Search

OBJECTIVE: The aim of this study was to examine perceptions including knowledge, attitudes, and beliefs about e-cigarettes among ethno-culturally diverse Latino adults living in the US, a rapidly growing minority group for which we know little about their e-cigarette perceptions. DESIGN: A total of 25 focus groups with Latinos (n = 180; ages 18 to 64 years) were conducted in 2014. E-cigarettes users and non-users were recruited via purposive sampling techniques. Participants completed brief questionnaires on sociodemographic factors and tobacco use. Focus group discussions were conducted in English and Spanish, audio-recorded, and transcribed. Data were analyzed using thematic analysis procedures. RESULTS: Participants were of diverse Latino backgrounds. Over one-third (35%) reported current cigarette smoking and 8% reported current e-cigarette or hookah use. Nonsmokers reported experimenting with e-cigarettes and hookah during social occasions. Participants’ perceptions towards e-cigarettes were generally formed in comparison to conventional cigarettes. Perceived benefits of using e-cigarettes included their utility as a smoking cessation aid, higher social acceptability, and lower harm compared to conventional cigarettes. Negative perceptions of e-cigarettes included lower overall satisfaction compared to conventional cigarettes and high content of toxins. Socio-cultural factors (e.g., gender roles, familismo, and simpatía) also influenced perceptions of e-cigarette of study participants. CONCLUSIONS: Overall, Latino adults knew relatively little about the potential health risks associated with e-cigarette use. The limited knowledge about and misinformation of e-cigarettes among this rapidly growing minority group have important public health implications. Findings may inform culturally tailored health communication campaigns, which are much needed among underserved US Latino populations in light of low effectiveness of tobacco control and regulatory efforts.

Contains fulltext : 288037.pdf (Publisher’s version ) (Closed access) BACKGROUND: The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs. METHODS: In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing. FINDINGS: Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL [geometric SD 5·7]; p

IntroductionCrohn’s disease (CD) is characterised by discontinuous, relapsing enteric inflammation. Instituting advanced therapies at an early stage to suppress inflammation aims to prevent future complications such as stricturing or penetrating disease, and subsequent surgical resection. Therapeutics are effective but associated with certain side-effects and relatively expensive. There is therefore an urgent need for robust methods to predict which newly diagnosed patients will develop disabling disease, to identify patients who are most likely to benefit from early, advanced therapies. We aim to determine if magnetic resonance enterography (MRE) features at diagnosis improve prediction of disabling CD within 5 years of diagnosis.Methods and analysisWe describe the protocol for a multicentre, non-randomised, single-arm, prospective study of adult patients with newly diagnosed CD. We will use patients already recruited to the METRIC study and extend their clinical follow-up, as well as a separate group of newly diagnosed patients who were not part of the METRIC trial (MRE within 3 months of diagnosis), to ensure an adequate sample size. Follow-up will extend for at least 4 years. The primary outcome is to evaluate the comparative predictive ability of prognostic models incorporating MRE severity scores (Magnetic resonance Enterography Global Score (MEGS), simplified MAgnetic Resonance Index of Activity (sMaRIA) and Lémann Index) versus models using standard characteristics alone to predict disabling CD (modified Beaugerie definition) within 5 years of new diagnosis.Ethics and disseminationThis study protocol achieved National Health Service Research Ethics Committee (NHS REC), London—Hampstead Research Ethics Committee approval (IRAS 217422). Our findings will be disseminated via conference presentations and peer-reviewed publications.Trial registration numberISRCTN76899103.

Findings on impact of mismatch repair deficiency (MMRd) on patient outcomes in endometrial cancer (EC) have been inconsistent to date. The objective of this study was to compare the oncologic outcomes and recurrence patterns between MMRd and MMR-intact (MMRi) endometrioid EC (EEC).Between 2015 and 2018, we prospectively recruited 492 EEC cases from three cancer centers in Ontario, Canada. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry (IHC). Clinicopathological, survival and recurrence patterns were compared between MMRd and MMRi cases.Of 492 EEC, 348 were MMRi (71%) and 144 were MMRd (29%) with median follow-up of 16.8 months (0-69.6). MMRd tumors tended to be grade 2 or 3 (56% vs. 29%, p 0.001), with propensity for lymphovascular space invasion (28% vs. 18%, p = 0.024), lymph node involvement (7% vs. 5%, p 0.001) and received more adjuvant treatment (46% vs. 33%, p = 0.027). This group also had significantly lower 3-year recurrence-free survival (78% vs. 90%, p = 0.014) although there was no difference in OS (p = 0.603). MMRd cases were more likely to recur in retroperitoneal lymph nodes (p = 0.045). Upon subgroup analysis, MLH1 methylated tumors had the worst prognostic features and survival outcomes.MLH1 methylated EECs exhibit more aggressive features compared to other MMRd and MMRi EECs. This may indicate an inherent difference in tumor biology, suggesting the importance of individualized management based on EC molecular phenotype.

Purpose: To determine whether the androgen receptor (AR) inhibitor, enzalutamide, improves effectiveness of endocrine therapy (ET) in hormone receptor–positive (HR+) breast cancer. Patients and Methods: In this phase II trial, patients with HR+/HER2 normal advanced/metastatic breast cancer were randomized 1:1 to exemestane 25 mg with placebo or exemestane 50 mg with enzalutamide 160 mg daily (NCT02007512). Two parallel cohorts enrolled patients with 0 (cohort 1) or 1 (cohort 2) prior ET for advanced disease. Progression-free survival (PFS) was the primary endpoint in the intent-to-treat (ITT) population of each cohort. Biomarkers were evaluated in an exploratory analysis. Results: Overall, 247 patients were randomized (cohort 1, n = 127 and cohort 2, n = 120). PFS was not improved in either cohort of the ITT population [HR, 0.82 (95% confidence interval (CI), 0.54–1.26); P = 0.3631 for cohort 1 and HR, 1.02 (95% CI, 0.66–1.59); P = 0.9212 for cohort 2]. In cohort 1, high levels of AR mRNA were associated with greater benefit of enzalutamide (Pinteraction = 0.0048). This effect was particularly apparent in patients with both high levels of AR mRNA and low levels of ESR1 mRNA [HR, 0.24 (95% CI, 0.10–0.60); P = 0.0011]. The most common any grade adverse events in the enzalutamide arms were nausea (39%) in cohort 1 and fatigue (37%) in cohort 2. Conclusions: Enzalutamide with exemestane was well tolerated. While PFS was not improved by the addition of enzalutamide to exemestane in an unselected population, ET-naïve patients with high AR mRNA levels, particularly in combination with low ESR1 mRNA levels, may benefit from enzalutamide with exemestane.

ObjectivesFor synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests.Methods30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing.ResultsOf 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with aPMS2pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium.ConclusionsThere was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.

Background For women with ovarian cancer (OC), the optimal screening strategy to identify Lynch syndrome (LS) has not been determined. In the current study, the authors compared the performance characteristics of various strategies combining mismatch repair (MMR) immunohistochemistry (IHC), microsatellite instability testing (MSI), and family history for the detection of LS. Methods Women with nonserous and/or nonmucinous ovarian cancer were recruited prospectively from 3 cancer centers in Ontario, Canada. All underwent germline testing for LS and completed a family history assessment. Tumors were assessed using MMR IHC and MSI. The sensitivity, specificity, and positive and negative predictive values of screening strategies were compared with the gold standard of a germline result. Results Of 215 women, germline data were available for 189 (88%); 13 women (7%) had pathogenic germline variants with 7 women with mutS homolog 6 (MSH6); 3 women with mutL homolog 1 (MLH1); 2 women with PMS1 homolog 2, mismatch repair system component (PMS2); and 1 woman with mutS homolog 2 (MSH2). A total of 28 women had MMR‐deficient tumors (13%); of these, 11 had pathogenic variants (39%). Sequential IHC (with MLH1 promoter methylation analysis on MLH1‐deficient tumors) followed by MSI for nonmethylated and/or MMR‐intact patients was the most sensitive (92.3%; 95% confidence interval, 64%‐99.8%) and specific (97.7%; 95% confidence interval, 94.2%‐99.4%) approach, missing 1 case of LS. IHC with MLH1 promoter methylation analysis missed 2 patients of LS. Family history was found to have the lowest sensitivity at 55%. Conclusions Sequential IHC (with MLH1 promoter methylation analysis) followed by MSI was found to be most sensitive. However, IHC with MLH1 promoter methylation analysis also performed well and is likely more cost‐effective and efficient in the clinical setting. The pretest probability of LS is high in patients with MMR deficiency and warrants universal screening for LS., Although the incidence of mismatch repair deficiency (MMRd) is low (13%) in patients with nonserous and/or nonmucinous ovarian cancer, the likelihood of having Lynch syndrome is high in patients with MMRd (39%). In the current study, immunohistochemistry for mismatch repair proteins (with MLH1 promoter methylation analysis performed on MLH1‐deficient tumors) is found to be highly sensitive (85%) and specific (98%), missing only 2 patients of Lynch syndrome.

