Using Verbal Autopsy to Measure Causes of Death: the Comparative Performance of Existing Methods.

Monitoring progress with disease and injury reduction in many populations will require widespread use of verbal autopsy (VA). Multiple methods have been developed for assigning cause of death from a VA but their application is restricted by uncertainty about their reliability. We investigated the validity of five automated VA methods for assigning cause of death: InterVA-4, Random Forest (RF), Simplified Symptom Pattern (SSP), Tariff method (Tariff), and King-Lu (KL), in addition to physician review of VA forms (PCVA), based on 12,535 cases from diverse populations for which the true cause of death had been reliably established. For adults, children, neonates and stillbirths, performance was assessed separately for individuals using sensitivity, specificity, Kappa, and chance-corrected concordance (CCC) and for populations using cause specific mortality fraction (CSMF) accuracy, with and without additional diagnostic information from prior contact with health services. A total of 500 train-test splits were used to ensure that results are robust to variation in the underlying cause of death distribution. Three automated diagnostic methods, Tariff, SSP, and RF, but not InterVA-4, performed better than physician review in all age groups, study sites, and for the majority of causes of death studied. For adults, CSMF accuracy ranged from 0.764 to 0.770, compared with 0.680 for PCVA and 0.625 for InterVA; CCC varied from 49.2% to 54.1%, compared with 42.2% for PCVA, and 23.8% for InterVA. For children, CSMF accuracy was 0.783 for Tariff, 0.678 for PCVA, and 0.520 for InterVA; CCC was 52.5% for Tariff, 44.5% for PCVA, and 30.3% for InterVA. For neonates, CSMF accuracy was 0.817 for Tariff, 0.719 for PCVA, and 0.629 for InterVA; CCC varied from 47.3% to 50.3% for the three automated methods, 29.3% for PCVA, and 19.4% for InterVA. The method with the highest sensitivity for a specific cause varied by cause. Physician review of verbal autopsy questionnaires is less accurate than automated methods in determining both individual and population causes of death. Overall, Tariff performs as well or better than other methods and should be widely applied in routine mortality surveillance systems with poor cause of death certification practices

Evidence-based, cost-effective interventions: how many newborn babies can we save?

In this second article of the neonatal survival series, we identify 16 interventions with proven efficacy (implementation under ideal conditions) for neonatal survival and combine them into packages for scaling up in health systems, according to three service delivery modes (outreach, family-community, and facility-based clinical care). All the packages of care are cost effective compared with single interventions. Universal (99%) coverage of these interventions could avert an estimated 41-72% of neonatal deaths worldwide. At 90% coverage, intrapartum and postnatal packages have similar effects on neonatal mortality--two-fold to three-fold greater than that of antenatal care. However, running costs are two-fold higher for intrapartum than for postnatal care. A combination of universal--ie, for all settings--outreach and family-community care at 90% coverage averts 18-37% of neonatal deaths. Most of this benefit is derived from family-community care, and greater effect is seen in settings with very high neonatal mortality. Reductions in neonatal mortality that exceed 50% can be achieved with an integrated, high-coverage programme of universal outreach and family-community care, consisting of 12% and 26%, respectively, of total running costs, plus universal facility-based clinical services, which make up 62% of the total cost. Early success in averting neonatal deaths is possible in settings with high mortality and weak health systems through outreach and family-community care, including health education to improve home-care practices, to create demand for skilled care, and to improve care seeking. Simultaneous expansion of clinical care for babies and mothers is essential to achieve the reduction in neonatal deaths needed to meet the Millennium Development Goal for child survival

1 year after The Lancet Neonatal Survival Series--was the call for action heard?

This article does not have an Abstract

Fecal microbiota transfer for refractory intestinal graft‐versus‐host disease — Experience from two German tertiary centers

Rationale Steroid refractory graft-vs-host disease (sr-GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo-HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr-GvHD. Objectives We studied the effects of FMT on sr-GvHD in allo-HCT patients from two German tertiary clinical centers (n = 11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre- and post-FMT (day -14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre- and post-FMT by 16S rRNA sequencing. Results Post-FMT, we observed no intervention-associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis-each 3/11 and vomiting-1/11). Stool frequencies and volumes were significantly reduced [pre- vs post-FMT (d14): P < .05, respectively] as well as clear attenuation regarding both grading and staging of sr-GvHD was present upon FMT. Moreover, IM analyses revealed an increase of alpha diversity as well as a compositional shifts toward the donor post-FMT. Conclusions In our study, we observed positive effects on sr-GVHD after FMT without the occurrence of major adverse events. Although these findings are in line with published data on beneficial effects of FMT in sr-GvHD, further randomized clinical studies are urgently needed to better define the clinical validity including mode of action