The gut ecosystem and immune tolerance.

The gastrointestinal tract is home to the largest microbial population in the human body. The gut microbiota plays significant roles in the development of the gut immune system and has a substantial impact on the maintenance of immune tolerance beginning in early life. These microbes interact with the immune system in a dynamic and interdependent manner. They generate immune signals by presenting a vast repertoire of antigenic determinants and microbial metabolites that influence the development, maturation and maintenance of immunological function and homeostasis. At the same time, both the innate and adaptive immune systems are involved in modulating a stable microbial ecosystem between the commensal and pathogenic microorganisms. Hence, the gut microbial population and the host immune system work together to maintain immune homeostasis synergistically. In susceptible hosts, disruption of such a harmonious state can greatly affect human health and lead to various auto-inflammatory and autoimmune disorders. In this review, we discuss our current understanding of the interactions between the gut microbiota and immunity with an emphasis on: a) important players of gut innate and adaptive immunity; b) the contribution of gut microbial metabolites; and c) the effect of disruption of innate and adaptive immunity as well as alteration of gut microbiome on the molecular mechanisms driving autoimmunity in various autoimmune diseases.

The Evolving Landscape of Fecal Microbial Transplantation.

The human gastrointestinal tract houses an enormous microbial ecosystem. Recent studies have shown that the gut microbiota plays significant physiological roles and maintains immune homeostasis in the human body. Dysbiosis, an imbalanced gut microbiome, can be associated with various disease states, as observed in infectious diseases, inflammatory diseases, autoimmune diseases, and cancer. Modulation of the gut microbiome has become a therapeutic target in treating these disorders. Fecal microbiota transplantation (FMT) from a healthy donor restores the normal gut microbiota homeostasis in the diseased host. Ample evidence has demonstrated the efficacy of FMT in recurrent Clostridioides difficile infection (rCDI). The application of FMT in other human diseases is gaining attention. This review aims to increase our understanding of the mechanisms of FMT and its efficacies in human diseases. We discuss the application, route of administration, limitations, safety, efficacies, and suggested mechanisms of FMT in rCDI, autoimmune diseases, and cancer. Finally, we address the future perspectives of FMT in human medicine.

Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers. METHODS: Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes. RESULTS: Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%). CONCLUSIONS: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.

A study of military recruitment strategies for dentists: possible implications for academia.

Results of the annual American Dental Education Association surveys of dental school seniors show approximately 10 percent of graduates enter federal government services while less than 1 percent enter dental academia. To examine this difference, this study sought the perceptions of senior dental students and junior military dental officers regarding their choice of a military career in order to determine how military recruitment strategies influenced their career decisions. Official documents explaining military recruitment efforts were requested from the military services and summarized. In-depth telephone interviews were conducted to gather perception data from the students and dental officers on successful strategies. By employing several strategies, the military was able to inform potential recruits about the benefits of being a dentist in the military. The opportunity to have the military finance a student's dental education was a successful military recruitment tool. Other enticing factors included guaranteed employment upon graduation, prestige associated with serving in the military, access to postgraduate training, minimal practice management responsibilities, and opportunities to continue learning and improve clinical skills without significant financial implications. It was concluded that dental education can use the same strategies to highlight the benefits of an academic career and offer many similar incentives that may encourage students to consider a career path in dental education.

Preventing paediatric admissions for respiratory disease: a qualitative analysis of the views of health care professionals.

RATIONALE: The number of emergency paediatric admissions is increasing each year. The reasons for this are unclear but may include increasing demand from parents, changes in GP working patterns, and an increase in unnecessary admissions. Respiratory disease is the commonest diagnostic category for emergency admission in childhood. AIMS: To generate hypotheses for reduction in unnecessary admissions for respiratory disease by qualitative analysis of the views of health care professionals, to determine the proportion of preventable admissions as perceived by clinicians, and to assess the modified Paediatric Appropriateness Evaluation Protocol against clinicians judgements of appropriateness of admission. DESIGN: Eight health care professionals analysed clinical data from primary and secondary care for 94 cases that were admitted to an emergency assessment unit and received a hospital discharge diagnosis of respiratory disease. They assessed whether each admission was appropriate, whether it was preventable, and how it might have been prevented. RESULTS: A total of 31% of cases admitted to the assessment unit (29/94) were classified as preventable by the majority of professionals assessing the case. Provision of additional support, monitoring, and observation in the community was cited as a means of prevention in 33/94 cases. There was poor agreement between the modified PAEP and clinicians' assessments of appropriateness of admission (kappa 0.1). CONCLUSIONS: If the agreed views of these experienced doctors and nurses are correct, provision of additional services in the community could be an important means of preventing emergency admissions for respiratory disease. This hypothesis should be tested by further research including the views of families. The study provides further evidence that the modified PAEP may not be valid for use in UK practice. If inappropriate admission rates are to be used to measure effectiveness of services we need to develop an objective measure of appropriateness valid for use in the UK.

A qualitative study of choosing and using an NHS Walk-in Centre.