BACKGROUND AND PURPOSE: Cavernous malformations occur most often in the brain but can occur in the spinal cord. Small studies of patients with familial cerebral cavernous malformations suggested a prevalence of spinal cord cavernous malformations of 20%–42%. We aimed to review our familial cohort and prospectively estimate the prevalence of spinal cord cavernous malformations. MATERIALS AND METHODS: We initially reviewed our familial cerebral cavernous malformations cohort for spinal cord cavernous malformations and reviewed clinical spine MR imaging examinations for sequence sensitivity. We then prospectively performed research MR imaging of the spinal cord in 29 patients from the familial cohort to estimate the prevalence. RESULTS: Gradient-based sequences identified the most spinal cord cavernous malformations on clinical MR images, forming the basis for developing our screening MR imaging. Screening spinal cord MR imaging demonstrated a prevalence of 72.4%, and a positive correlation with patient age and number of cerebral cavernous malformations. CONCLUSIONS: Spinal cord cavernous malformations occur commonly in the familial cerebral cavernous malformation population. Gradient-based sequences are the most sensitive and should be used when spinal cord cavernous malformations are suspected. This study establishes the prevalence in the familial population at around 70% and supports the idea that this condition is a progressive systemic disease that affects the entire central nervous system.

This study aimed to determine the influence of acute resistance exercise (RE) and biological sex on subjective gastrointestinal (GI) symptoms, GI epithelial damage, and GI permeability in resistance-trained males and females.Thirty resistance-trained men ( n = 15) and women ( n = 15) completed an RE bout and a nonexercise control (CON) session in a randomized counterbalanced design. The RE protocol used a load of 70% one-repetition maximum for 4 sets of 10 repetitions with a 90-s rest period length between sets and a 120-s rest period between exercises (squat, seated shoulder press, deadlift, bent-over row, and leg press). Blood samples were collected before exercise (PRE), immediately postexercise (IP), and 15-, 30-, and 60-min postexercise. Participants completed GI symptom questionnaires to assess subjective GI symptoms PRE, IP, and 60-min postexercise. Blood samples were assayed to quantify small intestine damage (I-FABP) and GI permeability (lactulose-rhamnose [L/R] ratio). Data were analyzed via separate repeated-measures ANOVA, and area under the curve (AUC) analyses were completed via one-way ANOVA.Participants reported greater GI symptoms in RE at IP compared with CON ( P0.001) with 70% of participants reporting at least one GI symptom with no differences between sexes. Nausea was the most reported GI symptom (63.3%), followed by vomiting (33.3%). I-FABP and L/R ratio did not exhibit differential responses between conditions. However, L/R ratio AUC was greater in males after RE than male CON ( P = 0.002) and both conditions for females ( P0.05). Furthermore, I-FABP AUC in the male RE condition was greater than both female conditions ( P0.05).Resistance-trained individuals experience GI distress after RE, with males incurring the greatest increases in markers of GI damage and permeability.

Psychological factors are broadly understood to contribute to overall health, but their contribution to wound healing is less well defined. Limited data exist on the association of preoperative psychological factors such as body image and postoperative complications. The present study analyzed the association between preoperative body image factors and postoperative complications following breast reconstruction.This was a prospective cohort study of 302 breast cancer patients undergoing breast reconstruction from 2011 to 2015. All patients completed the BREAST-Q; demographics, surgical details, and postoperative complications were recorded. The association of body image factors by means of the BREAST-Q and postoperative complications was analyzed.On univariate analysis, patients who reported lower preoperative satisfaction with how they appeared in the mirror unclothed, or felt less self-confident or attractive, were significantly more likely to develop an infection postoperatively. Preoperative satisfaction scores were not associated with complications when analyzed in a multivariate fashion. On binomial logistic regression analysis, after controlling for age, body mass index, reconstruction technique, and use of radiotherapy, patients who reported less preoperative satisfaction with how comfortably bras fit or how they appeared in a mirror unclothed were at an increased risk for delayed wound healing.Patients with lower preoperative body satisfaction were found to have an increased incidence of infections and delayed wound healing. Although postoperative outcomes are multifactorial, the data suggest that baseline psychological factors such as body image may play a role in postoperative outcomes. Broader use of prehabilitative therapies, targeted at psychosocial factors, may warrant further investigation to optimize postoperative outcomes.Risk, III.

Smoking burdens are greatest among underserved patients. Lung cancer screening (LCS) reduces mortality among individuals at risk for smoking-associated lung cancer. Although LCS programs must offer smoking cessation support, the interventions that best promote cessation among underserved patients in this setting are unknown. This stakeholder-engaged, pragmatic randomized clinical trial will compare the effectiveness of four interventions promoting smoking cessation among underserved patients referred for LCS. By using an additive study design, all four arms provide standard “ask–advise–refer” care. Arm 2 adds free or subsidized pharmacologic cessation aids, arm 3 adds financial incentives up to $600 for cessation, and arm 4 adds a mobile device–delivered episodic future thinking tool to promote attention to long-term health goals. We hypothesize that smoking abstinence rates will be higher with the addition of each intervention when compared with arm 1. We will enroll 3,200 adults with LCS orders at four U.S. health systems. Eligible patients include those who smoke at least one cigarette daily and self-identify as a member of an underserved group (i.e., is Black or Latinx, is a rural resident, completed a high school education or less, and/or has a household income

Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults.Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters.The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life.In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Background To investigate whether common variants in EPHB4 and RASA1 are associated with cerebral cavernous malformation (CCM) disease severity phenotypes, including intracranial hemorrhage (ICH), total and large lesion counts. Methods Familial CCM cases enrolled in the Brain Vascular Malformation Consortium were included (n = 338). Total lesions and large lesions (≥5 mm) were counted on MRI; clinical history of ICH at enrollment was assessed by medical records. Samples were genotyped on the Affymetrix Axiom Genome‐Wide LAT1 Human Array. We tested the association of seven common variants (three in EPHB4 and four in RASA1) using multivariable logistic regression for ICH (odds ratio, OR) and multivariable linear regression for total and large lesion counts (proportional increase, PI), adjusting for age, sex, and three principal components. Significance was based on Bonferroni adjustment for multiple comparisons (0.05/7 variants = 0.007). Results EPHB4 variants were not significantly associated with CCM severity phenotypes. One RASA1 intronic variant (rs72783711 A>C) was significantly associated with ICH (OR = 1.82, 95% CI = 1.21–2.37, p = 0.004) and nominally associated with large lesion count (PI = 1.17, 95% CI = 1.03–1.32, p = 0.02). Conclusion A common RASA1 variant may be associated with ICH and large lesion count in familial CCM. EPHB4 variants were not associated with any of the three CCM severity phenotypes., We investigated whether common variants in EPHB4 and RASA1 are associated with familial cerebral cavernous malformation (CCM) disease severity phenotypes, including intracranial hemorrhage (ICH), total and large lesion counts. EPHB4 variants were not associated with any of the three CCM severity phenotypes. However, an intronic RASA1 variant was significantly associated with ICH and large lesion count in familial CCM, suggesting that the Ras‐Erk pathway may play a role in CCM disease severity.

