Herbal Medicines for the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

Prebiotics and Probiotics for Gastrointestinal Disorders.

The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.

Preventative and therapeutic potential of nutrition for inflammatory bowel diseases: A narrative review.

Diet strongly shapes the gut microbiome and metabolome, which in turn influence intestinal inflammation in patients with inflammatory bowel disease (IBD). Separate from inflammation and malnutrition, diet's direct interactions with the gastrointestinal system can also provoke or attenuate a host of nonspecific gastrointestinal symptoms. Given these multifaceted effects of diet on inflammation and symptoms, nutrition has been investigated for its potential roles in the prevention and treatment of IBD. This review presents epidemiological, observational cohort, and clinical trial evidence that underlie our current understanding of nutrition for prevention and treatment of IBD.

Vitamin D for the treatment of inflammatory bowel disease.

BACKGROUND: Vitamin D possesses immunomodulatory properties and has been implicated in the pathogenesis and severity of inflammatory bowel disease (IBD). Animal studies and emerging epidemiological evidence have demonstrated an association between vitamin D deficiency and worse disease activity. However, the role of vitamin D for the treatment of IBD is unclear. OBJECTIVES: To evaluate the benefits and harms of vitamin D supplementation as a treatment for IBD. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was Jun 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people of all ages with active or inactive IBD comparing any dose of vitamin D with another dose of vitamin D, another intervention, placebo, or no intervention. We defined doses as: vitamin D (all doses), any-treatment-dose vitamin D (greater than 400 IU/day), high-treatment-dose vitamin D (greater than 1000 IU/day), low-treatment-dose vitamin D (400 IU/day to 1000 IU/day), and supplemental-dose vitamin D (less than 400 IU/day). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. clinical response for people with active disease, 2. clinical relapse for people in remission, 3. quality of life, and 4. withdrawals due to adverse events. Our secondary outcomes were 5. disease activity at end of study, 6. normalisation of vitamin D levels at end of study, and 7. total serious adverse events. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 22 RCTs with 1874 participants. Study duration ranged from four to 52 weeks. Ten studies enroled people with Crohn's disease (CD), five enroled people with ulcerative colitis (UC), and seven enroled people with CD and people with UC. Seventeen studies included adults, three included children, and two included both. Four studies enroled people with active disease, six enroled people in remission, and 12 enroled both. We assessed each study for risk of bias across seven individual domains. Five studies were at low risk of bias across all seven domains. Ten studies were at unclear risk of bias in at least one domain but with no areas of high risk of bias. Seven studies were at high risk of bias for blinding of participants and assessors. Vitamin D (all doses) versus placebo or no treatment Thirteen studies compared vitamin D against placebo or no treatment. We could not draw any conclusions on clinical response for UC as the certainty of the evidence was very low (risk ratio (RR) 4.00, 95% confidence interval (CI) 1.51 to 10.57; 1 study, 60 participants). There were no data on CD. There may be fewer clinical relapses for IBD when using vitamin D compared to placebo or no treatment (RR 0.57, 95% CI 0.34 to 0.96; 3 studies, 310 participants). The certainty of the evidence was low. We could not draw any conclusions on quality of life for IBD (standardised mean difference (SMD) -0.13, 95% CI -3.10 to 2.83 (the SMD value indicates a negligent decrease in quality of life, and the corresponding CIs indicate that the effect can range from a large decrease to a large increase in quality of life); 2 studies, 243 participants) or withdrawals due to adverse events for IBD (RR 1.97, 95% CI 0.18 to 21.27; 12 studies, 1251 participants; note 11 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 12). The certainty of the evidence was very low. High-treatment-dose vitamin D versus low-treatment-dose vitamin D Five studies compared high treatment vitamin D doses against low treatment vitamin D doses. There were no data on clinical response. There may be no difference in clinical relapse for CD (RR 0.48, 95% CI 0.23 to 1.01; 1 study, 34 participants). The certainty of the evidence was low. We could not draw any conclusions on withdrawals due to adverse events for IBD as the certainty of the evidence was very low (RR 0.89, 95% CI 0.06 to 13.08; 3 studies, 104 participants; note 2 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 3). The data on quality of life and disease activity could not be meta-analysed, were of very low certainty, and no conclusions could be drawn. Any-treatment-dose vitamin D versus supplemental-dose vitamin D Four studies compared treatment doses of vitamin D against supplemental doses. There were no data on clinical response and relapse. There were no data on quality of life that could be meta-analysed. We could not draw any conclusions on withdrawals due to adverse events for IBD as the certainty of the evidence was very low (RR 3.09, 95% CI 0.13 to 73.17; 4 studies, 233 participants; note 3 studies reported withdrawals but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 4). AUTHORS' CONCLUSIONS: There may be fewer clinical relapses when comparing vitamin D with placebo, but we cannot draw any conclusions on differences in clinical response, quality of life, or withdrawals, due to very low-certainty evidence. When comparing high and low doses of vitamin D, there were no data for clinical response, but there may be no difference in relapse for CD. We cannot draw conclusions on the other outcomes due to very low certainty evidence. Finally, comparing vitamin D (all doses) to supplemental-dose vitamin D, there were no data on clinical relapse or response, and we could not draw conclusions on other outcomes due to very low certainty evidence or missing data. It is difficult to make any clear recommendations for future research on the basis of the findings of this review. Future studies must be clear on the baseline populations, the purpose of vitamin D treatment, and, therefore, study an appropriate dosing strategy. Stakeholders in the field may wish to reach consensus on such issues prior to new studies.

