579 research outputs found
Vedolizumab for Treating Moderately to Severely Active Crohnâs Disease After Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe, active Crohnâs disease. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned as the Evidence Review Group (ERG) and produced a critical review of the evidence of the clinical effectiveness and cost effectiveness of the technology, based upon the companyâs submission to NICE. The GEMINI II and III trials formed the main supporting evidence for the intervention. Both studies were phase III, randomised, double-blind, placebo-controlled, multicentre trials designed to evaluate the efficacy and safety of vedolizumab. They included patients who were naĂŻve to tumour necrosis factor alpha antagonist (anti-TNF-α) therapy and patients who had an inadequate response to, loss of response to or intolerance of immunomodulators or anti-TNF-α agents. GEMINI II was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment (dosing at weeks 0 and 2, with assessment at week 6) and maintenance treatment (during weeks 6â52). In contrast, GEMINI III was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment only, with doses at weeks 0, 2 and 6, and assessment at weeks 6 and 10. In the absence of any direct head-to-head, randomised, controlled trials comparing vedolizumab with other relevant biologic therapies (adalimumab and infliximab) for the treatment of moderate-to-severe Crohnâs disease, the company conducted a network meta-analysis, which compared vedolizumab, adalimumab, infliximab and placebo for the outcomes of clinical response, enhanced clinical response, clinical remission and discontinuation due to adverse events. The company model estimated the incremental cost-effectiveness ratio (ICER) for vedolizumab compared with the standard of care (consisting of 5-aminosalicylic acids, corticosteroids and immunosuppressants) to be ÂŁ21,620 per quality-adjusted life-year (QALY) gained within the anti-TNF-α-failure population (which included a confidential patient access scheme for vedolizumab). The ICERs were above ÂŁ30,000 per QALY gained for the mixed intention-to-treat population (including both anti-TNF-α-naĂŻve and anti-TNF-α-failure populations) and in patients who were anti-TNF-α naĂŻve only. The ERG identified a number of limitations that were believed to limit the robustness of the results presented by the company. These limitations could not be addressed by the ERG without major restructuring of the economic model. Therefore, the ERG concluded that the results from the companyâs model needed to be interpreted with caution and that it was unclear whether the ICERs would increase or decrease following amendment of the identified structural issues
Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial
Rapid reduction of central line infections in hospitalized pediatric oncology patients through simple quality improvement methods
Background Pediatric hematologyâoncology (PHO) patients are at significant risk for developing central lineâassociated bloodstream infections (CLAâBSIs) due to their prolonged dependence on such catheters. Effective strategies to eliminate these preventable infections are urgently needed. In this study, we investigated the implementation of bundled central line maintenance practices and their effect on hospitalâacquired CLAâBSIs. Materials and Methods CLAâBSI rates were analyzed within a singleâinstitution's PHO unit between January 2005 and June 2011. In May 2008, a multidisciplinary quality improvement team developed techniques to improve the PHO unit's safety culture and implemented the use of catheter maintenance practices tailored to PHO patients. Data analysis was performed using timeâseries methods to evaluate the preâ and postâintervention effect of the practice changes. Results The preâintervention CLAâBSI incidence was 2.92 per 1,000âpatient days (PD) and coagulaseânegative Staphylococcus was the most prevalent pathogen (29%). In the postâintervention period, the CLAâBSI rate decreased substantially (45%) to 1.61 per 1,000âPD ( P â<â0.004). Early on, blood and marrow transplant (BMT) patients had a threefold higher CLAâBSI rate compared to nonâBMT patients ( P â<â0.033). With additional infection control countermeasures added to the bundled practices, BMT patients experienced a larger CLAâBSI rate reduction such that BMT and nonâBMT CLAâBSI rates were not significantly different postâintervention. Conclusions By adopting and effectively implementing uniform maintenance catheter care practices, learning multidisciplinary teamwork, and promoting a culture of patient safety, the CLAâBSI incidence in our study population was significantly reduced and maintained. Pediatr Blood Cancer 2013;60:262â269. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95163/1/24187_ftp.pd
The epidemiology and natural history of Crohnâs disease in population-based patient cohorts from North America: a systematic review
To quantify, through systematic review, the epidemiology and natural history of Crohnâs disease in North America. Methods:â The selected articles contained: (i) population-based samples of patients followed from the time of diagnosis; and (ii) objective diagnostic criteria for disease. Studies on the natural history of Crohnâs disease also contained sufficient follow-up. Data collection and analysis:â For prevalence studies, data on the incidence, prevalence, gender and age at diagnosis were extracted. For natural history studies, data on the disease activity, use of medications and surgery were extracted. Main results:â The prevalence of Crohnâs disease in North America ranges from 26.0 to 198.5 cases per 100â000 persons. The incidence rates range from 3.1 to 14.6 cases per 100â000 person-years. Most patients have a chronic intermittent disease course, while 13% have an unremitting disease course and 10% have a prolonged remission. Less than half require corticosteroids at any point. During any given year, approximately 10% are treated with corticosteroids and 30% are treated with 5-aminosalicylates. Up to 57% of patients require at least one surgical resection. Conclusions:â Between 400â000 and 600â000 patients in North America have Crohnâs disease, and the natural history is marked by frequent exacerbations requiring treatment with corticosteroids, 5-aminosalicylate products and surgery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72031/1/j.1365-2036.2002.01140.x.pd
