Assessing availability, prices, and market share of quality-assured malaria ACT and RDT in the private retail sector in Nigeria and Uganda.

BACKGROUND: An estimated 50% of suspected malaria cases in sub-Saharan Africa first seek care in the private sector, especially in private medicine retail outlets. Quality of care in these outlets is generally unknown but considered poor with many patients not receiving a confirmatory diagnosis or the recommended first-line artemisinin-based combination therapy (ACT). In 2010, a subsidy pilot scheme, the Affordable Medicines Facility malaria, was introduced to crowd out the use of monotherapies in favour of WHO-pre-qualified artemisinin-based combinations (WHO-PQ-ACTs) in the private health sector. The scheme improved the availability, market share, and cost of WHO-PQ-ACTs in countries like Nigeria and Uganda, but in 2018, the subsidies were halted in Nigeria and significantly reduced in Uganda. This paper presents findings from six retail audit surveys conducted from 2014 to 2021 in Nigeria and Uganda to assess whether the impact of subsidies on the price, availability, and market share of artemisinin-based combinations has been sustained after the subsidies were reduced or discontinued. METHODS: Six independent retail audits were conducted in private medicine retail outlets, including pharmacies, drug shops, and clinics in Nigeria (2016, 2018, 2021), and Uganda (2014, 2019, 2020) to assess the availability, price, and market share of anti-malarials, including WHO-PQ-ACTs and non-WHO-PQ-ACTs, and malaria rapid diagnostic tests (RDTs). RESULTS: Between 2016 and 2021, there was a 57% decrease in WHO-PQ-ACT availability in Nigeria and a 9% decrease in Uganda. During the same period, non-WHO-PQ-ACT availability increased in Nigeria by 41% and by 34% in Uganda. The price of WHO-PQ-ACTs increased by 42% in Nigeria to $0.68 and increased in Uganda by 24% to $0.95. The price of non-WHO-PQ-ACTs decreased in Nigeria by 26% to $1.08 and decreased in Uganda by 64% to $1.23. There was a 76% decrease in the market share of WHO-PQ-ACTs in Nigeria and a 17% decrease in Uganda. Malaria RDT availability remained low throughout. CONCLUSION: With the reduction or termination of subsidies for WHO-PQ-ACTs in Uganda and Nigeria, retail prices have increased, and retail prices of non-WHO-PQ-ACTs decreased, likely contributing to a shift of higher availability and increased use of non-WHO-PQ-ACTs.

Improving paediatric flow in an UK Paediatric Assessment Unit.

The 2010 Royal College of Paediatrics and Child Health (RCPCH) guidelines for acute paediatric services set standards for time to senior review for paediatric medical admissions in the UK as tier two doctor (registrar) review within 4 hours and consultant review within 14 hours. Our aim was to implement these standards in our unit through increasing proportions of reviews within these timeframes and measuring the impact on patient flow. Four quality improvement cycles were completed between March 2018 and March 2020 capturing data from 288 patient data sets. Recommendations included the extension of consultant on-site availability out of routine working hours (after cycle 1), highlighting patients awaiting consultant review during team handover (after cycle 2), and improving tier two doctor rostering (after cycle 3). After highlighting patients for consultant priority review, the proportion of patients seen within 14 hours improved from 53.3% (cycle 2) to 95% (cycle 3, p=0.005). Improved tier two doctor cover increased the proportion meeting registrar review within 4 hours from 82.9% (cycle 3) to 96.2% (cycle 4, p=0.028). A large proportion of paediatric patients were managed and discharged at tier two doctor level (65.6% over cycles 1-4). An inverse correlation was seen (R=-0.587) between time to discharge and the number of tier two doctors on shift (cycle 4). The interventions conducted demonstrated significant improvement in proportions of paediatric patients seen within the RCPCH timeframes. Adequate tier two doctor staffing is a priority for prompt review and discharge of acute paediatric patients. Future work aims to consider factors such as nursing rostering, bed management and the impact of COVID-19 on paediatric flow.

Making the most of small samples: Optimization of tissue allocation of pediatric solid tumors for clinical and research use.

