A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for ≥6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO™) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n = 24). Mean ItchRO™ weekly sum scores decreased from baseline to week 13/ET with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC

Challenges and opportunities in the management of portal hypertension

PhD ThesisPortal hypertension and Gastro-Oesophageal varices (GOV) can occur in early stage Primary Biliary Cirrhosis (PBC) and are associated with a poor prognosis. Screening with endoscopy however, is only recommended in advanced disease. Transjugular-intrahepatic-portosystemic shunting (TIPS) is a life saving procedure in patients with decompensated portal hypertension. Serial TIPS patency checks using a venogram, in stable patients, offers a unique opportunity to sample portal venous blood, and in doing so to study the role of the human intestinal mucosa in bio-transforming essential nutrients. The aim of this work was to create a non invasive, inexpensive, externally validated screening tool to identify PBC patients with GOV and to use in-situ TIPS as a novel route of access to sample portal venous blood to define the exact site of bio-transformation of folates in humans. A cross-sectional retrospective study of 330 PBC patients who underwent an OGD at Newcastle was used to create a predictive tool that was externally validated in PBC patients from Cambridge and Toronto. 48% of the Newcastle, 31% of the Cambridge and 22% of the Toronto cohorts of PBC patients had GOV. 25% (95% CI 18–32%) of the Newcastle cohort had GOV diagnosed at an index variceal bleed. Of the others, 37% (95% CI 28–46%) bled after a median of 1.5 years (IQR 3.75). Transplant-free survival was significantly better in those without GOV vs. those with GOV (p <0.001), but similar in patients with GOV that bled and those that did not (p = 0.1). The NVP score (%Probability of GOV) = 1 / [1+exp ^ − (9.186 + 0.001 * alkaline phosphatase in IU − 0.178*albumin in g/L − 0.015*platelet×109) was validated in external cohorts ii (AUROC 0.86). Cost consequences analyses revealed the NVP score to be as accurate as, but more economical than using either OGD directly or other risk scores for screening. A prospective cross-over study of portal and peripheral venous labelled folate concentrations following oral dosing with physiological doses of stable-isotopelabelled folic acid (FA) or 5-formyltetrahydrofolic acid (5-FTHF) in six subjects with a TIPS in situ was set up. At 15 minutes, a median 86% [range 60-88%] of labelled folate in the hepatic portal vein following a dose of FA was unmodified FA. In contrast, following a dose of 5-FTHF, only a median 3% [range 2-6%] of labelled folate in the portal vein was unmodified 5-FTHF; the rest being methylated to 5-MTHF, suggesting limited gut wall dihydrofolate reductase capacity and suggesting that the liver in humans, rather than the intestinal mucosa as previously thought, is the organ responsible for this process.BBSRC project grant which funded the folic acid stud

Opioid Prescription Usage after Benign Gynecologic Surgery: A Prospective Cohort Study

Study Objective To compare the amount of opioids (tablets and morphine milligram equivalents [MMEs]) prescribed by physicians and used by patients after benign gynecologic surgery. Design Prospective cohort study. Setting Tertiary center: main hospital operating room and outpatient surgery center. Patients Women undergoing benign gynecologic surgery. Interventions Major and minor gynecologic surgeries. Measurements and Main Results The surgery groups were minor laparoscopy (Minor), major minimally invasive (Major), and laparotomy (Laparotomy). Demographic, medical, and surgical data were abstracted from electronic medical records. On postoperative day (POD) 7, women completed a telephone survey describing pain levels, prescription use, and satisfaction with pain control. Patients who continued to use opioids for pain relief were surveyed on POD 14. If use continued, patients were surveyed again on POD 28. The primary outcome was amount of opioid prescribed compared with opioid used. Of 193 screened participants 172 were enrolled (89%), and data were analyzed for 154 (90%): 59 (38%) Major, 71 (56%) Minor, and 24 (16%) Laparotomy. The median number of tablets and MMEs prescribed was lowest for the Minor group (Minor, 24 tablets; Major, 30 tablets; Laparotomy, 30 tablets [p <.01]; Minor, 150 MMEs; Major, 225 MMEs; Laparotomy, 225 MMEs [p = .01]). We found no difference in the number of tablets (Minor, 8; Major, 8; Laparotomy, 9; p = .77) or MMEs used (Minor, 45 MMEs; Major, 45 MMEs; Laparotomy, 55 MME; p = .81) between the groups. On POD 7 there was no difference in median numerical rating scale pain scores (Minor, 3; Major, 2; Laparotomy, 2; p = .07) or satisfaction with analgesia on POD 7 (p = .44), 14 (p = .87), and 28 (p = .18). Patients with prior chronic pain used more total amounts of opioids (68 MME vs 30 MME, p <.01) and were more likely to require opioid refill (odds ratio, 10.4; 95% confidence interval, 1.3–83.6) compared with those without a similar history. Conclusion In this cohort, gynecologic surgeons prescribed nearly 3 times more opioid tablets and MMEs than was used by patients despite patients reporting similar levels of pain after minor and major surgeries

A study on the role of customer experience and consumer purchase decision in Luxury Fashion.