Background Inpatient health care facilities restricted inpatient visitation due to the COVID-19 pandemic. There is no existing evidence of how they communicated these policies to the public nor the impact of their communication choices on public perception. Objective This study aims to describe patterns of inpatient visitation policies during the initial peak of the COVID-19 pandemic in the United States and the communication of these policies to the general public, as well as to identify communication strategies that maximize positive impressions of the facility despite visitation restrictions. Methods We conducted a sequential, exploratory, mixed methods study including a qualitative analysis of COVID-19 era visitation policies published on Pennsylvania-based facility websites, as captured between April 30 and May 20, 2020 (ie, during the first peak of the COVID-19 pandemic in the United States). We also conducted a factorial survey-based experiment to test how key elements of hospitals’ visitation policy communication are associated with individuals’ willingness to seek care in October 2020. For analysis of the policies, we included all inpatient facilities in Pennsylvania. For the factorial experiment, US adults were drawn from internet research panels. The factorial survey-based experiment presented composite policies that varied in their justification for restricted visitation, the degree to which the facility expressed ownership of the policy, and the inclusion of family-centered care support plans. Our primary outcome was participants’ willingness to recommend the hypothetical facility using a 5-point Likert scale. Results We identified 104 unique policies on inpatient visitation from 363 facilities’ websites. The mean Flesch-Kincaid Grade Level for the policies was 14.2. Most policies prohibited family presence (99/104, 95.2%). Facilities justified the restricted visitation policies on the basis of community protection (59/104, 56.7%), authorities’ guidance or regulations (34/104, 32.7%), or scientific rationale (23/104, 22.1%). A minority (38/104, 36.5%) addressed how restrictive visitation may impair family-centered care. Most of the policies analyzed used passive voice to communicate restrictions. A total of 1321 participants completed the web-based survey. Visitation policy elements significantly associated with willingness to recommend the facility included justifications based on community protection (OR 1.44, 95% CI 1.24-1.68) or scientific rationale (OR 1.30, 95% CI 1.12-1.51), rather than those based on a governing authority. The facility expressed a high degree of ownership over the decision (OR 1.16, 95% CI 1.04-1.29), rather than a low degree of ownership; and inclusion of family-centered care support plans (OR 2.80, 95% CI 2.51-3.12), rather than no such support. Conclusions Health systems can immediately improve public receptiveness of restrictive visitation policies by emphasizing community protection, ownership over the facility’s policy, and promoting family-centered care.

BACKGROUND AND AIMS Stimulant drug users have a greater prevalence of risky driving behaviour. This study aimed to assess how far this association remains after adjusting for aggressiveness. DESIGN Cross-sectional interview study assessing associations between measures of risky driving behaviours as outcomes, measures of stimulant drug use as predictors and a measure of aggressiveness as a covariate. SETTING United States. PARTICIPANTS Data were drawn from wave 3 (2012-13) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III) (n = 36 309 aged ≥ 18 years). MEASUREMENTS Stimulant drug use, past-year DSM-5 stimulant use disorder, aggression and measures of risky driving were assessed using face-to-face interviews conducted using the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-5) and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). FINDINGS Overall, 2714 (8.3%) respondents indicated life-time stimulant use, and 112 (0.3%) met criteria for past-year DSM-5 stimulant use disorder. More than 10% of ongoing stimulant users and one-third of respondents with DSM-5 stimulant use disorder reported stimulant-specific driving under the influence of drugs (DUID) in the past-year (both P

BACKGROUND: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal. METHODS: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study. We enrolled anti-TNF-naive patients (aged ≥6 years) with active luminal Crohn's disease at the time of first exposure to infliximab or adalimumab between March 7, 2013, and July 15, 2016. Patients were evaluated for 12 months or until drug withdrawal. Demographic data, smoking status, age at diagnosis, disease duration, location, and behaviour, previous medical and drug history, and previous Crohn's disease-related surgeries were recorded at baseline. At every visit, disease activity score, weight, therapy, and adverse events were recorded; drug and total anti-drug antibody concentrations were also measured. Treatment failure endpoints were primary non-response at week 14, non-remission at week 54, and adverse events leading to drug withdrawal. We used regression analyses to identify which factors were associated with treatment failure. FINDINGS:We enrolled 955 patients treated with infliximab (753 with originator; 202 with biosimilar) and 655 treated with adalimumab. Primary non-response occurred in 295 (23·8%, 95% CI 21·4-26·2) of 1241 patients who were assessable at week 14. Non-remission at week 54 occurred in 764 (63·1%, 60·3-65·8) of 1211 patients who were assessable, and adverse events curtailed treatment in 126 (7·8%, 6·6-9·2) of 1610 patients. In multivariable analysis, the only factor independently associated with primary non-response was low drug concentration at week 14 (infliximab: odds ratio 0·35 [95% CI 0·20-0·62], p=0·00038; adalimumab: 0·13 [0·06-0·28], p

There is anecdotal and empirical evidence for black cat bias, the phenomenon where cats ( Felis silvestris catus) with black coats are viewed more negatively, adopted less often, and euthanized more often than lighter colored cats. Despite the anecdotal claims, there is scarce empirical evidence for black cat bias. Using evaluations of cat photos, the researchers examined differences in people’s attitudes toward black and non-black cats of various colorations on measures of perceived aggression, perceived friendliness, and willingness to adopt. The researchers also explored whether participants’ levels of religiosity, superstitious beliefs, and prejudicial racial attitudes were related to black cat bias. Finally, the researchers explored whether black cat bias was related to difficulties people had in reading the emotions of black cats compared to non-black cats. This study provided evidence of black cat bias in the sample. People exhibiting higher degrees of black cat bias had higher levels of superstition, but not religiosity or racial prejudice. Additionally, people who had difficulty reading the emotions of black cats tended to exhibit a stronger bias against adopting black cats.

Introduction Use of electronic nicotine delivery systems (ENDS) has increased markedly. We examined how current ENDS users differ in perceptions of tobacco and ENDS-related health risks as a function of cigarette smoking status. Methods We classified 1329 current ENDS users completing a national online survey based on cigarette smoking status, and employed linear and logistic regression to assess group differences in perceptions of tobacco-related health risks. Results The sample consisted of 38% Current Cigarette Smokers, 40% Former Cigarette Smokers, and 22% Non-Smokers. Our targeted recruitment strategy yielded a balance of key descriptive variables across participants. Significant differences were observed in race, employment and marital status across cigarette smoking status, but not in gender, education, income, or sexual orientation. Participants reported considerable perceived knowledge about health risks associated with tobacco use, but less regarding ENDS use. Current Smokers rated ENDS use as riskier than Non-Smokers, and considered cigarette use less risky for both users and bystanders. Current Smokers were more likely to perceive cardiovascular diseases, diabetes and cancer as the health risks associated with ENDS use. Former Smokers were more likely to perceive such risks with traditional tobacco use. Further, regardless of smoking status, perceived knowledge about the health risks of tobacco or ENDS use was positively associated with perceived likelihood of high risks of cardiovascular diseases and cancer. Conclusions Among current ENDS users, there were significant differences in perceived health risks based on cigarette smoking history. Improved health messaging can be achieved when cigarette smoking status is taken into account.

