AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases.

BACKGROUND & AIMS: Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome. METHODS: The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials. CONCLUSIONS: Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.

Genetic and transcriptomic landscape of colonic diverticulosis.

OBJECTIVE: Colonic diverticulosis is a prevalent condition among older adults, marked by the presence of thin-walled pockets in the colon wall that can become inflamed, infected, haemorrhage or rupture. We present a case-control genetic and transcriptomic study aimed at identifying the genetic and cellular determinants underlying this condition and the relationship with other gastrointestinal disorders. DESIGN: We conducted DNA and RNA sequencing on colonic tissue from 404 patients with (N=172) and without (N=232) diverticulosis. We investigated variation in the transcriptome associated with diverticulosis and further integrated this variation with single-cell RNA-seq data from the human intestine. We also integrated our expression quantitative trait loci with genome-wide association study using Mendelian randomisation (MR). Furthermore, a Polygenic Risk Score analysis gauged associations between diverticulosis severity and other gastrointestinal disorders. RESULTS: We discerned 38 genes with differential expression and 17 with varied transcript usage linked to diverticulosis, indicating tissue remodelling as a primary diverticula formation mechanism. Diverticula formation was primarily linked to stromal and epithelial cells in the colon including endothelial cells, myofibroblasts, fibroblasts, goblet, tuft, enterocytes, neurons and glia. MR highlighted five genes including CCN3, CRISPLD2, ENTPD7, PHGR1 and TNFSF13, with potential causal effects on diverticulosis. Notably, ENTPD7 upregulation was confirmed in diverticulosis cases. Additionally, diverticulosis severity was positively correlated with genetic predisposition to diverticulitis. CONCLUSION: Our results suggest that tissue remodelling is a primary mechanism for diverticula formation. Individuals with an increased genetic proclivity to diverticulitis exhibit a larger numbers of diverticula on colonoscopy.

Update on the Epidemiology and Management of Microscopic Colitis.

Microscopic colitis is an inflammatory bowel disease that commonly presents with debilitating chronic watery diarrhea. Recent epidemiologic studies and randomized trials of therapeutics have improved the understanding of the disease. Medications, such as nonsteroidal anti-inflammatories, proton pump inhibitors, and antidepressants, have traditionally been considered as the main risk factors for microscopic colitis. However, recent studies have challenged this observation. Additionally, several epidemiologic studies have identified other risk factors for the disease including older age, female sex, smoking, alcohol use, immune-mediated diseases, and select gastrointestinal infections. The diagnosis of microscopic colitis requires histologic assessment of colon biopsies with findings including increased in intraepithelial lymphocytes with or without expansion of the subepithelial collagen band. The pathophysiology is poorly understood but is thought to be related to an aberrant immune response to the luminal microenvironment in genetically susceptible individuals. Antidiarrheal medications, such as loperamide or bismuth subsalicylate, may be sufficient in patients with mild symptoms. In patients with more severe symptoms, treatment with budesonide is recommended. Maintenance therapy is often necessary and several potential treatment strategies are available. Biologic and small molecule treatments seem to be effective in patients who have failed budesonide. There is an unmet need to further define the pathophysiology of microscopic colitis. Additionally, trials with novel therapies, particularly in patients with budesonide-refractory disease, are needed.

Follow-Up Colonoscopy for Detection of Missed Colorectal Cancer After Diverticulitis.

BACKGROUND & AIMS: Colonoscopy often is recommended after an episode of diverticulitis to exclude missed colorectal cancer (CRC). This is a controversial recommendation based on limited evidence. We estimated the prevalence and odds of CRC and advanced colorectal neoplasia on colonoscopy in patients with diverticulitis compared with CRC screening. METHODS: Using data from the Gastrointestinal Quality Improvement Consortium registry, we performed a cross-sectional study with patients ≥40 years old undergoing outpatient colonoscopy for an indication of diverticulitis follow-up evaluation or CRC screening. The primary outcome was CRC. The secondary outcome was advanced colorectal neoplasia. Odds ratios (ORs) and 95% CIs were calculated. RESULTS: We identified 4,591,921 outpatient colonoscopies performed for screening and 91,993 colonoscopies for diverticulitis follow-up evaluation. CRC prevalence was 0.33% in colonoscopies for screening and 0.31% in colonoscopies for diverticulitis. Compared with screening, patients with diverticulitis were less likely to have CRC (adjusted OR, 0.84; 95% CI, 0.74-0.94). CRC prevalence decreased to 0.17% in colonoscopies performed for diverticulitis only. Compared with screening, patients with diverticulitis as the only indication were less likely to have CRC (adjusted OR, 0.49; 95% CI, 0.36-0.68). CRC prevalence increased to 1.43% in patients with complicated diverticulitis. Compared with screening, patients with complicated diverticulitis were more likely to have CRC (adjusted OR, 3.57; 95% CI, 1.59-8.01). CONCLUSIONS: The risk of CRC cancer is low in most patients with diverticulitis. Patients with complicated diverticulitis are the exception. Our results suggest that colonoscopy to detect missed CRC should include diverticulitis patients with a complication and those not current with CRC screening.

