Impact of maternal death reviews at a rural hospital in Zambia: a mixed methods study.

BACKGROUND: Maternal mortality in sub-Saharan Africa remains high despite programmatic efforts to improve maternal health. In 2007, the Zambian Ministry of Health mandated facility-based maternal death review (MDR) programs in line with World Health Organization recommendations. We assessed the impact of an [MDR program] at a district-level hospital in rural Zambia. METHODS: We conducted a mixed methods convergent study using hospital data on maternal mortality and audit reports of 106 maternal deaths from 2007 to 2011. To evaluate the overall impact of MDR on maternal mortality, we compared baseline (2007) to late (2010-11) post-intervention inpatient maternal mortality indicators. MDR committee reports were coded and dominant themes were extracted in a qualitative analysis. We assessed potential risk factors for maternal mortality in a before-and-after design comparing the periods 2008-09 and 2010-11. RESULTS: In-hospital maternal mortality declined from 23 per thousand live births in 2007 to 8 per thousand in 2010-11 (P < 0.01). Maternal case fatality for puerperal sepsis and uterine rupture decreased significantly from 63 and 32% in 2007 to 10 and 9% in 2010-11 (P < 0.01). No significant reduction was seen in case fatality due to postpartum hemorrhage. Qualitative analysis of risk factors for maternal mortality revealed four core themes: standards of practice, health systems, accessibility, and patient factors. Specific risk factors included delayed referral, missed diagnoses, intra-hospital delays in care, low medication inventory, and medical error. We found no statistically significant differences in the prevalence of risk factors between the before-and-after periods. CONCLUSIONS: Implementation of MDR was accompanied by a significant decrease in maternal mortality with reductions in maternal death from puerperal sepsis and uterine rupture, but not postpartum hemorrhage. Qualitative analysis of audit reports identified several modifiable risk factors within four core areas. Comparisons of potential explanatory factors did not show any differences over time. These results imply that MDR offers a means for hospitals to curtail maternal deaths, except deaths due to postpartum hemorrhage, suggesting additional interventions are needed. Documentation of MDR meetings provides an instrument to guide further quality improvements.

SEVUparin as a potential Adjunctive Treatment in children with severe malaria: A phase I trial safety and dose finding trial (SEVUSMAART).

Background: Even on the best antimalarial treatments (injectable artesunate) African children with severe malaria have poor outcomes with most deaths occurring early in the course of hospital admission (<24hours). Lactic acidosis, largely due to impairment of the microcirculatory flow due to parasite sequestration, is a main risk factor for poor outcome. There are no adjuvant treatments for severe malaria that target this complication. Sevuparin, a heparin-like drug, binds to Plasmodium falciparum erythrocyte membrane protein blocking merozoite invasion, preventing cytoadherence and transiently de-sequestering infected erythrocytes. Leading to improved microcirculatory flow by reversing/preventing parasite sequestration. If given early during admission this could result in improvements in outcomes. Sevuparin has been shown to be safe and well tolerated in adults with only some mild transient effects on activated partial thromboplastin time (APTT) were reported, without clinical consequences. Methods: A Phase I trial designed to provide data on safety, dosing, feasibility of sevuparin as an adjuvant therapy in Kenya and Zambian children with severe malaria complicated by lactic acidosis (> 2mmol/l). Three intravenous doses will be given at admission (0 hours), 8 and 16 hours. APPT will be measured 1 hour after each dose (to assess maximum toxicity). Studying 20 children will allow sufficient data on safety to be generated across a range of doses to identify the maximum tolerated dose (MTD) using the Continual Reassessment Method, which adapts or informs subsequent doses for each child based on the data from previously enrolled children. The MTD will be identified based on the dose-toxicity model updated by each previous patient's APTT results using standard methods. Conclusions: The results of the Phase I trial will identify the final dose to be tested in a Phase II trial in terms of both efficacy and safety outcomes. Registration: PACTR number: 202007890194806 (date 20/07/2020) ISRCTN32271864 (date 28/07/2021).