Objective Change in risk tolerance is a feature of multiple psychiatric disorders and may contribute to adverse outcomes. We used a probability discounting (PD) task to measure risk-taking behavior among individuals with bipolar disorder (BPAD), major depressive disorder (MDD), schizoaffective disorder (SCAD), and schizophrenia (SCZ). Method A PD task was administered to 117 patients and 88 healthy controls (HCs), along with a cognitive battery using the Cambridge Neuropsychological Test Automated Battery, and relevant symptomatology scales. We examined differences in PD rates between diagnostic groups, and compared with HCs, while controlling for potential confounding factors including measures of cognitive functioning. Results Individuals with a diagnosis of BPAD or SCAD/SCZ prefer smaller, more guaranteed rewards rather than larger, less likely rewards as compared with healthy controls (p = .002 and p = .034, respectively). There was no effect of performance on cognitive tasks, antipsychotic treatment, or symptomatology on the rate of probability discounting. Conclusion This study supports the transdiagnostic measurement of risk-taking behaviors, even when such behaviors are not the primary area of psychopathology. Quantifying risk-taking may enable targeted therapeutic strategies across disorders. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Purpose: Standard-of-care treatment for metastatic hormone receptor–positive (HR+), HER2-negative (HER2−) breast cancer includes endocrine therapy (ET) combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Optimal treatment after progression on CDK4/6i is unknown. The TRINITI-1 trial investigated ribociclib, a CDK4/6i that has recently demonstrated significant overall survival benefit in two phase III trials, in combination with everolimus and exemestane in patients with HR+, HER2− advanced breast cancer (ABC) after progression on a CDK4/6i. Patients and Methods: This multicenter, open-label, single-arm, phase I/II study included patients with locally advanced/metastatic HR+/HER2− breast cancer. The primary endpoint was clinical benefit rate (CBR) at week 24 among patients with ET-refractory disease with progression on a CDK4/6i. Other endpoints included safety and biomarker analysis. Results: Of 104 patients enrolled (phases I and II), 96 had prior CDK4/6i. Recommended phase II doses (all once daily days 1–28 of 28-day cycle) were ribociclib 300 mg, everolimus 2.5 mg, and exemestane 25 mg (group 1) and ribociclib 200 mg, everolimus 5 mg, and exemestane 25 mg (group 2). CBR among 95 efficacy-evaluable patients (phases I and II) at week 24 was 41.1% (95% confidence interval, 31.1–51.6), which met the primary endpoint (predetermined threshold: 10%). Common adverse events included neutropenia (69.2%) and stomatitis (40.4%). No new safety signals were observed; no grade 3/4 QTc prolongation was reported. Conclusions: Preliminary TRINITI-1 safety and efficacy results support further investigation of CDK4/6 blockade and targeting of the PI3K/AKT/mTOR signaling pathway in patients with ET-refractory HR+/HER2− ABC after progression on a CDK4/6i.

Purpose Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab. Methods Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety. Results Overall, 103 women were enrolled [median age 60 years (range 34–83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0–3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs. Conclusions Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination. ClinicalTrials.gov number NCT02091960

Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6–12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23–53) among 18 who had received TH and 46 (range 34–54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045). Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.

PURPOSE/BACKGROUND Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation. METHODS/PROCEDURES Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2). FINDINGS/RESULTS Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES. IMPLICATIONS/CONCLUSIONS These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.

Background This pooled analysis of MONALEESA trials evaluated the safety of ribociclib plus endocrine therapy (RIB + ET) with a focus on dose reductions in first-line patients. Methods In the dose reduction analysis, data were pooled from MONALEESA-2 (all patients), MONALEESA-3 (patients receiving treatment as first-line ET) and MONALEESA-7 (patients receiving combination therapy with an NSAI as initial ET). Efficacy was analysed by ribociclib relative dose intensity (DI). Safety was analysed in all patients in the trials (except those receiving tamoxifen in MONALEESA-7) and those with/without ≥1 ribociclib dose reduction. Results Of 818 women who received first-line RIB + ET, 41.8% required ≥1 dose reduction due to AEs (most commonly, neutropenia). Median RIB relative DI in patients without and with dose reductions was 99.3% and 65.6% in MONALEESA-2, 98.4% and 67.8% in MONALEESA-3 and 98·0% and 66·3% in MONALEESA-7. Median PFS was 24.8, 24.9 and 29.6 months for patients who received ≤71% (30th percentile), 72-96% (60th percentile) and 97-100% (90th percentile) RIB relative DI, respectively. No new safety signals emerged in the pooled safety analysis. Conclusions This analysis provides reassuring data showing that the clinical benefit of RIB is preserved when dose modifications are undertaken to manage AEs. Trial registration MONALEESA-2 (NCT01958021) first posted October 8, 2013; MONALEESA-3 (NCT02422615) first posted April 21, 2015; MONALEESA-7 (NCT02278120) first posted October 29, 2014.

Purpose Trilaciclib is a first-in-class CDK4/6 inhibitor that transiently arrests hematopoietic stem and progenitor cells (HSPCs) in the G1 phase of the cell cycle to preserve them from chemotherapy-induced damage (myelopreservation). We report integrated analyses of preclinical and clinical data that informed selection of the recommended Phase II dose (RP2D) used in trilaciclib trials in extensive-stage small cell lung cancer (ES-SCLC). Methods A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model developed from preclinical data guided selection of an optimal dose for G1 bone marrow arrest in a first-in-human Phase I study (G1T28-1-01). PK, PD, safety, and efficacy data from G1T28-1-01 and two Phase Ib/IIa studies (G1T28-02/-03) in ES-SCLC were analyzed to support RP2D selection. Results Model simulation of bone marrow arrest based on preclinical data predicted that a ≥ 192 mg/m2 dose would induce a 40–50% decrease in total bone marrow proliferation in humans and almost 100% cell cycle arrest of cycling HSPCs. Consistent with this model, analysis of bone marrow aspirates in healthy volunteers after trilaciclib 192 mg/m2 administration demonstrated almost 100% G1 arrest in HSPCs and 40% decrease in total bone marrow proliferation, with minimal toxicity. G1T28-02/-03 reported similar PK parameters with trilaciclib 200 mg/m2 but slightly lower exposures than expected compared with healthy volunteers; consequently, 240 and 280 mg/m2 doses were also tested to match healthy volunteer exposures. Based on PK and relevant safety data, 240 mg/m2 was selected as the RP2D, which was also favored by myelopreservation endpoints in G1T28-02/-03. Conclusion Integrated PK/PD, safety, and efficacy data support 240 mg/m2 as the RP2D for trilaciclib. ClinicalTrials.gov Identifiers NCT02243150; NCT02499770; NCT02514447.

Background Increases in fatal drug poisonings and hepatitis C infections associated with the opioid epidemic are relatively well defined, because passive surveillance systems for these conditions exist. Less described is the association between the opioid epidemic and skin, soft-tissue, and venous infections (SSTVIs), endocarditis, sepsis, and osteomyelitis. Methods Michigan hospitalizations between 2016 and 2018 that included an International Classification of Diseases, Tenth Revision, Clinical Modification, code indicating substance use were examined for codes indicative of infectious conditions associated with injecting drugs. Trends in these hospitalizations were examined, as were demographic characteristics, discharge disposition, payer, and cost data. Results Among hospitalized patients with a substance use diagnosis code, endocarditis, osteomyelitis, sepsis, and SSTVI hospitalizations increased by 33%, 35%, 24%, and 12%, respectively between 2016 and 2018. During this time frame, 1257 patients died or were discharged to hospice. All SSTVI hospitalizations resulted in >$1.3 billion in healthcare costs. Public insurance accounted for more than two-thirds of all hospitalization costs. Conclusions This study describes a method for performing surveillance for infection-related sequelae of injection drug use. Endocarditis, osteomyelitis, sepsis, and SSTVI hospitalizations have increased year over year between 2016 and 2018. These hospitalizations result in significant morbidity, mortality, and healthcare costs and should be a focus of future surveillance and prevention efforts.