Inverse Probability Weighting to Estimate Exposure Effects on the Burden of Recurrent Outcomes in the Presence of Competing Events.

Recurrent events-outcomes that an individual can experience repeatedly over the course of follow-up-are common in epidemiologic and health services research. Studies involving recurrent events often focus on time to first occurrence or on event rates, which assume constant hazards over time. In this paper, we contextualize recurrent event parameters of interest using counterfactual theory in a causal inference framework and describe an approach for estimating a target parameter referred to as the mean cumulative count. This approach leverages inverse probability weights to control measured confounding with an existing (and underutilized) nonparametric estimator of recurrent event burden first proposed by Dong et al. in 2015. We use simulations to demonstrate the unbiased estimation of the mean cumulative count using the weighted Dong-Yasui estimator in a variety of scenarios. The weighted Dong-Yasui estimator for the mean cumulative count allows researchers to use observational data to flexibly estimate and contrast the expected number of cumulative events experienced per individual by a given time point under different exposure regimens. We provide code to ease application of this method.

Diverticulosis Is Associated With Internal Hemorrhoids on Colonoscopy: Possible Clues to Etiology.

Hemorrhoids are a common but poorly understood gastrointestinal condition.1 Bowel habits and fiber consumption are frequently cited as risk factors for hemorrhoids, but research has been inconclusive.2 Recent genome-wide association studies (GWAS) have suggested an association between diverticular disease and hemorrhoids.3 We sought to investigate the association between colonic diverticulosis and internal hemorrhoids to validate the prediction from the GWAS.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021.

BACKGROUND & AIMS: Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States. METHODS: We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids' Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH). RESULTS: Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020. CONCLUSIONS: Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.

Alpha-Gal Sensitization in a US Screening Population Is Not Associated With a Decreased Meat Intake or Gastrointestinal Symptoms.

INTRODUCTION: Patients with alpha-gal syndrome, a delayed reaction to mammalian meat, can present with isolated gastrointestinal (GI) symptoms. We aimed to estimate the frequency of alpha-gal sensitization in a Southeastern US population and determine the association between sensitization and mammalian product dietary intake or GI symptoms. METHODS: We performed a cross-sectional study of participants who underwent a screening colonoscopy at our center between 2013 and 2015. We quantified serum alpha-gal immunoglobulin E antibodies in participants who were prospectively enrolled at screening colonoscopy and compared diet intake and lower GI symptoms reported in standardized questionnaires among those with elevated versus no alpha-gal IgE antibodies. RESULTS: Alpha-gal IgE antibodies were common-31.4% of screening colonoscopy participants (127 of 404) had elevated serum alpha-gal IgE >0.1 kU/L. Alpha-gal-sensitized participants endorsed similar rates of abdominal pain compared with those without alpha-gal antibodies (33% vs 38%, adjusted odds ratio 0.9, 95% confidence interval 0.7-1.3). Mammalian meat consumption did not differ based on alpha-gal sensitization status (average 1.43 servings/d in sensitized subjects vs 1.50 in alpha-gal IgE-negative subjects, P = 0.9). Alpha-gal-sensitized participants with levels ≥10 (n = 21) were overrepresented in the lowest quartiles of mammalian meat consumption, but not among those with GI symptoms in general. Participants with high alpha-gal antibody levels >2 kU/L (n = 45) or ≥10 U/L (n = 21) did not have a reduced mean daily mammalian meat intake compared with seronegative people. DISCUSSION: Elevated alpha-gal IgE antibodies were common and not associated with a reduced mammalian meat intake, abdominal pain, or diarrhea. Seropositivity did not predict symptomatic alpha-gal sensitization in this general screening population. Other host factors likely contribute to the phenotypic expression of alpha-gal syndrome.

