Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation.

BACKGROUNDGut decontamination (GD) can decrease the incidence and severity of acute graft-versus-host disease (aGVHD) in murine models of allogeneic hematopoietic cell transplantation (HCT). In this pilot study, we examined the impact of GD on gut microbiome composition and the incidence of aGVHD in HCT patients.METHODSWe randomized 20 patients undergoing allogeneic HCT to receive (GD) or not receive (no-GD) oral vancomycin-polymyxin B from day -5 through neutrophil engraftment. We evaluated shotgun metagenomic sequencing of serial stool samples to compare the composition and diversity of the gut microbiome between study arms. We assessed clinical outcomes in the 2 arms and performed strain-specific analyses of pathogens that caused bloodstream infections (BSI).RESULTSThe 2 arms did not differ in the predefined primary outcome of Shannon diversity of the gut microbiome at 2 weeks post-HCT (genus, P = 0.8; species, P = 0.44) or aGVHD incidence (P = 0.58). Immune reconstitution of T cell and B cell subsets was similar between groups. Five patients in the no-GD arm had 8 BSI episodes versus 1 episode in the GD arm (P = 0.09). The BSI-causing pathogens were traceable to the gut in 7 of 8 BSI episodes in the no-GD arm, including Staphylococcus species.CONCLUSIONWhile GD did not differentially affect Shannon diversity or clinical outcomes, our findings suggest that GD may protect against gut-derived BSI in HCT patients by decreasing the prevalence or abundance of gut pathogens.TRIAL REGISTRATIONClinicalTrials.gov NCT02641236.FUNDINGNIH, Damon Runyon Cancer Research Foundation, V Foundation, Sloan Foundation, Emerson Collective, and Stanford Maternal & Child Health Research Institute.

The Impact of Catastrophic Medical Insurance in China: A five-year patient-level panel study.

Background: In an effort to provide greater financial protection from the risk of large medical expenditures, China has gradually added catastrophic medical insurance (CMI) to the various basic insurance schemes. Tongxiang, a rural county in Zhejiang province, China, has had CMI since 2000 for their employee insurance scheme, and since 2014 for their resident insurance scheme. Methods: Compiling and analysing patient-level panel data over five years, we use a difference-in-difference approach to study the effect of the 2014 introduction of CMI for resident insurance beneficiaries in Tongxiang. In our study design, resident insurance beneficiaries are the treatment group, while employee insurance beneficiaries are the control group. Findings: We find that availability of CMI significantly increases medical expenditures among resident insurance beneficiaries, including for both inpatient and outpatient spending. Despite the greater financial protection, out-of-pocket expenditures increased, in part because patients accessed treatment more often at higher-level hospitals. Interpretation: Better financial coverage for catastrophic medical expenditures led to greater access and expenditures, not only for inpatient admissions-the category that most often leads to catastrophic expenditures-but for outpatient visits as well. These patterns of expenditure change with CMI may reflect both enhanced access to a patient's preferred site of care as well as the influence of incentives encouraging more care under fee-for-service payment. Funding: Stanford University's Freeman Spogli Institute for International Studies' Policy Implementation Lab and a Shorenstein Asia Pacific Research Center faculty research award provided funding for this project. Chinese translation of the abstract (Appendix 1).