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study.

BACKGROUND & AIMS: There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. METHODS: We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. RESULTS: We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P = .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). CONCLUSIONS: In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

Comparative Safety and Effectiveness of Biologic Therapy for Crohn's Disease: A CA-IBD Cohort Study.

BACKGROUND & AIMS: We compared the safety and effectiveness of tumor necrosis factor α (TNF-α) antagonists vs vedolizumab vs ustekinumab in patients with Crohn's disease (CD) in a multicenter cohort (CA-IBD). METHODS: We created an electronic health record-based cohort of adult patients with CD who were initiating a new biologic agent (TNF-α antagonists, ustekinumab, vedolizumab) from 5 health systems in California between 2010 and 2017. We compared the risk of serious infections (safety) and all-cause hospitalization and inflammatory bowel disease-related surgery (effectiveness) between different biologic classes using propensity score (PS) matching. RESULTS: As compared with TNF-α antagonists (n = 1030), 2:1 PS-matched, ustekinumab-treated patients with CD (n = 515) experienced a lower risk of serious infections (hazard ratio [HR], 0.36; 95% CI, 0.20-0.64), without any difference in the risk of hospitalization (HR, 0.99; 95% CI, 0.89-1.21) or surgery (HR, 1.08; 95% CI, 0.69-1.70). Compared with vedolizumab (n = 221), 1:1 PS-matched, ustekinumab-treated patients with CD (n = 221) experienced a lower risk of serious infections (HR, 0.20; 95% CI, 0.07-0.60), without significant differences in risk of hospitalization (HR, 0.76; 95% CI, 0.54-1.07) or surgery (HR, 1.42; 95% CI, 0.54-3.72). Compared with TNF-α antagonists (n = 442), 2:1 PS-matched, vedolizumab-treated patients with CD (n = 221) had a similar risk of serious infections (HR, 1.53; 95% CI, 0.84-2.78), hospitalization (HR, 1.32; 95% CI, 0.98-1.77), and surgery (HR, 0.63; 95% CI, 0.27-1.47). High comorbidity burden, concomitant opiate use, and prior hospitalization were associated with serious infections and hospitalization in biologic-treated patients with CD. CONCLUSION: In a multicenter cohort of biologic-treated patients with CD, ustekinumab was associated with a lower risk of serious infections compared with TNF-α antagonists and vedolizumab, without any differences in risk of hospitalization or surgery. The risk of serious infections was similar for TNF-α antagonists vs vedolizumab.

Optimizing the nutrition support care model: Analysis of survey data.

BACKGROUND: Malnutrition is underrecognized and underdiagnosed, despite high prevalence rates and associated poor clinical outcomes. The involvement of clinical nutrition experts, especially physicians, in the care of high-risk patients with malnutrition remains low despite evidence demonstrating lower complication rates with nutrition support team (NST) management. To facilitate solutions, a survey was designed to elucidate the nature of NSTs and physician involvement and identify needs for novel nutrition support care models. METHODS: This survey assessed demographics of NSTs, factors contributing to the success of NSTs, elements of nutrition education, and other barriers to professional growth. RESULTS: Of 255 respondents, 235 complete surveys were analyzed. The geographic distribution of respondents correlated with population concentrations of the United States (r = 90.8%, p < .0001). Most responding physicians (46/57; 80.7%) reported being a member of NSTs, compared with 56.5% (88/156) of dietitians. Of those not practicing in NSTs (N = 81/235, 34.4%), 12.3% (10/81) reported an NST was previously present at their institution but had been disbanded. Regarding NSTs, financial concerns were common (115/235; 48.9%), followed by leadership (72/235; 30.6%), and healthcare professional (HCP) interest (55/235; 23.4%). A majority (173/235; 73.6%) of all respondents wanted additional training in nutrition but reported insufficient protected time, ability to travel, or support from administrators or other HCPs. CONCLUSION: Core actions resulting from this survey focused on formalizing physician roles, increasing interdisciplinary nutrition support expertise, utilizing cost-effective screening for malnutrition, and implementing intervention protocols. Additional actions included increasing funding for clinical practice, education, and research, all within an expanded portfolio of pragmatic nutrition support care models.