Gastrointestinal outcomes among older women with endometrial cancer.

OBJECTIVE: Treatment for endometrial cancer may contribute to bowel dysfunction and other gastrointestinal outcomes. We investigated the risk of several gastrointestinal diagnoses among older women with endometrial cancer and matched women without a history of cancer. METHODS: Women aged 66 years and older diagnosed with endometrial cancer during 2004-2017 (N = 44,386) and matched women without a known cancer history (N = 221,219) were identified in the SEER-Medicare linked data. An index date was defined as the endometrial cancer diagnosis date in that matched set. ICD-9 and -10 diagnosis codes were used to define gastrointestinal outcomes, including constipation, abdominal pain, IBS, fecal incontinence, bowel obstruction, ileus, radiation enteritis or proctitis, colonic stricture, and vascular insufficiency of the bowel in the Medicare claims. Hazard ratios (HRs) for incident gastrointestinal diagnoses were estimated using multivariable Cox proportional hazards regression models. RESULTS: Compared to women without cancer, women with endometrial cancer had an increased risk of gastrointestinal symptoms after the index date, including constipation (HR = 2.27; 95% CI: 2.22-2.32), abdominal pain (HR = 2.94; 95% CI: 2.89-2.99), and fecal incontinence (HR = 1.96; 95% CI: 1.83-2.10). The risk of other gastrointestinal diagnoses was also higher among women with endometrial cancer (e.g., bowel obstruction: HR = 5.72; 95% CI: 5.47-5.98; ileus: HR = 7.22; 95% CI: 6.89-7.57). These associations were also apparent in sensitivity analyses limited to 1+ and 5+ years after the index date. CONCLUSIONS: Older women with endometrial cancer experience an excess risk of gastrointestinal diagnoses that may persist long after cancer diagnosis. Surveillance for these conditions may be a critical part of survivorship care.

AGA Clinical Practice Update on Medical Management of Colonic Diverticulitis: Expert Review.

Colonic diverticulitis is a painful gastrointestinal disease that recurs unpredictably and can lead to chronic gastrointestinal symptoms. Gastroenterologists commonly care for patients with this disease. The purpose of this Clinical Practice Update is to provide practical and evidence-based advice for management of diverticulitis. We reviewed systematic reviews, meta-analyses, randomized controlled trials, and observational studies to develop 14 best practices. In brief, computed tomography is often necessary to make a diagnosis. Rarely, a colon malignancy is misdiagnosed as diverticulitis. Whether patients should have a colonoscopy after an episode of diverticulitis depends on the patient's history, most recent colonoscopy, and disease severity and course. In patients with a history of diverticulitis and chronic symptoms, alternative diagnoses should be excluded with both imaging and lower endoscopy. Antibiotic treatment can be used selectively rather than routinely in immunocompetent patients with mild acute uncomplicated diverticulitis. Antibiotic treatment is strongly advised in immunocompromised patients. To reduce the risk of recurrence, patients should consume a high-quality diet, have a normal body mass index, be physically active, not smoke, and avoid nonsteroidal anti-inflammatory drug use except aspirin prescribed for secondary prevention of cardiovascular disease. At the same time, patients should understand that genetic factors also contribute to diverticulitis risk. Patients should be educated that the risk of complicated diverticulitis is highest with the first presentation. An elective segmental resection should not be advised based on the number of episodes. Instead, a discussion of elective segmental resection should be personalized to consider severity of disease, patient preferences and values, as well as risks and benefits.

Alcohol-Associated Liver Disease Mortality Increased From 2017 to 2020 and Accelerated During the COVID-19 Pandemic.

Alcohol consumption has risen substantially in the United States in the past 2 decades.1,2 Alcohol-associated liver disease (ALD) represents a greater inpatient financial burden than all other etiologies of cirrhosis combined3 and is now the leading indication for liver transplantation.4 A recent study reported that ALD mortality increased between 2006 and 2017.5 Since 2017, alcohol consumption has continued to rise, and more significantly during the COVID-19 pandemic.2 The aim of this research letter is to provide the most updated trends in ALD-related mortality in the United States and to quantify the rate of change of ALD-related mortality over time.

