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Importance: Decisions about whether to stop colorectal cancer (CRC) screening tests in older adults can be difficult and may benefit from shared decision-making (SDM)., Objective: To evaluate the effect of physician training in SDM and electronic previsit reminders (intervention) vs reminders only (comparator) on receipt of the patient-preferred approach to CRC screening and on overall CRC screening rates of older adults at 12 months., Design, Setting, and Participants: This was a secondary analysis of the Promoting Informed Decisions About Colorectal Cancer Screening in Older Adults (PRIMED) cluster randomized clinical trial. In the PRIMED trial, primary care physicians (PCPs) from 36 primary care practices in Massachusetts and Maine were enrolled between May 1 and August 30, 2019, and were randomized to the intervention group or the comparator group. Patients aged 76 to 85 years who were overdue for CRC screening and did not have a prior diagnosis of CRC enrolled between October 21, 2019, and April 8, 2021. Data analysis was performed between May 24, 2022, and May 10, 2023., Interventions: Primary care physicians in the intervention group completed an SDM training course and received previsit reminders of patients eligible for CRC testing discussion, whereas PCPs in the comparator group received reminders only., Main Outcomes and Measures: The primary outcome was concordance, or the percentage of patients who received their preferred screening approach. Postvisit surveys were administered to assess patient preference for testing, and electronic health record review was used to assess CRC testing at 12 months. Heterogeneity of treatment effect analyses examined interaction between study groups and different factors on concordance rates., Results: This study included 59 physicians and 466 older adults. Physicians had a mean (SD) age of 52.7 (9.4) years and a mean (SD) of 21.6 (10.2) years in practice; 30 (50.8%) were women and 16 (27.1%) reported prior training in SDM. Patients had a mean (SD) age of 80.3 (2.8) years; 249 (53.4%) were women and 238 (51.1%) reported excellent or very good overall health. Patients preferred stool-based tests (161 [34.5%]), followed by colonoscopy (116 [24.8%]) or no further screening (97 [20.8%]); 75 (16.1%) were not sure. The distribution of patient preferences was similar across groups (P = .36). At 12 months, test uptake was also similar for both the intervention group (29 [12.3%] for colonoscopy, 62 [26.3%] for stool-based tests, and 145 [61.4%] for no testing) and the comparator group (32 [13.9%] for colonoscopy, 35 [15.2%] for stool-based tests, and 163 [70.9%] for no testing; P = .08). Approximately half of patients in the intervention group received their preferred approach vs the comparator group (115 of 226 [50.9%] vs 103 of 223 [46.2%]; P = .47). Heterogeneity of treatment effect analyses found significantly higher rates with the intervention vs the comparator for patients with a strong intention to follow through with the preferred approach (adjusted odds ratio [AOR], 1.79 [95% CI, 1.11-2.89]; P = .02, P = .05 for interaction) and for patients who reported more than 5 minutes (AOR, 3.27 [95% CI, 1.25-8.59]; P = .02, P = .05 for interaction) of discussion with their PCP regarding screening. Higher rates were also observed among patients who reported 2 to 5 minutes of discussion with their PCP, although this finding was not significant (AOR, 1.89 [95% CI, 0.93-3.84]; P = .08, P = .05 for interaction)., Conclusions and Relevance: In this secondary analysis of a cluster randomized clinical trial, approximately half of older patients received their preferred approach to CRC screening. Physician training in SDM did not result in higher concordance rates overall but may have benefitted some subgroups. Future work to refine and evaluate clinical decision support (in the form of an electronic advisory or reminder) as well as focused SDM skills training for PCPs may promote high-quality, preference-concordant decisions about CRC testing for older adults., Trial Registration: ClinicalTrials.gov Identifier: NCT03959696.

Recent literature reports highlight the importance of the renal outer medullary potassium (ROMK) channel in renal sodium and potassium homeostasis and emphasize the potential impact that ROMK inhibitors could have as a novel mechanism diuretic in heart failure patients. A series of piperazine-based ROMK inhibitors were designed and optimized to achieve excellent ROMK potency, hERG selectivity, and ADME properties, which led to the identification of compound 28 (BMS-986308). BMS-986308 demonstrated efficacy in the volume-loaded rat diuresis model as well as promising in vitro and in vivo profiles and was therefore advanced to clinical development.

Objective: Understand how physicians' uncertainty tolerance (UT) in clinical care relates to their personal characteristics, perceptions and practices regarding shared decision making (SDM)., Methods: As part of a trial of SDM training about colorectal cancer screening, primary care physicians (n = 67) completed measures of their uncertainty tolerance in medical practice (Anxiety subscale of the Physician's Reactions to Uncertainty Scale, PRUS-A), and their SDM self-efficacy (confidence in SDM skills). Patients (N = 466) completed measures of SDM (SDM Process scale) after a clinical visit. Bivariate regression analyses and multilevel regression analyses examined relationships., Results: Higher UT was associated with greater physician age (p = .01) and years in practice (p = 0.015), but not sex or race. Higher UT was associated with greater SDM self-efficacy (p < 0.001), but not patient-reported SDM., Conclusion: Greater age and practice experience predict greater physician UT, suggesting that UT might be improved through training, while UT is associated with greater confidence in SDM, suggesting that improving UT might improve SDM. However, UT was unassociated with patient-reported SDM, raising the need for further studies of these relationships., Practice Implications: Developing and implementing training interventions aimed at increasing physician UT may be a promising way to promote SDM in clinical care., Competing Interests: Declaration of Competing Interest The study was funded through a Patient-Centered Outcomes Research Institute® (PCORI) Award (CDR-2017C3–9270). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. With regards to potential conflicts of interest for this study, all authors report grant support from PCORI (CDR-2017C3–9270) for the study activities. Dr. Sepucha reports grant funding from Agency for Healthcare Research and Quality and a contract with Blue Cross Blue Shield of Massachusetts. Dr. Atlas reports grant funding from the National Cancer Institute and the Risk Management Foundation of Harvard. Dr. Simmons reports paid expert testimony from the US Department of Justice for testimony on cancer screening in primary care malpractice cases. Dr. Richter reports support from Exact Sciences and CRICO., (Published by Elsevier B.V.)

PAR4 is a promising antithrombotic target with potential for separation of efficacy from bleeding risk relative to current antiplatelet therapies. In an effort to discover a novel PAR4 antagonist chemotype, a quinoxaline-based HTS hit 3 with low μM potency was identified. Optimization of the HTS hit through the use of positional SAR scanning and the design of conformationally constrained cores led to the discovery of a quinoxaline-benzothiazole series as potent and selective PAR4 antagonists. The lead compound 48 , possessing a 2 nM IC 50 against PAR4 activation by γ-thrombin in platelet-rich plasma (PRP) and greater than 2500-fold selectivity versus PAR1, demonstrated robust antithrombotic efficacy and minimal bleeding in the cynomolgus monkey models.

Aim: To examine the relationship between periodontal disease and tooth loss and risk of inflammatory bowel disease (IBD)., Methods: We conducted a prospective cohort study of 86,602 women from the Nurses' Health Study (1992-2016) and 50,349 men from the Health Professionals Follow-up Study (1986-2016) with available data on periodontal disease and tooth loss. Cases of IBD were initially reported by participants and then confirmed by medical record review. We used Cox proportional hazards modelling to estimate multivariable-adjusted hazard ratios (aHRs) and 95% CIs., Results: Through the end of follow-up, we documented 175 cases of Crohn's disease (CD) and 209 cases of ulcerative colitis (UC). After adjustment for potential risk factors, there was no association between periodontal disease and risk of CD (pooled aHR: 0.99, 95% CI: 0.65-1.52, p = 0.970) or UC (aHR: 0.99, 95% CI: 0.68-1.45, p = 0.971). Similarly, we did not observe an association between tooth loss and risk of CD (aHR: 0.72, 95% CI: 0.43-1.21, p = 0.218) or UC (aHR: 0.89, 95% CI: 0.58-1.36, p = 0.581) in the pooled analysis. The associations were not modified by sex, age, body mass index (BMI), smoking status or NSAID use (all p interaction  > 0.87)., Conclusion: In two large prospective cohort studies, we did not observe an association between periodontal disease and tooth loss and risk of CD or UC., (© 2023 John Wiley & Sons Ltd.)