Background. Patients may find clinical prediction models more useful if those models accounted for preferences for false-positive and false-negative predictive errors and for other model characteristics. Methods. We conducted a discrete choice experiment to compare preferences for characteristics of a hypothetical mortality prediction model among community-dwelling patients with chronic lung disease recruited from 3 clinics in Philadelphia. This design was chosen to allow us to quantify “exchange rates” between different characteristics of a prediction model. We provided previously validated educational modules to explain model attributes of sensitivity, specificity, confidence intervals (CI), and time horizons. Patients reported their interest in using prediction models themselves or having their physicians use them. Patients then chose between 2 hypothetical prediction models each containing varying levels of the 4 attributes across 12 tasks. Results. We completed interviews with 200 patients, among whom 95% correctly chose a strictly dominant model in an internal validity check. Patients’ interest in predictive information was high for use by themselves ( n = 169, 85%) and by their physicians ( n = 184, 92%). Interest in maximizing sensitivity and specificity were similar (0.88 percentage points of specificity equivalent to 1 point of sensitivity, 95% CI 0.72 to 1.05). Patients were willing to accept a reduction of 6.10 months (95% CI 3.66 to 8.54) in the predictive time horizon for a 1% increase in specificity. Discussion. Patients with chronic lung disease can articulate their preferences for the characteristics of hypothetical mortality prediction models and are highly interested in using such models as part of their care. Just as clinical care should become more patient centered, so should the characteristics of predictive models used to guide that care.

Hereditary diffuse gastric cancer (HDGC) is an inherited cancer syndrome associated with high lifetime risk of diffuse-type gastric cancer. Current guidelines recommend individuals with HDGC undergo prophylactic total gastrectomy (PTG) to eliminate this risk. However, PTG is associated with significant lifestyle changes, post-surgical recovery, and symptom burden. This study examined factors related to decision-making about PTG in three groups of individuals who: (1) underwent PTG immediately after receiving genetic testing results; (2) delayed PTG by ≥ 1 year or; (3) declined PTG. Participants were recruited from a familial gastric cancer registry at a tertiary care hospital. Patients with CDH1 pathogenic or likely pathogenic variants who contemplated and/or underwent PTG were eligible. 24 individuals contemplated PTG: 9 had immediate surgery (within a year), 8 delayed surgery, and 7 declined surgery. Data on PTG barriers and facilitators were obtained on all participants using quantitative surveys (n = 7), qualitative interviews (n = 8) or both methods (n = 9). PTG barriers included age, positive beliefs about screening, close relatives with negative PTG experiences, fertility-related concerns, and life stress. Facilitators included social support, trust in healthcare providers, understanding risk, negative beliefs about screening, family-related factors, positive or abnormal screening results, and positive attitude toward PTG. This study highlights factors related to the PTG decision-making process among individuals with HDGC from three distinct groups. Future research should explore educational interventions aimed at addressing surgery-related concerns and the limitations of screening, and might also consider incorporating close relatives as informational supports.

This study examined the differences in perceptions of one's health and one's child's health between parents with Lynch syndrome (LS) characterized with high versus low health anxiety. Twenty-one parents completed semistructured telephone interviews about their perceptions of their own health and the health of their children. Qualitative content analysis using a template coding approach examined the differences between parents with high and low health anxiety. Findings revealed that the most prevalent difference emerged on perceptions of personal health, showing individuals with high health anxiety reported more extreme worries, were more hypervigilant about physical symptoms, experienced the emotional and psychological consequences of LS as more negative and severe, and engaged in more dysfunctional coping strategies than those with low health anxiety. Unexpectedly, with regards to perceptions of their children, parents in the high and low health anxiety groups exhibited similar worries. However, high health anxiety parents reported using dysfunctional coping about their children's health more frequently than those with low health anxiety. The findings suggest that health anxiety is of clinical significance for individuals with LS. Accurately identifying and treating health anxiety among this population may be one avenue to reduce the distress experienced by LS carriers.

Objective: D-cycloserine (DCS) promotes consolidation of extinction learning. This study extends earlier work by examining whether DCS can enhance cognitive behavioral therapy (CBT) for delusions. Methods: adults reporting moderate or greater delusions were randomly assigned to receive 50 mg of DCS or placebo prior to 10 weekly CBT sessions. The primary outcome was change in severity of delusions measured with the Psychotic Symptom Rating Scale delusion subscale (PSYRATS-D). Secondary outcomes included persistence of response at 3 and 6 month follow-up and the effects of DCS on memory consolidation and cognitive flexibility. Fifty-eight participants were randomized and 44 completed the trial. Results: the DCS and placebo groups did not differ in change from baseline to end of CBT on PSYRATS-D, nor did DCS improve memory consolidation or cognitive flexibility compared to placebo. However, at the 3 month follow-up visit (week 24), 47% of participants who completed treatment with DCS reported a 20% or greater decrease on PSYRATS-D compared to 15% in the placebo group (p =.04). Change in distress across CBT sessions interacted with treatment group to predict change from baseline to week 24 in PSYRATS-D total score (p =.03) such that response at week 24 was greatest in DCS-treated participants who experienced a decrease in distress during CBT sessions. Conclusions: DCS augmentation of CBT did not improve delusions compared to placebo during treatment; however, DCS was associated with a higher response rate at 3-month follow-up. DCS may produce a delayed therapeutic effect, associated with successful CBT sessions, but this finding requires replication.

Background The authors evaluated mocetinostat (a class I/IV histone deacetylase inhibitor) in patients with urothelial carcinoma harboring inactivating mutations or deletions in CREB binding protein [CREBBP] and/or E1A binding protein p300 [EP300] histone acetyltransferase genes in a single‐arm, open‐label phase 2 study. Methods Eligible patients with platinum‐treated, advanced/metastatic disease received oral mocetinostat (at a dose of 70 mg 3 times per week [TIW] escalating to 90 mg TIW) in 28‐day cycles in a 3‐stage study (ClinicalTrials.gov identifier NCT02236195). The primary endpoint was the objective response rate. Results Genomic testing was feasible in 155 of 175 patients (89%). Qualifying tumor mutations were CREBBP (15%), EP300 (8%), and both CREBBP and EP300 (1%). A total of 17 patients were enrolled into stage 1 (the intent‐to‐treat population); no patients were enrolled in subsequent stages. One partial response was observed (11% [1 of 9 patients; the population that was evaluable for efficacy comprised 9 of the 15 planned patients]); activity was deemed insufficient to progress to stage 2 (null hypothesis: objective response rate of ≤15%). All patients experienced ≥1 adverse event, most commonly nausea (13 of 17 patients; 77%) and fatigue (12 of 17 patients; 71%). The median duration of treatment was 46 days; treatment interruptions (14 of 17 patients; 82%) and dose reductions (5 of 17 patients; 29%) were common. Mocetinostat exposure was lower than anticipated (dose‐normalized maximum serum concentration [Cmax] after TIW dosing of 0.2 ng/mL/mg). Conclusions To the authors’ knowledge, the current study represents the first clinical trial using genomic‐based selection to identify patients with urothelial cancer who are likely to benefit from selective histone deacetylase inhibition. Mocetinostat was associated with significant toxicities that impacted drug exposure and may have contributed to modest clinical activity in these pretreated patients. The efficacy observed was considered insufficient to warrant further investigation of mocetinostat as a single agent in this setting., After the genomic‐based selection of patients with urothelial cancer with inactivating mutations/deletions in the histone acetyltransferase genes CREBBP and/or EP300, single‐agent mocetinostat appears to be associated with significant toxicities that limit drug exposure. This may have contributed to the limited activity noted in the current phase 2 study (response rate of 11%) among heavily pretreated patients with platinum‐refractory disease.

BACKGROUND. Patients with schizophrenia (SCZ) experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymes that regulate cognitive circuitry; however, the role of HDACs in cognitive disorders, including SCZ, remains unknown in humans. We previously determined that HDAC2 mRNA levels were lower in dorsolateral prefrontal cortex (DLPFC) tissue from donors with SCZ compared with controls. Here we investigated the relationship between in vivo HDAC expression and cognitive impairment in patients with SCZ and matched healthy controls using [(11)C]Martinostat positron emission tomography (PET). METHODS. In a case-control study, relative [((11))C]Martinostat uptake was compared between 14 patients with SCZ or schizoaffective disorder (SCZ/SAD) and 17 controls using hypothesis-driven region-of-interest analysis and unbiased whole brain voxel-wise approaches. Clinical measures, including the MATRICS consensus cognitive battery, were administered. RESULTS. Relative HDAC expression was lower in the DLPFC of patients with SCZ/SAD compared with controls, and HDAC expression positively correlated with cognitive performance scores across groups. Patients with SCZ/SAD also showed lower relative HDAC expression in the dorsomedial prefrontal cortex and orbitofrontal gyrus, and higher relative HDAC expression in the cerebral white matter, pons, and cerebellum compared with controls. CONCLUSIONS. These findings provide in vivo evidence of HDAC dysregulation in patients with SCZ and suggest that altered HDAC expression may impact cognitive function in humans. FUNDING. National Institute of Mental Health (NIMH), Brain and Behavior Foundation, Massachusetts General Hospital (MGH), Athinoula A. Martinos Center for Biomedical Imaging, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH Shared Instrumentation Grant Program.

