PIVOT

To explore the mechanism of action and structural effects of MM-II, a dispersion of "empty" multilamellar large liposomes composed of dimyristoyl phosphatidylcholine (DMPC) and dipalmitoyl phosphatidylcholine (DPPC), which durably reduced pain in a phase 2b study in knee osteoarthritis (OA) patients. MM-II liposomes were manufactured using a defined ratio of DMPC and DPPC, resulting in a lipid phase transition temperature range overlapping with the temperature of human OA knees. MM-II cartilage coating in the presence and absence of compression load was assessed using labeled MM-II. Lubrication of damaged cartilage by MM-II was tested in cartilage-on-glass friction tests and pin-on-disc wear tests. Knee distribution of intra-articularly injected MM-II was assessed in healthy and OA rabbit knees. Structural effects were assessed using a rat OA model comparing to DPPC liposomes, DMPC liposomes, a mixture of DPPC and DMPC liposomes, and vehicle. In a pin-on-disc model, MM-II reduced cartilage wear by up to 44% compared to control. MM-II liposomes bound to cartilage discs preferentially under compression load. Coating of cartilage and menisci with MM-II was also observed in both healthy and OA rabbit knees. Cartilage-bound MM-II efficiently lubricated damaged cartilage discs. In a rat OA model, MM-II demonstrated 53% reduction in tibial cartilage degeneration and the least associated mononuclear cell recruitment compared to other groups. Reduction in cartilage degeneration by MM-II in OA rats is likely mediated through formation of a lubricative layer at the cartilage surface, though additional mechanisms could be mediating pain reduction demonstrated in clinical trials.

Infectious diseases remain a significant public health challenge in low- and middle-income countries (LMICs), with HIV, tuberculosis (TB), and malaria contributing significantly to morbidity and mortality. Community Health Workers (CHWs) play a pivotal role in addressing these diseases, yet evidence on the costs and cost-effectiveness of CHW-led interventions remains fragmented. We performed a scoping review, searching ten databases and the grey literature for original studies published between August 2015 and July 2024. Recognized search terms related to "Community Health Workers" and "Economic Evaluation(s)" in LMICs were utilized. Covidence software was employed to screen studies based on inclusion and exclusion criteria. Data on study methodology, costs and cost-related outcomes were then extracted, tabulated in a data-extraction form, and analysed using Microsoft Excel. Thirty-three studies representing 106 scenarios were included, predominantly from sub-Saharan Africa (61%). Over half the scenarios provide evidence about malaria (n = 59), followed by HIV (n = 31) and TB (n = 24). CHWs performed diverse roles, including delivering preventive education, case finding, diagnosis, treatment adherence support, counselling and referrals. The majority demonstrated that CHW programs were cost-effective compared to alternative service delivery models, most commonly facility-based care. These programs were particularly effective in improving treatment adherence and targeting high-priority populations. Costs per beneficiary ranged widely, from $1.20 to $26,556. This review highlights significant heterogeneity in methodologies and reporting, impeding comprehensive comparisons. Future research should emphasize standardized reporting, assess affordability, explore integrated CHW roles across multiple disease groups, and focus on generating evidence that supports priority-setting and resource allocation at the health system level.

BackgroundProgress in malaria elimination has been hindered by recent changes in mosquito behaviour and increased insecticide resistance in response to traditional vector control measures, such as indoor residual spraying and long-lasting insecticidal nets. There is, therefore, increasing interest in the use of larval source management (LSM) to supplement current insecticide-based interventions. However, LSM implementation requires the characterization of larval habitats at fine spatial and temporal scales to ensure interventions are well-placed and well-timed. Remotely sensed optical imagery captured via drones or satellites offers one way to monitor larval habitats remotely, but its use at large spatio-temporal scales has important limitations.MethodsA method using radar imagery is proposed to monitor flooding dynamics in individual rice fields, a primary larval habitat, over very large geographic areas relevant to national malaria control programmes aiming to implement LSM at scale. This is demonstrated for a 3971 km2 malaria-endemic district in Madagascar with over 17,000 rice fields. Rice field mapping on OpenStreetMap was combined with Sentinel-1 satellite imagery (radar, 10 m) from 2016 to 2022 to train a classification model of radar backscatter to identify rice fields with vegetated and open water, resulting in a time-series of weekly flooding dynamics for thousands of rice fields.ResultsFrom these time-series, over a dozen indicators useful for LSM implementation, such as the timing and frequency of flooding seasons, were obtained for each rice field. These monitoring tools were integrated into an interactive GIS dashboard for operational use by vector control programmes, with results available at multiple scales (district, sub-district, rice field) relevant for different phases of LSM intervention (e.g. prioritization of sites, implementation, follow-up).ConclusionsScale-up of these methods could enable wider implementation of evidence-based LSM interventions and reduce malaria burdens in contexts where irrigated agriculture is a major transmission driver.