Background: Microscopic colitis is a chronic inflammatory disease that most commonly affects post-menopausal women. Exogenous hormone use has recently been linked with increased risk of microscopic colitis. Yet, it is unclear whether levels of endogenous sex hormones are also associated with risk of microscopic colitis., Aim: To evaluate the association between prediagnostic plasma androgens and subsequent risk of microscopic colitis., Methods: We conducted a case-control study nested within prospective cohort studies of the Nurses' Health Study (NHS) and NHSII. Cases of microscopic colitis were each matched to two controls according to age, cohort, menopause status, fasting status, and season of plasma collection. Prediagnosis plasma levels of androgens including dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of microscopic colitis using conditional logistic regression models., Results: Our study included 96 cases of microscopic colitis matched to 190 controls. Plasma levels of testosterone were not associated with risk of microscopic colitis (P trend  = 0.70). Compared to participants in the lowest quartile of plasma testosterone levels, the aOR of microscopic colitis for women in the highest quartile was 0.88, 95% CI 0.45-1.71. Similarly, we did not observe an association between dehydroepiandrosterone sulfate and sex hormone-binding globulin and risk of microscopic colitis (all P trend  > 0.52)., Conclusion: Among women, prediagnostic circulating levels of testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin are not associated with risk of microscopic colitis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Thousands of colonoscopies were canceled during the initial surge of the COVID-19 pandemic. As facilities resumed services, some patients were hesitant to reschedule. The purpose of this study was to determine whether a decision aid plus telephone coaching would increase colorectal cancer (CRC) screening and improve patient reports of shared decision making (SDM). A randomized controlled trial assigned adults aged 45-75 without prior history of CRC who had a colonoscopy canceled from March to May 2020 to intervention (n = 400) or usual care control (n = 400) arms. The intervention arm received three-page decision aid and call from decision coach from September 2020 through November 2020. Screening rates were collected at 6 months. A subset (n = 250) in each arm was surveyed 8 weeks after randomization to assess SDM (scores range 0-4, higher scores indicating more SDM), decisional conflict, and screening preference. The sample was on average, 60 years old, 53% female, 74% White, non-Hispanic, and 11% Spanish speaking. More intervention arm patients were screened within 6 months (35% intervention vs 23% control, p < 0.001). The intervention respondents reported higher SDM scores (mean difference 0.7 [0.4, 0.9], p < 0.001) and less decisional conflict than controls (-21% [-35%, -7%], p = 0.003). The majority in both arms preferred screening versus delaying (68% intervention vs. 65% control, p = 0.75). An SDM approach that offered alternatives and incorporated patients' preferences resulted in higher screening rates. Patients who are overdue for CRC screening may benefit from proactive outreach with SDM support., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background and Aims: Informed consent should allow patients the appropriate time and conditions to make decisions about their care. However, consent is often obtained immediately prior to a colonoscopy. We conducted a quality improvement study to assess how a preprocedure consent video 2 days prior to an outpatient colonoscopy impacts patient satisfaction., Methods: Patients undergoing outpatient colonoscopy at a large academic medical center opted in to a text messaging platform for procedural information. Our intervention was an informed consent video 2 days before the colonoscopy. Our primary outcome was a composite patient satisfaction score. Pre and postintervention scores were compared using ordinal or multinomial logistic models to calculate odds ratios (OR) or relative risk ratios and 95% confidence intervals (CI), adjusting for age and sex., Results: 1109 and 1452 patients completed ≥1 survey question in the pre and postintervention phases, respectively. Overall patient satisfaction did not differ between groups [OR for a 1-point increment in satisfaction score between post- vs pre-intervention groups = 1.05; 95% CI: 0.90-1.22; P = .51]. Compared to preintervention, postintervention respondents were more likely to report higher satisfaction with time available to talk with their physician (OR of a 1-point increase in individual question response = 1.29; 95% CI: 1.09-1.54; P = .004). Compared to preintervention, more physicians in the postintervention phase rated satisfaction with consent process efficiency as "very satisfied" or "satisfied" ( P < .001)., Conclusion: An informed consent video prior to colonoscopy resulted in similar overall patient satisfaction. However, post-intervention, patients were more likely to report sufficient time to talk with their physician, and physicians reported higher satisfaction with consent efficiency., Competing Interests: Conflicts of Interest: These authors disclose the following Yousef R. Badran receives consulting fees from Aditum Bio and Goodpath (non-relevant to the current work). The remaining authors disclose no conflicts.

Background. Early in the COVID-19 pandemic colonoscopies for colorectal cancer (CRC) screening were canceled. Patient perceptions of the benefits and risks of routine screening relative to health concerns associated with the COVID-19 pandemic were unknown. Purpose. Assess patient anxiety, worry, and interest in CRC screening during the COVID-19 pandemic. Methods. A random sample of 200 patients aged 45 to 75 y with colonoscopy cancellation due to COVID-19 in March to May 2020 were surveyed. Anxiety, COVID-19 and CRC risk perceptions, COVID-19 and CRC worry, likelihood of following through with colonoscopy in the next month, and interest in alternatives to colonoscopy were assessed. Subsequent screening was tracked for 12 mo. Results. Respondents ( N  = 127/200, 63.5%) were on average 60 y old, female (59%), college educated (62% college degree or more), and White (91%). A substantial portion of patients (46%) stated they may not follow through with a colonoscopy in the next month. There was greater interest in stool-based testing than in delaying screening (48% v. 26%). Women, older patients, and patients indicating tolerance of uncertainty due to complexity reported they were less likely to follow through with colonoscopy in the next month. Greater interest in stool-based testing was related to lower perceptions of CRC risk. Greater interest in delaying screening was related to less worry about CRC and less tolerance of risk. Over 12 mo, 60% of participants completed screening. Patients who stated they were more likely to screen in the next month were more likely to complete CRC screening ( P  = 0.01). Conclusions. Respondents who had a colonoscopy canceled during the COVID-19 pandemic varied in interest in rescheduling the procedure. A shared decision-making approach may help patients address varying concerns and select the best approach to screening for them., Highlights: In the wake of the first wave of the COVID-19 pandemic, almost half of patients stated they were not likely to follow through with a colonoscopy in the short term, about half were interested in screening with a stool-based test, and only one-quarter were interested in delaying screening until next year.Patients who perceived themselves at higher risk of colorectal cancer were less interested in stool-based testing, and patients who were more worried about colorectal cancer were less interested in delaying screening.A shared decision-making approach may be necessary to tailor screening discussions for patients during subsequent waves of the pandemic, other occasions where resources are limited and patient preferences vary, or where patients hold conflicting views of screening., Competing Interests: With regard to potential conflicts of interest for this study, Dr. Atlas reports a grant from the National Cancer Institute, and Dr. Richter reports approximately 25% income derived from performing colonoscopy. All other authors report no conflicts outside receiving grant funding through their institution from PCORI for this study., (© The Author(s) 2022.)