There is little research examining the social patterning of electronic nicotine delivery system (ENDS) use. This study investigated the association between socioeconomic status (SES) (education, income, and employment status) and current and former ENDS use. Data were collected from 2561 participants from the American Heart Association Tobacco Regulatory and Addiction Center (A-TRAC) online survey. Participants were 18–64 years old and reported demographic, SES, and ENDS use. Poisson regression was used to estimate prevalence ratios (PR 95% confidence interval-CI) of participants’ current and former (vs. never) ENDS use. Models were adjusted for age, sex, sexual orientation, race/ethnicity, marital status, and reasons for ENDS use. In the unadjusted analysis, ENDS use was primarily patterned by education and employment status. College educated persons (versus those with less than a high school diploma) had a 37% greater prevalence of current ENDS use (PR 1.37, 95% CI 1.20–1.55), and a 16% greater prevalence of former ENDS use (PR 1.16, 95% CI 1.06–1.28) in the fully-adjusted model. Persons with household incomes above $90K (versus less than $20,000) had a greater prevalence of current (PR 1.30, 95% CI 1.19–1.41) and former (PR 1.17, 95% CI 1.05–1.30) ENDS use. Those who were employed (versus not employed) had a 13% greater prevalence of current ENDS use (PR: 1.13, 95% CI 1.07–1.19) after full adjustment. Higher SES (versus lower SES) persons were more likely to use ENDS.

Background The assessment of user preferences for performance characteristics of patient-oriented clinical prediction models is lacking. It is unknown if complex statistical aspects of prediction models are readily understandable by a general audience. Objective A pilot study was conducted among nonclinical audiences to determine the feasibility of interpreting statistical concepts that describe the performance of prediction models. Methods We conducted a cross-sectional electronic survey using the Amazon Mechanical Turk platform. The survey instrument included educational modules about predictive models, sensitivity, specificity, and confidence intervals (CIs). Follow-up questions tested participants' abilities to interpret these characteristics with both verbatim and gist knowledge. Objective and subjective numeracy were assessed using previously validated instruments. We also tested understanding of these concepts when embedded in a sample discrete choice experiment task to establish feasibility for future elicitation of preferences using a discrete choice experiment design. Multivariable linear regression was used to identify factors associated with correct interpretation of statistical concepts. Results Among 534 respondents who answered all nine questions, the mean correct responses was 95.9% (95% CI, 93.8–97.4) for sensitivity, 93.1% (95% CI, 90.5–95.0) for specificity, and 86.6% (95% CI, 83.3–89.3) for CIs. Verbatim interpretation was high for all concepts, but significantly higher than gist only for CIs (p Conclusion These results suggest that a nonclinical audience can interpret quantitative performance measures of predictive models with very high accuracy. Future development of patient-facing clinical prediction models can feasibly incorporate patient preferences for model features into their development.

Background: Spinal cord injury (SCI) occurring at the cervical levels can result in significantly impaired arm and hand function. People with cervical-level SCI desire improved use of their arms and hands, anticipating that regained function will result in improved independence and ultimately improved quality of life. Neuroprostheses provide the most promising method for significant gain in hand and arm function for persons with cervical-level SCI. Neuroprostheses utilize small electrical currents to activate peripheral motor nerves, resulting in controlled contraction of paralyzed muscles. Methods: A myoelectrically-controlled neuroprosthesis was evaluated in 15 arms in 13 individuals with cervical-level SCI. All individuals had motor level C5 or C6 tetraplegia. Results: This study demonstrates that an implanted neuroprosthesis utilizing myoelectric signal (MES)–controlled stimulation allows considerable flexibility in the control algorithms that can be utilized for a variety of arm and hand functions. Improved active range of motion, grip strength, and the ability to pick up and release objects were improved in all arms tested. Adverse events were few and were consistent with the experience with similar active implantable devices. Conclusion: For individuals with cervical SCI who are highly motivated, implanted neuroprostheses provide the opportunity to gain arm and hand function that cannot be gained through the use of orthotics or surgical intervention alone. Upper extremity neuroprostheses have been shown to provide increased function and independence for persons with cervical-level SCI.

Aim\ud \ud Crohn's anal fistula should be managed by a multidisciplinary team. There is no clearly defined ‘patient pathway’ from presentation to treatment. The aim of this study was to describe the patient route from presentation with symptomatic Crohn's anal fistula to starting anti-tumour necrosis factor (anti-TNF) therapy.\ud \ud \ud \ud Method\ud \ud Case note review was undertaken at three hospitals with established inflammatory bowel disease services. Patients with Crohn's anal fistula presenting between 2010 and 2015 were identified through clinical coding and local databases. Baseline demographics were captured. Patient records were interrogated to identify route of access, and clinical contacts during the patient pathway.\ud \ud \ud \ud Results\ud \ud Seventy-nine patients were included in the study, of whom 54 (68%) had an established diagnosis of Crohn's disease (CD). Median time from presentation to anti-TNF therapy was 204 days (174 vs 365 days for existing and new diagnosis of CD, respectively; P = 0.019). The mean number of surgical outpatient attendances, operations and MRI scans per patient was 1.03, 1.71 and 1.03, respectively. Patients attended a mean of 1.49 medical clinics. Seton insertion was the most common procedure, accounting for 48.6% of all operations. Where care episodes (‘clinical events per 30 days’) were infrequent this correlated with prolongation of the pathway (r = −0.87; P < 0.01).\ud \ud \ud \ud Conclusion\ud \ud This study highlights two key challenges in the treatment pathway: (i) delays in diagnosis of underlying CD in patients with anal fistula and (ii) the pathway to anti-TNF therapy is long, suggesting issues with service design and delivery. These should be addressed to improve patient experience and outcome.

Although college students represent a growing demographic of e-cigarette users, it is unclear how knowledgeable they are about the product they use. The lack of such knowledge could result in unsafe practices and greater health risks. Therefore, the purpose of the current study was to examine college student e-cigarette users’ knowledge about e-cigarette ingredients and health risks, how often they modify their devices, and whether they utilize reputable sources when searching for information regarding e-cigarettes. The participants were 183 undergraduate e-cigarette users (Mage = 19.98, SD = 1.98; 71.6% female; 85.8% White). Most participants correctly recognized that e-cigarettes increase the risk of cardiovascular disease and lung disease, but fewer than half recognized the increased risk of seizures and depression. Only one-third to one-half of participants correctly identified the toxic compounds commonly found in e-cigarettes, and most indicated that they would consult Google or a friend with questions about e-cigarettes. College student e-cigarette users are well-informed about many health risks associated with e-cigarettes. However, they are relatively unaware of the harmful substances in e-cigarettes and are seeking information from less reliable sources. Targeted public health campaigns educating college students about e-cigarettes, including where to seek reliable information, are needed.

Across 7 experiments (N = 3883), we demonstrate that communicators and targets make egocentric moral judgments of deception. Specifically, communicators focus more on the costs of deception to them-for example, the guilt they feel when they break a moral rule-whereas targets focus more on whether deception helps or harms them. As a result, communicators and targets make asymmetric judgments of prosocial lies of commission and omission: Communicators often believe that omitting information is more ethical than telling a prosocial lie, whereas targets often believe the opposite. We document these effects within the context of health care discussions, employee layoffs, and economic games, among both clinical populations (i.e., oncologists and cancer patients) and lay people. We identify moderators and downstream consequences of this asymmetry. We conclude by discussing psychological and practical implications for medicine, management, behavioral ethics, and human communication. (PsycINFO Database Record

Purpose Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Methods Postmenopausal women with HR+ , HER2− advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Results Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27–0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Conclusions Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2− de novo advanced breast cancer.

