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Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility, and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of interleukin 25 (IL-25) and that FMT protected in part by restoring IL-25 signaling. Here, we conducted a prospective study in humans to test if FMT induced IL-25 expression in the colons of patients with recurrent CDI (rCDI). Colonic biopsy specimens and blood were collected at the time of FMT and 60 days later. Colon biopsy specimens were analyzed for IL-25 protein levels, total tissue transcriptome, and epithelium-associated microbiota before and after FMT, and peripheral immune cells were immunophenotyped. FMT increased alpha diversity of the colonic microbiota and levels of IL-25 in colonic tissue. In addition, FMT increased expression of homeostatic genes and repressed inflammatory genes. Finally, circulating Th17 cells were decreased post-FMT. The increase in levels of the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for C. difficile infection for most patients; however, introducing a complex mixture of microbes also has had unintended consequences for some patients. Attempts to create a standardized probiotic therapeutic that recapitulates the efficacy of FMT have been unsuccessful to date. We sought to understand what immune markers are changed in patients undergoing FMT to treat recurrent C. difficile infection and identified an immune signaling molecule, IL-25, that was restored by FMT. This finding indicates that adjunctive therapy with IL-25 could be useful in treating C. difficile infection.

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Health professions education is that part of the education system which applies educational philosophy, theory, principles and practice in a complex relationship with busy clinical services, where education is not the primary role. While the goals are clear-to produce the health workforce that society needs to improve health outcomes-both education and healthcare systems continue to evolve concurrently amidst changes in knowledge, skills, population demographics and social contracts. In observing a significant anniversary of this journal, which sits at the junction of education and healthcare systems, it is appropriate to reflect on how the relationship is evolving. Health professions educators must listen to the voices of regulators, employers, students and patients when adapting to new service delivery models that emerge in response to pressures for change. The recent COVID-19 pandemic is one example of disruptive change, but other factors, such as population pressures and climate change, can also drive innovations that result in lasting change. Emerging technology may act as either a servant of change or a disruptor. There is a pressing need for interdisciplinary research that develops a theory and evidence base to strengthen sustainability of change.

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OBJECTIVE: To assess the effects of interventions aimed at involving older people with multimorbidity in decision-making about their healthcare during primary care consultations. METHODS: Cochrane methodological procedures were applied. Searches covered all relevant trial registries and databases. Randomised controlled trials were identified where interventions had been compared with usual care/ control/ another intervention. A narrative synthesis is presented; meta-analysis was not appropriate. RESULTS: 8160 abstracts and 54 full-text articles were screened. Three studies were included, involving 1879 patient participants. Interventions utilised behaviour change theory; cognitive-behavioural therapy and motivational interviewing; multidisciplinary, holistic patient review and organisational changes. No studies reported the primary outcome 'patient involvement in decision-making about their healthcare'. Patient involvement was evident in the theory underpinning interventions. Certainty of evidence (assessed using GRADE) was limited by small studies and inconsistency in secondary outcomes measured. CONCLUSION: The evidence base is currently too limited to interpret with certainty. Transparency in design and consistency in evaluation, using validated measures, is required for future interventions involving older patients with multimorbidity in decisions about their healthcare. PRACTICE IMPLICATIONS: There is a large gap between clinical guidelines for multimorbidity and an evidence base for implementation of their recommendations during primary care consultations with older people.

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Many new medical programs have been established during the last 20 years, and this trend seems set to continue as the health care needs of the world's populations become more complex and demand increases for more physicians to provide the necessary health care. In this paper, we address how best to establish a new medical school, based on our experiences in new ventures in several countries. Success requires a combination of boldness of vision, support from many stakeholder groups, adequate financial and human resources, educational expertise, confidence, patience, and persistence.