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies.

BACKGROUND: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. OBJECTIVE: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. DESIGN: Active-comparator, new-user, retrospective cohort studies. SETTING: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). PARTICIPANTS: Immunocompetent adults with diverticulitis in the outpatient setting. INTERVENTION: Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. MEASUREMENTS: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. RESULTS: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). LIMITATION: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. CONCLUSION: Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. PRIMARY FUNDING SOURCE: National Institutes of Health.

Sex and Race Disparities in Diverticulosis Prevalence.

BACKGROUND & AIMS: The prevalence of diverticulosis differs with demographic features of patients, but evidence is limited. Well-defined demographic studies are necessary to understand diverticulosis biology. We estimated the prevalence of diverticulosis among patients of different ages, sexes, and races and ethnicities and calculated odds ratios. DESIGN: Using data from an endoscopic database, we identified 271,181 colonoscopy procedures performed from 2000 through 2012 at 107 sites in the United States. Our analysis included individuals 40 years and older who underwent colonoscopy examination for average-risk screening. The outcome was any reported diverticulosis on colonoscopy. Multivariate analyses were performed using logistic regression to estimate odds ratios (ORs) and 95% CI values, adjusting for confounding variables. RESULTS: The prevalence of diverticulosis increased with age in men and women of all races and ethnicities. Women 40-49 years old had significantly lower odds of any diverticulosis (OR, 0.71; 95% CI, 0.63-0.80) compared with men 40-49 years old, after adjustment. The strength of this association decreased with age. Compared with non-Hispanic white individuals, non-Hispanic black individuals (OR, 0.80; 95% CI, 0.77-0.83) and Asian/Pacific Islanders (OR, 0.38; 95% CI, 0.35-0.41) had lower odds of any diverticulosis. However, non-Hispanic black individuals (OR, 1.53, 95% CI, 1.44-1.62) had increased odds of any proximal diverticulosis, whereas Asian/Pacific Islanders (OR, 3.12; 95% CI, 2.67-3.66) had increased odds of only proximal diverticulosis. CONCLUSIONS: In an analysis of data from 271,181 colonoscopy procedures, diverticulosis was less prevalent in women compared with men in the same age groups, indicating that sex hormones might affect pathogenesis. Differences in the odds of diverticulosis by race and ethnicity indicate a genetic contribution to risk.

Association of Obesity With Colonic Diverticulosis in Women.

BACKGROUND & AIMS: Obesity has been associated with an increased risk of colonic diverticulosis. Evidence for this association is limited. We assessed whether anthropometric measures of obesity were associated with colonic diverticulosis. METHODS: We analyzed data from a prospective study of 623 patients undergoing screening colonoscopies from 2013 through 2015; colonoscopies included examinations for diverticulosis. Body measurements were made the day of the procedure. Multivariate analyses were performed using modified Poisson regression to estimate prevalence ratios (PRs) and 95% CIs while adjusting for confounding variables. All analyses were stratified by sex. RESULTS: Among men, there was no association between any measure of obesity and diverticulosis. After adjustment, women with an obese body mass index (BMI ≥ 30) had an increased risk of any diverticulosis (PR, 1.48; 95% CI, 1.08-2.04) compared with women with a normal body mass index (BMI 18.5-24.9). The strength of this association was greater for more than 5 diverticula (PR, 2.05; 95% CI, 1.23-3.40). There was no significant association between measures of central obesity and diverticulosis in women. Stratified by sex, colonic diverticulosis was significantly less prevalent in women compared with men before the age of 51 years (29% vs 45%, P = .06). The prevalence of diverticulosis did not differ by sex in older age groups. CONCLUSIONS: In an analysis of data from 623 patients undergoing screening colonoscopies, we found that obesity (BMI ≥30) significantly increased the risk of colonic diverticulosis in women but not men. Colonic diverticulosis was less prevalent in premenopausal-age women compared with similar-age men. These findings suggest that sex hormones may influence the development of diverticulosis.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018.