The particular topic of factors influencing consumer purchase decision and customer experience in luxury fashion was chosen as experience is one of the most up coming factors for specially luxury industry. The topic is covered under six different chapters to give an in depth understanding of the significance of customer experience, sustainability, and luxury fashion. The literature used to justify the subject is from scholarly journals. There are many concepts covered under this subject like greenwashing, circular economy, experience economy, and sustainable fashion and so on. The research method chosen was a qualitative approach wherein the in depth interview method with selective coding and thematic analysis were applied to analyse the research. A data structure is been prepared after the data collection and analysis in order to sum up the lumpsum amount of data collected from the interviews and to understand the differences and similarities the research has from the literature applied. The direct quotes have also been used as way to show evidence of the research conducted. Lastly the conclusion includes a brief summary of the findings and literature with further limitations and directions for future research

A study on the role of customer experience and consumer purchase decision in Luxury Fashion.

The particular topic of factors influencing consumer purchase decision and customer experience in luxury fashion was chosen as experience is one of the most up coming factors for specially luxury industry. The topic is covered under six different chapters to give an in depth understanding of the significance of customer experience, sustainability, and luxury fashion. The literature used to justify the subject is from scholarly journals. There are many concepts covered under this subject like greenwashing, circular economy, experience economy, and sustainable fashion and so on. The research method chosen was a qualitative approach wherein the in depth interview method with selective coding and thematic analysis were applied to analyse the research. A data structure is been prepared after the data collection and analysis in order to sum up the lumpsum amount of data collected from the interviews and to understand the differences and similarities the research has from the literature applied. The direct quotes have also been used as way to show evidence of the research conducted. Lastly the conclusion includes a brief summary of the findings and literature with further limitations and directions for future research

Optimal Photon Counting Receiver for Sub-Dead-Time Signal Transmission

In many practical scenarios, single-photon avalanche diodes (SPADs) are good solutions to improve the performance of optical communication systems due to their high sensitivity to photon arrival. SPAD receivers can be implemented in large arrays to achieve higher data rates and additional protection against background light; however, they suffer from a significant intersymbol interference (ISI) if the SPAD dead time is comparable or larger than the symbol duration, i.e., sub-dead-time signal transmission. This work proposes a novel detection scheme designed for high-speed SPAD-based systems to effectively mitigate the degradation induced by ISI. Different from traditional receivers, in the proposed scheme, the information extracted from both the counts and arrival times of photons are utilised for the optimal symbol detection in the presence of non-linear and random ISI effect due to dead time. Our extensive numerical and experimental results demonstrate the superiority of the proposed photon time information based detection (PTID) scheme in terms of both BER performance and background light tolerance of the communication link. In addition, a linear approximation of the SPAD-based channel is investigated, which illustrates that the traditional equalization methods are effective under some specific circumstances

Contraindicated drug–drug interactions associated with oral antimicrobial agents prescribed in the ambulatory care setting in the United States

Objectives Antimicrobial agents are commonly used in ambulatory care settings. Our objective was to examine national-level patterns of contraindications between oral antibacterial or antifungal agents and patients' other oral medications in the US ambulatory care setting. Methods This cross-sectional study included multiple year pooled data (2003–2011) from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS Outpatient Department). Visits by adults (age ≥18 years) in ambulatory settings in the United States who were prescribed oral antibacterial or antifungal agents were evaluated for potential drug–drug interaction (DDI) contraindications. Findings with relative standard error >30% or unweighted sample size <30 were not reported because these were deemed unreliable estimates. Results From 2003 to 2011, there were 1 235 000 outpatient visits (proportion = 0.52%; 95% confidence interval (CI), 0.29–0.74) in which a patient was prescribed an antimicrobial agent associated with a contraindicated DDI. The most prevalent antimicrobials with contraindicated combination among outpatients were simultaneous use of macrolide-containing products (erythromycin or clarithromycin) with statin medication–containing products (simvastatin or lovastatin) (841 864 visits, proportion = 1.91%; 95% CI, 0.96–2.86). The next most common combination was use of fluoroquinolones with antiarrhythmic agents (amiodarone, sotalol, quinidine or procainamide) (365 622 visits, proportion = 0.19%; 95% CI, 0.06–0.32). Conclusions Providers should be aware of potential contraindicated DDIs when prescribing antibiotics, especially macrolides and fluoroquinolones

