scholarly journals Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation

2019 ◽  
Vol 23 (63) ◽  
pp. 1-190 ◽  
Author(s):  
Abdullah Pandor ◽  
Daniel Horner ◽  
Sarah Davis ◽  
Steve Goodacre ◽  
John W Stevens ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lower Limb ◽  
Meta Analysis ◽  
Cost Effective ◽  
Health Technology ◽  
Risk Of Bleeding ◽  
Prognostic Accuracy ◽  
Risk Predictors ◽  
Qaly Threshold ◽  
Pharmacological Thromboprophylaxis

Background Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis. Objectives To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research. Data sources Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field. Review methods Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services. Results Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84–89% and specificity of 46–55%. Limitations Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling. Conclusions Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain. Future work Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis. Study registration This study is registered as PROSPERO CRD42017058688. Funding The National Institute for Health Research Health Technology Assessment programme.

scholarly journals A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study

2016 ◽  
Vol 20 (64) ◽  
pp. 1-86 ◽  
Author(s):  
Rebecca K Simmons ◽  
Knut Borch-Johnsen ◽  
Torsten Lauritzen ◽  
Guy EHM Rutten ◽  
Annelli Sandbæk ◽  
...  
Keyword(s):  
Risk Factors ◽  
Patient Reported Outcomes ◽  
Cost Effective ◽  
Well Being ◽  
Health Technology ◽  
Patient Reported ◽  
All Cause Mortality

BackgroundIntensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain.ObjectiveTo quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes.DesignPragmatic, multicentre, cluster-randomised, parallel-group trial.SettingThree hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK.ParticipantsIndividuals aged 40–69 years with screen-detected diabetes.InterventionsScreening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol.Main outcome measuresThe primary end point was a composite of first cardiovascular event (cardiovascular mortality/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3;©Isis Innovation Ltd 2010; seewww.dtu.ox.ac.uk/outcomesmodel(accessed 27 January 2016)].ResultsWe included 3055 (RC,n = 1377; IT,n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml/minute; RC 6.44 ml/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost £981 per patient and was not cost-effective at costs ≥ £631 per patient.ConclusionsCompared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted.Trial registrationClinicalTrials.gov NCT00237549.Funding detailsThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 64. See the NIHR Journals Library website for further project information.

scholarly journals Kinematic risk factors for lower limb tendinopathy in distance runners: A systematic review and meta-analysis

2019 ◽  
Vol 69 ◽  
pp. 13-24 ◽  
Author(s):  
Seyed Hamed Mousavi ◽  
Juha M. Hijmans ◽  
Reza Rajabi ◽  
Ron Diercks ◽  
Johannes Zwerver ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Lower Limb ◽  
Meta Analysis ◽  
Distance Runners

scholarly journals Risk factors for development of lower limb osteoarthritis in physically demanding occupations: A systematic review and meta-analysis

2020 ◽  
Vol 86 ◽  
pp. 103097 ◽  
Author(s):  
Elisa F.D. Canetti ◽  
Ben Schram ◽  
Robin M. Orr ◽  
Joseph Knapik ◽  
Rodney Pope
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Lower Limb ◽  
Meta Analysis

scholarly journals Can we predict relapse in Graves’ disease? Results from a systematic review and meta-analysis

2017 ◽  
Vol 176 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Tristan Struja ◽  
Hannah Fehlberg ◽  
Alexander Kutz ◽  
Larissa Guebelin ◽  
Christian Degen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Thyroid Volume ◽  
Case Control ◽  
Graves Disease ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Prognostic Accuracy

