A review of the role of intermittent fasting in the management of inflammatory bowel disease.

Intermittent fasting (IF) may be a weight management strategy for patients with inflammatory bowel disease (IBD). The aim of this short narrative review is to summarize the evidence related to IF in the management of IBD. A literature search of English publications related to IF or time-restricted feeding and IBD, Crohn's disease, or ulcerative colitis was conducted in PubMed and Google Scholar. Four publications on studies of IF in IBD were found: three randomized controlled trials in animal models of colitis and one prospective observational study in patients with IBD. The results from animal studies suggest either moderate or no changes in weight but improvements in colitis with IF. These improvements may be mediated through changes in the gut microbiome, decreased oxidative stress and increased colonic short-chain fatty acids. The study in humans was small and uncontrolled, and it did not assess changes in weight, making it difficult to draw conclusions around the effects of IF on changes in weight or disease course. Given that preclinical evidence suggests intermittent fasting may play a beneficial role in IBD, randomized controlled trials in large patients with active disease are warranted to determine whether intermittent fasting could be an integrated therapy for patients with IBD management, either for weight or for disease management. These studies should also explore the potential mechanisms of action related to intermittent fasting.

Systematic review and meta-analysis of randomised controlled trials: Medical therapies for the treatment and prevention of pouchitis.

BACKGROUND AND AIMS: We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis. METHODS: Randomised controlled trials (RCTs) of medical therapy in adults with or without pouchitis were searched to March 2022. Primary outcomes included clinical remission/response, maintenance of remission and prevention of pouchitis. RESULTS: Twenty RCTs (N = 830) were included. Acute pouchitis: One study compared ciprofloxacin with metronidazole. At 2 weeks, 100% (7/7) of ciprofloxacin participants achieved remission, compared with 67% (6/9) of metronidazole participants (RR: 1.44, 95% CI: 0.88-2.35, very low certainty evidence). One study compared budesonide enemas with oral metronidazole. Fifty percent (6/12) of budesonide participants achieved remission compared with 43% (6/14) of metronidazole participants (RR: 1.17, 95% CI: 0.51-2.67, low certainty evidence). Chronic pouchitis: Two studies (n = 76) assessed De Simone Formulation. Eighty-five percent (34/40) of De Simone Formulation participants maintained remission at 9-12 months compared with 3% (1/36) placebo participants (RR: 18.50, 95% CI: 3.86-88.56, moderate certainty evidence). One study assessed vedolizumab. Thirty-one percent (16/51) of vedolizumab participants achieved clinical remission at 14 weeks compared with 10% (5/51) of placebo participants (RR: 3.20, 95% CI: 1.27-8.08, moderate certainty evidence). PROPHYLAXIS: Two studies assessed De Simone Formulation. Ninety percent (18/20) of De Simone Formulation participants did not develop pouchitis compared with 60% (12/20) of placebo participants (RR: 1.50, 95% CI: 1.02-2.21, moderate certainty evidence). CONCLUSIONS: Apart from vedolizumab and the De Simone formulation, the effects of other medical interventions for pouchitis are uncertain.

Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use. AIMS: To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021). RESULTS: Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p < 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group. CONCLUSION: Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.

Declining Colectomy Rates for Nonmalignant Colorectal Polyps in a Large, Ethnically Diverse, Community-Based Population.

INTRODUCTION: Despite studies showing improved safety, efficacy, and cost-effectiveness of endoscopic resection for nonmalignant colorectal polyps, colectomy rates for nonmalignant colorectal polyps have been increasing in the United States and Europe. Given this alarming trend, we aimed to investigate whether colectomy rates for nonmalignant colorectal polyps are increasing or declining in a large, integrated, community-based healthcare system with access to advanced endoscopic resection procedures. METHODS: We identified all individuals aged 50-85 years who underwent a colonoscopy between 2008 and 2018 and were diagnosed with a nonmalignant colorectal polyp(s) at the Kaiser Permanente Northern California integrated healthcare system. Among these individuals, we identified those who underwent a colectomy for nonmalignant colorectal polyps within 12 months after the colonoscopy. We calculated annual colectomy rates for nonmalignant colorectal polyps and stratified rates by age, sex, and race and ethnicity. Changes in rates over time were tested by the Cochran-Armitage test for a linear trend. RESULTS: Among 229,730 patients who were diagnosed with nonmalignant colorectal polyps between 2008 and 2018, 1,611 patients underwent a colectomy. Colectomy rates for nonmalignant colorectal polyps decreased significantly from 125 per 10,000 patients with nonmalignant polyps in 2008 to 12 per 10,000 patients with nonmalignant polyps in 2018 (P < 0.001 for trend). When stratified by age, sex, and race and ethnicity, colectomy rates for nonmalignant colorectal polyps also significantly declined from 2008 to 2018. DISCUSSION: In a large, ethnically diverse, community-based population in the United States, we found that colectomy rates for nonmalignant colorectal polyps declined significantly over the past decade likely because of the establishment of advanced endoscopy centers, improved care coordination, and an organized colorectal cancer screening program.

Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn's disease: a systematic review and network meta-analysis.

