Gluten-free diet adherence in adult coeliac disease: Exploring multiple perspectives

Background: Coeliac disease is an autoimmune disease triggered by an inappropriate immune response to dietary gluten. This condition affects around 1% of the population and can lead to serious health complications, including nutrient deficiencies, infertility, osteoporosis and cancer. Symptoms, such as diarrhoea, pain, fatigue and bloating, can be debilitating. The only treatment is a life-long gluten-free diet. Up to 58% of adult patients have sub-optimal adherence to a gluten-free diet, yet the reasons for this are poorly understood. The aim of this study was to gain a better understanding of the factors affecting adherence to a gluten-free diet in adult coeliac patients. Methods: Concept mapping is a participatory mixed method that involves generation of ideas through brainstorming. Ideas are prioritised and grouped for similarity by participants, producing visual concept maps that represent participants’ perceptions about what affects adherence to a gluten-free diet. Results: Seventy-three participants were recruited (34 adult coeliac patients; 21 adults who live with them (household members); and 18 healthcare professionals). Analysis revealed a concept map containing 13 thematic clusters: The high cost of gluten-free food was perceived to be the most important factor. Healthcare professionals perceived the availability of gluten-free sandwiches to be significantly less important than people with 3 coeliac disease and household members. Other factors included: knowledge and information about coeliac disease and the gluten-free diet; access to gluten-free food; motivation and support; and difficulties eating away from home. There was a high degree of consistency between the perceptions of the three stakeholder groups. Conclusions: This study identified a complex interplay of factors associated with adherence to a gluten-free diet and their relative importance. This study provides a better understanding of how to support adherence to a gluten free diet in adults with coeliac disease. This knowledge could be used to inform interventions to improve dietary adherence

Informal Caregivers’ Experience During Acute Exacerbation of COPD in Older Adults: A Dissertation

Chronic obstructive pulmonary disease (COPD) has been recognized as a leading cause of mortality in older adults involving acute exacerbations as life-threatening events that lead to frequent hospitalization for care. Informal caregivers have been essential to helping older adults with COPD during an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A lack of empirical knowledge exists regarding the experience of informal caregivers of older adults with AECOPD in situation awareness for recognizing, understanding, and responding to an AECOPD in an emergent situation. This qualitative descriptive study explored situation awareness and its components of perception, comprehension and projection of next steps, including the caregiver’s confidence level during the AECOPD event. Fifteen informal caregivers, ages 31-77 years (mean age 48), who provided care for older adults with COPD were interviewed from an underserved community health center. The overarching theme derived from this study was something was wrong and something needed to be done. Subthemes emerged as a heightened sense of awareness, caregiver tipping point, planning next steps, caregiver confidence, and caregiver commitment. This study utilized situation awareness theory as a relevant guiding framework in exploring the experience of lay informal caregivers caring for older adults with AECOPD events. Study findings provided a description of the complex processes involved, including confidence level, for informal caregiver’s in situation awareness to recognize and respond to an AECOPD event in the older adult. Future targeted interventions need to address strategies to enhance individualized care for older adults with AECOPD events for managing care at home

Effect of a Multidisciplinary Team Approach to Eradicate Central Line Associated Blood-Stream Infections (CLABSI)

Introduction: CLABSI remains a significant problem in the intensive care unit. Hypothesis: A multimodal approach for the insertion and care of CVC will prevent CLABSI. Methods: A Critical Care Operations Committee was formed to transform care in 8 intensive care units (ICU) in an academic medical center in 9/2004. One goal was to reduce CLABSI. Using evidence based medicine, a clinical practice guideline was developed that incorporated the use of maximum barrier precautions, chlorhexidine skin preparation, avoidance of the femoral insertion site, dedicated catheter cart, a check list, the tracking of high risk CVC, anti-septic or antimicrobial impregnated catheters, a recommendation to use ultrasound guidance when inserting CVC in the internal jugular vein, daily determination of the need for the CVC and treatment of CLABSI as a critical event.CLABSI were adjudicated by the hospital epidemiologist and CVC days were tracked. Rates of CLABSI were followed from 9/2004 through 7/2011. The Spearman correlation coefficient was used for statistical evaluation. A p Results: CLABSI rates (per 1000 catheter-days) declined dramatically from 2004 to 2011 (p Conclusions: A multimodal approach to CVC insertion and care reduces CLABSI by over 90%. Our ultimate goal is the complete eradication of CRBSI in our institution

Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial

PURPOSE In COLUMBUS part 1, patients with advanced BRAF$^{V600}$-mutant melanoma were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice a day (COMBO450), vemurafenib 960 mg twice a day, or encorafenib 300 mg once daily (ENCO300). As previously reported, COMBO450 improved progression-free survival (PFS) versus vemurafenib (part 1 primary end point) and ENCO300 (part 1 key secondary end point; not statistically significant). Part 2, requested by the US Food and Drug Administration, evaluated the contribution of binimetinib by maintaining the same encorafenib dosage in the combination (encorafenib 300 mg once daily plus binimetinib 45 mg twice daily [COMBO300]) and ENCO300 arms. METHODS In part 2, patients were randomly assigned 3:1 to COMBO300 or ENCO300. ENCO300 (parts 1 and 2) data were combined, per protocol, for PFS analysis (key secondary end point) by a blinded independent review committee (BIRC). Other analyses included overall response rate (ORR), overall survival, and safety. RESULTS Two hundred fifty-eight patients received COMBO300, and 86 received ENCO300. Per protocol, ENCO300 arms (parts 1 and 2 combined) were also evaluated (n = 280). The median follow-up for ENCO300 was 40.8 months (part 1) and 57.1 months (part 2). The median PFS (95% CI) was 12.9 months (10.9 to 14.9) for COMBO300 versus 9.2  months (7.4 to 11.1) for ENCO300 (parts 1  and  2) and 7.4  months (5.6 to 9.2) for ENCO300 (part 2). The hazard ratio (95% CI) for COMBO300 was 0.74 (0.60 to 0.92; two-sided P = .003) versus ENCO300 (parts 1  and  2). The ORR by BIRC (95% CI) was 68% (62 to 74) and 51% (45 to 57) for COMBO300 and ENCO300 (parts 1  and  2), respectively. COMBO300 had greater relative dose intensity and fewer grade 3/4 adverse events than ENCO300. CONCLUSION COMBO300 improved PFS, ORR, and tolerability compared with ENCO300, confirming the contribution of binimetinib to efficacy and safety

An empirical approach to the nucleation of sulfuric acid droplets in the atmosphere

We use quantum mechanical evaluations of the Gibbs free energy of the hydrates of sulfuric acid, H2SO4. nH2O and (H2SO4)2 . nH2O to evaluate an empirical surface tension for sulfuric acid-water clusters containing few molecules. We use this surface tension to evaluate nucleation rates using classical heteromolecular theory. At low temperatures (T 213 K) the nucleation rates obtained with the empirical surface tensions are signifi cantly greater than those using bulk values of the surface tension. At higher temperatures the difference disappears

Profiles in Community-Engaged Learning

To provide a snapshot of the many impressive manifestations of community-engaged learning at the University of San Francisco, a 2014-2015 Faculty Learning Community (FLC), supported by the Center for Teaching Excellence (CTE), has collected the following profiles of selected faculty members across all the schools and colleges. This report was prepared by members of the CTE’s Faculty Learning Community on Community-Engaged Learning: Kevin D. Lo, Facilitator (School of Management), Emma Fuentes (School of Education), David Holler (College of Arts and Sciences), Tim Iglesias (School of Law), Susan Roberta Katz (School of Education), Star Moore (Leo T. McCarthy Center for Public Service and the Common Good), Chenit Ong-Flaherty (School of Nursing and Health Professions), Jennifer Parlamis (School of Management) Susan Pauly-O’Neill (School of Nursing and Health Professions). Our intent with this report is to offer USF administrators and incoming faculty members a sense of what’s being done well in community-engaged learning (CEL), while also pointing out what challenges remain as we establish our identity as a university that prioritizes community engagement. (Incidentally, we prefer the term “community-engaged learning” to “service-learning,” which we feel more precisely defines the scope of our activities. For more about this designation, please see the Executive Report on Community Engaged Learning issued by this same committee in June 2015.) Community-engaged learning as defined by Eyler and Giles is “a form of experiential education where learning occurs through a cycle of action and reflection as students . . . seek to achieve real objectives for the community and deeper understanding and skills for themselves. In the process, students link personal and social development with academic and cognitive development . . . experience enhances understanding; understanding leads to more effective action.” (qtd. in Bandy, Vanderbilt Center for Teaching, “What Is Service Learning or Community Engagement?”). We invited at least two faculty members from each school/college to answer several questions about the application of CEL in their courses. After providing a brief overview of activities in each course, we asked each professor what works well and what challenges persist. The successes and the challenges, as you’ll see, vary widely, and yet they clearly delineate, limited though our present sample size is, the great variety and energy and commitment our faculty have demonstrated in working with community partners and students. It is our hope that this report is merely the beginning of a much more ambitious project to be taken up by the McCarthy Center which will provide many more profiles of professors in the months and years to come