BACKGROUND & AIMS: Estimates of disease burden can inform national health priorities for research, clinical care, and policy. We aimed to estimate health care use and spending among gastrointestinal (GI) (including luminal, liver, and pancreatic) diseases in the United States. METHODS: We estimated health care use and spending based on the most currently available administrative claims from commercial and Medicare Supplemental plans, data from the GI Quality Improvement Consortium Registry, and national databases. RESULTS: In 2015, annual health care expenditures for gastrointestinal diseases totaled $135.9 billion. Hepatitis ($23.3 billion), esophageal disorders ($18.1 billion), biliary tract disease ($10.3 billion), abdominal pain ($10.2 billion), and inflammatory bowel disease ($7.2 billion) were the most expensive. Yearly, there were more than 54.4 million ambulatory visits with a primary diagnosis for a GI disease, 3.0 million hospital admissions, and 540,500 all-cause 30-day readmissions. There were 266,600 new cases of GI cancers diagnosed and 144,300 cancer deaths. Each year, there were 97,700 deaths from non-malignant GI diseases. An estimated 11.0 million colonoscopies, 6.1 million upper endoscopies, 313,000 flexible sigmoidoscopies, 178,400 upper endoscopic ultrasound examinations, and 169,500 endoscopic retrograde cholangiopancreatography procedures were performed annually. Among average-risk persons aged 50-75 years who underwent colonoscopy, 34.6% had 1 or more adenomatous polyps, 4.7% had 1 or more advanced adenomatous polyps, and 5.7% had 1 or more serrated polyps removed. CONCLUSIONS: GI diseases contribute substantially to health care use in the United States. Total expenditures for GI diseases are $135.9 billion annually-greater than for other common diseases. Expenditures are likely to continue increasing.

Rising Mortality From Alcohol-Associated Liver Disease in the United States in the 21st Century.

OBJECTIVES: In contrast with other developed nations, life expectancy is decreasing in the United States, in part due to increasing mortality from alcohol-associated liver disease (ALD). Up-to-date estimates of ALD mortality are necessary for setting public health priorities to reverse this concerning trend. We therefore aimed to assess current (2017) estimates of ALD mortality and temporal trends from 1999 to 2017. METHODS: Using national data from the Centers for Disease Control and Prevention, we analyzed stratified ALD mortality rates between 1999 and 2017. We determined the age-adjusted death rates, stratified by sex and categorized by age, race/ethnicity, urbanization, and census region. We also identified statistically significant changes in the annual rate difference (ARD), annual percentage change (APC), and average APC in ALD mortality. RESULTS: In 2017, mortality from ALD was higher than any other year since 1999 with age-adjusted rates of 13.1 per 100,000 (95% confidence interval [CI] 12.9-13.3) in men and 5.6 per 100,000 (95% CI 5.4-5.7) in women. Mortality was highest among men and women who were middle aged, Native American, and from rural areas. Since 2006, ALD mortality has increased in almost every age group and race with the exception of non-Hispanic black men. Absolute increases in mortality rates have been particularly pronounced in Native American women (2005-2017 ARD 0.8, 95% CI 0.6-0.9), non-Hispanic/white men (2006-2017 ARD 0.4, 95% CI 0.3-0.4), and non-Hispanic/white women (2013-2017 ARD 0.4, 95% CI 0.3-0.5). DISCUSSION: Mortality from ALD is increasing over time in most demographic groups. Increased effort is needed to develop targeted public health strategies to address high and increasing ALD mortality.

Practice patterns and adherence to clinical guidelines for diagnosis and management of eosinophilic esophagitis among gastroenterologists.