Treatment-refractory ulcerative colitis responsive to indigo naturalis.

BACKGROUND: Indigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model. METHODS: This open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500 mg/day or 1.5 g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression. RESULTS: Ten of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN. CONCLUSION: IN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation. TRIAL REGISTRATION NUMBER: NCT02442960.

Fish Oil for Inflammatory Bowel Disease: Panacea or Placebo?

Dietary supplements have increasingly gained popularity over the years not only to replete micronutrient deficiencies but for their use in treatment of disease. The popularity of dietary supplements for inflammatory bowel diseases (IBD) arises from their perceived ease of use, potential disease-modifying benefits, and perceived safety. Overall, randomized controlled trials have not consistently shown a benefit of fish oil for the maintenance of remission with Crohn's disease. The inconsistency of these findings highlights the need for more studies that are powered to clarify the context in which omega-3 fatty acids might have a role in the treatment algorithm of IBD.

Declining Rates of Surgery for Inflammatory Bowel Disease in the Era of Biologic Therapy.

BACKGROUND: Medical therapy for inflammatory bowel disease (IBD) has markedly advanced since the introduction of biologic therapeutics, although surgery remains an important therapeutic strategy for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated how rates of bowel resection surgery and post-operative mortality for IBD have changed over the last decade in the era of biologic therapies. METHODS: The Nationwide Readmission Database (NRD) was queried for patients with IBD (based on ICD-9 and -10 diagnosis and procedure codes) who were hospitalized between 2010 and 2017. Longitudinal trends in bowel resection surgery, urgent surgery, and post-operative mortality were analyzed. RESULTS: During the 8-year period, a total of 1795,266 IBD-related hospitalizations (1,072,110 with CD and 723,156 with UC) were evaluated. There was an increase in the annual number of IBD patients hospitalized, but a statistically significant decrease in the proportion of IBD patients undergoing surgery, from 10 to 8.8% (p < 0.001) for CD and 7.7 to 7.5% (p < 0.001) for UC. From 2014 through 2017, the proportion of urgent surgeries remained stable around 25% (p = 0.16) for CD and decreased from 21 to 14% (p < 0.001) for UC. For CD, the rate of post-operative 30-day mortality varied between 1.2 and 1.6% and for UC decreased from 5.8 to 2.3% (p < 0.001). CONCLUSIONS: Analysis of a nationwide dataset from 2010 to 2017 determined that despite an increase in total admissions for IBD, a smaller proportion of hospitalized patients underwent surgery. A greater proportion of surgeries for UC were performed on an elective basis, and overall the rates of post-operative mortality for CD and UC decreased. The growth of biologic medical therapy during the study period highlights a probable contributing factor for the observed changes.