Objective: To estimate the proportion of cases of Crohn's disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors., Design: In a prospective cohort study of US adults from the Nurses' Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable risk scores (MRS; 0-6) for CD and UC based on established lifestyle risk factors, and healthy lifestyle scores (HLS; 0-9) derived from American healthy lifestyle recommendations. We calculated the population attributable risk by comparing the incidence of CD and UC between low-risk (CD-MRS≤1, UC-MRS≤2, HLS≥7) and high-risk groups. We externally validated our findings in three European cohorts: the Swedish Mammography Cohort (n=37 275), Cohort of Swedish Men (n=40 810) and European Prospective Investigation into Cancer and Nutrition (n=404 144)., Results: Over 5 117 021 person-years of follow-up (NHS, HPFS: 1986-2016; NHSII: 1991-2017), we documented 346 CD and 456 UC cases. Adherence to a low MRS could have prevented 42.9% (95% CI 12.2% to 66.1%) of CD and 44.4% (95% CI 9.0% to 69.8%) of UC cases. Similarly, adherence to a healthy lifestyle could have prevented 61.1% (95% CI 16.8% to 84.9%) of CD and 42.2% (95% CI 1.7% to 70.9%) of UC cases. In our validation cohorts, adherence to a low MRS and healthy lifestyle could have, respectively, prevented 43.9%-51.2% and 48.8%-60.4% of CD cases and 20.6%-27.8% and 46.8%-56.3% of UC cases., Conclusions: Across six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification., Competing Interests: Competing interests: HK is supported by the American College of Gastroenterology Senior Research Award and the Beker Foundation; HK has received consulting fees from Abbvie and Takeda; HK has also received grant funding from Pfizer and Takeda. ATC is the Stuart and Suzanne MGH Research Scholar. JFL reports funding from Janssen corporation for work unrelated to this manuscript. OO has been PI on projects at Karolinska Institutet, partly financed by investigator-initiated grants from Janssen, Takeda and Ferring, and Karolinska Institutet has received fees for lectures and participation on advisory boards from Janssen, Ferring, Takeda and Pfizer; OO also reports a grant to Karolinska Institutet from Pfizer in the context of a national safety monitoring program. ATC has received consulting fees from Bayer Pharma AG, Pfizer and Boehringer Ingelheim for work unrelated to this manuscript. SC has received travel grants from Abbvie and Takeda., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Migrants experience several challenges en route to or in their host country. Current legislation in Russia imposes a permanent ban on international migrants with HIV obtaining a residence permit in Russia. Using qualitative methodology, we conducted semi-structured interviews with 15 international migrants who have lived with HIV in Russia and 12 interviews with healthcare providers in Russia. With the help of Bonnington's temporal framework, the study finds that the HIV-positive status of migrants becomes a biographical event that interrupts their migration cycle, thereby leading to the disruption of their normal life course which results in 'short term planning' and instability. Although most people living with HIV face similar challenges, Russian law concerning international migrants living with HIV worsens their living experience in Russia. International migrants living with HIV further face social exclusion, serious stigma and discrimination. The results show that the country's demand for migrants with HIV to leave the country to reduce the spread of HIV in Russia is counterproductive: it does not mobilise heath-seeking behaviour among migrants. Therefore, such legislation has to be amended to encourage international migrants living with HIV to access adequate HIV services.

Introduction: Continuous left ventricular assist devices (LVADs) offer hemodynamic support in advanced and decompensated heart failure but are often complicated by gastrointestinal bleeding (GIB) in medically fragile patients., Methods: We performed a retrospective analysis of 475 consecutive patients who underwent LVAD implantation at the Massachusetts General Hospital and Tufts Medical Center from 2008 to 2019 and identified 128 patients with clinically significant GIB. Clinical characteristics of each bleeding event, including procedures and interventions, were recorded. We examined LVAD patients with overt and occult presentations to determine diagnostic endoscopic yield and analyzed predictors of recurrent GIB., Results: We identified 128 unique patients with LVAD implantation complicated by GIB. No significant difference was observed based on study center, underlying cardiomyopathy, race/ethnicity, serum indices, and medications used. Overt bleeders presented more commonly during LVAD implantation admission ( P = 0.001) than occult bleeders. Occult bleed presentations had only 1 lower and no middle GI bleed source identified, despite similar workups to overt bleeds. Destination therapy (e.g., among nontransplant candidates) LVAD implantation (odds ratio 2.38, 95% confidence interval 1.05-5.58) and a history of GIB (odds ratio 3.85, 95% confidence interval 1.29-12.7) were independently associated with an increased risk of recurrent GIB-related hospitalization., Discussion: Our findings confirm a high rate of GIB, especially in destination LVAD patients, and show a low diagnostic yield for colonoscopy and middle GI bleed assessments in LVAD patients with occult bleeds. Overt bleeding was more common and associated with vascular malformations. Although endoscopic interventions stopped active hemorrhage, GIB often recurred., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background & Aims: We examined whether relationships between known risk factors for Crohn's disease (CD) and ulcerative colitis (UC) differ according to disease phenotype, defined by Montreal classification, at the time of diagnosis., Methods: We performed a prospective cohort study of 208,070 adults from the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS). Dietary, lifestyle, and medical data were obtained at baseline and every 2-4 years. We confirmed cases of inflammatory bowel disease (IBD) and their phenotypes via medical record review. We tested for heterogeneity across CD subtypes using the likelihood ratio test and for linear heterogeneity across UC subtypes using the meta-regression method., Results: We ascertained 346 cases of CD and 456 cases of UC over 5,117,021 person-years of follow-up (1986-2016 for NHS and HPFS; 1991-2017 for NHSII). Fiber intake was associated with decreased risk for ileocolonic but not ileal or colonic CD (P heterogeneity  = .04). Physical activity was associated with decreased risk of nonstricturing and nonpenetrating CD but not of penetrating CD (P heterogeneity  = .02). Higher body mass index and current smoking were associated with decreased risk of proctitis and left-sided UC but not of pan-UC (P linear heterogeneity = .004 and .02, respectively). The associations between other risk factors examined and risk of CD and UC did not differ by disease phenotype (all P heterogeneity > .06)., Conclusions: In 3 large prospective cohorts, we observed that dietary and lifestyle risk factors for IBD may differ according to disease phenotype. These findings highlight the need for disease stratification in future epidemiologic studies., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Agonism of the apelin receptor (APJ) has demonstrated beneficial effects in models of heart failure. We have previously disclosed compounds such as 4, which showed good APJ agonist activity but were metabolized to the mono-demethylated, non-interconverting atropisomer metabolites. Herein, we detail the design and optimization of a novel series of N-linked APJ agonists with good potency, metabolic stability, and rat pharmacokinetic profile, which are unable to undergo the same metabolic mono-demethylation cleavage., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A useful protocol for achieving decarboxylative cross-coupling (DCC) of redox-active esters (RAE, isolated or generated in situ) and halo(hetero)arenes is reported. This pragmatically focused study employs a unique Ag-Ni electrocatalytic platform to overcome numerous limitations that have plagued this strategically powerful transformation. In its optimized form, coupling partners can be combined in a surprisingly simple way: open to the air, using technical-grade solvents, an inexpensive ligand and Ni source, and substoichiometric AgNO 3 , proceeding at room temperature with a simple commercial potentiostat. Most importantly, all of the results are placed into context by benchmarking with state-of-the-art methods. Applications are presented that simplify synthesis and rapidly enable access to challenging chemical space. Finally, adaptation to multiple scale regimes, ranging from parallel milligram-based synthesis to decagram recirculating flow is presented.