Fatigue and insomnia are common debilitating symptoms associated with multiple sclerosis (MS). Negative subjective appraisals of symptoms may influence both insomnia and fatigue severity, but this relationship has not been examined among those with MS. The relationship between insomnia symptoms and both physical and cognitive fatigue were examined. Health-related self-efficacy, fatigue catastrophization, and rumination were examined as potential mediators of the relationship between insomnia symptoms and fatigue.Participants diagnosed with MS (N = 115) were recruited from hospital and community settings in a large metropolitan city.Participants completed self-report questionnaires, including: Modified Fatigue Impact, Insomnia Severity Index, MS Quality of Life Questionnaire-54, Fatigue Catastrophizing Scale, Multidimensional Health Locus of Control Scale, and the Rumination-Reflection Questionnaire. Two multiple mediation analyses were performed using bootstrapping techniques, examining the cognitive and physical domains of fatigue as separate outcomes.Mediation analyses revealed a significant association between insomnia symptom severity and the cognitive and physical domains of fatigue. Fatigue catastrophizing was the only significant mediator, accounting for 25% of the variance in the relationship between insomnia symptoms and the cognitive fatigue. However, fatigue catastrophizing did not significantly mediate the relationship between insomnia symptoms and physical fatigue, indicating physical and cognitive fatigue may reflect distinct processes in fatigue expression in those with MS.

International Federations in Paralympic sport should develop evidence based classification, based on the relative strength of association between impairment and activities that determine sport specific performance. The purpose of the current study was to assess the relationship between trunk strength impairment and three activities that determine performance in Wheelchair Rugby, and to determine whether this relationship supports the concept of “natural classes”. Trunk muscle strength and three determinants of performance were assessed in 27 athletes The correlations between lateral trunk muscle strength and the determinant tilting the chair, and between forward trunk muscle strength and the determinants 1 m acceleration and sprint momentum were calculated. To group athletes based on impairment, K-means cluster analysis was used to group athletes according to how much trunk muscle strength affected the activities. There were significant, moderate to strong correlations between left-right strength and chair tilting (r = .50), between forward strength and 1 m acceleration (r = .59) and between forward strength and sprint momentum (r = .79). Cluster analysis indicated at least one cut-point in performance with a decrease in impairment in all three wheelchair activities, supporting the concept of “natural classes”. This article is protected by copyright. All rights reserved.

This phase I trial evaluated the safety, pharmacokinetic profile, and antitumor activity of investigational oral TORC1/2 inhibitor TAK-228 plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. Sixty-seven patients received TAK-228 6–40 mg via three dosing schedules; once daily for 3 days (QDx3d QW) or 5 days per week (QDx5d QW), and once weekly (QW) plus paclitaxel 80 mg/m2 (dose-escalation phase, n = 47) and with/without trastuzumab 2 mg/kg (expansion phase, n = 20). Doses were escalated using a modified 3 + 3 design, based upon dose-limiting toxicities in cycle 1. TAK-228 pharmacokinetics exhibited dose-dependent increase in exposure when dosed with paclitaxel and no apparent differences when administered with or 24 h after paclitaxel. Dose-limiting toxicities were dehydration, diarrhea, stomatitis, fatigue, rash, thrombocytopenia, neutropenia, leukopenia, and nausea. The maximum tolerated dose of TAK-228 was determined as 10-mg QDx3d QW; the expansion phase proceeded with 8-mg QDx3d QW. Overall, the most common grade ≥3 drug-related toxicities were neutropenia (21%), diarrhea (12%), and hyperglycemia (12%). Of 54 response-evaluable patients, eight achieved partial response and six had stable disease lasting ≥6 months. TAK-228 demonstrated a safety profile consistent with other TORC inhibitors and promising preliminary antitumor activity in a range of tumor types; no meaningful difference was noted in the pharmacokinetics of TAK-228 when administered with or 24 h after paclitaxel. These findings support further investigation of TAK-228 in combination with other agents including paclitaxel, with/without trastuzumab, in patients with advanced solid tumors. NCT01351350.

Objective To better understand variation in reported rates of delirium, this study characterized delirium occurrence rate by department of service and primary admitting diagnosis. Method Nine consecutive years (2005–2013) of general hospital admissions (N=831,348) were identified across two academic medical centers using electronic health records. The primary admitting diagnosis and the treating clinical department were used to calculate occurrence rates of a previously published delirium definition composed of billing codes and natural language processing of discharge summaries. Results Delirium rates varied significantly across both admitting diagnosis group ( X 2 10 =12786, p X 2 6 =12106, p p p Conclusions The frequency of delirium varies significantly across admitting diagnosis and hospital department. Both admitting diagnosis and department of care are even stronger predictors of risk than age; as such, simple risk stratification may offer avenues for targeted prevention and treatment efforts.

Although diabetes mellitus (DM) is a known risk factor for surgical complications in general, there is little published evidence to establish such an effect among patients undergoing breast reconstruction (BR). The purpose of this study was to assess the impact of DM on complications in patients undergoing postmastectomy BR.Patients who underwent BR at our institution from November 2002 to November 2012 were identified. Clinical and demographic data of patients with type 1 or type 2 DM were reviewed. Complications occurring within 60 days of surgery were compared between diabetic and nondiabetic patients for both autologous and nonautologous reconstruction types.A total of 1371 BR were performed in 1035 patients. There were 877 (64.0%) autologous reconstructions and 494 (36.0%) implant-based reconstructions. Patients with DM (n = 64) had significantly higher preoperative blood glucose levels (137.5 vs 100.1, P0.05). Postoperatively, DM patients reconstructed with implants had a significantly higher incidence of delayed wound healing (22.2% vs 9.7%; P = 0.04). This was not observed in patients with DM reconstructed with autologous tissue (7.4% vs 6.6%; P = 0.70). Diabetic patients had a significantly higher incidence of hypertension and were older than nondiabetic patients. To control for these variables and other potential confounders, multiple logistic regression analysis was performed. Again, diabetic patients had a significantly higher incidence of delayed wound healing following implant-based reconstruction (odds ratio, 2.52, 95% confidence interval = 1.2-6.2) but not autologous reconstruction (odds ratio, 0.97; 95% confidence interval = 0.2-4.6).Diabetes heightens the risk of wound healing complications among patients undergoing implant-based reconstruction.

Familial cerebral cavernous malformations due to the common Hispanic mutation (FCCM1-CHM) is an endemic condition among the Hispanic population of the Southwestern United States associated with significant morbidity and mortality. Cutaneous vascular malformations (CVMs) can be found in individuals with FCCM1-CHM, but their morphology, prevalence, and association with cerebral cavernous malformations (CCMs) has not been well characterized. A cross-sectional study of 140 individuals with confirmed FCCM1-CHM was performed with statistical analyses of CVM, CCM, and patient characteristics. We then compared these findings to other cohorts with Familial cerebral cavernous malformations (FCCM) due to other mutations. We observed a higher overall prevalence and a different predominant morphological subtype of CVM compared to previous FCCM cohorts. While the number of CVMs was not a reliable indicator of the number of CCMs present, each person with one or more CVMs had evidence of central nervous system (CNS) disease. Awareness of the morphology of these cutaneous lesions can aid in the diagnosis of individuals with FCCM-CHM in Hispanic patients or those with family history of CCM.

