Single-use negative-pressure wound therapy versus conventional dressings for closed surgical incisions: systematic literature review and meta-analysis.

BACKGROUND: Surgical-site complications (SSCs) remain a significant cause of morbidity and mortality, particularly in high-risk patients. The aim of this study was to determine whether prophylactic use of a specific single-use negative-pressure wound therapy (sNPWT) device reduced the incidence of SSCs after closed surgical incisions compared with conventional dressings. METHODS: A systematic literature review was performed using MEDLINE, Embase and the Cochrane Library to identify articles published from January 2011 to August 2018. RCTs and observational studies comparing PICO™ sNPWT with conventional dressings, with at least 10 patients in each treatment arm, were included. Meta-analyses were performed to determine odds ratios (ORs) or mean differences (MDs), as appropriate. PRISMA guidelines were followed. The primary outcome was surgical-site infection (SSI). Secondary outcomes were other SSCs and hospital efficiencies. Risk of bias was assessed. RESULTS: Of 6197 citations screened, 29 studies enrolling 5614 patients were included in the review; all studies included patients with risk factors for SSCs. sNPWT reduced the number of SSIs (OR 0.37, 95 per cent c.i. 0.28 to 0.50; number needed to treat (NNT) 20). sNPWT reduced the odds of wound dehiscence (OR 0.70, 0.53 to 0.92; NNT 26), seroma (OR 0.23, 0.11 to 0.45; NNT 13) and necrosis (OR 0.11, 0.03 to 0.39; NNT 12). Mean length of hospital stay was shorter in patients who underwent sNPWT (MD -1.75, 95 per cent c.i. -2.69 to -0.81). CONCLUSION: Use of the sNPWT device in patients with risk factors reduced the incidence of SSCs and the mean length of hospital stay.

Lithium or an atypical antipsychotic drug in the management of treatment-resistant depression: a systematic review and economic evaluation.

BACKGROUND: Patients with treatment-resistant depression (TRD) are those with major depressive disorder that has not responded adequately to treatment. The causes of depression are not fully understood, although there is evidence to suggest that depression is a complex interaction among biological, genetic, psychosocial and environmental factors. Strategies available for the treatment of patients with TRD include pharmacological, non-pharmacological, and psychological and psychosocial interventions. Pharmacological treatment options include switching to a different antidepressant, the addition of another antidepressant of a different class, or use of an augmenting agent, such as anticonvulsants, lithium or atypical antipsychotics (AAPs). However, there is limited evidence available on the effectiveness of these strategies in the treatment of TRD. OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of augmentation of selective serotonin reuptake inhibitor (SSRI) antidepressant therapy with either lithium or an AAP drug in the management of people with treatment-resistant unipolar depression, defined as failure to respond to two or more antidepressant drugs in their current episode of depression. DATA SOURCES: Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, PsycINFO and NHS Economic Evaluation Database (NHS EED). All databases were searched from inception to August 2011. Additional data were obtained from manufacturers. REVIEW METHODS: Systematic reviews of studies evaluating clinical effectiveness, economic analyses and quality of life (QoL) were executed. Quality assessment according to predefined criteria was undertaken independently by two reviewers. Pairwise meta-analyses and mixed-treatment comparisons (MTCs) using both fixed- and random-effects models were undertaken based on intention-to-treat analyses. A probabilistic de novo mathematical model was developed to synthesise the available data on costs and clinical outcomes from the UK NHS perspective over a 1-year time horizon (8 weeks of acute treatment captured by a decision tree and 10 months of maintenance treatment captured by a Markov model). RESULTS: Twelve randomised controlled trials (RCTs) were identified in the review of clinical effectiveness literature; 10 considered SSRI + AAP compared with SSRI + placebo/no treatment, one considered SSRI + AAP compared with SSRI + lithium and one considered SSRI + lithium compared with SSRI + placebo. The RCTs included in the primary analyses used fluoxetine as the background SSRI and olanzapine as the AAP. Results of the MTC showed a non-significant trend in favour of lithium augmentation for response [lithium a priori odds ratio (OR) 1.29; 95% credible interval (CrI) 0.11 to 5.32; lithium post hoc OR 4.15; 95% CrI 0.25 to 20.34 (the trial informing the comparison with lithium reported response using two different definitions)], mean change in Montgomery-Åsberg Depression Rating Scale score from baseline (mean difference - 1.47, 95% CrI - 9.10 to 6.41) and all-cause withdrawals (OR 0.74, 95% CrI 0.10 to 2.66). Four economic evaluations (none directly addressing the review question) and 17 studies that reported on QoL were identified and summarised in narrative reviews. The results of the de novo modelling indicate that augmentation of SSRI with lithium dominates augmentation of an SSRI with AAP (i.e. it resulted in cost savings of £905 per person per year and generated more health benefits, estimated to be 0.03 quality-adjusted life-years). However, sensitivity analyses showed that the model was highly sensitive to changes in acute treatment efficacy (response and remission) or discontinuation. The model was not sensitive to changes in other parameters. LIMITATIONS: In patients with TRD, there is a lack of direct evidence comparing the clinical effectiveness of augmenting an SSRI with an AAP compared with augmenting with lithium. RCTs were identified which facilitated comparison of adding AAP with adding lithium via a MTC. However, variations in the definitions of response implemented in the RCTs, together with differences in patient baseline characteristics across RCTs, introduce bias into the analysis. The direction and extent of the bias is uncertain. CONCLUSIONS: Augmentation of SSRIs with lithium or AAP is likely to be beneficial in people with TRD. Clinical evaluation based on the limited evidence identified in this research indicates no statistically significant difference between the two augmentation strategies. Cost-effectiveness analyses suggest that augmentation with lithium is less expensive and more effective than augmentation with AAP. However, the uncertainty in the clinical estimates of discontinuation and treatment response is reflected in the model results. A RCT comparing the two augmentation strategies, reporting relevant outcomes, including QoL, is needed. STUDY REGISTRATION: PROSPERO CRD42011001464.