BACKGROUND: NHS Walk-in Centres have been introduced to improve access to healthcare in the UK. Little is understood about why people choose Walk-in Centres from among the range of options available to them. OBJECTIVES: To explore users' accounts of choosing and using an NHS Walk-in Centre. METHODS: Semi-structured interviews with 23 users who had recently attended an NHS Walk-in Centre were conducted. Analysis was based on the constant comparative method. RESULTS: Participants' accounts revealed two types of service use: those who knew what was wrong with them and had a clear idea of what treatment was required, and those seeking professional advice. Users reported "solidarity" with the NHS and other NHS users, and were highly sensitive to the demands on both Accident and Emergency and GP services in their choice of services. The Walk-in Centre appeared to function as a means of overcoming the barriers to healthcare associated with other healthcare services, although there was some lack of clarity about the purpose of the Walk-in Centre. CONCLUSIONS: Users' accounts suggest that NHS Walk-in Centres improve access to healthcare by opening up an alternative means of seeking a professional opinion or treatment. It is especially important in allowing people to use the NHS without feeling that they are increasing the burden on general practice and A&E facilities, and to feel that they are behaving responsibly while still meeting their own needs.

Effect of NHS walk-in centre on local primary healthcare services: before and after observational study.

OBJECTIVE: To assess the effect of an NHS walk-in centre on local primary and emergency healthcare services. DESIGN: Before and after observational study. SETTING: Loughborough, which had an NHS walk-in centre, and Market Harborough, the control town. PARTICIPANTS: 12 general practices. MAIN OUTCOME MEASURES: Mean daily rate of emergency general practitioner consultations, mean number of half days to the sixth bookable routine appointment, and attendance rates at out of hours services, minor injuries units, and accident and emergency departments. RESULTS: The change between the before and after study periods was not significantly different in the two towns for daily rate of emergency general practice consultations (mean difference -0.02/1000 population, 95% confidence interval -0.75 to 0.71), the time to the sixth bookable routine appointment (-0.24 half-days, -1.85 to 1.37), and daily rate of attendances at out of hours services (0.07/1000 population, -0.06 to 0.19). However, attendance at the local minor injuries unit was significantly higher in Loughborough than Market Harborough (rate ratio 1.22, 1.12 to 1.33). Non-ambulance attendances at accident and emergency departments fell less in Loughborough than Market Harborough (rate ratio 1.17, 1.03 to 1.33). CONCLUSIONS: The NHS walk-in centre did not greatly affect the workload of local general practitioners. However, the workload of the local minor injuries unit increased significantly, probably because it was in the same building as the walk-in centre.

Can safety assurance procedures in the food industry be used to evaluate a medical screening programme? The application of the Hazard Analysis and Critical Control Point system to an antenatal serum screening programme for Down's syndrome. Stage 1: identifying significant hazards.

RATIONALE, AIMS AND OBJECTIVES: Routine review of the Leicestershire district antenatal screening programme for Down's syndrome was carried out by its steering group. This raised suspicions that there were problems with the delivery of the programme. The steering group commissioned a project to adapt the Hazard Analysis and Critical Control Point (HACCP) system, as used in the food industry, to investigate this. The HACCP system is a systematic qualitative approach to problem identification and solution taken from the perspective of the production workers. This paper presents the first stage of the process, the hazard analysis. METHODS: Preliminary work comprised the preparation and verification of a flow diagram of the screening programme. Data about problems (termed hazards) perceived by Leicestershire health care staff delivering the screening programme were collected by observation, interview and telephone. The problems reported were categorized and assessed to identify those of sufficient importance in terms of their consequences or frequency of occurrence to merit the development of control measures. Hazards relating to operational issues were categorized according to the section of the programme to which they related. RESULTS AND CONCLUSIONS: A total of 16 categories of hazard were identified. In addition, nine groups of hazards constituting barriers to delivery of the screening programme as a whole were identified. The HACCP process made these hazards explicit. The first stage of the HACCP system proved a useful tool to identify problems experienced delivering a Down's serum screening programme and to assess which were sufficiently serious to require the development of control measures.

Can safety assurance procedures in the food industry be used to evaluate a medical screening programme? The application of the Hazard Analysis and Critical Control Point system to an antenatal serum screening programme for Down's syndrome. Stage 2: overcoming the hazards in programme delivery.

RATIONALE, AIMS AND OBJECTIVES: An adaptation of the first stage of the systematic qualitative tool, the Hazard Analysis and Critical Control Point (HACCP) system from the food industry, was used to identify problems in the delivery of a district-wide antenatal screening programme for Down's syndrome. The aim of the second stage, described here, was to develop specific solutions (termed controls) for these problems. METHODS: The views of staff delivering the programme and of members of the Down's screening steering group were used to identify control measures. The steering group members were also asked to identify which controls were critical to a risk management strategy, i.e. whether a control was essential to eliminate the hazard or if other control measures operating further down-line would be sufficient. The control measures were piloted both to determine if they were operationally feasible and whether they were practical in the context of staff workload and attitude. Two main control measures were the development of a rolling education programme for staff and of a written protocol with a checklist to verify stepwise delivery of the Down's screening programme. The checklist was designed to be included in the notes of every pregnant woman to enable audit of the offer of screening and delivery of each step of the screening programme. The control measures were all tailored specifically to overcome the problems reported by staff during the first stage of the work, the hazard analysis. RESULTS AND CONCLUSIONS: The HACCP system proved useful in confirming the existence of problems in delivery of a Down's serum screening programme and in determining solutions tailored to overcome those problems. Future work is required to monitor and evaluate the usefulness of the control measures implemented.