A novel model of autologous tooth transplantation for the study of nerve recruitment.

BACKGROUND: Limited treatment options exist for damaged nerves and despite impressive advances in tissue engineering, scientists and clinicians have yet to fully replicate nerve development and recruitment. Innervation is a critical feature for normal organ function. While most organs are innervated prior to birth, a rare example of postnatal nerve recruitment occurs in the natural development of secondary teeth during adolescence. Many animals undergo postnatal shedding of deciduous teeth with development and eruption of secondary teeth, a process requiring recruitment of nerve and vasculature to each tooth pulp for viability. Here, the investigators created a novel model for the study of postnatal innervation by exploiting the natural phenomenon of tooth-driven nerve recruitment. METHODS: The investigators theorized that developing teeth possess a special capacity to induce innervation which could be harnessed in a clinical setting for nerve regeneration, and hyptothesized that a transplant model could be created to capture this phenomenon. In this descriptive study, a rat model of autologous tooth transplantation and de novo nerve recruitment was developed by surgically transferring whole developing molars to the autologous tibia. RESULTS: Downstream histological analysis performed 6 to 14 weeks after surgery demonstrated integration of molar into tibia in 81% of postoperative rats, with progressive pulpal expression of nerve marker ß-tubulin III suggestive of neuronal recruitment. CONCLUSIONS: These findings provide a novel model for the study of organ transplantation and support the theory that developing dental tissues may retain nerve-inductive properties postnatally.

Risankizumab Is Effective for The Management of Crohn's Disease of the Pouch.

In this prospective, multicenter observational study of highly refractory patients with Crohn's disease of the pouch, risankizumab achieved the primary outcome of clinical remission in 50% and the more stringent secondary outcome of antibiotic- and steroid-free remission in 30.8% at 12 weeks.

Predictive Factors of Non-Inflammatory Small Bowel Obstruction After Bowel Resection in Crohn's Patients.

Background: The aim of the study was to investigate the risk factors associated with the development of small bowel obstruction (SBO) in Crohn's disease (CD) after small bowel resection (SBR) that are not due to active/recurrent inflammation. Methods: We conducted a retrospective cohort study of patients who had SBR for active or complicated CD. Abstracted data included demographics, phenotype, therapies for CD, endoscopic disease recurrence, and several surgical variables. The primary outcome was the development of non-inflammatory SBO (NI-SBO) within 5 years after SBR. Results: A total of 335 patients were included. The cumulative rates of NI-SBO at 6 months, 1 year, and 5 years were 5 (1.5%), 8 (2.4%), and 29 (8.9%), respectively. Variables associated with the development of NI-SBO were active macroscopic or microscopic inflammation in the surgical margins (13 (56%) vs. 65 (27%), P = 0.004), open resection (vs. laparoscopic resection) (12 (41.4%) vs. 60 (19.5%), P = 0.0006) and a higher median number of previous resections (2 (interquartile range (IQR) 2 - 3) vs. 1 (IQR 1 - 2), P = 0.0002). Only 21% of patients who developed NI-SBO required surgical intervention. Conclusions: The incidence of NI-SBO after SBR in CD is low and associated with inflammation at the margins of the resected bowel, previous bowel resections, and an open laparotomy approach. Most NI-SBOs resolve with medical management.

Real-World Effectiveness of Ustekinumab in Ulcerative Colitis in a United States Multicenter Cohort Consortium.

BACKGROUND: Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC. METHODS: We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin. RESULTS: A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission. CONCLUSIONS: In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted.

Ustekinumab was shown to be efficacious and safe in a population of patients with refractory ulcerative colitis. Those patients with exposure to multiple drug classes and higher disease burden at baseline are less likely to respond.

Structural brain morphometry differences and similarities between young patients with Crohn's disease in remission and healthy young and old controls.