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OBJECTIVES: Evaluating children's oral health status and treatment needs is challenging. We aim to build oral health assessment toolkits to predict Children's Oral Health Status Index (COHSI) score and referral for treatment needs (RFTN) of oral health. Parent and Child toolkits consist of short-form survey items (12 for children and 8 for parents) with and without children's demographic information (7 questions) to predict the child's oral health status and need for treatment. METHODS: Data were collected from 12 dental practices in Los Angeles County from 2015 to 2016. We predicted COHSI score and RFTN using random Bootstrap samples with manually introduced Gaussian noise together with machine learning algorithms, such as Extreme Gradient Boosting and Naive Bayesian algorithms (using R). The toolkits predicted the probability of treatment needs and the COHSI score with percentile (ranking). The performance of the toolkits was evaluated internally and externally by residual mean square error (RMSE), correlation, sensitivity and specificity. RESULTS: The toolkits were developed based on survey responses from 545 families with children aged 2 to 17 y. The sensitivity and specificity for predicting RFTN were 93% and 49% respectively with the external data. The correlation(s) between predicted and clinically determined COHSI was 0.88 (and 0.91 for its percentile). The RMSEs of the COHSI toolkit were 4.2 for COHSI (and 1.3 for its percentile). CONCLUSIONS: Survey responses from children and their parents/guardians are predictive for clinical outcomes. The toolkits can be used by oral health programs at baseline among school populations. The toolkits can also be used to quantify differences between pre- and post-dental care program implementation. The toolkits' predicted oral health scores can be used to stratify samples in oral health research. KNOWLEDGE TRANSFER STATEMENT: This study creates the oral health toolkits that combine self- and proxy- reported short forms with children's demographic characteristics to predict children's oral health and treatment needs using Machine Learning algorithms. The toolkits can be used by oral health programs at baseline among school populations to quantify differences between pre and post dental care program implementation. The toolkits can also be used to stratify samples according to the treatment needs and oral health status.

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Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infections (rCDIs). We assessed the benefits of a multidisciplinary C. difficile clinic for screening FMT eligibility in patients with rCDI. Patients seen at the University of Virginia Complicated C. difficile Clinic (CCDC) underwent comprehensive evaluation for possible FMT. Patients were eligible for FMT if there was history of greater than two episodes of rCDI. Patients were evaluated for the outcome after evaluation in the clinic. A total of 113 patients were evaluated: 77 were eligible for FMT, of which 25 patients did not undergo FMT. The rate of recurrence at three months and all-cause mortality were 4.5% and 7% for patients who received FMT and 16.7% and 12.5% for eligible patients who did not receive FMT. There were 36 patients who were not eligible for FMT, with two or fewer recurrences and a recurrence rate of 8.8% and all-cause mortality of 6%. One in three patients screened for FMT had a nutritional deficiency diagnosed, with zinc deficiency being most common (20%). Additional diagnoses, including inflammatory bowel disease, were made during the evaluation. FMT is a highly effective treatment for rCDI, most notably in patients with multiple recurrences. A systematic approach for evaluating patients with rCDI helps identify patients who benefit most from FMT and those who have other conditions.

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Alteration of the normal gut-liver axis is important in primary sclerosing cholangitis (PSC). Lack of effective medical therapy for PSC makes microbiome restoration an alluring therapeutic target. Allegretti et al. performed an open-label safety trial of fecal microbiota transplant (FMT) in noncirrhotic PSC patients with inflammatory bowel disease in remission on minimal therapy. FMT was safe in this population, and after FMT, there was a stable, early increase in microbial diversity and donor engraftment with mixed effects on alkaline phosphatase but no significant change in fecal bile acid profile. Further trials are needed to find whether FMT has a role to play in PSC therapy.

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BACKGROUND: Video capsule endoscopy provides noninvasive visualization of the small bowel, but yield is often limited by debris. At our institution, preparation with polyethylene glycol (PEG) and simethicone is used to improve visualization. AIMS: We hypothesized that linaclotide and simethicone would yield equal to better results. METHODS: We enrolled 29 subjects for the experimental regimen of linaclotide and simethicone. We maintained standard NPO status, clear liquid period, and simethicone dose. Subjects received 290 µg of linaclotide 1 h prior to capsule. We randomly selected 30 historical PEG controls. Two blinded gastroenterologists graded visualization as ideal/excellent, good, fair, or poor and measured small bowel transit time. RESULTS: Thirteen men and 16 women were enrolled with an average age of 61. There was no significant difference in exam quality between linaclotide and control. Preparation was rated as ideal/excellent or good in 19 of 28 of linaclotide and 18 of 28 PEG subjects when recorder entered the small bowel (p = 0.78, chi-square). Median small bowel transit was 192 min (linaclotide) versus 202 min (PEG), respectively (p = 0.93, t test). Three studies (1 linaclotide and 2 PEG) failed to leave the stomach; 1 linaclotide subject had recorder failure. Diagnostic yield was similar (18/29 for linaclotide and 16/30 for PEG, p = 0.50, chi-square). There were no serious side effects. No differences in age, sex, BMI, or frequency of diabetes, GERD, or gastroparesis were measured between the groups. CONCLUSIONS: Single-dose linaclotide 1 h before capsule endoscopy was equally effective when compared to PEG in terms of visualization and transit time. This trial was registered at ClincialTrials.gov, number NCT02465385.