BackgroundIdentification of pretreatment risk factors predicting relapse in patients with hyperthyroidism of Graves’ disease after stopping anti-thyroid drugs (ATD) is decisive to guide therapeutic options.PurposeWe performed a systematic search and meta-analysis to study predictors for relapse after stopping ATD in patients with Graves’ disease.MethodsBased on a pre-specified protocol, we searched PubMed, EMBASE and Cochrane in July 2015 for case–control, controlled and randomized-controlled trials reporting risk factors for relapse after stopping ATD. The primary endpoint was relapse of disease until follow-up. PRISMA and SIGN statements were used for reviewing the data and assessing the quality of included trials.ResultsWe included 54 trials with a total of 7595 participants. Most trials were small with moderate-to-high risk for bias. Ten trials were assessed only qualitatively (2227 patients), genomic data were reported in 13 trials (2178 patients) and 31 trials (4346 patients) were assessed quantitatively. In total, there were 3696 relapses in 7595 patients (48.7%). By using random-effects meta-analysis, orbitopathy, smoking, thyroid volume measured by sonography, goiter size, fT4, tT3, TRAb and TBII were significantly associated with relapse, whereas male vs female sex, age and initial tT4 level did not show significant associations.ConclusionsThis analysis found several risk factors to predict relapse in Graves’ disease, which can be combined in a risk score. Prospective studies should evaluate the prognostic accuracy of such a score to guide treatment decisions.

scholarly journals Lower limb arthroplasty: can we produce a tool to predict outcome and failure, and is it cost-effective? An epidemiological study

2017 ◽  
Vol 5 (12) ◽  
pp. 1-246 ◽  
Author(s):  
Nigel Arden ◽  
Doug Altman ◽  
David Beard ◽  
Andrew Carr ◽  
Nicholas Clarke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Markov Model ◽  
Lower Limb ◽  
Prospective Cohort ◽  
Cost Effective ◽  
Preoperative Pain ◽  
Predictive Tool ◽  
Predictive Tools ◽  
Increased Risk ◽  
Patient Reported

BackgroundAlthough hip and knee arthroplasties are considered to be common elective cost-effective operations, up to one-quarter of patients are not satisfied with the operation. A number of risk factors for implant failure are known, but little is known about the predictors of patient-reported outcomes.Objectives(1) Describe current and future needs for lower limb arthroplasties in the UK; (2) describe important risk factors for poor surgery outcomes and combine them to produce predictive tools (for hip and knee separately) for poor outcomes; (3) produce a Markov model to enable a detailed health economic analysis of hip/knee arthroplasty, and for implementing the predictive tool; and (4) test the practicality of the prediction tools in a pragmatic prospective cohort of lower limb arthroplasty.DesignThe programme was arranged into four work packages. The first three work packages used the data from large existing data sets such as Clinical Practice Research Datalink, Hospital Episode Statistics and the National Joint Registry. Work package 4 established a pragmatic cohort of lower limb arthroplasty to test the practicality of the predictive tools developed within the programme.ResultsThe estimated number of total knee replacements (TKRs) and total hip replacements (THRs) performed in the UK in 2015 was 85,019 and 72,418, respectively. Between 1991 and 2006, the estimated age-standardised rates (per 100,000 person-years) for a THR increased from 60.3 to 144.6 for women and from 35.8 to 88.6 for men. The rates for TKR increased from 42.5 to 138.7 for women and from 28.7 to 99.4 for men. The strongest predictors for poor outcomes were preoperative pain/function scores, deprivation, age, mental health score and radiographic variable pattern of joint space narrowing. We found a weak association between body mass index (BMI) and outcomes; however, increased BMI did increase the risk of revision surgery (a 5-kg/m2rise in BMI increased THR revision risk by 10.4% and TKR revision risk by 7.7%). We also confirmed that osteoarthritis (OA) severity and migration pattern of the hip predicted patient-reported outcome measures. The hip predictive tool that we developed performed well, with a correctedR2of 23.1% and had good calibration, with only slight overestimation of Oxford Hip Score in the lowest decile of outcome. The knee tool developed performed less well, with a correctedR2of 20.2%; however, it had good calibration. The analysis was restricted by the relatively limited number of variables available in the extant data sets, something that could be addressed in future studies. We found that the use of bisphosphonates reduced the risk of revision knee and hip surgery by 46%. Hormone replacement therapy reduced the risk by 38%, if used for at least 6 months postoperatively. We found that an increased risk of postoperative fracture was prevented by bisphosphonate use. This result, being observational in nature, will require confirmation in a randomised controlled trial. The Markov model distinguished between outcome categories following primary and revision procedures. The resulting outcome prediction tool for THR and TKR reduced the number and proportion of unsatisfactory outcomes after the operation, saving NHS resources in the process. The highest savings per quality-adjusted life-year (QALY) forgone were reported from the oldest patient subgroups (men and women aged ≥ 80 years), with a reported incremental cost-effectiveness ratio of around £1200 saved per QALY forgone for THRs. In the prospective cohort of arthroplasty, the performance of the knee model was modest (R2 = 0.14) and that of the hip model poor (R2 = 0.04). However, the addition of the radiographic OA variable improved the performance of the hip model (R2 = 0.125 vs. 0.110) and high-sensitivity C-reactive protein improved the performance of the knee model (R2 = 0.230 vs. 0.216). These data will ideally need replication in an external cohort of a similar design. The data are not necessarily applicable to other health systems or countries.ConclusionThe number of total hip and knee replacements will increase in the next decade. High BMI, although clinically insignificant, is associated with an increased risk of revision surgery and postoperative complications. Preoperative pain/function, the pattern of joint space narrowing, deprivation index and level of education were found to be the strongest predictors for THR. Bisphosphonates and hormone therapy proved to be beneficial for patients undergoing lower limb replacement. The addition of new predictors collected from the prospective cohort of arthroplasty slightly improved the performance of the predictive tools, suggesting that the potential improvements in both tools can be achieved using the plethora of extra variables from the validation cohort. Although currently it would not be cost-effective to implement the predictive tools in a health-care setting, we feel that the addition of extensive risk factors will improve the performances of the predictive tools as well as the Markov model, and will prove to be beneficial in terms of cost-effectiveness. Future analyses are under way and awaiting more promising provisional results.Future workFurther research should focus on defining and predicting the most important outcome to the patient.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

scholarly journals A prognostic model, including quantitative fetal fibronectin, to predict preterm labour: the QUIDS meta-analysis and prospective cohort study

2021 ◽  
Vol 25 (52) ◽  
pp. 1-168
Author(s):  
Sarah J Stock ◽  
Margaret Horne ◽  
Merel Bruijn ◽  
Helen White ◽  
Robert Heggie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Preterm Birth ◽  
Prospective Cohort ◽  
Prognostic Model ◽  
Preterm Labour ◽  
Meta Analysis ◽  
Health Technology ◽  
Spontaneous Preterm Birth ◽  
Fetal Fibronectin

Background The diagnosis of preterm labour is challenging. False-positive diagnoses are common and result in unnecessary, potentially harmful treatments (e.g. tocolytics, antenatal corticosteroids and magnesium sulphate) and costly hospital admissions. Measurement of fetal fibronectin in vaginal fluid is a biochemical test that can indicate impending preterm birth. Objectives To develop an externally validated prognostic model using quantitative fetal fibronectin concentration, in combination with clinical risk factors, for the prediction of spontaneous preterm birth and to assess its cost-effectiveness. Design The study comprised (1) a qualitative study to establish the decisional needs of pregnant women and their caregivers, (2) an individual participant data meta-analysis of existing studies to develop a prognostic model for spontaneous preterm birth within 7 days in women with symptoms of preterm labour based on quantitative fetal fibronectin and clinical risk factors, (3) external validation of the prognostic model in a prospective cohort study across 26 UK centres, (4) a model-based economic evaluation comparing the prognostic model with qualitative fetal fibronectin, and quantitative fetal fibronectin with cervical length measurement, in terms of cost per QALY gained and (5) a qualitative assessment of the acceptability of quantitative fetal fibronectin. Data sources/setting The model was developed using data from five European prospective cohort studies of quantitative fetal fibronectin. The UK prospective cohort study was carried out across 26 UK centres. Participants Pregnant women at 22+0–34+6 weeks’ gestation with signs and symptoms of preterm labour. Health technology being assessed Quantitative fetal fibronectin. Main outcome measures Spontaneous preterm birth within 7 days. Results The individual participant data meta-analysis included 1783 women and 139 events of spontaneous preterm birth within 7 days (event rate 7.8%). The prognostic model that was developed included quantitative fetal fibronectin, smoking, ethnicity, nulliparity and multiple pregnancy. The model was externally validated in a cohort of 2837 women, with 83 events of spontaneous preterm birth within 7 days (event rate 2.93%), an area under the curve of 0.89 (95% confidence interval 0.84 to 0.93), a calibration slope of 1.22 and a Nagelkerke R 2 of 0.34. The economic analysis found that the prognostic model was cost-effective compared with using qualitative fetal fibronectin at a threshold for hospital admission and treatment of ≥ 2% risk of preterm birth within 7 days. Limitations The outcome proportion (spontaneous preterm birth within 7 days of test) was 2.9% in the validation study. This is in line with other studies, but having slightly fewer than 100 events is a limitation in model validation. Conclusions A prognostic model that included quantitative fetal fibronectin and clinical risk factors showed excellent performance in the prediction of spontaneous preterm birth within 7 days of test, was cost-effective and can be used to inform a decision support tool to help guide management decisions for women with threatened preterm labour. Future work The prognostic model will be embedded in electronic maternity records and a mobile telephone application, enabling ongoing data collection for further refinement and validation of the model. Study registration This study is registered as PROSPERO CRD42015027590 and Current Controlled Trials ISRCTN41598423. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 52. See the NIHR Journals Library website for further project information.

Risk Factors for Surgical Site Infection After Lower Limb Revascularization Surgery in Adults with Peripheral Artery Disease: Protocol for a Systematic Review and Meta-Analysis (Preprint)

2021 ◽  
Author(s):  
Derek J. Roberts ◽  
Sudhir K. Nagpal ◽  
Henry T. Stelfox ◽  
Timothy Brandys ◽  
Vicente Corrales-Medina ◽  
...  
Keyword(s):  
Risk Factors ◽  
Surgical Site Infection ◽  
Peripheral Artery Disease ◽  
Lower Limb ◽  
Meta Analysis ◽  
Site Infection ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Revascularization Surgery ◽  
Cumulative Evidence

BACKGROUND Surgical site infections are common, costly, and associated with increased morbidity and potentially mortality after lower limb revascularization surgery (i.e., arterial bypass, endarterectomy, and patch angioplasty). Identifying evidence-informed risk factors for surgical site infection in patients undergoing these surgeries is therefore important. OBJECTIVE We aim to conduct a systematic review and meta-analysis of prognostic studies to identify, synthesize, and determine the certainty in the cumulative evidence associated with reported risk factors for early and delayed surgical site infection after lower limb revascularization surgery in patients with peripheral artery disease. METHODS We will search MEDLINE, EMBASE, the seven databases in Evidence-Based Medicine Reviews, review articles identified during the search, and included article bibliographies. We will include studies of adults (≥18-years-of-age) with peripheral artery disease that reported odds ratios, risk ratios, or hazard ratios adjusted for the presence of other risk factors or confounding variables and relating the potential risk factor(s) of interest to development of surgical site infection after lower limb revascularization surgery. We will exclude studies that did not adjust for confounding, exclusively examined certain high-risk patient cohorts, or included >20% of patients who underwent surgery for indications other than peripheral artery disease. The primary outcomes will be early (in-hospital or ≤30-day) surgical site infection and Szilagyi grade I (cellulitis involving the wound), grade II (infection involving subcutaneous tissue), and grade III (infection involving the vascular graft) surgical site infection. Two investigators will independently extract data and evaluate study risk of bias using the Quality in Prognosis Studies tool. Adjusted risk factor estimates with similar definitions will be pooled using DerSimonian and Laird random-effects models. Heterogeneity will be explored using stratified meta-analyses and meta-regression. Finally, we will use the Grading of Recommendations, Assessment, Development, and Evaluation approach to determine certainty in the estimates of association between the reported risk factors and development of surgical site infection. RESULTS The protocol was submitted to PROSPERO, the international register of systematic reviews, on March 12, 2021. CONCLUSIONS This study will identify, synthesize, and determine the certainty in the cumulative evidence associated with risk factors for early and delayed surgical site infection after lower limb revascularization surgery in patients with peripheral artery disease. Results will be used to inform practice, clinical practice statements and guidelines, and subsequent research. CLINICALTRIAL Submitted to PROSPER on March 12, 2021.

Sign in / Sign up

Export Citation Format

Share Document