Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn's Disease Regardless of Prior Biologic Exposure.

BACKGROUND & AIMS: Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849], U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease. Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status. METHODS: Patients were randomized to placebo or upadacitinib 45 mg (UPA45) for 12 weeks (induction). UPA45 clinical responders were enrolled in U-ENDURE and rerandomized to placebo, upadacitinib 15 mg, or upadacitinib 30 mg (UPA30) for 52 weeks. Assessments were by prior biologic failure. RESULTS: Of 1021 patients, 733 (71.8%) had prior biologic failure. Across outcomes and subgroups, upadacitinib-treated patients achieved higher rates vs placebo. During induction, upadacitinib had higher rates vs placebo for clinical remission based on stool frequency/abdominal pain score (without failure: 54.0% vs 28.3%; with failure: 42.2% vs 14.1%) and endoscopic response (without failure: 52.0% vs 16.2%; with failure: 35.7% vs 5.3%). In maintenance, the greatest treatment effect (upadacitinib vs placebo) was among patients with prior biologic failure treated with UPA30 (clinical remission without failure: 58.5% vs 32.7%; with failure: 42.5% vs 8.7%; endoscopic response without failure: 43.9% vs 17.9%; with failure: 38.9% vs 4.0%). Patients without vs with prior biologic failure had fewer adverse events. CONCLUSIONS: Upadacitinib led to higher absolutes rates of clinical and endoscopic outcomes in patients without vs with prior biologic failure. Patients treated with upadacitinib achieved greater rates of clinical and endoscopic improvements vs placebo, regardless of prior biologic exposure. CLINICALTRIALS: gov: NCT03345849, NCT03345836, NCT03345823.

Upadacitinib Reduces Crohn's Disease Symptoms Within the First Week of Induction Therapy.

BACKGROUND & AIMS: Upadacitinib (UPA), an oral Janus kinase inhibitor, is approved to treat moderately to severely active Crohn's disease (CD). Because symptomatic response is an important initial treatment goal for patients, we evaluated the rapidity of symptomatic improvement in patients with CD receiving UPA 45 mg once daily (UPA45) induction therapy. METHODS: This post hoc analysis included pooled data from 2 phase 3, multicenter, double-blind, 12-week induction trials (U-EXCEL and U-EXCEED) and 1 maintenance trial (U-ENDURE). Daily diary data for the first 15 days of UPA45 or placebo (PBO) treatment were used to analyze improvement in very soft/liquid stool frequency (SF) and abdominal pain score (APS). Clinical outcomes were evaluated at every study visit. RESULTS: Overall, 1021 patients (n = 674 UPA45; n = 347 PBO) were analyzed. UPA45 demonstrated greater efficacy vs PBO for SF <3 and APS ≤1, providing rapid relief by day 5 or 6, regardless of prior biologic exposure. Mean changes in SF and APS were greater with UPA45 beginning at week 2 (-2.0 and -0.5, respectively; P < .001) and were maintained through week 12 (-3.0 and -1.0, respectively; P < .001) vs PBO. The first achievement of daily SF/APS clinical remission occurred earlier with UPA45 (median, 13 d) vs PBO (median, 32 d), and patients treated with UPA45 showed improved rates of SF/APS clinical remission (21.1% UPA45 vs 8.9% PBO) and clinical response (58.8% UPA45 vs 37.9% PBO) starting at week 2 (both P ≤ .01). CONCLUSIONS: UPA45 provided rapid relief of clinical symptoms within the first week of treatment in patients with CD. CLINICALTRIALS: gov numbers: NCT03345849, NCT03345836, and NCT03345823.

Factors leading to satisfaction with counseling for Labor after Cesarean among Latina women in the United States.

BACKGROUND: Cesarean birth, especially repeat cesarean, is associated with significantly higher morbidity than vaginal birth. Appropriately counseling women who are candidates for labor after cesarean (LAC) has the potential to confer significant health benefits for women. Little guidance exists about optimal counseling techniques, especially for Latina women. The aim of this study was to evaluate satisfaction among Latinas about how LAC counseling is performed, specifically as it relates to shared decision making. METHODS: We conducted a qualitative study of pregnant women at several clinics in a Federally Qualified Health Center system in Utah. We interviewed eleven Latina women about satisfaction with recent LAC counseling with a specific aim of obtaining rich, personal narratives rather than reaching data saturation. A codebook representing the most common themes was developed. RESULTS: Three major themes emerged related to LAC counseling including influences on satisfaction, influences on the birth decision process, and preferences surrounding method and timing of counseling. Women experienced greater satisfaction from providers who used jargon-free communication, were perceived as trustworthy, cared about her experiences, and empowered her to make an informed decision. Women's decisions were influenced by prior birth experiences, desire for a safe delivery and easy recovery, and future family planning. CONCLUSIONS: Understanding the aspects of LAC counseling that are most meaningful for Latina women can promote effective communication between patient and provider and improve patient satisfaction. Globally, our findings highlight the importance of evaluating the experiences and preferences of minority groups; majority populations cannot be assumed to speak for minority populations.

