenges with HIV commodities in low and middle-income countries (LMICs) are identified and categorized using literature review and expert experiences. Solutions are described on the basis of lessons learned from global HIV initiatives. Opportunities to further advance NCD supply chain systems are recommended. RESULTS: Supply chain challenges can be organized into two groups: 1) resource mobilization and 2) resource utilization. Global HIV initiatives have responded to resource mobilization challenges by increasing availability of funding, filling human resource gaps, improving essential storage and creating better transport mechanisms and information technology infrastructure. These initiatives have assisted in better resource utilization by strengthening procurement processes, standardizing and simplifying supply chain systems, reducing integrity and security vulnerabilities and harnessing the power of better data. Advances achieved through HIV initiatives are readily transferrable to NCD supply chains with minimal additional investment. Research opportunities exist to identify the most efficient and cost-effective ways to develop more reliable supply chains for NCDs.