ABSTRACTData on population health are vital to evidence-based decision making but are rarely adequately localized or updated in continuous time. They also suffer from low ascertainment rates, particularly in rural areas where barriers to healthcare can cause infrequent touch points with the health system. Here, we demonstrate a novel statistical method to estimate the incidence of endemic diseases at the community level from passive surveillance data collected at primary health centers. The zero-corrected, gravity-based (ZERO-G) estimator explicitly models sampling intensity as a function of health facility characteristics and statistically accounts for extremely low rates of ascertainment. The result is a standardized, real-time estimate of disease incidence at a spatial resolution nearly ten times finer than typically reported by facility-based passive surveillance systems. We assessed the robustness of this method by applying it to a case study of field-collected malaria incidence rates from a rural health district in southeastern Madagascar. The ZERO-G estimator decreased geographic and financial bias in the dataset by over 90% and doubled the agreement rate between spatial patterns in malaria incidence and incidence estimates derived from prevalence surveys. The ZERO-G estimator is a promising method for adjusting passive surveillance data of common, endemic diseases, increasing the availability of continuously updated, high quality surveillance datasets at the community scale.

Abstract Background Survivors of childhood cancer are at lifelong risk of morbidity (such as new cancers or heart failure) and premature mortality because of their cancer treatment. These are termed late effects. Therefore, they require lifelong, risk-tailored surveillance. However, most adult survivors of childhood cancer do not complete recommended surveillance tests such as mammograms or echocardiograms. Working with survivors, family physicians, and health-system partners, we are designing a provincial support system for high-priority tests, informed by principles of implementation science, behavioral science and design-thinking. Methods Our multi-phase process was as follows: Step 1: a qualitative study to explore intervention components essential to accessing surveillance tests; Step 2: a workshop with childhood cancer survivors, family physicians and health system stakeholders that used the Step 1 findings and ‘personas’ (a series of fictional but data-informed characters) to develop and tailor the intervention for different survivor groups Step 3: intervention prototype development; and step 4: iterative user-testing. Results The qualitative study of 30 survivors and 7 family physicians found a high desire for information on surveillance for late effects. Respondents indicated that in addition to providing personalized information, the intervention should help patients book appointments when they are due. Insights from the workshop included the importance of partnering with both family physicians and survivorship clinics and providing emotional support for survivors that may experience distress upon learning of their risk for late effects. In our user-testing process, prototypes went through iterations that incorporated feedback from users regarding usability and functionality. We sought to address the needs of survivors and physicians while balancing the capacity and infrastructure available for a life-long intervention via our health system partners. Conclusion In partnership with childhood cancer survivors, family physicians, and health-system partners, we elucidated the barriers and enablers to accessing guideline-recommended surveillance tests and designed a multi-faceted solution that will support survivors and their family physician. The next step is to evaluate the intervention in a pragmatic randomized control trial.

BackgroundDespite the life-saving work they perform, community health workers (CHWs) have long been subject to global debate about their remuneration. There is now, however, an emerging consensus that CHWs should be paid. As the discussion evolves from whether to financially remunerate CHWs to how to do so, there is an urgent need to better understand the types of CHW payment models and their implications.MethodsThis study examines the legal framework on CHW compensation in five countries: Brazil, Ghana, Nigeria, Rwanda, and South Africa. In order to map the characteristics of each approach, a review of the regulatory framework governing CHW compensation in each country was undertaken. Law firms in each of the five countries were engaged to support the identification and interpretation of relevant legal documents. To guide the search and aid in the creation of uniform country profiles, a standardized set of questions was developed, covering: (i) legal requirements for CHW compensation, (ii) CHW compensation mechanisms, and (iii) CHW legal protections and benefits.ResultsThe five countries profiled represent possible archetypes for CHW compensation: Brazil (public), Ghana (volunteer-based), Nigeria (private), Rwanda (cooperatives with performance based incentives) and South Africa (hybrid public/private). Advantages and disadvantages of each model with respect to (i) CHWs, in terms of financial protection, and (ii) the health system, in terms of ease of implementation, are outlined.ConclusionsWhile a strong legal framework does not necessarily translate into high-quality implementation of compensation practices, it is the first necessary step. Certain approaches to CHW compensation – particularly public-sector or models with public sector wage floors – best institutionalize recommended CHW protections. Political will and long-term financing often remain challenges; removing ecosystem barriers – such as multilateral and bilateral restrictions on the payment of salaries – can help governments institutionalize CHW payment.