Little Cigars are More Toxic than Cigarettes and Uniquely Change the Airway Gene and Protein Expression.

Little cigars (LCs) are regulated differently than cigarettes, allowing them to be potentially targeted at youth/young adults. We exposed human bronchial epithelial cultures (HBECs) to air or whole tobacco smoke from cigarettes vs. LCs. Chronic smoke exposure increased the number of dead cells, lactate dehydrogenase release, and interleukin-8 (IL-8) secretion and decreased apical cilia, cystic fibrosis transmembrane conductance regulator (CFTR) protein levels, and transepithelial resistance. These adverse effects were significantly greater in LC-exposed HBECs than cigarette exposed cultures. LC-exposure also elicited unique gene expression changes and altered the proteomic profiles of airway apical secretions compared to cigarette-exposed HBECs. Gas chromatography-mass spectrometry (GC-MS) analysis indicated that LCs produced more chemicals than cigarettes, suggesting that the increased chemical load of LCs may be the cause of the greater toxicity. This is the first study of the biological effects of LCs on pulmonary epithelia and our observations strongly suggest that LCs pose a more severe danger to human health than cigarettes.

Screening, diagnosis, and management of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) affects approximately 6% of pregnancies in the United States, and it is increasing in prevalence. Pregnant women without known diabetes mellitus should be screened for GDM after 24 weeks of gestation. Treatment of GDM results in a statistically significant decrease in the incidence of preeclampsia, shoulder dystocia, and macrosomia. Initial management includes glucose monitoring and lifestyle modifications. If glucose levels remain above target values, pharmacologic therapy with metformin, glyburide, or insulin should begin. Antenatal testing is customary for women requiring medications. Induction of labor should not occur before 39 weeks in women with GDM, unless glycemic control is poor or another indication for delivery is present. Unless otherwise indicated, scheduled cesarean delivery should be considered only in women with an estimated fetal weight greater than 4,500 g. Women with a history of GDM are at high risk of subsequently developing diabetes. These patients should be screened six to 12 weeks postpartum for persistently abnormal glucose metabolism, and should undergo screening for diabetes every three years thereafter.

Beliefs about gender differences in methods and causes of suicide.

Forty undergraduate students (20 males, 20 females) made judgments about the relationship between an individual's gender and the method of suicide most likely to be chosen by that individual. The perceived relationship between different precipitating events for suicide and the method of suicide were also examined, as were the participants' judgments about the moral justification of suicide in response to different traumatic situations. The results indicated clear and consistent beliefs about the relationship between the gender of the potential suicide victim, the method of suicide likely to be chosen, and whether or not the cause of the suicide was judged harshly or sympathetically. Understanding how the gender of an at-risk individual interacts with an observer's beliefs and moral perspective should help us predict when suicide threats will be taken seriously and what form of intervention will take place.

Focus groups of Y-K Delta Alaska Natives: attitudes toward tobacco use and tobacco dependence interventions.

BACKGROUND: Tobacco dependence interventions developed for Alaska Natives are virtually nonexistent. Alaska Natives residing on the Yukon-Kuskokwim (Y--K) Delta in southwestern Alaska use a unique form of smokeless tobacco (ST) known as Iqmik. This study employed focus group methodology to explore attitudes toward tobacco use and tobacco dependence interventions among Alaska Natives residing on the Y-K Delta. METHODS: Twelve focus groups of former and current tobacco users were conducted in four villages in the Y-K Delta. Participants were 35 adults (83% female) and 22 adolescents (27% female). Participants completed a brief demographic and tobacco use history form. Statements from the focus groups were transcribed for content coding and analysis of the major themes. RESULTS: Use of Iqmik in the villages is thought to be ubiquitous. Y-K Delta Alaska Natives are introduced to Iqmik at a very young age. Iqmik is mostly used and prepared by young Alaska Natives and adult women. There are few perceived adverse health effects of Iqmik or other tobacco use. Although there is interest in stopping, there is a perceived lack of availability of tobacco dependence interventions. The major barriers to preventing the initiation of and stopping tobacco use are the social acceptance and widespread use and availability of tobacco. CONCLUSION: The attitudes toward tobacco and identified barriers to stopping will be useful in developing tobacco dependence interventions for Alaska Natives.