Financially incentivized knowledge assessments to improve provider compliance with treatment guidelines: a cluster-randomized controlled trial

BACKGROUND: Despite increasing access to health care, under-5 mortality remains high in many parts of Sub-Saharan Africa. Interventions to improve quality of care have mostly focused on additional training for medical staff, but generally shown little impact. We will assess the impact of financially incentivized quarterly provider knowledge assessment on compliance with Integrated Management of Childhood Illness (IMCI) protocols in Congo, DRC. METHODS: Out of a total of 1738 facilities currently receiving results-based financing under an ongoing health financing program, 110 facilities were chosen for this study. All health care workers providing outpatient services to children under age 5 in these facilities will be included in the study. Facilities were randomized with equal probability to control and treatment. Treatment facilities will receive quarterly medical staff knowledge assessments using interactive vignettes. Performance on these vignettes will be rewarded through financial bonus payments to facilities. A baseline survey of health worker knowledge was conducted in 2018. An endline assessment is scheduled to start in the second half of 2021. The primary outcome of interest is health worker compliance with Integrated Management of Childhood Illness (IMCI) guidelines. Compliance will be verified through direct observation of medical staff-patient interactions. DISCUSSION: This is to our knowledge the first trial assessing whether linking health financing to health care worker performance on knowledge assessments can increase compliance with under-5 case management protocols. TRIAL REGISTRATION: ClinicalTrials.gov NCT04634019 . Registered on November 18, 2020

Quality of care for children with severe disease in the Democratic Republic of the Congo

BACKGROUND: Despite the almost universal adoption of Integrated Management of Childhood Illness (IMCI) guidelines for the diagnosis and treatment of sick children under the age of five in low- and middle-income countries, child mortality remains high in many settings. One possible explanation of the continued high mortality burden is lack of compliance with diagnostic and treatment protocols. We test this hypothesis in a sample of children with severe illness in the Democratic Republic of the Congo (DRC). METHODS: One thousand one hundred eighty under-five clinical visits were observed across a regionally representative sample of 321 facilities in the DRC. Based on a detailed list of disease symptoms observed, patients with severe febrile disease (including malaria), severe pneumonia, and severe dehydration were identified. For all three disease categories, treatments were then compared to recommended case management following IMCI guidelines. RESULTS: Out of 1180 under-five consultations observed, 332 patients (28%) had signs of severe febrile disease, 189 patients (16%) had signs of severe pneumonia, and 19 patients (2%) had signs of severe dehydration. Overall, providers gave the IMCI-recommended treatment in 42% of cases of these three severe diseases. Less than 15% of children with severe disease were recommended to receive in-patient care either in the facility they visited or in a higher-level facility. CONCLUSIONS: These results suggest that adherence to IMCI protocols for severe disease remains remarkably low in the DRC. There is a critical need to identify and implement effective approaches for improving the quality of care for severely ill children in settings with high child mortality

Multi-scale genomic, transcriptomic and proteomic analysis of colorectal cancer cell lines to identify novel biomarkers

This work was partially funded by the Strategic Educational Pathways Scholarship (Malta). The scholarship is part-financed by the European Union – European Social Fund (ESF) under Operational Programme II – Cohesion Policy 2007-2013, “Empowering People for More Jobs and a Better Quality of Life”. This project was additionally funded by Medical Research Scotland.Selecting colorectal cancer (CRC) patients likely to respond to therapy remains a clinical challenge. The objectives of this study were to establish which genes were differentially expressed with respect to treatment sensitivity and relate this to copy number in a panel of 15 CRC cell lines. Copy number variations of the identified genes were assessed in a cohort of CRCs. IC50’s were measured for 5-fluorouracil, oxaliplatin, and BEZ-235, a PI3K/mTOR inhibitor. Cell lines were profiled using array comparative genomic hybridisation, Illumina gene expression analysis, reverse phase protein arrays, and targeted sequencing of KRAS hotspot mutations. Frequent gains were observed at 2p, 3q, 5p, 7p, 7q, 8q, 12p, 13q, 14q, and 17q and losses at 2q, 3p, 5q, 8p, 9p, 9q, 14q, 18q, and 20p. Frequently gained regions contained EGFR, PIK3CA, MYC, SMO, TRIB1, FZD1, and BRCA2, while frequently lost regions contained FHIT and MACROD2. TRIB1 was selected for further study. Gene enrichment analysis showed that differentially expressed genes with respect to treatment response were involved in Wnt signalling, EGF receptor signalling, apoptosis, cell cycle, and angiogenesis. Stepwise integration of copy number and gene expression data yielded 47 candidate genes that were significantly correlated. PDCD6 was differentially expressed in all three treatment responses. Tissue microarrays were constructed for a cohort of 118 CRC patients and TRIB1 and MYC amplifications were measured using fluorescence in situ hybridisation. TRIB1 and MYC were amplified in 14.5% and 7.4% of the cohort, respectively, and these amplifications were significantly correlated (p≤0.0001). TRIB1 protein expression in the patient cohort was significantly correlated with pERK, Akt, and Caspase 3 expression. In conclusion, a set of candidate predictive biomarkers for 5-fluorouracil, oxaliplatin, and BEZ235 are described that warrant further study. Amplification of the putative oncogene TRIB1 has been described for the first time in a cohort of CRC patients.Publisher PDFPeer reviewe