Real-world practice patterns of eosinophilic esophagitis (EoE) among gastroenterologists are not well-described. The aim is to describe practice patterns of EoE diagnosis and management and assess concordance with consensus guidelines. We conducted a cross-sectional online survey of gastroenterologists in the USA using Qualtrics, which was dispersed through the North Carolina Society of Gastroenterology (NCSG) and the American College of Gastroenterology member listservs. A similar survey was sent to NCSG members in 2010 and responses were compared in a subanalysis. Of 240 respondents, 37% (n = 80) worked in an academic setting versus 63% (n = 138) community practice setting. Providers saw a median of 18 (interquartile range 2-100) EoE patients annually and 24% (n = 52) were 'very familiar' with EoE guidelines. A proton-pump inhibitor (PPI) trial was required by 37% of providers prior to EoE diagnosis. In total, 60% used a ≥15 eosinophils per high-power field cut point for diagnosis and 62% biopsied from the proximal and distal esophagus on initial exam. Only 12% (n = 28) followed EoE diagnosis guidelines. For first-line treatment, 7% used dietary therapy, 32% topical steroids, and 61% used PPIs; 67% used fluticasone as first-line steroid; 41% used maintenance steroid treatment in responders. In the NCSG cohort, a higher proportion in 2017 followed guideline diagnosis recommendations compared with 2010 (14% vs. 3%; P = 0.03) and a higher proportion used dietary therapy as first-line treatment (13% vs. 3%; P = 0.046). There is variability in EoE practice patterns for EoE management, with management differing markedly from consensus guidelines. Further education and guideline dissemination are needed to standardize practice.

Decreased Tenofovir Diphosphate Concentrations in a Transgender Female Cohort: Implications for Human Immunodeficiency Virus Preexposure Prophylaxis.

Feminizing hormone therapy (FHT) may interact with human immunodeficiency virus preexposure prophylaxis (PrEP). We found that transgender women who took FHT exhibited a 7-fold lower rectal tissue ratio of PrEP's active metabolites vs competing deoxynucleotides compared to cisgender women and men (P = .03) that inversely correlated with estradiol (ρ = -0.79; P < .05). Thus, FHT may negatively impact PrEP efficacy. Clinical Trials Registration . NCT02983110.

Rethinking What We Know About Hemorrhoids.

Although hemorrhoids are responsible for considerable economic cost and personal suffering, they have received surprisingly little research attention. In the United States, hemorrhoids are the third most common outpatient gastrointestinal diagnosis with nearly 4 million office and emergency department visits annually. The etiology of hemorrhoids is speculative. A low-fiber diet and constipation have historically been thought to increase the risk for hemorrhoids, but not proven. Symptoms commonly attributed to hemorrhoids include bleeding, pain, pruritus, fecal seepage, prolapse, and mucus discharge. Research has found that these symptoms were equally reported by patients with and without hemorrhoids. Medical therapies for hemorrhoids have not been formally studied except for fiber where the results have been inconsistent. A number of office-based interventions such as rubber band ligation and infrared coagulation are widely used and economically favorable for practitioners. Surgical procedures are effective at eliminating hemorrhoids but may be painful. Given the burden of disease and numerous gaps in our understanding, the time has come for targeted research to understand the cause, symptoms, and best treatment for patients with symptomatic hemorrhoids.

Increasing Rates of Surgery for Patients With Nonmalignant Colorectal Polyps in the United States.

BACKGROUND & AIMS: Despite the availability of endoscopic therapy, many patients in the United States undergo surgical resection for nonmalignant colorectal polyps. We aimed to quantify and examine trends in the use of surgery for nonmalignant colorectal polyps in a nationally representative sample. METHODS: We analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample for 2000 through 2014. We included all adult patients who underwent elective colectomy or proctectomy and had a diagnosis of either nonmalignant colorectal polyp or colorectal cancer. We compared trends in surgery for nonmalignant colorectal polyps with surgery for colorectal cancer and calculated age, sex, race, region, and teaching status/bed-size-specific incidence rates of surgery for nonmalignant colorectal polyps. RESULTS: From 2000 through 2014, there were 1,230,458 surgeries for nonmalignant colorectal polyps and colorectal cancer in the United States. Among those surgeries, 25% were performed for nonmalignant colorectal polyps. The incidence of surgery for nonmalignant colorectal polyps has increased significantly, from 5.9 in 2000 to 9.4 in 2014 per 100,000 adults (incidence rate difference, 3.56; 95% confidence interval 3.40-3.72), while the incidence of surgery for colorectal cancer has significantly decreased, from 31.5 to 24.7 surgeries per 100,000 adults (incidence rate difference, -6.80; 95% confidence interval -7.11 to -6.49). The incidence of surgery for nonmalignant colorectal polyps has been increasing among individuals age 20 to 79, in men and women and including all races and ethnicities. CONCLUSIONS: In an analysis of a large, nationally representative sample, we found that surgery for nonmalignant colorectal polyps is common and has significantly increased over the past 14 years.