Probabilistic cost-effectiveness analysis of cascade screening for familial hypercholesterolaemia using alternative diagnostic and identification strategies.

OBJECTIVE: To estimate the probabilistic cost-effectiveness of cascade screening methods in familial hypercholesterolaemia (FH) from the UK NHS perspective. DESIGN: Economic evaluation (cost utility analysis) comparing four cascade screening strategies for FH: Using low-density lipoprotein (LDL) cholesterol measurements to diagnose affected relatives (cholesterol method); cascading only in patients with a causative mutation identified and using DNA tests to diagnose relatives (DNA method); DNA testing combined with LDL-cholesterol testing in families with no mutation identified, only in patients with clinically defined 'definite' FH (DNA+DFH method); DNA testing combined with LDL-cholesterol testing in no-mutation families of both 'definite' and 'probable' FH patients (DNA+DFH+PFH). A probabilistic model was constructed to estimate the treatment benefit from statins, with all diagnosed individuals receiving high-intensity statin treatment. POPULATION: A cohort of 1000 people suspected of having FH aged 50 years for index cases and 30 years for relatives, followed for a lifetime. MAIN OUTCOMES: Costs, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER). RESULTS: The DNA+DFH+PFH method was the most cost-effective cascade screening strategy. The ICER was estimated at £3666/QALY. Using this strategy, of the tested relatives 30.6% will be true positives, 6.3% false positives, 61.9% true negatives and 1.1% false negatives. Probabilistic sensitivity analysis showed that this approach is 100% cost-effective using the conventional benchmark for cost-effective treatments in the NHS of between £20,000 and £30,000 per QALY gained. CONCLUSION: Cascade testing of relatives of patients with DFH and PFH is cost-effective when using a combination of DNA testing for known family mutations and LDL-cholesterol levels in the remaining families. The approach is more cost-effective than current primary prevention screening strategies.

Cost-effectiveness analysis of the use of a high-intensity statin compared to a low-intensity statin in the management of patients with familial hypercholesterolaemia.

OBJECTIVES: To estimate, using probabilistic decision-analytic modelling techniques, the cost effectiveness of treating familial hypercholesterolaemia (FH) patients with high-intensity statins compared to treatment with low-intensity statins. For the purpose of this economic analysis, and based on their known differences, statins were categorised as high intensity if they produce greater LDL-cholesterol reductions than simvastatin 40 mg (e.g., simvastatin 80 mg and appropriate doses of atorvastatin and rosuvastatin or combination of statins + ezetimibe). METHODS: A lifetime Markov model was developed to estimate the incremental cost per quality adjusted life year (QALY) of treating a hypothetical cohort of 1000 FH patients aged between 20 and 70 years. Baseline coronary heart disease risks reported in the NICE TA 94 on statins, and age-adjusted risk of cardiovascular disease reported in the FH population, were used to populate the model. A meta-analysis estimate of the reduction in cardiovascular events from using high-intensity compared with low-intensity statins was obtained from published trials. Results were interpreted using a cost-effectiveness threshold of pound20 000/QALY. RESULTS: Fewer cardiovascular events and deaths were predicted to occur in the group treated with higher-intensity statins, and the incremental cost-effectiveness ratio (ICER) was estimated at pound11 103/QALY. The ICER remained below the pound20 000 threshold for 20-39-year-olds and 40-59-year-olds, but rose above this threshold in individuals aged over 60 years. One-way sensitivity analysis showed that results were most sensitive to variation in treatment effect on mortality and the cost of high-intensity statins. CONCLUSIONS: Modelling demonstrates that high-intensity statins are cost-effective for the treatment of younger FH patients. If, as is likely, the relative price of high-intensity statins fall in the future as they come off patent, then their cost effectiveness will improve further.