Introduction Prior research has shown that tobacco companies target point-of-sale (POS) marketing to low-income communities. This research assessed the association between demographic characteristics and venue type with purchasing tobacco products in response to marketing. Methods Using Population Assessment of Tobacco and Health (PATH) Study Wave 1 Adult data, this analysis compared promotion awareness and purchase influence among current smokers. Results Tobacco promotions were more likely to be noticed at convenience stores, gas stations, or tobacco stores than at other outlets. Smokers who bought their cigarettes at these outlets were more likely to purchase a brand other than their usual brand because of marketing. Smokers below the poverty level had greater odds than others to have noticed tobacco ads and to indicate purchase influence. Conclusions Point-of-sale marketing is effective in garnering the attention of low-income populations and influencing their tobacco purchases. Enforcing retailers' adherence to regulations is vital.

OBJECTIVE. The purpose of this study was to investigate whether MRI-typical and MRI-atypical intraosseous vascular malformations are associated with familial cerebral cavernous malformation (FCCM). MATERIALS AND METHODS. In a retrospective matched case-control study, two radiologists reviewed the spinal imaging, both CT and MRI, of 22 patients with FCCM seen between 2006 and 2017 and of age- and sex-matched control subjects for MRI-typical and MRI-atypical intraosseous vascular malformations. Quantitative analysis of lesions identified included vertebral level, size, and number of lesions. Pathologic samples from two lesions were analyzed for histologic and immunohistochemical features. Whether the presence of typical, atypical, and total intraosseous vascular malformations differed between patients and control subjects was tested. For patients with complete spinal imaging, whether intraosseous vascular malformations were associated with age, sex, brain lesion count, and spinal lesion count was also tested. RESULTS. MRI-atypical intraosseous vertebral malformations were more commonly present in patients with FCCM (p = 0.003). Sixteen lesions were found in nine patients and none in the control group. The numbers of MRI-typical intraosseous vascular malformations were similar between patients and control subjects (p = 0.480). Age was associated with typical intraosseous vascular malformations (p = 0.027), though not with atypical malformations. MRI-atypical malformations were larger (mean diameter double) than MRI-typical malformations (p = 0.023). Histologic analysis of two lesions from different patients with pathologic collapse revealed the same histologic features consistent with combined capillary-venous malformations. CONCLUSION. Vertebral capillary-venous malformations (MRI-atypical intraosseous vascular malformations) are common in patients with FCCM and may have a more aggressive clinical course than MRI-typical malformations.

Background Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation). Preclinically, trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity. Patients and methods This was a phase Ib (open-label, dose-finding) and phase II (randomized, double-blind placebo-controlled) study of the safety, efficacy and PK of trilaciclib in combination with etoposide/carboplatin (E/P) therapy for treatment-naive extensive-stage small-cell lung cancer patients. Patients received trilaciclib or placebo before E/P on days 1–3 of each cycle. Select end points were prespecified to assess the effect of trilaciclib on myelosuppression and antitumor efficacy. Results A total of 122 patients were enrolled, with 19 patients in part 1 and 75 patients in part 2 receiving study drug. Improvements were seen with trilaciclib in neutrophil, RBC (red blood cell) and lymphocyte measures. Safety on trilaciclib+E/P was improved with fewer ≥G3 adverse events (AEs) in trilaciclib (50%) versus placebo (83.8%), primarily due to less hematological toxicity. No trilaciclib-related ≥G3 AEs occurred. Antitumor efficacy assessment for trilaciclib versus placebo, respectively, showed: ORR (66.7% versus 56.8%, P = 0.3831); median PFS [6.2 versus 5.0 m; hazard ratio (HR) 0.71; P = 0.1695]; and OS (10.9 versus 10.6 m; HR 0.87; P = 0.6107). Conclusion Trilaciclib demonstrated an improvement in the patient's tolerability of chemotherapy as shown by myelopreservation across multiple hematopoietic lineages resulting in fewer supportive care interventions and dose reductions, improved safety profile, and no detriment to antitumor efficacy. These data demonstrate strong proof-of-concept for trilaciclib's myelopreservation benefits. Clinical Trail number NCT02499770.

BackgroundMagnetic resonance enterography and enteric ultrasonography are used to image Crohn’s disease patients. Their diagnostic accuracy for presence, extent and activity of enteric Crohn’s disease was compared.ObjectiveTo compare diagnostic accuracy, observer variability, acceptability, diagnostic impact and cost-effectiveness of magnetic resonance enterography and ultrasonography in newly diagnosed or relapsing Crohn’s disease.DesignProspective multicentre cohort study.SettingEight NHS hospitals.ParticipantsConsecutive participants aged ≥ 16 years, newly diagnosed with Crohn’s disease or with established Crohn’s disease and suspected relapse.InterventionsMagnetic resonance enterography and ultrasonography.Main outcome measuresThe primary outcome was per-participant sensitivity difference between magnetic resonance enterography and ultrasonography for small bowel Crohn’s disease extent. Secondary outcomes included sensitivity and specificity for small bowel Crohn’s disease and colonic Crohn’s disease extent, and sensitivity and specificity for small bowel Crohn’s disease and colonic Crohn’s disease presence; identification of active disease; interobserver variation; participant acceptability; diagnostic impact; and cost-effectiveness.ResultsOut of the 518 participants assessed, 335 entered the trial, with 51 excluded, giving a final cohort of 284 (133 and 151 in new diagnosis and suspected relapse cohorts, respectively). Across the whole cohort, for small bowel Crohn’s disease extent, magnetic resonance enterography sensitivity [80%, 95% confidence interval (CI) 72% to 86%] was significantly greater than ultrasonography sensitivity (70%, 95% CI 62% to 78%), with a 10% difference (95% CI 1% to 18%;p = 0.027). For small bowel Crohn’s disease extent, magnetic resonance enterography specificity (95%, 95% CI 85% to 98%) was significantly greater than ultrasonography specificity (81%, 95% CI 64% to 91%), with a 14% difference (95% CI 1% to 27%). For small bowel Crohn’s disease presence, magnetic resonance enterography sensitivity (97%, 95% CI 91% to 99%) was significantly greater than ultrasonography sensitivity (92%, 95% CI 84% to 96%), with a 5% difference (95% CI 1% to 9%). For small bowel Crohn’s disease presence, magnetic resonance enterography specificity was 96% (95% CI 86% to 99%) and ultrasonography specificity was 84% (95% CI 65% to 94%), with a 12% difference (95% CI 0% to 25%). Test sensitivities for small bowel Crohn’s disease presence and extent were similar in the two cohorts. For colonic Crohn’s disease presence in newly diagnosed participants, ultrasonography sensitivity (67%, 95% CI 49% to 81%) was significantly greater than magnetic resonance enterography sensitivity (47%, 95% CI 31% to 64%), with a 20% difference (95% CI 1% to 39%). For active small bowel Crohn’s disease, magnetic resonance enterography sensitivity (96%, 95% CI 92% to 99%) was significantly greater than ultrasonography sensitivity (90%, 95% CI 82% to 95%), with a 6% difference (95% CI 2% to 11%). There was some disagreement between readers for both tests. A total of 88% of participants rated magnetic resonance enterography as very or fairly acceptable, which is significantly lower than the percentage (99%) of participants who did so for ultrasonography. Therapeutic decisions based on magnetic resonance enterography alone and ultrasonography alone agreed with the final decision in 122 out of 158 (77%) cases and 124 out of 158 (78%) cases, respectively. There were no differences in costs or quality-adjusted life-years between tests.LimitationsMagnetic resonance enterography and ultrasonography scans were interpreted by practitioners blinded to clinical data (but not participant cohort), which does not reflect use in clinical practice.ConclusionsMagnetic resonance enterography has higher accuracy for detecting the presence, extent and activity of small bowel Crohn’s disease than ultrasonography does. Both tests have variable interobserver agreement and are broadly acceptable to participants, although ultrasonography produces less participant burden. Diagnostic impact and cost-effectiveness are similar. Recommendations for future work include investigation of the comparative utility of magnetic resonance enterography and ultrasonography for treatment response assessment and investigation of non-specific abdominal symptoms to confirm or refute Crohn’s disease.Trial registrationCurrent Controlled Trials ISRCTN03982913.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 23, No. 42. See the NIHR Journals Library website for further project information.