Background and Aims: We examined smoking behaviour changes after diagnoses of Crohn's disease [CD] and ulcerative colitis [UC] and evaluated their impact on mortality., Methods: Study population included incident CD or UC cases from three cohorts of the Nurses' Health Study [NHS], NHSII, and Health Professionals Follow-up Study. Smoking and other risk factors were prospectively assessed. Smoking behaviour changes were categorised as never, former [i.e., quit smoking before diagnosis], quitters [i.e., quit smoking after diagnosis], and current [i.e., continue smoking after diagnosis]. Follow-up for date and cause of death was completed through linkage to the National Death Index. Cox proportional hazard regression was used to estimate hazard ratios [HRs] and 95% confidence intervals [CIs]., Results: Among 909 eligible CD and UC cases, 45% were never smokers, 38% were past smokers, and 16% were active smokers at the time of diagnosis. Among active smokers, 70% of patients with CD and 44% of patients with UC continued to smoke after diagnosis. In patients with CD, compared with current smokers, the multivariable-adjusted HRs [95% CI] of death were 0.19 [0.10 to 0.38] for never smokers, 0.31 [0.16 to 0.57] for former smokers, and 0.41 [0.18 to 0.93] for quitters. Similarly for UC, compared with current smokers, we observed a reduced risk of mortality for never smokers [HR = 0.23, 95% CI 0.10 to 0.51], former smokers [HR = 0.23, 95% CI 0.11 to 0.48], and quitters [HR = 0.28, 95% CI 0.11 to 0.72]., Conclusions: In three cohorts of health professionals, a substantial proportion of patients with new diagnosis of CD and UC and history of smoking continued to smoke after diagnosis. Smoking cessation around the time of diagnosis was associated with a significant reduction in mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC., Methods: We conducted a prospective cohort study of 209,902 participants (age range, 28.5-66.7 years) enrolled in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs)., Results: Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (Ptrend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86-1.67) for consumers of 0.1-4.9 g/day of alcohol, 1.90 (95% CI, 1.34-2.71) for consumers of 5-14.9 g/day, and 2.31 (95% CI, 1.54-3.46) for consumers of ≥15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (Pheterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04-1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91-1.12) or liquor (aHR, 1.00; 95% CI, 0.92-1.09)., Conclusions: Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Protease-activated receptor 4 (PAR4) is a G-protein coupled receptor that is expressed on human platelets and activated by the coagulation enzyme thrombin. PAR4 plays a key role in blood coagulation, and its importance in pathological thrombosis has been increasingly recognized in recent years. Herein, we describe the optimization of a series of imidazothiadiazole PAR4 antagonists to a first-in-class clinical candidate, BMS-986120 ( 43 ), and a backup clinical candidate, BMS-986141 ( 49 ). Both compounds demonstrated excellent antithrombotic efficacy and minimal bleeding time prolongation in monkey models relative to the clinically important antiplatelet agent clopidogrel and provide a potential opportunity to improve the standard of care in the treatment of arterial thrombosis.

Introduction: Delays in inpatient colonoscopy are commonly caused by inadequate bowel preparation and result in increased hospital length of stay (LOS) and healthcare costs. Low-volume bowel preparation (LV-BP; sodium sulfate, potassium sulfate, and magnesium sulfate ) has been shown to improve outpatient bowel preparation quality compared with standard high-volume bowel preparations (HV-BP; polyethylene glycol ). However, its efficacy in hospitalized patients has not been well-studied. We assessed the impact of LV-BP on time to colonoscopy, hospital LOS, and bowel preparation quality among inpatients., Methods: We performed a propensity score-matched analysis of adult inpatients undergoing colonoscopy who received either LV-BP or HV-BP before colonoscopy at a quaternary academic medical center. Multivariate regression models with feature selection were developed to assess the association between LV-BP and study outcomes., Results: Among 1,807 inpatients included in this study, 293 and 1,514 patients received LV-BP and HV-BP, respectively. Among the propensity score-matched population, LV-BP was associated with a shorter time to colonoscopy (β: -0.43 [95% confidence interval: -0.56 to -0.30]) while having similar odds of adequate preparation (odds ratio: 1.02 [95% confidence interval: 0.71-1.46]; P = 0.92). LV-BP was also significantly associated with decreased hospital LOS among older patients (age ≥ 75 years), patients with chronic kidney disease, and patients who were hospitalized with gastrointestinal bleeding., Discussion: LV-BP is associated with decreased time to colonoscopy in hospitalized patients. Older inpatients, inpatients with chronic kidney disease, and inpatients with gastrointestinal bleeding may particularly benefit from LV-BP. Prospective studies are needed to further establish the role of LV-BP for inpatient colonoscopies., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background & Aims: The rising incidence of inflammatory bowel disease in regions undergoing Westernization has coincided with the increase in ultra-processed food (UPF) consumption over the past few decades. We aimed to examine the association between consumption of UPFs and the risk of Crohn's disease (CD) and ulcerative colitis (UC)., Methods: We performed a prospective cohort study of 3 nationwide cohorts of health professionals in the United States-the Nurses' Health Study (1986-2014), the Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2012). We employed Cox proportional hazards models with adjustment for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CD and UC according to self-reported consumption of UPFs., Results: The study included 245,112 participants. Over 5,468,444 person-years of follow-up, we documented 369 incident cases of CD and 488 incident cases of UC. The median age at diagnosis was 56 years (range, 29-85 years). Compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (HR, 1.70; 95% CI, 1.23-2.35; P trend  = .0008). Among different UPF subgroups, ultra-processed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies showed the strongest positive associations with CD risk (HR per 1 standard deviation increase in intake, 1.18 [95% CI, 1.07-1.29], 1.11 [95% CI, 1.01-1.22], and 1.14 [95% CI, 1.02-1.27], respectively). There was no consistent association between UPF intake and UC risk., Conclusions: Higher UPF intake was associated with an increased risk of incident CD. Further studies are needed to identify specific contributory dietary components., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: We evaluated factors that can predict the adequacy of bowel preparation in patients with chronic constipation undergoing colonoscopy., Materials and Methods: We identified patients with chronic constipation who underwent anorectal manometry and at least 1 colonoscopy at 2 tertiary referral centers from 2003 to 2019. We also identified a subgroup of patients who underwent colonic transit testing through radiopaque marker testing. We determined demographic, medical, and constipation-related factors associated with poor bowel preparation and their effect on standardized quality metrics using univariate and multivariate analyses., Results: We identified 274 patients with chronic constipation who underwent anorectal manometry testing. Both outlet dysfunction (prolonged balloon expulsion) and slow-transit constipation were associated with suboptimal bowel preparation. Outlet dysfunction was also associated with decreased cecal intubation rates, adenoma detection rates, and sessile serrated polyp detection rates. In multivariable analyses controlling for demographics and known factors associated with poor bowel preparation, outlet dysfunction was associated with an almost 3-fold odds of suboptimal bowel preparation [odds ratio (OR): 2.9; 95% confidence interval (CI): 1.6-5.1] and a 3-fold reduction in cecal intubation rates (OR: 0.3; 95% CI: 0.1-0.8). Among those with radiopaque marker colonic transit testing available, slow-transit constipation was associated with a >2-fold odds of suboptimal bowel preparation (OR: 2.2; 95% CI: 1.1-4.4)., Conclusions: Among a cohort of patients with chronic constipation undergoing colonoscopy, outlet dysfunction was associated with suboptimal bowel preparation and other quality metrics. Constipated patients with a rectal evacuation disorder may represent a subgroup of patients that could benefit from individualized strategies for better bowel preparation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Perfluoroalkyl substances (PFASs) are synthetic compounds used in a wide variety of industrial and consumer applications. An association between PFAS exposure and risk of ulcerative colitis (UC) has been reported in a highly exposed population. However, data are limited on risk of inflammatory bowel diseases (IBD) among individuals with background population levels of PFAS exposure., Objectives: We set out to examine the association between plasma PFAS concentrations and risk of IBD among women in two population-based, prospective cohort studies in which pre-diagnostic blood specimens were available., Methods: We conducted a nested case-control study in the Nurses' Health Study and Nurses' Health Study II cohorts. We identified 73 participants with incident Crohn's disease (CD) and 80 participants with incident UC who had provided blood samples before diagnosis. Cases were matched 1:2 to IBD-free controls. Plasma concentrations of five major PFASs were measured by liquid chromatography and tandem mass spectrometry. We used conditional logistic models to estimated odds ratios for risk of IBD according to log 10 -transformed PFAS concentrations, adjusting for potential confounders., Results: In multivariable models, we observed inverse associations between plasma concentrations of three PFASs and risk of CD (all P ≤ 0.012 for a standard deviation increase in log 10 PFAS). The inverse association with CD was strongest for perfluorodecanoate, where, compared to the lowest tertile, the odds ratio (OR) for the highest tertile was 0.39 (95% confidence interval, 0.17-0.92). No associations were observed between PFAS concentrations and UC risk., Discussion: Our results do not support the hypothesis that elevated PFAS exposure is associated with higher risk of UC. Contrary to expectation, our data suggest that circulating concentrations of some PFASs may be inversely associated with CD development., (Copyright © 2021. Published by Elsevier Inc.)