An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition

Mitogen-activated protein kinase (MAPK) pathway antagonists induce profound clinical responses in advanced cutaneous melanoma, but complete remissions are frustrated by the development of acquired resistance. Before resistance emerges, adaptive responses establish a mutation-independent drug tolerance. Antagonizing these adaptive responses could improve drug effects, thereby thwarting the emergence of acquired resistance. In this study, we reveal that inflammatory niches consisting of tumor-associated macrophages and fibroblasts contribute to treatment tolerance through a cytokine-signaling network that involves macrophage-derived IL-1β and fibroblast-derived CXCR2 ligands. Fibroblasts require IL-1β to produce CXCR2 ligands, and loss of host IL-1R signaling in vivo reduces melanoma growth. In tumors from patients on treatment, signaling from inflammatory niches is amplified in the presence of MAPK inhibitors. Signaling from inflammatory niches counteracts combined BRAF/MEK (MAPK/extracellular signal–regulated kinase kinase) inhibitor treatment, and consequently, inhibiting IL-1R or CXCR2 signaling in vivo enhanced the efficacy of MAPK inhibitors. We conclude that melanoma inflammatory niches adapt to and confer drug tolerance toward BRAF and MEK inhibitors early during treatmen

Ethical frameworks for quality improvement activities: An analysis of international practice

Purpose: To examine international approaches to the ethical oversight and regulation of quality improvement and clinical audit in healthcare systems. Data sources: We searched grey literature including websites of national research and ethics regulatory bodies and health departments of selected countries. Study selection: National guidance documents were included from six countries: Ireland, England, Australia, New Zealand, the United States of America and Canada. Data extraction: Data were extracted from 19 documents using an a priori framework developed from the published literature. Results: We organised data under five themes: ethical frameworks; guidance on ethical review; consent, vulnerable groups and personal health data. Quality improvement activity tended to be outside the scope of the ethics frameworks in most countries. Only New Zealand had integrated national ethics standards for both research and quality improvement. Across countries, there is consensus that this activity should not be automatically exempted from ethical review, but requires proportionate review or organisational oversight for minimal risk projects. In the majority of countries, there is a lack of guidance on participant consent, use of personal health information and inclusion of vulnerable groups in routine quality improvement. Conclusion: Where countries fail to provide specific ethics frameworks for quality improvement, guidance is dispersed across several organisations which may lack legal certainty. Our review demonstrates a need for appropriate oversight and responsive infrastructure for quality improvement underpinned by ethical frameworks that build equivalence with research oversight. It outlines aspects of good practice, especially The New Zealand framework that integrates research and quality improvement ethics

DNA Repair in Prostate Cancer: Biology and Clinical Implications

CONTEXT: For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. OBJECTIVE: To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease. EVIDENCE ACQUISITION: A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer. EVIDENCE SYNTHESIS: We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC. CONCLUSIONS: Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies. PATIENT SUMMARY: Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed

Patient-directed self-management of pain (PaDSMaP) compared to treatment as usual following total knee replacement; a randomised controlled trial

Background Self-administration of medicines by patients whilst in hospital is being increasingly promoted despite little evidence to show the risks and benefits. Pain control after total knee replacement (TKR) is known to be poor. The aim of the study was to determine if patients operated on with a TKR who self-medicate their oral analgesics in the immediate post-operative period have better pain control than those who receive their pain control by nurse-led drug rounds (Treatment as Usual (TAU)). Methods A prospective, parallel design, open-label, randomised controlled trial comparing pain control in patient-directed self-management of pain (PaDSMaP) with nurse control of oral analgesia (TAU) after a TKR. Between July 2011 and March 2013, 144 self-medicating adults were recruited at a secondary care teaching hospital in the UK. TAU patients (n = 71) were given medications by a nurse after their TKR. PaDSMaP patients (n = 73) took oral medications for analgesia and co-morbidities after two 20 min training sessions reinforced with four booklets. Primary outcome was pain (100 mm visual analogue scale (VAS)) at 3 days following TKR surgery or at discharge (whichever came soonest). Seven patients did not undergo surgery for reasons unrelated to the study and were excluded from the intention-to-treat (ITT) analysis. Results ITT analysis did not detect any significant differences between the two groups’ pain scores. A per protocol (but underpowered) analysis of the 60% of patients able to self-medicate found reduced pain compared to the TAU group at day 3/discharge, (VAS -9.9 mm, 95% CI -18.7, − 1.1). One patient in the self-medicating group over-medicated but suffered no harm. Conclusion Self-medicating patients did not have better (lower) pain scores compared to the nurse-managed patients following TKR. This cohort of patients were elderly with multiple co-morbidities and may not be the ideal target group for self-medication