Introduction: Crohn's disease (CD), one of the main phenotypes of inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. It can impact the function of gastrointestinal secretions, as well as increasing the intestinal permeability leading to an aberrant immunological response and subsequent intestinal inflammation. Studies have reported anatomical and functional brain changes in Crohn's Disease patients (CDs), possibly due to increased inflammatory markers and microglial cells that play key roles in communicating between the brain, gut, and systemic immune system. To date, no studies have demonstrated similarities between morphological brain changes seen in IBD and brain morphometry observed in older healthy controls.. Methods: For the present study, twelve young CDs in remission (M = 26.08 years, SD = 4.9 years, 7 male) were recruited from an IBD Clinic. Data from 12 young age-matched healthy controls (HCs) (24.5 years, SD = 3.6 years, 8 male) and 12 older HCs (59 years, SD = 8 years, 8 male), previously collected for a different study under a similar MR protocol, were analyzed as controls. T1 weighted images and structural image processing techniques were used to extract surface-based brain measures, to test our hypothesis that young CDs have different brain surface morphometry than their age-matched young HCs and furthermore, appear more similar to older HCs. The phonemic verbal fluency (VF) task (the Controlled Oral Word Association Test, COWAT) (Benton, 1976) was administered to test verbal cognitive ability and executive control. Results/Discussion: On the whole, CDs had more brain regions with differences in brain morphometry measures when compared to the young HCs as compared to the old HCs, suggesting that CD has an effect on the brain that makes it appear more similar to old HCs. Additionally, our study demonstrates this atypical brain morphometry is associated with function on a cognitive task. These results suggest that even younger CDs may be showing some evidence of structural brain changes that demonstrate increased resemblance to older HC brains rather than their similarly aged healthy counterparts.

Changes in Therapy Are Not Associated With Increased Remission in Patients With Crohn's Disease of the Pouch.

INTRODUCTION: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch. METHODS: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch. RESULTS: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status. DISCUSSION: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

Racial, Ethnic, and Geographic Disparities in Immunization Rates Among Patients With Inflammatory Bowel Disease.

Background and Aims: Racial and ethnic disparities exist in the treatment of IBD. These disparities exist in adult vaccine uptake among the general population and may extend to patients with IBD. The primary aim of this study was to determine whether racial, ethnic, or geographic disparities existed in influenza vaccine uptake among patients with IBD. Methods: We performed a multicenter, retrospective cohort study evaluating adult vaccine uptake among patients with IBD seen at two tertiary referral centers between September 2019 and February 2020. The primary outcome was to determine if racial/ethnic and geographic disparities existed in influenza vaccine uptake for the two prior seasons. Our secondary outcomes were to determine if disparities existed for pneumococcal, zoster, or hepatitis B vaccines. Results: Among the 2453 patients who met the inclusion criteria, most identified as non-Hispanic White (89.9%), were on immunosuppressive therapy (74.5%), and received the influenza vaccine in both seasons (56.0%). Older age (prevalence ratio (PR) 0.98; 95% confidence interval (95%CI) 0.98-0.99; P < .001) and non-Hispanic White patients (PR 0.76, 95%CI 0.59-0.98, P < 0.03) were significantly more likely to be immunized. Black patients (PR 1.37; 95%CI 1.18-1.59; P < .001) and those living in underserved geographic areas (PR 1.35; 95%CI 1.17-1.56; P < 0.001) were less likely to be immunized. Racial/ethnic and geographic disparities were identified for pneumococcal, zoster, and hepatitis B vaccine uptake. Conclusions: Racial and ethnic vaccination uptake disparities exist among patients with IBD; patients from medically underserved areas are also vulnerable to these disparities Studies identifying patient, provider, and system-level opportunities to address these disparities are needed.

Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study.

BACKGROUND & AIMS: We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. METHODS: We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. RESULTS: A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P = .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. CONCLUSIONS: Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.

Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions of the Pouch in a Prospective Cohort.

Background: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited. Methods: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals. Results: Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations. Conclusions: In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population.

Patients With Inflammatory Bowel Diseases and Higher Visceral Adipose Tissue Burden May Benefit From Higher Infliximab Concentrations to Achieve Remission.

INTRODUCTION: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD. METHODS: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement. RESULTS: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17-0.64], P < 0.001 and odds ratio per µg/mL: 1.11 [95% confidence interval: 1.05-1.19], P < 0.001). DISCUSSION: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission.