INTRODUCTION: Tissue from pediatric solid tumors is in high demand for use in high-impact research studies, making the allocation of tissue from an anatomic pathology laboratory challenging. We designed, implemented, and assessed an interdepartmental process to optimize tissue allocation of pediatric solid tumors for both clinical care and research. METHODS: Oncologists, pathologists, surgeons, interventional radiologists, pathology technical staff, and clinical research coordinators participated in the workflow design. Procedures were created to address patient identification and consent, prioritization of protocols, electronic communication of requests, tissue preparation, and distribution. Pathologists were surveyed about the value of the new workflow. RESULTS: Over a 5-year period, 644 pediatric solid tumor patients consented to one or more studies requesting archival or fresh tissue. Patients had a variety of tumor types, with many rare and singular diagnoses. Sixty-seven percent of 1768 research requests were fulfilled. Requests for archival tissue were fulfilled at a significantly higher rate than those for fresh tissue (P > .001), and requests from resection specimens were fulfilled at a significantly higher rate than those from biopsies (P > .0001). In an anonymous survey, seven of seven pathologists reported that the process had improved since the introduction of the electronic communication model. CONCLUSIONS: A collaborative and informed model for tissue allocation is successful in distributing archival and fresh tissue for clinical research studies. Our workflows and policies have gained pathologists' approval and streamlined our processes. As clinical and research programs evolve, a thoughtful tissue allocation process will facilitate ongoing research.

Expanding access to parasite-based malaria diagnosis through retail drug shops in Tanzania: evidence from a randomized trial and implications for treatment.

BACKGROUND: Tanzania has seen a reduction in the fraction of fevers caused by malaria, likely due in part to scale-up of control measures. While national guidelines require parasite-based diagnosis prior to treatment, it is estimated that more than half of suspected malaria treatment-seeking in Tanzania initiates in the private retail sector, where diagnosis by malaria rapid diagnostic test (RDT) or microscopy is illegal. This pilot study investigated whether the introduction of RDTs into Accredited Drug Dispensing Outlets (ADDOs) under realistic market conditions would improve case management practices. METHODS: Dispensers from ADDOs in two intervention districts in Tanzania were trained to stock and perform RDTs and monitored quarterly. Each district was assigned a different recommended retail price to evaluate the need for a subsidy. Malaria RDT and artemisinin-based combination therapy (ACT) uptake and availability were measured pre-intervention and 1 year post-intervention through structured surveys of ADDO owners and exiting customers in both intervention districts and one contiguous control district. Descriptive analysis and logistic regression were used to compare the three districts and identify predictive variables for testing. RESULTS AND DISCUSSION: A total of 310 dispensers from 262 ADDOs were trained to stock and perform RDTs. RDT availability in intervention ADDOs increased from 1% (n = 172) to 73% (n = 163) during the study; ACT medicines were available in 75% of 260 pre-intervention and 68% of 254 post-intervention ADDOs. Pre-treatment testing performed within the ADDO increased from 0 to 65% of suspected malaria patients who visited a shop (95% CI 60.8-69.6%) with no difference between intervention districts. Overall parasite-based diagnosis increased from 19 to 74% in intervention districts and from 3 to 18% in the control district. Prior knowledge of RDT availability (aOR = 1.9, p = 0.03) and RDT experience (aOR = 1.9, p = 0.01) were predictors for testing. Adherence data indicated that 75% of malaria positives received ACT, while 3% of negatives received ACT. CONCLUSIONS: Trained and supervised ADDO dispensers in rural Tanzania performed and sold RDTs under real market conditions to two-thirds of suspected malaria patients during this one-year pilot. These results support the hypothesis that introducing RDTs into regulated private retail sector settings can improve malaria testing and treatment practices without an RDT subsidy. Trial registration ISRCTN ISRCTN14115509.

The association of area-level social class and tobacco use with adverse breast cancer characteristics among white and black women: evidence from Maryland, 1992-2003.