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BACKGROUND: Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT. METHODS: We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013-9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency. RESULTS: Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66 µg/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR = 11.327, 95% CI = 2.162-59.336, p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR = 0.102, 95% CI = 0.015-0.704, p=0.021). CONCLUSION: Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.

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OBJECTIVE: To examine child and parent reports about the child's oral health and assess the associations of these reports with clinical assessments of oral health status by dental examiners. METHODS: Surveys with 139 items for children and 133 items for parents were administered by Audio Computer-Assisted Self-Interview Software. In addition, the Children's Oral Health Status Index (COHSI) was computed from a dental examination. RESULTS: A total of 334 families with children ages 8 to 17 y participated at 12 dental practices in Los Angeles County. Ordinary least squares regression models were estimated separately for child and parent surveys to identify items uniquely associated with the COHSI. Ten of 139 items the children reported regarding their oral health were associated with the COHSI. The strongest associations were found for child's age, aesthetic factors (straight teeth and pleased with teeth), and cognitive factors related to perception of dental appearance (pleased/happy with the look of the child's mouth, teeth, and jaws). Nine of 133 parent items about the child's oral health were associated with the COHSI in the parent model, notably being a single parent, parent's gender, parent born in the United States, pleased or happy with the look of their child's teeth, and accessing the Internet. CONCLUSION: These child and parent survey items have potential to be used to assess oral health status for groups of children in programs and practices in lieu of dental screenings. KNOWLEDGE TRANSLATION STATEMENT: The paper's results inform the development of a toolkit that can be used by schools, public health agencies, and dental programs to identify children with low oral health status based on parents' and children's responses to survey items across demographic, physical, mental, and social domains. These survey items can be used to inform parents of the desirability of proactively addressing inadequacies in their child's oral health status, enabling them to more rationally address dental needs.

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Despite generally positive outcomes and high rates of satisfaction, living kidney donors are at risk for both medical and psychosocial problems. In this review, the authors summarize non-end-stage renal disease (ESRD) risks for donors and describe limitations to the data. We review the evidence of medical risks (e.g. increased cardiovascular disease and mortality, preeclampsia) and psychosocial risks (e.g. mood disturbance, financial burden). We then discuss the evidence of differential risks among subsets and the impact of postdonation events (e.g. development of diabetes). Collectively, available evidence indicates the following. (1) Recognizing the importance of non-ESRD risks has been overshadowed by analyses of the reported risk of ESRD. This imbalance should be remedied. (2) There is little quantification of the true contribution of donation to medical and psychosocial outcomes. (3) Most studies, to date, have been retrospective, with limited sample sizes and diversity and with less-than-ideal controls for comparison of outcomes. (4) Many postdonation events (diabetes and hypertension) can now be reasonably predicted, and their association with adverse outcomes can be quantified. (5) Mechanisms and systems need to be implemented to evaluate and care for donors who develop medical and/or psychosocial problems. (6) Costs to donors are a significant burden, and making donation financially neutral should be a priority.

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BACKGROUND: Total abdominal colectomy (TAC) is the standard surgical treatment of Clostridium difficile infection (CDI). An alternative therapy, loop ileostomy and colonic lavage (IL), was described in 2011, but the results have never been validated. METHODS: Patients treated surgically for CDI between April 2011 and June 2015 were included. Bivariable analysis was used to compare 30-day mortality, 1-year mortality, CDI recurrence, colon preservation and ileostomy reversal. RESULTS: Ten IL patients and thirteen TAC patients were identified. 30-day mortality (30% vs 23%, p = 1.0) and 1-year mortality (40% vs 46%, p = 1.0) were similar. Four IL and three TAC patients (57% vs 30%, p = 0.35) experienced recurrent CDI. All six surviving IL patients had successful colon preservation; five underwent ileostomy reversal compared to three in the TAC group (83% vs 43%, p = 0.27). CONCLUSIONS: Although IL allowed colon preservation and return of intestinal continuity in most patients, IL did not decrease mortality or recurrent CDI when compared to TAC.