Combination Therapy With Immunomodulators Improves the Pharmacokinetics of Infliximab But Not Vedolizumab or Ustekinumab.

BACKGROUND AND AIMS: The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics. METHODS: This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity. The primary outcomes were infliximab, vedolizumab, and ustekinumab concentrations as well as anti-drug antibodies (ADAs). RESULTS: A total of 369 patients were recruited (113 infliximab, 133 vedolizumab, and 123 ustekinumab). Patients with 6-TGN levels ≥146 pmol per 8 × 108 red blood cells (RBCs), and those receiving combination therapy with thiopurine or oral methotrexate had significantly higher infliximab concentrations when compared with monotherapy (median levels of 17.4 µg/mL on thiopurine with 6-TGN ≥146 pmol per 8 × 108 RBCs, 17.1 on methotrexate, and 3.9 on infliximab monotherapy; P = .001 for both comparisons). However, there was no association between the use of immunomodulators and 6-TGN concentrations with vedolizumab (median levels of 8.8 on thiopurine with 6-TGN ≥152 pmol per 8 × 108 RBCs, 6.8 on methotrexate, and 10.5 on vedolizumab monotherapy; P > .05 for both comparisons) or ustekinumab median concentrations (median levels of 5.0 on thiopurine with 6-TGN ≥154 pmol per 8 × 108 RBCs, 5.2 on methotrexate and 7.0 on ustekinumab monotherapy; P > .05 for both comparisons). Fourteen (12%) patients had anti-infliximab antibodies, while 1 patient had ADAs in each of the other drug cohorts. CONCLUSIONS: Achieving higher 6-TGN levels or the use of methotrexate improved the pharmacokinetics of infliximab. Conversely, these data do not support the use of combination therapy to augment pharmacokinetics with vedolizumab or ustekinumab.

Treatment Patterns and Standardized Outcome Assessments Among Patients With Inflammatory Conditions of the Pouch in a Prospective Multicenter Registry.

Background: Much of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders. Methods: We used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn's disease (CD) of the pouch. We obtained detailed clinical and demographic data at the time of enrollment, along with patient-reported outcome (PRO) measures. Results: We enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). Among all patients, 55% were on a biologic or small molecule therapy. Patients with CD of the pouch were more likely to use several classes of therapy (P < .001). Among patients with active disease at the time of enrollment, 23% with CARP and 40% with CD of the pouch were in clinical remission at 6 months after enrollment. Conclusions: In a population where most patients had refractory inflammatory conditions of the pouch, we established a framework to evaluate PROs and clinical effectiveness. This infrastructure will be valuable for long-term studies of real-world effectiveness for pouch-related disorders.

Clinical Improvement With Pyridostigmine in a Patient With Acetylcholine Receptor Antibody-Associated Autoimmune Gastrointestinal Dysmotility.

Autoimmune gastrointestinal dysmotility (AGID) is a rare form of limited autoimmune dysautonomia caused by autoantibodies against the enteric nervous system. Our patient was a 53-year-old man with 1 year of bloating, intolerance of oral intake, and recurrent ileus. Esophageal manometry showed aperistalsis and hypotensive lower sphincter, consistent with scleroderma esophagus. However, because the patient had no other sequelae of this disease, AGID was considered. Serologic evaluation revealed ganglionic acetylcholine receptor autoantibodies. Treatment with pyridostigmine led to resolution of symptoms. Early recognition of AGID should be considered when manometry shows scleroderma esophagus in patients without other evidence of systemic sclerosis.

Outcomes in patients with inflammatory bowel disease and acute gastrointestinal symptoms who test indeterminate for Clostridioides difficile.