Probiotics for induction of remission in Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract, in which the pathogenesis is believed to be partly influenced by the gut microbiome. Probiotics can be used to manipulate the microbiome and have therefore been considered as a potential therapy for CD. There is some evidence that probiotics benefit other gastrointestinal conditions, such as irritable bowel syndrome and ulcerative colitis, but their efficacy in CD is unclear. This is the first update of a Cochrane Review previously published in 2008. OBJECTIVES: To assess the efficacy and safety of probiotics for the induction of remission in CD. SEARCH METHODS: The following electronic databases were searched: MEDLINE (from inception to 6 July 2020), Embase (from inception to 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane IBD Review Group Specialised Trials Register, World Health Organization (WHO) International Clinical Trials Registry, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared probiotics with placebo or any other non-probiotic intervention for the induction of remission in CD were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of included studies. The primary outcome was clinical remission. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes. MAIN RESULTS: There were two studies that met criteria for inclusion. One study from Germany had 11 adult participants with mild-to-moderate CD, who were treated with a one-week course of corticosteroids and antibiotics (ciprofloxacin 500 mg twice daily and metronidazole 250 mg three times a day), followed by randomised assignment to Lactobacillus rhamnosus strain GG (two billion colony-forming units per day) or corn starch placebo. The other study from the United Kingdom (UK) had 35 adult participants with active CD (CDAI score of 150 to 450) randomised to receive a synbiotic treatment (comprised of freeze-dried Bifidobacterium longum and a commercial product) or placebo. The overall risk of bias was low in one study, whereas the other study had unclear risk of bias in relation to random sequence generation, allocation concealment, and blinding. There was no evidence of a difference between the use of probiotics and placebo for the induction of remission in CD (RR 1.06; 95% CI 0.65 to 1.71; 2 studies, 46 participants) after six months. There was no difference in adverse events between probiotics and placebo (RR 2.55; 95% CI 0.11 to 58.60; 2 studies, 46 participants). The evidence for both outcomes was of very low certainty due to risk of bias and imprecision. AUTHORS' CONCLUSIONS: The available evidence is very uncertain about the efficacy or safety of probiotics, when compared with placebo, for induction of remission in Crohn's disease. There is a lack of well-designed RCTs in this area and further research is needed.

Stopping Mesalamine Therapy in Patients With Crohn's Disease Starting Biologic Therapy Does Not Increase Risk of Adverse Outcomes.

BACKGROUND & AIMS: Little is known about the effects of discontinuing mesalamine therapy for patients with Crohn's disease (CD) who initiate therapy with an anti-tumor necrosis factor (anti-TNF) agent. We analyzed data from 2 national population cohorts to compare outcomes of patients with CD already on mesalamine therapy who started treatment with an anti-TNF agent and then either stopped or continued mesalamine. METHODS: The primary outcome was any adverse clinical event, defined as a composite of new corticosteroid use or CD-related hospitalization or surgery. We collected data from the Truven MarketScan (IBM, Armonk, NY) health claims database in the United States and the Danish health registers. Our analysis included patients with CD who started anti-TNF therapy after at least 90 days of oral mesalamine therapy. Patients were classified as stopping mesalamine if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors, and health care utilization. Adjusted hazard ratios with 95% CIs were calculated, comparing stopping mesalamine with continuing mesalamine. RESULTS: A total of 3178 patients with CD were included in our final analysis (2960 in the United States and 218 in Denmark). Stopping mesalamine after initiating anti-TNF therapy was not associated with an increased risk of adverse clinical events in the US cohort (adjusted hazard ratio, 0.89; 95% CI, 0.77-1.03; P = .13) or in the Danish cohort (adjusted hazard ratio, 1.13; 95% CI, 0.68-1.87; P = .63). Similar results were obtained from sensitivity analyses of concomitant immunomodulator use and duration of mesalamine treatment before initiation of anti-TNF therapy. CONCLUSIONS: In a retrospective analysis of 2 national databases, we found that stopping mesalamine therapy for patients with CD who were starting anti-TNF therapy did not increase their risk of adverse clinical events. These results should be validated in a prospective study.