The Community IntraVenous Antibiotic Study (CIVAS): a mixed methods evaluation of patient preferences for and cost effectiveness of different service models for delivering outpatient parenteral antimicrobial therapy

Background: Outpatient parenteral antimicrobial therapy (OPAT) is widely used in most developed countries, providing considerable opportunities for improved cost savings. However, it is implemented only partially in the UK, using a variety of service models. Objectives: The aims of this research were to (1) establish the extent of OPAT service models in England and identify their development; (2) evaluate patients’ preferences for different OPAT service delivery models; (3) assess the cost-effectiveness of different OPAT service delivery models; and (4) convene a consensus panel to consider our evidence and make recommendations. Methods: This mixed-methods study included seven centres providing OPAT using four main service models: (1) hospital outpatient (HO) attendance; (2) specialist nurse (SN) visiting at home; (3) general nurse (GN) visiting at home; and (4) self-administration (SA) or carer administration. Health-care providers were surveyed and interviewed to explore the implementation of OPAT services in England. OPAT patients were interviewed to determine key service attributes to develop a discrete choice experiment (DCE). This was used to perform a quantitative analysis of their preferences and attitudes. Anonymised OPAT case data were used to model cost-effectiveness with both Markov and simulation modelling methods. An expert panel reviewed the evidence and made recommendations for future service provision and further research. Results: The systematic review revealed limited robust literature but suggested that HO is least effective and SN is most effective. Qualitative study participants felt that different models of care were suited to different types of patient and they also identified key service attributes. The DCE indicated that type of service was the most important factor, with SN being strongly preferred to HO and SA. Preferences were influenced by attitudes to health care. The results from both Markov and simulation models suggest that a SN model is the optimal service for short treatment courses (up to 7 days). Net monetary benefit (NMB) values for HO, GN and SN services were £2493, £2547 and £2655, respectively. For longer treatment, SA appears to be optimal, although SNs provide slightly higher benefits at increased cost. NMB values for HO, GN, SN and SA services were £8240, £9550, £10,388 and £10,644, respectively. The simulation model provided useful information for planning OPAT services. The expert panel requested more guidance for service providers and commissioners. Overall, they agreed that mixed service models were preferable. Limitations: Recruitment to the qualitative study was suboptimal in the very elderly and ethnic minorities, so the preferences of patients from these groups might not be represented. The study recruited from Yorkshire, so the findings may not be applicable nationally. Conclusions: The quantitative preference analysis and economic modelling favoured a SN model, although there are differences between sociodemographic groups. SA provides cost savings for long-term treatment but is not appropriate for all. Future work: Further research is necessary to replicate our results in other regions and populations and to evaluate mixed service models. The simulation modelling and DCE methods used here may be applicable in other health-care settings. Funding: The National Institute for Health Research Health Service and Delivery Research programme

Identification of gender differences in ultrasound milestone assessments during emergency medicine residency training: a pilot study

Objectives: Prior literature suggests that incongruities between male and female resident's procedural competency may be explained by gender bias during the evaluation process. There are no known studies investigating gender differences in the assessment of ultrasound-based procedural skills among emergency medicine (EM) residents. The purpose of this study was to evaluate for gender differences in ultrasound milestone assessments among EM residents. Methods: This is a retrospective study including EM residents. Milestone assessment data were collected from a total of 3 Accreditation Council for Graduate Medical Education (ACGME) EM residency programs representing a 3-year period The outcome measures included mean milestone levels, milestone levels at baseline and graduation and differences in milestone achievement between female and male EM residents. An unpaired Student's t-test was used to compare milestone scores between female and male residents. Results: A total of 456 ultrasound milestone evaluations were collected from 91 EM residents (34 females [37%] and 57 males [63%]). No significant differences were noted in the overall mean milestone level between females (2.3 +/- 0.6) and males (2.2 +/- 0.6) (P=0.387). There were no significant differences noted in the ultrasound milestone level between females (0.8 +/- 0.6) and males (0.7 +/- 0.7) at baseline (P=0.754). Although it did not reach statistical significance (P=0.197), the increase in the mean ultrasound milestone level from baseline to graduation was greater in males (3.4 +/- 0.7) compared to females (3.1 +/- 0.7). Conclusion: Overall, there were no statistically significant differences in the mean ultrasound milestone levels between females and males. The rate of ultrasound milestone level achievement during EM residency training at our institution had a slight tendency to be higher for males than females in the observed residency programs; however, this also did not reach statistical significance. Possible gender bias while evaluating ultrasound milestone levels needs to be further studied on a larger scale.Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]