Background: Inflammatory bowel disease (IBD) and Clostridioides difficile infection (CDI) can present with similar symptoms. The current preferred method for diagnosing CDI is the nucleic acid amplification test (NAAT) for C. difficile in stool, followed by reflex toxin enzyme immunoassay (EIA) when NAAT is positive. The clinical significance of NAAT(+)/EIA(-) in the IBD population is uncertain. Methods: This retrospective cohort included IBD patients who presented with acute onset of gastrointestinal symptoms and a C. difficile NAAT(+) test. The primary outcome was C. difficile recurrence within 12 months. Other outcomes examined included hospital admissions within 30 days of CDI, change of IBD maintenance therapy within 90 days of CDI, and complications such as bowel resection or death. Results: A total of 71 patients were included. Eighty-four percent of the tests were EIA(-) and among the EIA(-) 88% were treated with antibiotics. Outcomes between EIA(+) and EIA(-) were not significantly different in terms of recurrences, admissions, changes to IBD medications or complications. Outcomes were also similar when comparing those who received antibiotic therapy to those who did not. Conclusions: Our cohort did not demonstrate a significant difference in outcomes between EIA(+) and EIA(-) C. difficile patients. Treatment for EIA(-) patients did not improve outcomes. Even though there may be a role for antibiotic therapy in IBD patients who test NAAT(+)/EIA(-) for C. difficile, further studies will be needed to identify that subpopulation.

Serum trough levels of infliximab are not associated with peripheral arthralgia activity in patients with inflammatory bowel disease.

BACKGROUND: Infliximab is an efficacious therapy for inflammatory bowel disease and may play a role in management of some extraintestinal manifestations. While higher trough levels of infliximab are associated with higher rates of disease remission, the association between trough levels of infliximab and arthralgia activity characterised as an extraintestinal manifestation has yet to be defined. OBJECTIVE: We aimed to assess the association between serum trough levels of infliximab and peripheral arthralgia activity in patients with inflammatory bowel disease. DESIGN: In this cross-sectional study, we identified patients with inflammatory bowel disease on infliximab therapy with known history of arthralgias attributed to an extraintestinal manifestation. Collected variables included disease phenotype, medications (such as thiopurines or methotrexate), Harvey Bradshaw Index, partial Mayo score, C reactive protein, trough levels of infliximab and anti-infliximab antibodies. The primary outcome was active patient-reported arthralgia. RESULTS: Out of 267 patients included, 65 (24.4%) had active arthralgias at the time the trough level of infliximab was measured. No significant differences in trough levels were seen between those patients with and without arthralgias. Patients on combination therapy with methotrexate or thiopurines or those with detectable anti-infliximab antibodies were not more likely to have inactive arthralgias (OR 0.99, 95% CI 0.57 to 1.74, p=0.99 and OR 1.94, 95% CI 0.9 to 4.1, p=0.09, respectively). CONCLUSIONS: This study suggests that although therapeutic drug monitoring of infliximab can have a role in the management of Crohn's disease and ulcerative colitis, it does not seem to be useful in managing arthralgias associated with inflammatory bowel disease.

Psoriasis: To Vaccinate or Not to Vaccinate?

Psoriasis is a chronic, inflammatory, autoimmune disease characterized by red, dry, itchy, and scaly patches of abnormal skin growth on the elbows, knees, and/or scalp, which can negatively impact a patient's quality of life and activities of daily living. Both genetic predispositions and environmental factors, which can vary in susceptibility and effect, including infection, stress, medications, and cold temperatures, can lead to the onset of psoriasis and progression of the condition. This review aims to highlight recent advances in understanding the pathophysiology of psoriasis and provide insight into the importance of vaccinations and their role in reducing the risk of infection in psoriasis patients. Vaccination has been shown to reduce the risk of infection in psoriasis patients and those with other autoimmune diseases. Still, vaccination remains limited among autoimmune disease patients. Awareness of the benefits of vaccination needs to be raised among healthcare professionals due to the overarching impact on these patients' lives. The focus of this literature review is to examine the existing data to determine whether vaccination is beneficial for psoriasis patients. Herein, we primarily focus on influenza, pneumococcal, and herpes zoster vaccines and whether immunization benefits or adversely affects psoriasis patients. Overall, we found that most psoriasis and vaccine literature support immunization of this patient population, particularly with non-live attenuated vaccines; however, more studies are needed to fully develop a vaccine recommendation schedule for psoriasis patients.

St. John's Wort-Induced Supraventricular Tachycardia.