Dietary interventions for induction and maintenance of remission in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic mucosal inflammation, frequent hospitalizations, adverse health economics, and compromised quality of life. Diet has been hypothesised to influence IBD activity. OBJECTIVES: To evaluate the efficacy and safety of dietary interventions on IBD outcomes. SEARCH METHODS: We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, Clinicaltrials.gov and the WHO ICTRP from inception to 31 January 2019. We also scanned reference lists of included studies, relevant reviews and guidelines. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared the effects of dietary manipulations to other diets in participants with IBD. Studies that exclusively focused on enteral nutrition, oral nutrient supplementation, medical foods, probiotics, and parenteral nutrition were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, extracted data and assessed bias using the risk of bias tool. We conducted meta-analyses where possible using a random-effects model and calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We assessed the certainty of evidence using GRADE. MAIN RESULTS: The review included 18 RCTs with 1878 participants. The studies assessed different dietary interventions for active CD (six studies), inactive CD (seven studies), active UC (one study) and inactive UC (four studies). Dietary interventions involved either the consumption of low amounts or complete exclusion of one or more food groups known to trigger IBD symptoms. There was limited scope for data pooling as the interventions and control diets were diverse. The studies were mostly inadequately powered. Fourteen studies were rated as high risk of bias. The other studies were rated as unclear risk of bias.The effect of high fiber, low refined carbohydrates, low microparticle diet, low calcium diet, symptoms-guided diet and highly restricted organic diet on clinical remission in active CD is uncertain. At 4 weeks, remission was induced in: 100% (4/4) of participants in the low refined carbohydrates diet group compared to 0% (0/3) of participants in the control group (RR 7.20, 95% CI 0.53 to 97.83; 7 participants; 1 study; very low certainty evidence). At 16 weeks, 44% (23/52) of participants in the low microparticle diet achieved clinical remission compared to 25% (13/51) of control-group participants (RR 3.13, 95% CI 0.22 to 43.84; 103 participants; 2 studies; I² = 73%; very low certainty evidence). Fifty per cent (16/32) of participants in the symptoms-guided diet group achieved clinical remission compared to 0% (0/19) of control group participants (RR 20.00, 95% CI 1.27 to 315.40; 51 participants ; 1 study; very low certainty evidence) (follow-up unclear). At 24 weeks, 50% (4/8) of participants in the highly restricted organic diet achieved clinical remission compared to 50% (5/10) of participants in the control group (RR 1.00, 95% CI 0.39 to 2.53; 18 participants; 1 study; very low certainty evidence). At 16 weeks, 37% (16/43) participants following a low calcium diet achieved clinical remission compared to 30% (12/40) in the control group (RR 1.24, 95% CI 0.67 to 2.29; 83 participants; 1 study; very low certainty evidence).The effect of low refined carbohydrate diets, symptoms-guided diets and low red processed meat diets on relapse in inactive CD is uncertain. At 12 to 24 months, 67% (176/264) of participants in low refined carbohydrate diet relapsed compared to 64% (193/303) in the control group (RR 1.04, 95% CI 0.87 to 1.25; 567 participants; 3 studies; I² = 35%; low certainty evidence). At 6 to 24 months, 48% (24/50) of participants in the symptoms-guided diet group relapsed compared to 83% (40/48) participants in the control diet (RR 0.53, 95% CI 0.28 to 1.01; 98 participants ; 2 studies; I² = 54%; low certainty evidence). At 48 weeks, 66% (63/96) of participants in the low red and processed meat diet group relapsed compared to 63% (75/118) of the control group (RR 1.03, 95% CI 0.85 to 1.26; 214 participants; 1 study; low certainty evidence). At 12 months, 0% (0/16) of participants on an exclusion diet comprised of low disaccharides / grains / saturated fats / red and processed meat experienced clinical relapse compared to 26% (10/38) of participants on a control group (RR 0.11, 95% CI 0.01 to 1.76; 54 participants; 1 study; very low certainty evidence).The effect of a symptoms-guided diet on clinical remission in active UC is uncertain. At six weeks, 36% (4/11) of symptoms-guided diet participants achieved remission compared to 0% (0/10) of usual diet participants (RR 8.25, 95% CI 0.50 to 136.33; 21 participants; 1 study; very low certainty evidence).The effect of the Alberta-based anti-inflammatory diet, the Carrageenan-free diet or milk-free diet on relapse rates in inactive UC is uncertain. At 6 months, 36% (5/14) of participants in the Alberta-based anti-inflammatory diet group relapsed compared to 29% (4/14) of participants in the control group (RR 1.25, 95% CI 0.42 to 3.70; 28 participants; 1 study; very low certainty evidence). Thirty per cent (3/10) of participants following the carrageenan-free diet for 12 months relapsed compared to 60% (3/5) of the participants in the control group (RR 0.50, 95% CI 0.15 to 1.64; 15 participants; 1 study; very low certainty evidence). At 12 months, 59% (23/39) of milk free diet participants relapsed compared to 68% (26/38) of control diet participants (RR 0.83, 95% CI 0.60 to 1.15; 77 participants; 2 studies; I² = 0%; low certainty evidence).None of the included studies reported on diet-related adverse events. AUTHORS' CONCLUSIONS: The effects of dietary interventions on CD and UC are uncertain. Thus no firm conclusions regarding the benefits and harms of dietary interventions in CD and UC can be drawn. There is need for consensus on the composition of dietary interventions in IBD and more RCTs are required to evaluate these interventions. Currently, there are at least five ongoing studies (estimated enrollment of 498 participants). This review will be updated when the results of these studies are available.

Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts.

OBJECTIVE: The benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA. DESIGN: Our primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA. RESULTS: A total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF. CONCLUSION: In two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.