Background and Aims: Performing colonoscopy can be technically challenging in female patients. Female patients may prefer having a female endoscopist. This preference, coupled with the fact that there are fewer female endoscopists, may result in gender differences in colonoscopy practice. We hypothesized that the duration of female colonoscopy is longer and that female endoscopists perform a higher proportion of female colonoscopy than male colleagues. We explored the potential revenue implications of gender differences in screening colonoscopy., Methods: We analyzed procedure time and gender differences in 16,573 screening colonoscopies performed by 27 male and 7 female endoscopists over a three-year period in one large academic practice. We modeled the potential revenue impacts of differences in procedure duration, proportion of female colonoscopy and the frequency of detected adenomas., Results: We found that screening colonoscopy takes 8.8% more time to complete in female patients compared to male patients for all endoscopists (p < 0.001), and that female endoscopists perform an average of 71.2% female exams compared to male endoscopists, who perform an average of 50.8% female exams (p < 0.001). Female patients had a lower detection adenoma rate (ADR), reducing the frequency of polypectomy and reimbursement in an RVU model. The observed gender differences could account for an estimated 9.6% revenue loss per 8-h session for a female gastroenterologist performing screening colonoscopy compared to a male counterpart., Conclusion: Longer colonoscopy duration in females, increased proportion of female colonoscopies for female endoscopists and lower ADR in females may contribute to the gender gap in physician pay in gastroenterology., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with cirrhosis and ascites experience frequent hospital admissions, leading to poor quality of life and high healthcare costs. Monitoring weight is a component of ascites care and telemonitoring may improve outcomes and costs. Goals We aimed to evaluate the cost and outcomes of current care compared to a telemonitoring system for ascites. Study We developed a decision-analytic model that examined 100 simulated patients over a 6-month horizon. We compared usual care to a new telemonitoring program, which we estimate costs $50,000/6 months., Results: The cost of standard of care for 100 patients with cirrhotic ascites over a 6-month period is $167,500 more expensive than telemonitoring. By varying parameter probabilities by ± 10% and outcome costs by ± 20%, we found that standard of care remains more expensive than care with a telemonitoring intervention by $9400 to $340,200 per 6-month period. Standard of care leads to 9 more admissions (range 4 to 12) than a telemonitoring intervention, while telemonitoring leads to 9 more outpatient visits (range 6 to 9) and 28 additional outpatient large volume paracenteses (LVPs) (range 17 to 28). With more and less expensive telemonitoring interventions, standard of care remained more expensive. With 50% adherence to the intervention, standard of care was $89,848 more expensive., Conclusions: In almost all probability and cost scenarios, a telemonitoring intervention is cost-saving for the management of cirrhotic ascites. Using hospital admissions as a surrogate for quality of care, patient outcomes are improved primarily though more proactive medical intervention and more LVPs., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As members of the Clinical Practice Committee (CPC) of the Society for General Internal Medicine (SGIM), we support practice innovation and transformation to achieve a more just system by which all people can achieve and maintain optimal health. The COVID-19 pandemic has tested the US healthcare delivery system and sharpened our national awareness of long-standing and ingrained system shortcomings. In the face of crisis, SGIM members innovated and energetically mobilized to focus on the immediate needs of our patients and communities. Reflecting on these experiences, we are called to consider what was learned from the pandemic that applies to the future of healthcare delivery. CPC members include leaders in primary care delivery, practice finance, quality of care, patient safety, hospital practice, and health policy. CPC members provide expertise in clinical practice, serving as primary care doctors, hospitalists, and patient advocates who understand the intensity of care needed for those with severe COVID-19 infections, the disproportionate impact of the pandemic on Black and Brown communities, the struggles created for those with poor access to care, and the physical and emotional impact it has placed on patients, families, and clinicians. In this consensus statement, we summarize lessons learned from the 2020-2021 pandemic and their broader implications for reform in healthcare delivery. We provide a platform for future work by identifying many interactive elements of healthcare delivery that must be simultaneously addressed in order to ensure that care is accessible, equitably provided, patient-centered, and cost-effective., (© 2021. Society of General Internal Medicine.)

Background & Aims: Diet is thought to play a role in the development of inflammatory bowel disease (IBD), though it is unknown whether gluten intake confers risk of IBD. The aim of this study was to determine the relationship between gluten intake and risk of incident Crohn's disease (CD) and ulcerative colitis (UC)., Methods: We performed a prospective cohort study of 208,280 US participants from the Nurses' Health Study (1986-2016), Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2016) who did not have IBD at baseline or celiac disease, and who completed semiquantitative food frequency questionnaires. We used Cox proportional hazards modeling to estimate the risk of IBD according to quintiles of cumulative average energy-adjusted dietary gluten intake over the follow-up period., Results: We documented 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up evaluation. Dietary gluten intake was not associated with risk of IBD. Compared with participants in the lowest quintile of gluten intake, the adjusted hazard ratios and 95% CIs for participants in the highest quintile of gluten intake were 1.16 (95% CI, 0.82-1.64; P trend  = .41) for CD and 1.04 (95% CI, 0.75-1.44; P trend  = .64) for UC. Adjusting for primary sources of gluten intake did not materially change our estimates., Conclusions: In 3 large adult US prospective cohorts, gluten intake was not associated with risk of CD or UC. Our findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: There are limited data on alcohol dose and types and risk of Crohn's Disease (CD) and Ulcerative Colitis (UC). We therefore sought to comprehensively examine the association between alcohol consumption and risk of CD and UC., Methods: We conducted a prospective cohort study of 237,835 participants from the Nurses' Health Study, Nurses' Health Study II, and Health Professional Follow-Up Study. Alcohol consumption was obtained through questionnaires submitted every four years; additional covariates were obtained at two or four-year intervals. Cases were confirmed independently by two physicians through medical record review. We used Cox proportional hazards regression to estimate age and multivariable-adjusted hazards ratios and 95% confidence intervals., Results: Across 5,170,474 person-years of follow-up, 370 cases of CD and 486 cases of UC were documented. Increased consumption of alcohol intake was not associated with CD (Ptrend = 0.455) or UC (Ptrend = 0.745). Compared to non-users, the MV-adjusted HRs for 15.0 + g/day of alcohol intake group were 0.84 (95% CI 0.56, 1.24) for CD and 1.08 (95% CI 0.77, 1.51) for UC. In analyses of alcohol subtypes, we observed that only moderate consumption of beer (>1-4 servings/week) was marginally associated with reduced risk of CD, while consumption of >4 servings/week of liquor was associated with an increased risk of UC., Conclusion: This prospective study did not identify a relationship between overall alcohol consumption and risk of CD or UC. Our suggestive associations between alcohol types and risk of CD and UC deserve additional investigation., (© 2021 John Wiley & Sons Ltd.)