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BACKGROUND: Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) patients report similar gastrointestinal (GI) symptoms, yet comparisons of symptom severity between groups and with the general population (GP) are lacking. METHODS: We compared Patient-Reported Outcomes Measurement Information System (PROMIS® ) GI symptom scales measuring gastro-esophageal reflux (GER), disrupted swallowing, diarrhea, bowel incontinence, nausea/vomiting, constipation, belly pain, and gas/bloating in: (i) USA GP sample, (ii) IBS patients, and (iii) IBD patients from tertiary care and community populations. Symptom severity scores were based on T-score metric with mean 50±10 (standard deviation) relative to the GP. KEY RESULTS: Of 1643 patients enrolled, there were 253 IBS patients (68% F, mean age 45±15 years), 213 IBD patients (46% F, mean age 41±14 years), and 1177 GP subjects (57% F, mean age 46±16 years). IBS patients reported greater severity of GER, disrupted swallowing, nausea/vomiting, belly pain, gas/bloating, and constipation symptoms than their IBD counterparts (all P<.05). Compared to the GP, IBD patients had worse belly pain, gas/bloating, diarrhea, and bowel incontinence, but less severe GER and disrupted swallowing (all P<.05), and IBS patients had more severe nausea/vomiting, belly pain, gas/bloating, and constipation (all P<.05). Women had more severe belly pain and gas/bloating than men, whereas men had more severe bowel incontinence (all P<.05). CONCLUSION & INFERENCES: IBS and IBD are associated with more severe GI symptoms compared to the GP excluding esophageal symptoms. Unlike IBD, IBS is not characterized by observable GI inflammation but patients report more severe upper and lower GI symptoms.

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In the United States, live organ donation can be a costly and burdensome undertaking for donors. While most donation-related medical expenses are covered, many donors still face lost wages, travel expenses, incidentals, and potential for future insurability problems. Despite widespread consensus that live donors (LD) should not be responsible for the costs associated with donation, little has changed to alleviate financial burdens for LDs in the last decade. To achieve this goal, the transplant community must actively pursue strategies and policies to eliminate unreimbursed out-of-pocket costs to LDs. Costs should be more appropriately distributed across all stakeholders; this will also make live donation possible for people who, in the current system, cannot afford to proceed. We propose the goal of LD "financial neutrality," offer an operational definition to include the coverage/reimbursement of all medical, travel, and lodging costs, along with lost wages, related to the act of donating an organ, and guidance for consideration of medical care coverage, and wage and other expense reimbursement. The intent of this report is to provide a foundation to inform discussion within the transplant community and to advance initiatives for policy and resource allocation.

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Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

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The independent living donor advocate (ILDA) serves a mandated and supportive role in the care of the living organ donor, yet qualifications and role requirements are not clearly defined. Guidance comes from Centers for Medicare and Medicaid Services (CMS) Conditions for Transplant Center Participation and interpretive guidelines, Organ Procurement and Transplantation Network (OPTN) Policy and CMS and OPTN site surveys, yet interpretation of regulations varies. Herein, the AST Living Donor Community of Practice (LDCOP) offers seven recommendations to clarify and optimize the ILDA role: (a) the ILDA must have a certain skill set rather than a specific profession, (b) the ILDA must be educated and demonstrate competence in core knowledge components, (c) the ILDA's primary role is to assess components of informed consent, (d) centers must develop a transparent system to define ILDA independence, (e) the ILDA should have a reporting structure outside the transplant center, (f) the ILDA's role should be integrated throughout the donor care continuum, (g) the ILDA role should include a narrow "veto power." We address controversies in ILDA implementation, and offer pathways to maximize benefits and minimize limitations of approaches that may each meet regulatory requirements but confer different practice benefits. We propose a research agenda to explore the impact of the ILDA.

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