Eluxadoline Benefits Patients With Irritable Bowel Syndrome With Diarrhea in a Phase 2 Study

Background & AimsSimultaneous agonism of the μ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea (IBS-D) without constipating side effects. We evaluated the efficacy and safety of a minimally absorbed, μ-opioid receptor agonist and δ-opioid receptor antagonist (eluxadoline) in a phase 2 study in patients with IBS-D.MethodsWe randomly assigned 807 patients to groups that received oral placebo twice daily or 5, 25, 100, or 200 mg oral eluxadoline for 12 weeks. The primary end point was clinical response at week 4, defined by a mean reduction in daily pain score from baseline of ≥30%, and of at least 2 points on 0−10 scale, as well as a stool consistency score of 3 or 4 on the Bristol Stool Scale (1–7) for at least 66% of daily diary entries during that week.ResultsSignificantly more patients receiving 25 mg (12.0%) or 200 mg (13.8%) eluxadoline met the primary end point of clinical response than patients given placebo (5.7%; P < .05). Patients receiving eluxadoline at 100 mg and 200 mg also had greater improvements in bowel movement frequency and urgency, global symptoms, quality of life, and adequate relief assessments (P < .05). Additionally, patients receiving 100 mg (28.0%) or 200 mg (28.5%) eluxadoline were significantly more likely than those receiving placebo (13.8%; P < .005) to meet the US Food and Drug Administration response end point during the full 12 weeks of the study. Eluxadoline was well tolerated with a low incidence of constipation.ConclusionsIn a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D. ClinicalTrials.gov number, NCT0113027

Grieving, Valuing, and Viewing Differently: The Global War on Terror's American Toll

In March 2003 (the eve of Iraq’s invasion) the George W. Bush Administration reissued, extended, and enforced a Directive prohibiting the publication and broadcast of images and videos capturing the ritual repatriation of America’s war dead. This Directive (known as the Dover Ban) is exemplary of a wider set of more subtle processes and practices of American statecraft working to move suffering and dead American soldiers out of the American public eye’s sight. This is due, I argue, to dominant (Government and Military) bodies knowing, valuing, and counting generic soldier material as but a “precious resource” with which to fuel the GWoT. However, my investigation into the (in)visibility of suffering and dead American soldiers since 9/11 reveals that subordinate yet challenging American bodies could not be stopped from knowing, valuing, and counting American soldiers differently—in life, injury, and death. Indeed, regarding American soldiers as grievable persons, the challenging actions discussed in this article demonstrate how Americans were moved to demand and take the right to count and account for soldiers’ suffering and deaths in public and the very face of dominant bodies that “don’t do body counts”

Psychosocial factors and ageing in older lesbian, gay and bisexual people: a systematic review of the literature

Aims and objectives: To synthesise and evaluate the extant literature investigating the psychosocial influences on ageing as a lesbian, gay or bisexual person, in order to develop understanding about these influences and guide future research in the area. Background: Research suggests there may be specific psychological and social factors relevant to ageing for individuals with a non-heterosexual identity. Design: A systematic review was conducted on empirical research involving lesbian, gay and bisexual individuals aged 60 or above. Methods: The Cochrane Database, PsychINFO, MEDLINE, Web of Science and Google Scholar were searched and 41 studies met inclusion criteria. The majority had not been reviewed in earlier review articles. Results: Findings were within two domains: psychological, consisting of sub-themes relating to identity, mental health and body image; and social, consisting of relationships, social support, discrimination, caregiving and receiving, community, accessing services and housing. The results suggest lesbian, gay and bisexual individuals mostly adjust well to ageing identities, with mediating influences including self-acceptance and connection with peers. Challenges experienced included ageism and heteronormative health and social care services; intimate friendships, social support and respectful professionals mitigated such threats and facilitated successful ageing. Methodological issues related to sampling procedures, such as purposive sampling through the gay community and limited generalisability due to the homogeneity of participants. Additionally, there was a widespread lack of heterosexual control groups. However, most studies used appropriate measures and acknowledged inherent limitations. Conclusion: Psychosocial influences included the challenge of societal stigma, but also resilience individuals demonstrate through a positive attitude. These factors must continue to be investigated for services to best meet the needs of this population. Relevance to clinical practice: Clinicians are well placed to assist individuals draw on resilience when facing ageing challenges. Also, clinicians should be aware older people may have prior negative experiences of accessing services and try to involve ‘families of choice’ in care planning