Introduction: Low colorectal cancer (CRC) screening rates among Hispanic and Latino patients result in advanced disease at the time of diagnosis and decreased survival chances., Methods: We performed a prospective study at an academic endoscopy center in Boston, Massachusetts from May 1, 2019 to January 31, 2020. We identified 887 Spanishspeaking patients as controls and enrolled 412 (59%) Spanish-speaking patients in a short message service (SMS) program for pre-procedure instructions., Results: Intervention and control group participants were similar in age, sex, and indications. Patients receiving SMS messages were less likely to no-show or cancel last minute (OR=1.66, 95%CI=0.44-0.83, p=.002) and had more adequate bowel preparations compared with the control arm (OR=1.55, 95%CI=0.45-0.92, p=.01). Overall, 93% (117/126) of patients stated they would "highly recommend" the program to others., Conclusions: Our automated SMS reminders for colonoscopy preparation increased appointment adherence, bowel preparation quality, and showed good patient satisfaction among Spanish speakers.

Background: Although immune-mediated diseases (IMDs) including inflammatory bowel diseases (IBDs) are known to cluster, to what extent this is due to common environmental influences is unknown., Aim: To examine the incidence of IBD in individuals with another IMD., Methods: We used data from the prospective Nurses' Health Study II cohort (1995-2017) to examine the effect of diagnoses of several common IMDs on subsequent risk of Crohn's disease (CD) or ulcerative colitis (UC) using Cox proportional hazards models, adjusting for detailed diet and lifestyle confounders., Results: We documented 132 cases of CD and 186 cases of UC over 2 016 163 person-years of follow-up (median age at IBD diagnosis 50 years). Compared to participants with no history of IMD, the HRs of CD for those with 1 and ≥ 2 IMDs were 2.57 (95% CI 1.77-3.74) and 2.74 (95% CI 1.36 to 5.49), respectively (P trend  < 0.0001). This association was only modestly attenuated by adjustment for environmental risk factors (HR 2.35 and 2.46, respectively). The risk of UC was not increased, with multivariable-adjusted HRs of 1.22 (95% CI 0.85-1.76) and 1.33 (95% CI 0.67-2.65) for those with 1 and ≥ 2 IMDs, respectively, compared to those with none (P trend 0.16) (P heterogeneity comparing CD and UC 0.037). Asthma, atopic dermatitis, psoriasis and rosacea were individually associated with higher risk of CD (HR ranging from 2.15 to 3.39) but not UC., Conclusions: Individuals with one or more IMDs are at an increased risk for CD but not UC., (© 2020 John Wiley & Sons Ltd.)

Background & Aims: It is not clear whether a healthy lifestyle affects mortality of patients with inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC)., Methods: We collected data form the Nurses' Health Study (1986-2014), Nurses' Health Study II (1991-2015), and Health Professionals Follow-up Study (1986-2014), which assess lifestyles with serial questionnaires. We estimated joint and individual associations between 5 healthy lifestyle factors after IBD diagnosis (never smoking, body mass index 18.5-24.9 kg/m 2 , vigorous physical activity in the highest 50% with non-zero value, alternate Mediterranean diet score ≥4, and light drinking [0.1-5.0 g/d]) and mortality using Cox proportional hazards models., Results: We documented 83 deaths in 363 patients with CD during 4741 person-years and 80 deaths in 465 patients with UC during 6061 person-years. The median age of IBD diagnosis was 55 y. Compared to patients with IBD with no healthy lifestyle factors, patients with IBD with 3-5 healthy lifestyle factors had a significant reduction in all-cause mortality (hazard ratio [HR], 0.29; 95% CI, 0.16-0.52; P trend < .0001). This reduction was significant in patients with CD (P trend  = .003) as well as in patients with UC (P trend  = .0003). Individual associations were more than 25 pack-years (HR, 1.92; 95% CI, 1.24-2.97; P trend < .0001), physical activity (HR according to quintiles, 0.55-0.31; P trend  = .001), Mediterranean diet (HR, 0.69; 95% CI, 0.49-0.98), and alcohol consumption (HR 0.1-5 g/d 0.61; 95% CI, 0.39-0.95 vs HR >15 g/d 1.84; 95% CI, 1.02-3.32). The findings did not change when we adjusted for family history of IBD, immunomodulator use, and IBD-related surgery., Conclusions: In an analysis of data from 3 large cohort studies, we associated adherence to a healthy lifestyle with reduced mortality in patients with CD or UC., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Patient navigation (PN) improves initial colorectal cancer (CRC) screening in underserved populations. Whether the impact persists and improves the timeliness of follow-up screening colonoscopy (FSC) is not known. Patients receiving PN at initial colonoscopy between 2010-2011 with findings requiring FSC were matched to unnavigated patients requiring FSC. The primary outcome was proportion of patients with timely FSC, defined as colonoscopy within six months of recommendation. Of 216 patients in the study 103 (48%) completed FSC: 33 of 62 (53%) who received PN compared with 70 of 154 (45%) in the control group (p=.30). After adjusting for insurance, education, language and visits, navigated patients had higher odds (AOR=1.53, 95% CI 0.80-2.92) of timely FSC completion compared with unnavigated patients. Timely FSC completion in underserved patients is low. Patients navigated for initial colonoscopy or not had similar rates of FSC completion. Future studies should investigate navigation for FSC to improve equity in CRC.

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE 2 , 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults ( N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8-12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (-4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group ( P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; P = 0.018) or 325 mg/day (-28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769., (©2020 American Association for Cancer Research.)

Background: Ascites is a common, painful, and serious complication of cirrhosis. Body weight is a reliable proxy for ascites volume; therefore, daily weight monitoring is recommended to optimize ascites management., Objective: This study aims to evaluate the feasibility of a smartphone app in facilitating outpatient ascites management., Methods: In this feasibility study, patients with cirrhotic ascites requiring active management were identified in both inpatient and outpatient settings. Patients were provided with a Bluetooth-connected scale, which transmitted weight data to a smartphone app and then via the internet to an electronic medical record (EMR). Weights were monitored every weekday. In the event of a weight change of ≥5 lbs in 1 week, patients were called and administered a short symptom questionnaire, and providers received an email alert. The primary outcomes of this study were the percentage of enrolled days during which weight data were successfully transmitted to an EMR and the percentage of weight alerts that prompted responses by the provider., Results: In this study, 25 patients were enrolled: 12 (48%) were male, and the mean age was 58 (SD 13; range 35-81) years. A total of 18 (72%) inpatients were enrolled. Weight data were successfully transmitted to an EMR during 71.2% (697/979) of the study enrollment days, with technology issues reported on 16.5% (162/979) of the days. Of a total of 79 weight change alerts fired, 41 (52%) were triggered by weight loss and 38 (48%) were by weight gain. Providers responded in some fashion to 66 (84%) of the weight alerts and intervened in response to 45 (57%) of the alerts, for example, by contacting the patient, scheduling clinic or paracentesis appointments, modifying the diuretic dose, or requesting a laboratory workup. Providers responded equally to weight increase and decrease alerts (P=.87). The staff called patients a mean of 3.7 (SD 3.5) times per patient, and the number of phone calls correlated with technology issues (r=0.60; P=.002). A total of 60% (15/25) of the patients chose to extend their participation beyond 30 days. A total of 17 patient readmissions occurred during the study period, with only 4 (24%) related to ascites., Conclusions: We demonstrated the feasibility of a smartphone app to facilitate the management of ascites and reported excellent rates of patient and provider engagement. This innovation could enable early therapeutic intervention, thereby decreasing the burden of morbidity and mortality among patients with cirrhosis., (©Patricia Bloom, Thomas Wang, Madeline Marx, Michelle Tagerman, Bradley Green, Ashwini Arvind, Jasmine Ha, Judith Bloom, James M Richter. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 02.09.2020.)