Fad Diets: Hype or Hope?

PURPOSE OF REVIEW: Obesity continues to be a growing concern globally due to association with a number of comorbidities and contributing significantly to increase in health care expenditures. Despite availability of a number of treatment modalities, lifestyle modification with dietary modification and exercise continues to be the foundation. However, the standard model of lifestyle modification is not efficacious or sustainable for many patients leading them to seek alternative approaches. We conducted a comprehensive literature review to present the data regarding efficacy and sustainability of many common dietary approaches. RECENT FINDINGS: Building upon previous work, recent randomized controlled trials have compared many popular diets head to head in varying patient populations. Along with the weight changes, studies have investigated the changes in metabolic parameters, inflammatory markers, and cardiac risk factor reduction. Though the studies do not show superiority of one diet compared to the other, the preventive benefits and other favorable metabolic changes of the diets make them worthy of consideration.

Nutritional Interventions in the Patient with Inflammatory Bowel Disease.

Nutritional strategies have been explored as primary or adjunct therapies for inflammatory bowel disease (IBD). Exclusive enteral nutrition is effective for the induction of remission in Crohn disease and is recommended as a first-line therapy for children. Dietary strategies focus on adjusting the ratio of consumed nutrients that are proinflammatory or antiinflammatory. Treatments with dietary supplements focus on the antiinflammatory effects of the individual supplements (eg, curcumin, omega-3 fatty acids, vitamin D) or their positive effects on the intestinal microbiome (eg, prebiotics, probiotics). This article discusses the role of diets and dietary supplements in the treatment of IBD.

Treatment With Biologic Agents Has Not Reduced Surgeries Among Patients With Crohn's Disease With Short Bowel Syndrome.

BACKGROUND & AIMS: Little is known about the effects of biologic agents used to treat Crohn's disease (CD) on its long-term complications, such as short bowel syndrome and intestinal failure (SBS-IF). We evaluated trends in small bowel resections and health care utilization among patients with CD with and without SBS-IF. METHODS: We collected data on the National Inpatient Sample on 2,989,185 patients hospitalized with CD in the United States before the time period in which CD was treated with biologic agents (1993-1997) and after biologic therapy became widespread (1998-2014). We used Poisson and linear regression analyses to evaluate trends for small bowel resections and health care utilization among patients with CD with and without SBS-IF. Multivariable models were adjusted for age, sex, Charlson-Deyo comorbidity index, payer source, hospital size, region, and teaching status. RESULTS: The proportions of patients who underwent resection did not significantly change during the period before biologic therapy (121.8 per 1000 hospitalizations in 1993 to 110.1 per 1000 hospitalizations in 1997; P trend =.14) but decreased significantly during the period after biologic therapy began (99.0 per 1000 hospitalizations in 1998 to 64.6 per 1000 hospitalizations in 2014; P trend < .01). However, among patients with SBS-IF, similar proportions of patients underwent resection during the period before biologic therapy (0.7 per 1000 hospitalizations in 1993 to 0.7 per 1000 hospitalizations in 1997; P trend = .92) and during the period after biologic therapy (0.6 per 1000 hospitalizations in 1998 to 0.7 per 1000 hospitalizations in 2014; P trend = .06). Rates of hospitalization for patients with SBS-IF increased from 16.5 per 1000 hospitalizations in 1998 to 19.5 per 1000 hospitalizations in 2014 (P trend < .01). SBS-IF hospitalizations were associated with longer lengths of stay (P < .01) and greater total charges (P < .01). CONCLUSIONS: In a study of the United States population, we found that the use of biologic agents to treat CD reduced the proportion of patients undergoing resection, but not among patients with SBS-IF. These findings indicate that biologic agents reduce some but not all features of CD. Studies are needed to identify patients at risk for SBS-IF, prevent and treat this complication, and identify new treatments.

Dietary Supplement Therapies for Inflammatory Bowel Disease: Crohn's Disease and Ulcerative Colitis.

Inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease are chronic relapsing and remitting chronic diseases for which there is no cure. The treatment of IBD frequently requires immunosuppressive and biologic therapies which carry an increased risk of infections and possible malignancy. There is a continued search for safer and more natural therapies in the treatment of IBD. This review aims to summarize the most current literature on the use of dietary supplements for the treatment of IBD. Specifically, the efficacy and adverse effects of vitamin D, fish oil, probiotics, prebiotics, curcumin, Boswellia serrata, aloe vera and cannabis sativa are reviewed.