St. John's wort, a non-FDA-approved over-the-counter (OTC) herbal supplement with antidepressant activity known as Hypericum perforatum, has been found to induce supraventricular tachycardia (SVT) in the absence of any underlying structural cardiac abnormality or known medical history via currently unclear pathophysiology. In this case presentation, the authors present a case of a 33-year-old female who presented with recurrent episodes of palpitations one month after initiating St. John's wort for the treatment of depression, which ultimately resolved upon cessation of the herbal supplement. Therefore, the postulated insinuating event is suspected to be the ingestion of St. John's wort. This will be the first documented case of St. John's wort-induced SVT. This case study brings into question the safety of the use of this agent as an OTC supplement for the management of depression. Further investigation is required to aid in the knowledge and understanding of the causative mechanism and to identify those patients who are at potentially heightened risks of such manifestations.

Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib. METHODS: We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States. Patients were followed up for a median of 6 months (interquartile range, 2.7-11.5 mo). AEs were captured using a standardized data collection instrument before study initiation and at weeks 8, 16, 26, 39, and 52. Serious AEs were defined as life-threatening or resulting in a hospitalization, disability, or discontinuation of therapy. Logistic regression was performed to examine risk factors for AEs. RESULTS: AEs occurred in 41 patients (15.7%); most were infections (N = 13; 5.0%). The incidence rate of any AE was 27.2 (95% CI, 24.4-30.7 per 100 patient-years of follow-up evaluation). Fifteen were serious AEs (36.6% of AEs), and tofacitinib was discontinued for 12 patients (4.6% of cohort). The incidence rates of serious AEs was 10.0 (95% CI, 8.9-11.2 per 100 patient-years of follow-up evaluation). Five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day). CONCLUSIONS: Real-world safety signals for tofacitinib are similar to those for clinical trials, with AEs reported from almost 16% of patients. HZ infection and VTE occurred in patients receiving 10 mg tofacitinib twice per day. These results support dose de-escalation after induction therapy, to reduce the risk of AEs.

Real-World Effectiveness and Safety of Tofacitinib in Crohn's Disease and IBD-U: A Multicenter Study From the TROPIC Consortium.

The safety and efficacy of tofacitinib in Crohn's disease (CD) has been studied in 2 phase II trials in patients with moderate-to-severe CD with no new safety signals observed, but no significant difference from placebo in the primary efficacy endpoint of clinical response.1-3 However, post hoc analyses and smaller studies have observed clinical and biologic response to tofacitinib in patients with CD.2,4,5 There is a paucity of real-world effectiveness and safety data for tofacitinib in non-Food and Drug Administration label usage in patients with CD and patients with inflammatory bowel disease-unclassified (IBD-U).

Psychometric properties of measures of substance use: a systematic review and meta-analysis of reliability, validity and diagnostic test accuracy.

BACKGROUND: Synthesis of psychometric properties of substance use measures to identify patterns of use and substance use disorders remains limited. To address this gap, we sought to systematically evaluate the psychometric properties of measures to detect substance use and misuse. METHODS: We conducted a systematic review and meta-analysis of literature on measures of substance classes associated with HIV risk (heroin, methamphetamine, cocaine, ecstasy, alcohol) that were published in English before June 2016 that reported at least one of the following psychometric outcomes of interest: internal consistency (alpha), test-retest/inter-rater reliability (kappa), sensitivity, specificity, positive predictive value, and negative predictive value. We used meta-analytic techniques to generate pooled summary estimates for these outcomes using random effects and hierarchical logistic regression models. RESULTS: Findings across 387 paper revealed that overall, 65% of pooled estimates for alpha were in the range of fair-to-excellent; 44% of estimates for kappa were in the range of fair-to-excellent. In addition, 69, 97, 37 and 96% of pooled estimates for sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were in the range of moderate-to-excellent. CONCLUSION: We conclude that many substance use measures had pooled summary estimates that were at the fair/moderate-to-excellent range across different psychometric outcomes. Most scales were conducted in English, within the United States, highlighting the need to test and validate these measures in more diverse settings. Additionally, the majority of studies had high risk of bias, indicating a need for more studies with higher methodological quality.