Background & Aims: Inflammation is a potential mechanism through which diet modulates the onset of inflammatory bowel disease. We analyzed data from 3 large prospective cohorts to determine the effects of dietary inflammatory potential on the risk of developing Crohn's disease (CD) and ulcerative colitis (UC)., Methods: We collected data from 166,903 women and 41,931 men in the Nurses' Health Study (1984-2014), Nurses' Health Study II (1991-2015), and Health Professionals Follow-up Study (1986-2012). Empirical dietary inflammatory pattern (EDIP) scores were calculated based on the weighted sums of 18 food groups obtained via food frequency questionnaires. Self-reported CD and UC were confirmed by medical record review. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: We documented 328 cases of CD and 428 cases of UC over 4,949,938 person-years of follow-up. The median age at IBD diagnosis was 55 years (range 29-85 years). Compared with participants in the lowest quartile of cumulative average EDIP score, those in the highest quartile (highest dietary inflammatory potential) had a 51% higher risk of CD (HR 1.51; 95% CI 1.10-2.07; P trend  = .01). Compared with participants with persistently low EDIP scores (at 2 time points, separated by 8 years), those with a shift from a low to high inflammatory potential of diet or persistently consumed a proinflammatory diet had greater risk of CD (HR 2.05; 95% CI 1.10-3.79 and HR 1.77; 95% CI 1.10-2.84). In contrast, dietary inflammatory potential was not associated with the risk of developing UC (P trend  = .62)., Conclusions: In an analysis of 3 large prospective cohorts, we found dietary patterns with high inflammatory potential to be associated with increased risk of CD but not UC., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Pd(II)-catalyzed C-H lactonization of o -methyl benzoic acid substrates has been achieved using molecular oxygen as the oxidant. This finding provides a rare example of C-H oxygenation through Pd(II)/Pd(0) catalysis as well as a method to construct biologically important benzolactone scaffolds. The use of a gas mixture of 5% oxygen in nitrogen demonstrated the possibility for its application in pharmaceutical manufacturing.

The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia., Competing Interests: Declaration of interests C.H. is a member of the Seres Therapeutics scientific advisory board. A.T.C is a Stuart and Suzanne Steele MGH Research Scholar., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The critical role of the gut microbiome in microscopic colitis (MC) is evident by the observation that fecal diversion is associated with resolution of mucosal inflammation while restoration of fecal stream is associated with recurrence of disease. 1 Characterization of the composition and function of the gut microbiome in MC therefore could provide insights into disease pathogenesis., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Many patients struggle with colonoscopy preparation, which is complex and can be an uncomfortable as well as a time-consuming process. The confusion and anxiety from the preprocedure process may lead patients to delay their colonoscopy or skip it altogether. Digital health technology that focuses on patient engagement can play an important role in promoting colorectal cancer screening. Methods: A digital preprocedure instruction program was implemented for outpatient colonoscopy by sending critical reminders and instructions to patients through a series of short message service messages and/or emails. Eligible patients included English speakers on GoLYTELY ® /NuLYTELY ® or MiraLAX ® preparation regimens with a valid cellphone or email address in the electronic health record. We examined the impact of digital instructions on bowel preparation quality, no-show and same-day cancellations over a 3-month period between an intervention group of 756 patients and a control group of 2,103 patients. Patients who enrolled in the digital instructions also received a patient satisfaction survey. Results: Our controlled study demonstrated the effectiveness of digital instructions to reduce no-show and same-day cancellation rates for outpatient colonoscopy from 10.40% to 6.08% ( p < 0.001). Bowel preparation quality was not significantly different between the two groups ( p  = 0.23). However, 90% of patients who enrolled in the program rated their satisfaction with the digital reminders very highly. Discussion: A digital preprocedure instruction program can have a positive impact on operational efficiency, quality of care, and patient satisfaction. This study shows how digital health tools can effectively engage patients scheduled for a colonoscopy, increase appointment adherence, and, therefore, lead to better cancer screening.

Saturated azacycles are commonly encountered in bioactive compounds and approved therapeutic agents. The development of methods for functionalization of the α-methylene C-H bonds of these highly privileged building blocks is of great importance, especially in drug discovery. While much effort has been dedicated toward this goal by using a directed C-H activation approach, the development of directing groups that are both general as well as practical remains a significant challenge. Herein, the design and development of novel amidoxime directing groups is described for Ir(I)-catalyzed α-C(sp 3 )-H alkylation of saturated azacycles using readily available olefins as coupling partners. This protocol extends the scope of saturated azacycles to piperidines, azepane, and tetrahydroisoquinoline that are incompatible with our previously reported directing group. A variety of olefin coupling partners, including previously unreactive disubstituted terminal olefins and internal olefins, are compatible with this transformation. The selectivity for a branched α-C(sp 3 )-alkylation product is also observed for the first time when acrylate is used as the reaction partner. The development of practical, one-step installation and removal protocols further adds to the utility of amidoxime directing groups.

Metal-halide perovskites show excellent properties for photovoltaic and optoelectronic applications, with power conversion efficiencies of solar cell and LEDs exceeding 20%. Being solution processed, these polycrystalline materials likely contain a large density of defects compared to melt-grown semiconductors. Surprisingly, typical effects from defects (absorption below the bandgap, low fill factor and open circuit voltage in devices, strong nonradiative recombination) are not observed. In this work, we study thin films of metal-halide perovskites CH 3 NH 3 PbX 3 (X = Br, I) with ultrafast multidimensional optical spectroscopy to resolve the dynamics of band and defect states. We observe a shared ground state between the band-edge transitions and a continuum of sub-bandgap states, which extends at least 350 meV below the band edge). We explain the comparatively large bleaching of the dark sub-bandgap states with oscillator strength borrowing from the band-edge transition. Our results show that upon valence to conduction band excitation, such subgap states are instantaneously bleached for large parts of the carrier lifetime and conversely that most dark sub-bandgap states can be populated by light excitation. This observation helps to unravel the photophysical origin of the unexpected optoelectronic properties of these materials.

Background: Factors associated with interval colorectal cancer (CRC) development in the inflammatory bowel disease (IBD) population remain unclear., Aims: Among a cohort of patients with interval CRC, we aimed to evaluate IBD characteristics, colonoscopy quality indicators, and surveillance guideline adherence., Methods: We performed a retrospective review of IBD- and non-IBD-associated interval CRCs diagnosed between January 2007 and December 2014 within a large US healthcare system. We evaluated risk factors for CRC among patients with IBD. We assessed adherence to surveillance guidelines according to the American Society for Gastrointestinal Endoscopy (IBD surveillance) and the US Multi-Society Task Force on Colorectal Cancer (polyp surveillance). We compared colonoscopy quality measures between patients with and without IBD., Results: Among 5345 cases of colonic adenocarcinoma, we detected 15 IBD-associated cases of interval CRC and 230 non-IBD-associated cases of interval CRC. Compared to patients without IBD, IBD patients were younger (54.5 vs. 70.4 years; p < 0.0001) and experienced a shorter interval between index colonoscopy and CRC diagnosis (20.7 vs. 35.1 months; p = 0.0009). Fifty three percent (8/15) of interval CRCs in IBD patients were detected within surveillance guidelines. All IBD patients with interval CRC detected after guideline surveillance interval had high-risk features, including active inflammation, previous low-grade or indefinite dysplasia, multiple pseudopolyps on index colonoscopy, or a first-degree relative with CRC. There were no differences in colonoscopy quality measures between patients with and without IBD., Conclusions: This study stresses the importance of strict short-interval surveillance for IBD patients with high-risk features, including active inflammation on index colonoscopy.

