Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial.

BACKGROUND: To date, evidence for the efficacy of fecal microbiota transplantation (FMT) in recurrent Clostridium difficile infection (CDI) has been limited to case series and open-label clinical trials. OBJECTIVE: To determine the efficacy and safety of FMT for treatment of recurrent CDI. DESIGN: Randomized, controlled, double-blind clinical trial. (ClinicalTrials.gov: NCT01703494). SETTING: Two academic medical centers. PATIENTS: 46 patients who had 3 or more recurrences of CDI and received a full course of vancomycin for their most recent acute episode. INTERVENTION: Fecal microbiota transplantation with donor stool (heterologous) or patient's own stool (autologous) administered by colonoscopy. MEASUREMENTS: The primary end point was resolution of diarrhea without the need for further anti-CDI therapy during the 8-week follow-up. Safety data were compared between treatment groups via review of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 6 months after FMT. Fecal microbiota analyses were performed on patients' stool before and after FMT and also on donors' stool. RESULTS: In the intention-to-treat analysis, 20 of 22 patients (90.9%) in the donor FMT group achieved clinical cure compared with 15 of 24 (62.5%) in the autologous FMT group (P = 0.042). Resolution after autologous FMT differed by site (9 of 10 vs. 6 of 14 [P = 0.033]). All 9 patients who developed recurrent CDI after autologous FMT were free of further CDI after subsequent donor FMT. There were no SAEs related to FMT. Donor FMT restored gut bacterial community diversity and composition to resemble that of healthy donors. LIMITATION: The study included only patients who had 3 or more recurrences and excluded those who were immunocompromised and aged 75 years or older. CONCLUSION: Donor stool administered via colonoscopy seemed safe and was more efficacious than autologous FMT in preventing further CDI episodes. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases.

Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial.

BACKGROUND: Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown. METHODS AND RESULTS: In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin. CONCLUSIONS: Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.

Baseline characteristics of participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial.

BACKGROUND: Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in patients with chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD before reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD. OBJECTIVES: To describe the baseline characteristics of renal transplant recipients enrolled in a clinical trial of homocysteine lowering with a standard multivitamin containing high doses of folic acid and vitamins B(6) and B(12) aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine concentration, and prevalence of diabetes and previous cardiovascular disease (CVD). STUDY DESIGN: Cross-sectional survey within a randomized controlled trial cohort. SETTING & PARTICIPANTS: Participants were recruited from kidney transplant clinics in the United States, Canada, and Brazil. Eligible participants had increased levels of homocysteine (> or =12.0 micromol/L in men and > or =11.0 micromol/L in women) and kidney function measured by means of Cockroft-Gault estimated creatinine clearance of 30 mL/min or greater. RESULTS: Of 4,110 randomly assigned participants, 38.9% had diabetes and 19.5% had previous CVD. Mean total homocysteine concentration was 17.1 +/- 6.3 (SD) micromol/L, whereas mean creatinine clearance was 66.4 +/- 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate consistent with stages 2 to 3 CKD (i.e., 30 to 89 mL/min). LIMITATIONS: Analysis is based on cross-sectional data from a randomized controlled trial, self-report of comorbid illnesses, and level of kidney function was estimated. CONCLUSIONS: A large population of stable renal transplant recipients who are at high risk of the development of CVD (both de novo and recurrent) has been recruited into the Folic Acid for Vascular Outcome Reduction in Transplantation Trial and are likely to experience a sufficient number of events to address the primary hypothesis of the trial.

Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial.