BACKGROUND: In breast cancer, worse disease characteristics are associated with fewer social resources and black race. However, it is unknown whether social gradients have similar impact across race, and whether behaviors, including tobacco use, may explain a portion of the social gradient. METHODS: We modeled relationships between area-level social class, tobacco spending and tumor characteristics, using 50,062 white and black cases diagnosed from 1992-2003 in Maryland, a racially and economically diverse state on the east coast of the United States. Multi-level models estimated the effect of area-level social class and tobacco consumption on tumor grade, size, and stage at diagnosis. RESULTS: Adjusting for race, age and year of diagnosis, higher social class was associated with lower risk for tumors with histological grade 3 or 4 (O.R. 0.96, 95% C.I. 0.94,0.99), those diagnosed at SEER stage 2 or later (O.R. 0.89, 95% C.I. 0.86, 0.91), and tumor size >2 cm (O.R. 0.87, 95% C.I. 0.84, 0.90). Higher tobacco spending was associated with higher risk for higher grade (O.R. 1.01, 1.00, 1.03) and larger tumors (O.R. 1.03, 95% C.I. 1.01, 1.06), but was not statistically significantly related to later stage (O.R. 1.00, 95% C.I. 0.98, 1.02). Social class was less protective for black women, but tobacco effects were not race-specific. CONCLUSIONS: Results suggest that in one U.S. geographic area, there is a differential protection from social class for black and white women, supporting use of intersectionality theory in breast cancer disparities investigations. Area-level tobacco consumption may capture cases' direct use and second hand smoke exposure, but also may identify neighborhoods with excess cancer-related behavioral or environmental exposures, beyond those measured by social class. Given the growing global burden of both tobacco addiction and aggressive breast cancer, similar investigations across diverse geographic areas are warranted.

Price subsidies increase the use of private sector ACTs: evidence from a systematic review.

BACKGROUND: Although artemisinin combination therapies (ACTs) are the recommended first-line treatment for uncomplicated malaria in most endemic countries, they have been prohibitively expensive in the retail sector where many suspected malaria cases purchase treatment. ACT subsidies seek to stimulate consumer demand for the drugs over cheaper but often ineffective alternatives by reducing their prices. Recent evidence from eight regions implementing such subsidies suggests that they are generally successful in improving availability of the drugs and decreasing their retail prices, but it remains unclear whether these outcomes translate to improved use by patients with suspected malaria. METHODS: A systematic literature review was conducted to identify reports of experimental or programmatic ACT subsidies to assess the impact of subsidies on consumer use. Relationships between price, use and potential confounding factors were examined using logistic and repeated measures binomial regression models, and approximate magnitudes of associations were assessed with linear regression. In total, 40 studies, 14 peer-reviewed and 26 non-peer-reviewed, were eligible for inclusion in the analysis. The reviewed studies found a substantial increase in private sector ACT use following the introduction of a subsidy. Overall, each $1 decrease in price was linked to a 24 percentage point increase in the fraction of suspected malaria cases purchasing ACTs (R(2) = 0.302). No significant differences were evident in this relationship when comparing the poorest and richest groups, rural vs urban populations or children vs adults. CONCLUSIONS: These findings suggest that ACT price reductions can increase their use for suspected malaria, even within poorer, more remote populations that may be most at risk of malaria mortality. Whether a subsidy is appropriate will depend upon local context, including treatment-seeking behaviours and malaria prevalence. This review provides an initial foundation for policymakers to make evidence-based decisions regarding ACT price reductions to increase use of potentially life-saving drugs.

Malaria resurgence: a systematic review and assessment of its causes.

BACKGROUND: Considerable declines in malaria have accompanied increased funding for control since the year 2000, but historical failures to maintain gains against the disease underscore the fragility of these successes. Although malaria transmission can be suppressed by effective control measures, in the absence of active intervention malaria will return to an intrinsic equilibrium determined by factors related to ecology, efficiency of mosquito vectors, and socioeconomic characteristics. Understanding where and why resurgence has occurred historically can help current and future malaria control programmes avoid the mistakes of the past. METHODS: A systematic review of the literature was conducted to identify historical malaria resurgence events. All suggested causes of these events were categorized according to whether they were related to weakened malaria control programmes, increased potential for malaria transmission, or technical obstacles like resistance. RESULTS: The review identified 75 resurgence events in 61 countries, occurring from the 1930s through the 2000s. Almost all resurgence events (68/75 = 91%) were attributed at least in part to the weakening of malaria control programmes for a variety of reasons, of which resource constraints were the most common (39/68 = 57%). Over half of the events (44/75 = 59%) were attributed in part to increases in the intrinsic potential for malaria transmission, while only 24/75 (32%) were attributed to vector or drug resistance. CONCLUSIONS: Given that most malaria resurgences have been linked to weakening of control programmes, there is an urgent need to develop practical solutions to the financial and operational threats to effectively sustaining today's successful malaria control programmes.