Abstract Despite the widespread global adoption of community health (CH) systems, there are evidence gaps in how to best deliver community-based care aligned with global best practice in remote settings where access to health care is limited and community health workers (CHWs) may be the only available providers. PIVOT partnered with the Ministry of Public Health to pilot a new two-pronged approach for care delivery in rural Madagascar: one CHW provided care at a stationary CH site while 2-5 additional CHWs provided care via proactive household visits. The pilot included professionalization of the CHW workforce (i.e. recruitment, training, financial incentive) and twice monthly supervision of CHWs. We evaluated the impact of the CH pilot on utilization and quality of integrated community case management (iCCM) in the first six months of implementation (October 2019-March 2020).We compared utilization and proxy measures of quality of care (defined as adherence to the iCCM protocol for diagnosis, classification of disease severity, treatment) in the intervention commune and five comparison communes, using a quasi-experimental study design and relying on routinely collected programmatic data. Average per capita monthly under-five visits were 0.28 in the intervention commune and 0.22 in the comparison communes. In the intervention commune, 40.0% of visits were completed at the household via proactive care. CHWs completed all steps of the iCCM protocol in 77.8% of observed visits in the intervention commune (vs 49.5% in the comparison communes, p-value=<0.001). A two-pronged approach to CH delivery and professionalization of the CHW workforce increased utilization and demonstrated satisfactory quality of care. National stakeholders and program managers should evaluate program re-design at a local level prior to national or district-wide scale-up.

BACKGROUND It is well reported that tracking physical activity can lead to sustained exercise routines, which can decrease disease risk. However, most stop using trackers within a couple months of initial use. The reasons people stop using activity trackers can be varied and personal. Understanding the reasons for discontinued use could lead to greater acceptance of tracking and more regular exercise engagement. OBJECTIVE The aim of this study was to determine the individualistic reasons for nonengagement with activity trackers. METHODS Overweight and obese participants (n=30) were enrolled and allowed to choose an activity tracker of their choice to use for 9 weeks. Questionnaires were administered at the beginning and end of the study to collect data on their technology use, as well as social, physiological, and psychological attributes that may influence tracker use. Closeout interviews were also conducted to further identify individual influencers and attributes. In addition, daily steps were collected from the activity tracker. RESULTS The results of the study indicate that participants typically valued the knowledge of their activity level the activity tracker provided, but it was not a sufficient motivator to overcome personal barriers to maintain or increase exercise engagement. Participants identified as extrinsically motivated were more influenced by wearing an activity tracker than those who were intrinsically motivated. During the study, participants who reported either owning multiple technology devices or knowing someone who used multiple devices were more likely to remain engaged with their activity tracker. CONCLUSIONS This study lays the foundation for developing a smart app that could promote individual engagement with activity trackers.

ABSTRACTBackground and Purpose: The prevention of falls and fall-related fractures following menopause is an important health initiative. The Fracture Prevention Screening Algorithm (FPSA) uniquely uses fracture risk to prompt fall risk assessment to classify both fall and fracture risk in individuals. The purpose of this study was to determine whether use of the FPSA accurately predicted self-reported falls in post-menopausal women over one year. Methods: 142 postmenopausal women were recruited. Based on Fracture Risk Assessment Tool (FRAX®) scores, women with a ≥3% 10-year probability of hip fracture (high risk), or who self-identified as having balance problems or a fall history, underwent the Functional Gait Assessment (FGA) to estimate fall risk (high risk = ≤22/30). This allowed classification on the FPSA into one of four risk categories: low fall/low fracture risk; low fall/high fracture risk; high fall/low fracture risk; high fall/high fracture risk. Participants were contacted monthly for one year to determine fall and injury occurrence. Results: Fall/injury surveillance was conducted with 136 subjects over one year. Compared to women in the low fall/low fracture risk group, both high fall risk groups demonstrated significantly greater fall rates. Falls were 81–89% more likely in women with FGA scores of 22/30 or less. All injuries were rare events across all risk strata and did not differ between risk groups. Conclusion: These findings support the use of fracture risk as a trigger for fall screening to comprehensively classify risk in post-menopausal women as proposed by the FPSA.