Impacts of performance-based financing on health system performance: evidence from the Democratic Republic of Congo

Abstract Background Health systems’ weakness remains one of the primary obstacles towards achieving universal access to quality healthcare in low-income settings. Performance-based financing (PBF) programs have been increasingly used to increase access to quality care in LMICs. However, evidence on the impacts of these programs remains fragmented and inconclusive. We analyze the health system impacts of the PBF program in the Democratic Republic of the Congo (DRC), one of the largest such programs introduced in LMICs to date. Methods We used a health systems perspective to analyze the benefits of PBF relative to unconditional financing of health facilities. Fifty-eight health zones in six provinces were randomly assigned to either a control group (28 zones) in which facilities received unconditional transfers or to a PBF program (30 zones) that started at the end of 2016. Follow-up data collection took place in 2021–2022 and included health facility assessments, health worker interviews, direct observations of consultations and deliveries, patient exit interviews, and household surveys. Using multivariate regression models, we estimated the impact of the program on 55 outcomes in seven health system domains: structural quality, technical process quality, non-technical process quality, service fees, facility management, providers’ satisfaction, and service coverage. We used random-effects meta-analysis to generate pooled average estimates within each domain. Results The PBF program improved the structural quality of health facilities by 4 percentage points (ppts) (95% CI 0.01–0.08), technical process quality by 5 ppts (0.03–0.07), and non-technical process by 2 ppts (0–0.04). PBF also increased coverage of priority health services by 3 ppts (0.02–0.04). Improvements were also observed for facility management (9 ppts, 0.04–0.15), service fee policies, and users’ satisfaction with service affordability (14 ppts, 0.07–0.20). Service fees and health workers’ satisfaction were not affected by the program. Conclusions The results suggest that well-designed PBF programs can lead to improvements in most health systems domains relative to comparable unconditional financing. However, the large persisting gaps suggest that additional changes, such as allocating more resources to the health system and reforming the human resources for health management, will be necessary in DRC to achieve the ambitious global universal health coverage and mortality goals. Trial registration American Economics Association Trial registry AEARCTR-0002880

Identification of a mitochondrial superoxide dismutase with an unusual targeting sequence in Plasmodium falciparum.

The intraerythrocytic stages of Plasmodium falciparum are exposed to oxidative stress and require functional anti-oxidant systems to survive. In addition to the parasite's known iron-dependent superoxide dismutase PfSOD1, a second SOD gene (PfSOD2) interrupted by 8 introns was identified on chromosome 6. Molecular modelling shows that the structure of PfSOD2 is similar to other iron-dependent SODs and phylogenetic analysis suggests PfSOD1 and PfSOD2 are the result of an ancestral gene duplication. The deduced amino acid sequence of PfSOD2 is similar to PfSOD1 but has a long N-terminal extension. Immunofluorescence studies show that PfSOD1 is cytosolic, whereas the N-terminal extension of PfSOD2 targets a green fluorescent protein fusion into the parasite's mitochondrion. Both SOD genes are transcribed during the erythrocytic cycle with PfSOD1 mRNA levels up to 35-fold higher than those of PfSOD2. Northern blots demonstrated that the mRNA levels of both SOD genes are up-regulated upon exposure to oxidative stress.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe