2 - Schools incorporating the Life Sciences and Medicine
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Item Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura(2009-09) Mowatt, Graham; Boachie, Charles; Crowther, Mark; Fraser, Cynthia Mary; Hernandez, Rodolfo Andres; Jia, Xueli; Ternent, Laura; University of Aberdeen.Other Applied Health Sciences; University of Aberdeen.Health Economics Research UnitItem Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura : A Single Technology Appraisal(NIHR Health Technology Assessment programme, 2008-12) Boyers, Dwayne; Jia, Xueli; Crowther, M; Jenkinson, David James; Fraser, Cynthia Mary; Mowatt, Graham; University of Aberdeen.Other Applied Health SciencesItem Systematic review of the safety and efficacy of foam sclerotherapy for venous disease of the lower limbs(2007-08) Jia, X.; Mowatt, Graham; Burr, Jennifer Margaret; Cassar, Kevin; Cook, Jonathan Alistair; Fraser, Cynthia Mary; University of Aberdeen.Other Applied Health SciencesItem Systematic review of the clinical effectiveness and cost-effectiveness of laparoscopic surgery for inguinal hernia repair.(2005) McCormack, Kirsty; Wake, B.; Gonzalez Perez, Juan Gregorio; Fraser, Cynthia Mary; Cook, Jonathan Alistair; McIntosh, Emma; Vale, Luke David; Grant, Adrian Maxwell; University of Aberdeen.Other Applied Health SciencesItem Screening tests for detecting open angle glaucoma : systematic review and meta-analysis(The Association for Research in Vision and Ophthalmology, Inc., 2008-07-09) Mowatt, Graham; Burr, Jennifer Margaret; Cook, Jonathan Alistair; Siddiqui, M. A. Rehman; Ramsay, Craig R; Fraser, Cynthia Mary; Azuara-Blanco, Augusto; Deeks, Jonathan JPURPOSE. To assess the comparative accuracy of potential screening tests for open angle glaucoma (OAG). METHODS. Medline, Embase, Biosis (to November 2005), Science Citation Index (to December 2005), and The Cochrane Library (Issue 4, 2005) were searched. Studies assessing candidate screening tests for detecting OAG in persons older than 40 years that reported true and false positives and negatives were included. Meta-analysis was undertaken using the hierarchical summary receiver operating characteristic model. RESULTS. Forty studies enrolling over 48,000 people reported nine tests. Most tests were reported by only a few studies. Frequency-doubling technology (FDT; C-20-1) was significantly more sensitive than ophthalmoscopy (30, 95% credible interval [CrI] 0–62) and Goldmann applanation tonometry (GAT; 45, 95% CrI 17–68), whereas threshold standard automated perimetry (SAP) and Heidelberg Retinal Tomograph (HRT II) were both more sensitive than GAT (41, 95% CrI 14–64 and 39, 95% CrI 3–64, respectively). GAT was more specific than both FDT C-20-5 (19, 95% CrI 0-53) and threshold SAP (14, 95% CrI 1-37). Judging performance by diagnostic odds ratio, FDT, oculokinetic perimetry, and HRT II are promising tests. Ophthalmoscopy, SAP, retinal photography, and GAT had relatively poor performance as single tests. These findings are based on heterogeneous data of limited quality and as such are associated with considerable uncertainty. CONCLUSIONS. No test or group of tests was clearly superior for glaucoma screening. Further research is needed to evaluate the comparative accuracy of the most promising tests.Item Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura : a single technology appraisal(Gray, 2009) Mowatt, Graham; Boachie, C; Crowther, M; Fraser, Cynthia Mary; Hernández, Rodolfo Andrés; Jia, X; Ternent, LauraThis paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of romiplostim for the treatment of adults with chronic immune or idiopathic thrombocytopenic purpura (ITP) based upon a review of the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission’s evidence came from two relatively high-quality randomised controlled trials (RCTs). The ERG found no evidence that any important data were missed or that data extraction was inaccurate. In both RCTs more patients in the romiplostim than in the placebo group achieved a durable platelet response [non-splenectomised patients: romiplostim 25/41 (61%), placebo 1/21 (5%), odds ratio (OR) 24.45, 95% confidence interval (CI) 3.34 to 179.18; splenectomised patients: romiplostim 16/42 (38%), placebo 0/21 (0%), OR 8.5 (95% CI 1.15 to 372)] and an overall platelet response [non splenectomised patients: romiplostim 36/41 (88%), placebo 3/21 (14%), OR 34.74, 95% CI 7.77 to 155.38; splenectomised patients: romiplostim 33/42 (79%), placebo 0/21 (0%), OR 16.6 (95% CI 2.37 to 706]. The difference in mean period with a platelet response was 13.9 weeks (95% CI 10.5 to 17.4) in favour of romiplostim in the RCT of non-splectomised patients and 12.1 weeks (95% CI 8.7 to 15.6) in favour of romiplostim in the RCT of splectomised patients. The manufacturer’s economic model evaluated the cost-effectiveness of romiplostim compared with standard care. The ERG had concerns about the way the decision problem was addressed in the economic model and about the non-adjustment of findings for confounding factors. In non-splenectomised patients, using romiplostim as a first option treatment, the base-case incremental costeffectiveness ratio (ICER) was £14,840 per quality adjusted life-year (QALY). In splenectomised patients the ICER was £14,655 per QALY. Additional sensitivity analyses performed by the ERG identified two issues of importance: whether individuals entered the model on watch and rescue or on active therapy in the comparator arm (ICER £21,674 per QALY for non-splenectomised patients, £29,771 per QALY for splenectomised patients); whether it was assumed that any unused medicine would be wasted. Combining all of the separate sensitivity analyses, and assuming that watch and rescue was not the first-line treatment, increased the ICERs further (non-splenectomised £37,290 per QALY; splenectomised £131,017 per QALY). In conclusion, the manufacturer’s submission and additional work conducted by the ERG suggest that romiplostim has short-term efficacy for the treatment of ITP, but there is no robust evidence on long-term effectiveness or cost-effectiveness of romiplostim compared with relevant comparators.Item Systematic review of economic evaluations of laparoscopic surgery for colorectal cancer(Wiley-Blackwell, 2008) Hernández, Rodolfo Andrés; De Verteuil, Robyn; Fraser, Cynthia Mary; Vale, Luke David; Aberdeen Health Technology Assessment Group; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health SciencesObjective Colorectal cancer is one of the most common cancers and the standard surgical treatment for this cancer is open resection (OS), but laparoscopic surgery (LS) may be an alternative treatment. In 2000, a Health Technology Assessment (HTA) review found little evidence on costs and cost-effectiveness in comparing the two methods. The evidence base has since expanded and this study systematically reviews the economic evaluations on the subject published since 2000. Method Systematic review of studies reporting costs and outcomes of LS vs OS for colorectal cancer. National Health Service Economic Evaluation Database (NHS EED) methods for abstract writing were followed. Studies were summarized and incremental cost-effectiveness ratios (ICER) for common outcomes were calculated. Results Five studies met the inclusion criteria. LS generally had higher healthcare costs. Most studies reported longer operational time and shorter length of stay and similar long-term outcomes with LS vs OS. Only one outcome, complications, was common across all studies but results lacked consistency (e.g. in two studies, OS was less costly but more effective; in another study, LS was less costly but more effective; and in the further two studies, LS could potentially be cost effective depending on the decision-makers' willingness to pay for the health gain). Conclusion The evidence on cost-effectiveness is not consistent. LS was generally more costly than OS. However, the effectiveness data used in individual economic evaluation were imprecise and unreliable when compared with data from systematic reviews of effectiveness. Nevertheless, short-term benefits of LS (e.g. shorter recovery) may make LS appear less costly when productivity gains are considered.Item Efficacy and safety of using mesh or grafts in surgery for anterior and/or posterior vaginal wall prolapse: systematic review and meta-analysis.(Elsevier Science, 2008) Jia, Xueli; Glazener, Cathryn Margaret Anne; Mowatt, Graham; MacLennan, Graeme Stewart; Fraser, Cynthia Mary; Bain, Christine; Burr, Jennifer MargaretBackground The efficacy and safety of mesh/graft in surgery for anterior or posterior pelvic organ prolapse is uncertain. Objectives To systematically review the efficacy and safety of mesh/graft for anterior or posterior vaginal wall prolapse surgery. Search strategy Electronic databases and conference proceedings were searched, experts and manufacturers contacted and reference lists of retrieved papers scanned. Selection criteria Randomised controlled trials (RCTs), non-randomised comparative studies, registries, case series involving at least 50 women, and RCTs published as conference abstracts from 2005 onwards. Data collection and analysis One reviewer screened titles/abstracts, undertook data extraction, and assessed study quality. Data analysis was conducted for three subgroups: anterior, posterior, and anterior and/or posterior repair (not reported separately). Results Forty-nine studies involving 4569 women treated with mesh/graft were included. Study quality was generally high. Median follow up was 13 months (range 1 to 51). In anterior repair, there was short-term evidence that mesh/graft (any type) significantly reduced objective prolapse recurrence rates compared with no mesh/graft (relative risk 0.48, 95% CI 0.32-0.72). Non-absorbable synthetic mesh had a significantly lower objective prolapse recurrence rate (8.8%, 48/548) than absorbable synthetic mesh (23.1%, 63/273) and biological graft (17.9%, 186/1041), but a higher erosion rate (10.2%, 68/666) than synthetic mesh (0.7%, 1/147) and biological graft (6.0%, 35/581). There was insufficient information to compare any of the other outcomes regardless of prolapse type. Conclusion Evidence for most outcomes was too sparse to provide meaningful conclusions. Rigorous long-term RCTs are required to determine the comparative efficacy of using mesh/graft.Item 64-slice computed tomography angiography in the diagnosis and assessment of coronary artery disease : systematic review and meta-analysis(BMJ, 2008) Mowatt, Graham; Cook, Jonathan Alistair; Hillis, Graham Scott; Walker, Shonagh Mary; Fraser, Cynthia Mary; Jia, Xueli; Waugh, Norman Robert; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health SciencesObjective To assess whether 64-slice computed tomography (CT) angiography might replace some coronary angiography (CA) for diagnosis and assessment of coronary artery disease (CAD). Methods We searched electronic databases, conference proceedings and scanned reference lists of included studies. Eligible studies compared 64-slice CT with a reference standard of CA in adults with suspected/known CAD, reporting sensitivity and specificity or true and false positives and negatives. Data were pooled using the hierarchical summary receiver operating characteristic model. Results Forty studies were included; 28 provided sufficient data for inclusion in the meta-analyses, all using a cutoff of ≥ 50% stenosis to define significant CAD. In patient-based detection (n=1286) 64-slice CT pooled sensitivity was 99% (95% credible interval (CrI) 97 to 99%), specificity 89% (95% CrI 83 to 94%), median positive predictive value (PPV) across studies 93% (range 64 to 100%) and negative predictive value (NPV) 100% (range 86 to 100%). In segment-based detection (n=14,199) 64-slice CT pooled sensitivity was 90% (95% CrI 85 to 94%), specificity 97% (95% CrI 95 to 98%), median positive predictive value (PPV) across studies 76% (range 44 to 93%) and negative predictive value (NPV) 99% (range 95 to 100%). Conclusions 64-slice CT is highly sensitive for patient-based detection of CAD and has high NPV. An ability to rule out significant CAD means that it may have a role in the assessment of chest pain, particularly when the diagnosis remains uncertain despite clinical evaluation and simple non-invasive testing.Item Systematic review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients(National Institute for Health Research, 2009-01) Mowatt, Graham; Houston, G.; Hernández, Rodolfo Andrés; De Verteuil, Robyn; Fraser, Cynthia Mary; Cuthbertson, Brian; Vale, Luke David; University of Aberdeen, School of Medicine & Dentistry, Division of Applied Health SciencesObjectives: To assess the effectiveness and costeffectiveness of oesophageal Doppler monitoring (ODM) compared with conventional clinical assessment and other methods of monitoring cardiovascular function. Data sources: Electronic databases and relevant websites from 1990 to May 2007 were searched. Review methods: This review was based on a systematic review conducted by the US Agency for Healthcare Research and Quality (AHRQ), supplemented by evidence from any additional studies identified. Comparator interventions for effectiveness were standard care, pulmonary artery catheters (PACs), pulse contour analysis monitoring and lithium or thermodilution cardiac monitoring. Data were extracted on mortality, length of stay overall and in critical care, complications and quality of life. The economic assessment evaluated strategies involving ODM compared with standard care, PACs, pulse contour analysis monitoring and lithium or thermodilution cardiac monitoring. Results: The AHRQ report contained eight RCTs and was judged to be of high quality overall. Four comparisons were reported: ODM plus central venous pressure (CVP) monitoring plus conventional assessment vs CVP monitoring plus conventional assessment during surgery; ODM plus conventional assessment vs CVP monitoring plus conventional assessment during surgery; ODM plus conventional assessment vs conventional assessment during surgery; and ODM plus CVP monitoring plus conventional assessment vs CVP monitoring plus conventional assessment postoperatively. Five studies compared ODM plus CVP monitoring plus conventional assessment with CVP monitoring plus conventional assessment during surgery. There were fewer deaths [Peto odds ratio (OR) 0.13, 95% CI 0.02–0.96], fewer major complications (Peto OR 0.12, 95% CI 0.04–0.31), fewer total complications (fixed-effects OR 0.43, 95% CI 0.26–0.71) and shorter length of stay (pooled estimate not presented, 95% CI –2.21 to –0.57) in the ODM group. The results of the meta analysis of mortality should be treated with caution owing to the low number of events and low overall number of patients in the combined totals. Three studies compared ODM plus conventional assessment with conventional assessment during surgery. There was no evidence of a difference in mortality (fixed-effects OR 0.81, 95% CI 0.23–2.77). Length of hospital stay was shorter in all three studies in the ODM group. Two studies compared ODM plus CVP monitoring plus conventional assessment vs CVP monitoring plus conventional assessment in critically ill patients. The patient groups were quite different (cardiac surgery and major trauma) and neither study, nor a meta-analysis, showed a statistically significant difference in mortality (fixed-effects OR 0.84, 95% CI 0.41–1.70). Fewer patients in the ODM group experienced complications (OR 0.49, 95% CI 0.30–0.81) and both studies reported a statistically significant shorter median length of hospital stay in that group. No economic evaluations that met the inclusion criteria were identified from the existing literature so a series of balance sheets was constructed. The results show that ODM strategies are likely to be cost-effective. Conclusions: More formal economic evaluation would allow better use of the available data. All identified studies were conducted in unconscious patients. However, further research is needed to evaluate new ODM probes that may be tolerated by awake patients. Given the paucity of the existing economic evidence base, any further primary research should include an economic evaluation or should provide data suitable for use in an economic model.