Transition and Reflection in the Use of Health Information: The Case of Pediatric Bone Marrow Transplant Caregivers
ABSTRACT The impact of health information on caregivers is of increasing interest to HCI/CSCW in designing systems to support the social and emotional dimensions of managing health. Drawing on an interview study, as well as corroborating data including a multi-year ethnography, we detail the practices of caregivers (particularly parents) in a bone marrow transplant (BMT) center. We examine the interconnections between information and emotion work performed by caregivers through a liminal lens, highlighting the BMT experience as a time of transition and reflection in which caregivers must quickly adapt to the new social world of the hospital and learn to manage a wide range of patient needs. The transition from parent to 'caregiver' is challenging, placing additional emotional burdens on the intensive information work for managing BMT. As a time of reflection, the BMT experience also provides an occasion for generative thinking and alternative approaches to health management. Our study findings call for health systems that reflect a design paradigm focused on 'transforming lives' rather than 'transferring information.' Autho
Integrating Teaching and Research in Undergraduate Biology Laboratory Education
A course recently designed and implemented at Stanford University applies practical suggestions for creating research-based undergraduate courses that benefit both teaching and research
Correct quantum chemistry in a minimal basis from effective Hamiltonians
We describe how to create ab-initio effective Hamiltonians that qualitatively
describe correct chemistry even when used with a minimal basis. The
Hamiltonians are obtained by folding correlation down from a large parent basis
into a small, or minimal, target basis, using the machinery of canonical
transformations. We demonstrate the quality of these effective Hamiltonians to
correctly capture a wide range of excited states in water, nitrogen, and
ethylene, and to describe ground and excited state bond-breaking in nitrogen
and the chromium dimer, all in small or minimal basis sets
Standard Colonic Lavage Alters the Natural State of Mucosal-Associated Microbiota in the Human Colon
Past studies of the human intestinal microbiota are potentially confounded by the common practice of using bowel-cleansing preparations. We examined if colonic lavage changes the natural state of enteric mucosal-adherent microbes in healthy human subjects.Twelve healthy individuals were divided into three groups; experimental group, control group one, and control group two. Subjects in the experimental group underwent an un-prepped flexible sigmoidoscopy with biopsies. Within two weeks, subjects were given a standard polyethylene glycol-based bowel cleansing preparation followed by a second flexible sigmoidoscopy. Subjects in control group one underwent two un-prepped flexible sigmoidoscopies within one week. Subjects in the second control group underwent an un-prepped flexible sigmoidoscopy followed by a second flexible sigmoidoscopy after a 24-hour clear liquid diet within one week. The mucosa-associated microbial communities from the two procedures in each subject were compared using 16S rRNA gene based terminal restriction fragment length polymorphism (T-RFLP), and library cloning and sequencing.Clone library sequencing analysis showed that there were changes in the composition of the mucosa-associated microbiota in subjects after colonic lavage. These changes were not observed in our control groups. Standard bowel preparation altered the diversity of mucosa-associated microbiota. Taxonomic classification did not reveal significant changes at the phylum level, but there were differences observed at the genus level.Standard bowel cleansing preparation altered the mucosal-adherent microbiota in all of our subjects, although the degree of change was variable. These findings underscore the importance of considering the confounding effects of bowel preparation when designing experiments exploring the gut microbiota
Carbonate-Templated Self-Assembly of an Alkylthiolate-Bridged Cadmium Macrocycle
In the presence of Cd(ClO4)2 and a base, a new mixed N,S-donor alkylthiolate ligand supported both carbonate formation from atmospheric CO2 and the self-assembly of a novel bicapped puckered (CdS)6 molecular wheel. The remarkable stability of the complex was demonstrated by slow intermolecular ligand exchange on the 2J(HH) and J(111/113Cd1H) time scales at elevated temperature. Both CO2 and the base were required to convert amorphous âCdLClO4â precipitated in the absence of air to the carbonate complex. The complex shares structural features with the ζ-carbonic anhydrase class associating cadmium(II) with the biogeochemical cycling of carbon and is the first structurally characterized carbonate complex of any metal involving an alkylthiolate ligand
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