BACKGROUND: Patients with chronic kidney disease, including kidney transplant recipients, are at high risk for cardiovascular disease (CVD). In addition to the constellation of traditional CVD risk factors in chronic kidney disease, elevated total homocysteine (tHcy) is notably more prevalent among the general population. The Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial is designed to evaluate whether lowering tHcy using vitamin supplementation reduces CVD events in renal transplant recipients. METHODS: FAVORIT is a multicenter double-blind randomized controlled clinical trial. Participants are clinically stable renal transplant recipients who are 6 months or longer posttransplant with elevated tHcy. Patients are randomized to a multivitamin that includes either a high-dose or low-dose of folic acid (5 or 0 mg), vitamin B6 (50 or 1.4 mg), and vitamin B12 (1000 or 2 microg). The primary end point is a composite of incident or recurrent CVD outcomes, that is, coronary heart, cerebrovascular, or abdominal aortic/lower extremity arterial events. A sample size of 4000 is estimated to provide 87% power to detect a 20% treatment effect. Recruitment is expected to continue until July 2006, with follow-up through June 2010. RESULTS: From August 2002 through December 2004, 2234 of the target 4000 patients were enrolled. In accordance with trial design, mean (SD) screening tHcy was elevated (17.4 +/- 6.2 micromol/L), and mean (SD) estimated creatinine clearance was consistent with stable renal function (58.0 +/- 18.6 mL/min). Evaluating baseline results to date, 42% of the randomized participants had a history of diabetes mellitus, and 21% had prevalent CVD. CONCLUSIONS: The FAVORIT trial is designed with sufficient power and follow-up time to detect a clinically relevant change in CVD risk between renal transplant recipients receiving a high or low tHcy-lowering folic acid multivitamin. Preliminary screening and baseline data support the trial's objectives.

Are there gender differences in self-reported smoking practices? Correlation with thiocyanate and cotinine levels in smokers and nonsmokers from the Pawtucket Heart Health Program.

OBJECTIVES: This study compared serum cotinine and thiocyanate in assessment of self-reported smoking behavior among 1400 men and 1809 women from two New England communities. METHODS: Serum thiocyanate and serum cotinine levels were analyzed on 2411 and 798 survey respondents, respectively, in an attempt to provide an objective measurement for validation of self-reported smoking behaviors that were obtained through an in-home interviewer-administered questionnaire. Cross-sectional household surveys were conducted with randomly selected men and women, aged 18-65, between 1981 and 1993 as part of the evaluation of the Pawtucket Heart Health Program. RESULTS: Among smokers, the thiocyanate test had similar rates of agreement for women(88.0%) and for men (89.3%). However, among nonsmokers, thiocyanate had higher rates of agreement for women (91.5%) than for men (85.2%). For cotinine, the rates of agreement among smokers were higher for women (91.6%) than for men (89.7%). Similarly, the rates of agreement among nonsmokers were also higher for women (93.9%) than for men (91.9%). Overall,serum cotinine had a higher concordance rate than serum thiocyanate for both men and women. CONCLUSIONS: Although our results suggested that there were some differences in self-reporting of smoking status by gender, results were quite similar between self-reports of smoking and both biochemical tests. The results obtained from this large population-based study from two New England communities lend credibility to the use of self-reports as a low-cost accurate approach to obtaining information on smoking behaviors among both men and women in large population-based health surveys.

Linkages in the rural continuum: the balanced budget act and beyond.

PURPOSE: This study examined how rural hospitals altered their postacute and long-term care strategies after the Balanced Budget Act of 1997 (BBA97). DESIGN AND METHODS: A nationally representative sample of 540 rural hospital discharge planners were interviewed in 1997. In the year 2000, 513 of 540 discharge planners were reinterviewed. The study is a descriptive analysis of how rural hospitals formed new and altered existing organizational strategies during a time of turbulent changes in federal government reimbursement policy. We classify rural hospital strategic behavior in 1997 according to the Miles and Snow typology of Prospectors, Analyzers, Defenders, and Reactors, and then we examine how the various hospital types altered key strategies following BBA97. RESULTS: Between 1997 and 2000, more than 26% of sampled rural hospitals that did not participate in the swing-bed program in 1997 (44/167) had chosen to do so in 2000, whereas only 3% of those using swing beds in 1997 had eliminated them (12/346). Other strategies such as divestiture of hospital-based nursing homes were related to concurrent swing-bed adoption. Rural hospitals also increased their reliance on formal linkages with external providers of long-term care. IMPLICATIONS: After the BBA97 reimbursement changes, rural hospitals increased their reliance on swing beds and formal linkages to external providers. We observed changes in overall strategy types, away from the Defender and toward the Prospector and Analyzer strategy types. Our findings illustrate the importance of swing beds as a critical buffer for rural hospitals challenged by the uncertainty of the post-BBA97 environment.