CKD-MBD after kidney transplantation

Successful kidney transplantation corrects many of the metabolic abnormalities associated with chronic kidney disease (CKD); however, skeletal and cardiovascular morbidity remain prevalent in pediatric kidney transplant recipients and current recommendations from the Kidney Disease Improving Global Outcomes (KDIGO) working group suggest that bone disease—including turnover, mineralization, volume, linear growth, and strength—as well as cardiovascular disease be evaluated in all patients with CKD. Although few studies have examined bone histology after renal transplantation, current data suggest that bone turnover and mineralization are altered in the majority of patients and that biochemical parameters are poor predictors of bone histology in this population. Dual energy X-ray absorptiometry (DXA) scanning, although widely performed, has significant limitations in the pediatric transplant population and values have not been shown to correlate with fracture risk; thus, DXA is not recommended as a tool for the assessment of bone density. Newer imaging techniques, including computed tomography (quantitative CT (QCT), peripheral QCT (pQCT), high resolution pQCT (HR-pQCT) and magnetic resonance imaging (MRI)), which provide volumetric assessments of bone density and are able to discriminate bone microarchitecture, show promise in the assessment of bone strength; however, future studies are needed to define the value of these techniques in the diagnosis and treatment of renal osteodystrophy in pediatric renal transplant recipients

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Randomized, Double-Blind, Phase II, Multicenter Study Evaluating the Safety/Tolerability and Efficacy of JNJ-Q2, a Novel Fluoroquinolone, Compared with Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infection ▿ †

JNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind, multicenter, phase II noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients with acute bacterial skin and skin structure infections (ABSSSI). The prespecified criterion for noninferiority was 15%. Primary intent-to-treat analysis was unable to declare noninferiority, as the risk difference lower bound of the 95% confidence interval between treatments was 19% at 36 to 84 h postrandomization for the composite end point of lesion assessment and temperature. Prespecified clinical cure rates 2 to 14 days after completion of therapy were similar (83.1% for JNJ-Q2 versus 82.1% for linezolid). Post hoc analyses revealed that JNJ-Q2 was statistically noninferior to linezolid (61.4% versus 57.7%, respectively; P = 0.024) based on the 2010 FDA guidance, which defines treatment success as lack of lesion spread and afebrile status within 48 to 72 h postrandomization. Despite evidence of systemic disease, <5% of patients presented with fever, suggesting fever is not a compelling surrogate measure of systemic disease resolution for this indication. Nausea and vomiting were the most common adverse events. Of the patients, 86% (104/121) had S. aureus isolated from the infection site; 63% of these were MRSA. The results suggest JNJ-Q2 shows promise as an effective treatment for ABSSSI, demonstrating (i) efficacy for early clinical response (i.e., lack of spread of lesions and absence of fever at 48 to 72 h), and (ii) cure rates for ABSSSI pathogens (especially MRSA) consistent with the historical literature

The Press, Volume 17, Issue 11, November 12, 1980

The Press, Volume 17, Issue 11 includes: The Residence Action Committee endorses the concept of an autonomous Press; Mike O’Bright endorses Press autonomy, saying it will give BUSU access to more funds in order to diversify and grow the Union; June Chenard explores Brock professor Dr. John Mayer’s naturally growing project, the Karma Buddhist College; Cat’s Caboose is discontinuing its half price dinner coupons due to some Brock students reusing the coupons and abusing the system