Algorithms or biomarkers in patients with lower DGBI?

BACKGROUND: Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut-brain interactions (DGBI) affecting the lower digestive tract including irritable bowel syndrome and chronic idiopathic constipation. Such algorithms are based on sequential therapeutic trials and modifying the treatment strategy based on efficacy and adverse events. PURPOSE: The aims of this review are to evaluate the evidence for efficacy of second- and third-line pharmacotherapies and to assess the evidence for the alternative option to manage subgroups of patients with symptoms suggestive of lower DGBI based on diagnostic tests or documented dysfunctions. The preeminent tests to identify such subgroups that present with symptoms that overlap with lower DGBI are detailed: digital rectal examination as well as anorectal manometry and balloon expulsion for evacuation disorders, detailed measurements of colonic transit, and diagnosis of bile acid diarrhea or carbohydrate malabsorption based on biochemical measurements. The review also addresses the cost implications of screening to exclude alternative diagnoses and the costs of therapy associated with the therapeutic options following an algorithmic approach to treatment from the perspective of society, insurer, or patient. Finally, the costs of the diagnostic tests to identify actionable biomarkers and the evidence of efficacy of individualized therapy based on formal diagnosis or documentation of abnormal functions are detailed in the review.

The goals for successful development of treatment in gastroparesis.

BACKGROUND: Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades. PURPOSE: The objectives of this review are to develop an understanding of the goals of treatment, the evidence-based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence-based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof-of-efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof-of-efficacy, placebo-controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis.

Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile Infection: Systematic Review and Meta-analysis.

BACKGROUND: Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI. AIM: This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI. METHODS: A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates. RESULTS: Two hundred and forty patients from 10 studies (8 case series, 1 case-control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low. CONCLUSION: FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.

Update on the new 9-valent vaccine for human papillomavirus prevention.

OBJECTIVE: To provide family physicians with information on the efficacy, safety, public health effects, and cost-effectiveness of the 9-valent human papillomavirus (HPV) vaccine. QUALITY OF EVIDENCE: Relevant publications in PubMed up to May 2015 were reviewed and analyzed. Most evidence cited is level I (randomized controlled trials and meta-analyses) or level II (cross-sectional, case-control, and epidemiologic studies). Government reports and recommendations are also referenced. MAIN MESSAGE: The 9-valent HPV vaccine, which protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, is safe and effective and will further reduce the incidence of HPV infection, as well as HPV-related cancers. It can also indirectly protect unvaccinated individuals through herd immunity. With an effective vaccination program, most cervical cancers can be prevented. Analyses show that the cost-effectiveness of the 9-valent HPV vaccine in female patients is comparable to the original quadrivalent HPV vaccine (which protects against HPV types 6, 11, 16, and 18) currently in use. However, the usefulness of vaccinating male patients with the 9-valent HPV vaccine needs further investigation. CONCLUSION: The 9-valent HPV vaccine offers more protection against HPV than the quadrivalent HPV vaccine does and is as safe. Analysis of cost-effectiveness favours its use, at least in adolescent girls. Therefore, physicians should recommend the 9-valent HPV vaccine to patients instead of the quadrivalent HPV vaccine.

Single ether group in a glycol-based ultra-thin layer prevents surface fouling from undiluted serum.

Through systematic structural modification, it is shown that the internal, single oxygen atom of simple monoethylene glycol-based organic films is essential for radically altering the fouling behaviour of quartz against undiluted serum, as characterized by the electromagnetic piezoelectric acoustic sensor. The synergy is strongest with distal hydroxyls.