BACKGROUND: Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease. METHODS: We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. FINDINGS: The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias. INTERPRETATION: Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission. FUNDING: None.

Gender Disparities in Food Security, Dietary Intake, and Nutritional Health in the United States.

INTRODUCTION: Food insecurity is associated with negative nutritional outcomes and is experienced differently by women vs men. We evaluated the effects of gender on food insecurity and dietary intake in the United States. METHODS: Data from the National Health and Nutrition Examination Survey (2007-2016) were analyzed. Survey-weighted linear and logistic regression models were used to evaluate predictors of food security and the effect of food security on dietary consumption and body anthropometrics. Gender was modeled as a covariable and as an effect modifier. RESULTS: A total of 30,251 respondents were included. Approximately 15.1% (95% confidence interval [CI]: 14.1%-16.1%) of participants were food insecure. This increased over time from 11.7% in 2007-2008 to 18.2% in 2015-2016. A higher proportion of women experienced food insecurity compared with men (53.3% vs 46.7%, P = 0.02), although this was not significant after adjusting for poverty and other confounders (adjusted odds ratio 1.01; 95% CI: 0.93-1.09; P = 0.81). Among food insecure women, 32.4% (95% CI: 30.0%-34.9%) received emergency food assistance and 75.0% (95% CI: 71.5%-78.2%) received supplemental nutrition assistance benefits. Relative to men, food insecure women were less likely to meet the recommended dietary allowance of most macronutrients and micronutrients. They were also significantly more likely to be obese, have a wider waist circumference, and have higher total body fat percentage (P interaction all <0.001). DISCUSSION: Food insecurity represents a substantial public health challenge in the United States that differentially affects women compared with men. Alternative strategies may be required to meet the nutritional requirements for food insecure women.

Systematic review with meta-analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies.

BACKGROUND: Aminosalicylates are the most frequently prescribed treatment for ulcerative colitis (UC). In the absence of empirical evidence, clinicians are uncertain whether to continue aminosalicylates in patients with UC after escalating therapy. AIMS: To quantify concomitant aminosalicylate use in UC randomised clinical trials (RCTs), identify factors associated with their use, and estimate treatment costs of concomitant aminosalicylate therapy. METHODS: MEDLINE, Embase, and CENTRAL were searched from inception to 1 March 2017 for placebo-controlled RCTs of immunosuppressants, biologics, or oral small molecules in adults with UC. The proportion of patients prescribed concomitant aminosalicylates at trial entry was pooled using a random-effects model. Meta-regression was performed to assess trial-level factors associated with aminosalicylate use. Treatment costs were estimated using 2018 formulary data from five Canadian provinces. RESULTS: Thirty-two trials were included (23 induction only, nine induction, and maintenance trials). The pooled proportion of patients co-prescribed aminosalicylates was 80.7% (95% CI 75.5%-85.1%), with considerable observed heterogeneity (I2  = 95%). In univariable meta-regression, aminosalicylate use was not associated with trial design, setting, year of publication, disease severity, disease duration, or drug class. The estimated direct annual treatment cost of concomitant aminosalicylates is ~$20 million for the Canadian UC population, assuming conservative estimates of UC prevalence, aminosalicylate use and dose, and the lowest cost formulation. CONCLUSIONS: Approximately 80% of UC patients entering clinical trials of immunosuppressants, biologics, or oral small molecules continue to use aminosalicylates. An RCT is needed to inform the benefits and harms of continuing vs stopping aminosalicylates in patients escalating therapy.

Major components of orange oil inhibit Staphylococcus aureus growth and biofilm formation, and alter its virulence factors.

Bovine mastitis is a costly disease in the dairy industry and does not always respond to antibiotic treatment. The major components of terpeneless, cold-pressed Valencia orange oil - citral, linalool, decanal and valencene - were examined as potential alternative treatments for Staphylococcus aureus-associated mastitis. The minimum inhibitory concentration (MIC) of all four components against S. aureus was determined after incubation for 24 h. Growth inhibition assays were performed for all effective components on S. aureus for either a 3 h or 72 h treatment. These components were tested for the ability to disrupt pre-formed S. aureus biofilms after 24 h of treatment by measuring absorbance at 540 nm. Cytotoxicity against immortalized bovine mammary epithelial (MAC-T) cells was measured using an MTT assay following a 1 h exposure. Only concentrations below the 50 % cytostatic concentration (CC50) were used in an adherence and invasion assay of S. aureus on MAC-T cells, and for measurements of virulence and biofilm gene expression via qPCR. The MICs of citral and linalool were 0.02 % and 0.12 %, respectively, but decanal and valencene were ineffective. Citral and linalool were capable of inhibiting growth of S. aureus after 24 h at their MIC values and inhibited pre-formed biofilms of S. aureus . The concentrations below the CC50 were 0.02 % for citral and 0.12 % for linalool. These concentrations inhibited the adhesion and invasion ability of S. aureus and downregulated virulence genes. Only 0.12 % linalool downregulated the expression of S. aureus biofilm-forming genes. These components should be considered for further in vivo study.