Optoelectronic devices based on conjugated polymers often rely on multilayer device architectures, as it is difficult to design all the different functional requirements, in particular the need for efficient luminescence and fast carrier transport, into a single polymer. Here we study the photophysics of a recently discovered class of conjugated polymers with high charge carrier mobility and low degree of energetic disorder and investigate whether it is possible in this system to achieve by molecular design a high photoluminescence quantum yield without sacrificing carrier mobility. Tracing exciton dynamics over femtosecond to microsecond time scales, we show that nearly all nonradiative exciton recombination arises from interactions between chromophores on different chains. We evaluate the temperature dependence and role of electron-phonon coupling leading to fast internal conversion in systems with strong interchain coupling and the extent to which this can be turned off by varying side chain substitution. By sterically decreasing interchain interaction, we present an effective approach to increase the fluorescence quantum yield of low-energy gap polymers. We present a red-NIR-emitting amorphous polymer with the highest reported film luminescence quantum efficiency of 18% whose mobility concurrently exceeds that of amorphous-Si. This is a key result toward the development of single-layer optoelectronic devices that require both properties.

Background & Aims: Obesity promotes intestinal inflammation and might contribute to the pathogenesis of inflammatory bowel disease. We examined the association between obesity and risk of microscopic colitis in a prospective cohort study., Methods: We collected data from 192,101 women enrolled in the Nurses' Health Study (NHS) (from 1986 through 2014) or the NHSII (from 1991 through 2015). Anthropomorphic and lifestyle information were self-reported biennially. Obesity was defined using body mass index (BMI). Microscopic colitis was confirmed by review of medical records. We used Cox proportional hazard models to estimate adjusted hazard ratios (aHRs) and 95% CIs., Results: Among the participants in the NHS and NHSII, we confirmed 244 cases of microscopic colitis during 4,223,868 person-years of follow-up evaluation. Higher BMI was associated inversely with risk of microscopic colitis (Ptrend < .001). Compared with women with BMIs ranging from 18.5 to 20.9 kg/m 2 , the aHRs were 0.61 (95% CI, 0.41-0.91) for overweight women (BMI, 25-29.9 kg/m 2 ) and 0.50 (95% CI, 0.32-0.79) for obese women (BMI ≥ 30 kg/m 2 ). The aHR for each 5-kg/m 2 increase in BMI was 0.79 (95% CI, 0.69-0.90). Weight gain since early adulthood (age, 18 y) also was associated inversely with risk of microscopic colitis (Ptrend = .001). The aHR for each 10-kg weight gain since early adulthood was 0.85 (95% CI, 0.77-0.94). The associations were not modified by age, cohort, physical activity, or smoking status (all Pinteraction ≥ .26)., Conclusions: Unlike many other immune- and metabolic-related disorders, obesity and weight gain since early adulthood were associated with a lower risk of microscopic colitis, based on an analysis of participants in the NHS and NHSII., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Deploy and evaluate a gastroenterology (GI) electronic consultation (e-consult) program. E-consults are a promising approach to enhance provider communication, facilitate timely specialty advice and may replace some outpatient visits., Study: As part of our health system's efforts to provide more cost-effective care under risk-based contracts, we implemented an e-consult program where referring providers submit patient-specific clinical questions electronically via an electronic referral system. A GI consultant then reviews the patient's record and provides a written recommendation back to the referring physician. For our program evaluation, we conducted chart reviews of each e-consult to understand how the program was being used and surveyed the participating providers and consultants., Results: From September 2015 to March 2016, we received 144 e-consults, with most questions concerning GI symptoms or abnormal hepatology labs. Only 36% of e-consults recommended an in-person GI consult or procedure. In our survey of participating providers, referring providers strongly agreed that the GI e-consults promoted good patient care (88%) and were satisfied with the program (84%). The majority of GI consultants felt strongly that e-consults were useful for referring providers and their patients, but that current reimbursement and time allotted were not adequate., Conclusions: We report on the implementation of a GI e-consult program within an ACO, showing that many clinical questions could be answered using this mechanism. E-consults in gastroenterology have the potential to reduce unnecessary visits and/or procedures for patients who can be managed by their primary provider, potentially increasing access for other patients.

Efficient conjugated polymer optoelectronic devices benefit from concomitantly high luminescence and high charge carrier mobility. This is difficult to achieve, as interchain interactions, which are needed to ensure efficient charge transport, tend also to reduce radiative recombination and lead to solid-state quenching effects. Many studies detail strategies for reducing these interactions to increase luminescence, or modifying chain packing motifs to improve percolation charge transport; however achieving these properties together has proved elusive. Here, we show that properly designed amorphous donor-alt-acceptor conjugated polymers can circumvent this problem; combining a tuneable energy gap, fast radiative recombination rates and luminescence quantum efficiencies >15% with high carrier mobilities exceeding 2.4 cm 2 /Vs. We use photoluminescence from exciton states pinned to close-crossing points to study the interplay between mobility and luminescence. These materials show promise towards realising advanced optoelectronic devices based on conjugated polymers, including electrically-driven polymer lasers.

One source of instability in perovskite solar cells (PSCs) is interfacial defects, particularly those that exist between the perovskite and the hole transport layer (HTL). We demonstrate that thermally evaporated dopant-free tetracene (120 nm) on top of the perovskite layer, capped with a lithium-doped Spiro-OMeTAD layer (200 nm) and top gold electrode, offers an excellent hole-extracting stack with minimal interfacial defect levels. For a perovskite layer interfaced between these graded HTLs and a mesoporous TiO 2 electron-extracting layer, its photoluminescence yield reaches 15% compared to 5% for the perovskite layer interfaced between TiO 2 and Spiro-OMeTAD alone. For PSCs with graded HTL structure, we demonstrate efficiency of up to 21.6% and an extended power output of over 550 hours of continuous illumination at AM1.5G, retaining more than 90% of the initial performance and thus validating our approach. Our findings represent a breakthrough in the construction of stable PSCs with minimized nonradiative losses.

Objective: Microscopic colitis is a common cause of chronic watery diarrhea among the elderly. Although the prevalence of celiac disease appears to be higher in patients with microscopic colitis, the relationship between dietary gluten intake and risk of microscopic colitis among individuals without celiac disease has not been explored., Methods: We conducted a prospective study of 160,744 US women without celiac disease enrolled in the Nurses' Health Study (NHS) and the NHSII. Dietary gluten intake was estimated using validated food frequency questionnaires every 4 years. Microscopic colitis was confirmed through medical records review. We used Cox proportional hazard modeling to estimate the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI)., Results: We documented 219 incident cases of microscopic colitis over more than 20 years of follow-up encompassing 3,716,718 person-years (crude incidence rate: 5.9/100,000 person-years) in NHS and NHSII. Dietary gluten intake was not associated with risk of microscopic colitis (Ptrend = 0.88). Compared to individuals in the lowest quintile of energy-adjusted gluten intake, the adjusted HR of microscopic colitis was 1.18 (95% CI: 0.77-1.78) for the middle quintile and 1.03 (95% CI: 0.67-1.58) for the highest quintile. Additional adjustment for primary dietary sources of gluten including refined and whole grains did not materially alter the effect estimates (All Ptrend ≥ 0.69). The null association did not differ according to lymphocytic or collagenous subtypes (Pheterogeneity = 0.72) and was not modified by age, smoking status, or body mass index (All Pinteraction ≥ 0.17)., Conclusions: Dietary gluten intake during adulthood was not associated with risk of microscopic colitis among women without celiac disease.