An Analysis of 183 Heart Transplants for Pediatric or Congenital Heart Disease-Impact of High Panel Reactive Antibody.

BACKGROUND: We reviewed our management strategy and outcome data for all 179 patients with pediatric and/or congenital heart disease who underwent 183 heart transplants from January 1, 2011, to December 31, 2021, and evaluated the impact of elevated panel reactive antibody (PRA). METHODS: High PRA was defined as PRA >10%. Univariate associations with long-term survival were assessed with Cox proportional hazards models. Impact of high PRA on survival was estimated with multivariable models. RESULTS: PRA >10% was present in 60 of 183 transplants (32.8%), who were more likely to have prior cardiac surgery, higher number of prior cardiac operations, prior sternotomy, prior heart transplant, and positive crossmatch (24 of 60 [40.0%] vs 11 of 123 [8.9%], P < .0001). Univariate associations with long-term survival include acquired heart disease vs congenital or retransplant (hazard ratio [HR], 0.18; 95% CI, 0.053-0.593; P = .005), prior cardiac surgery (HR, 5.6; 95% CI, 1.32-23.75; P = .020), number of prior cardiac operations (HR, 1.3 for each additional surgery; 95% CI, 1.12-1.50; P = .0004), single ventricle (HR, 2.4; 95% CI, 1.05-5.48; P = .038), and preoperative renal dysfunction (HR, 3.4; 95% CI, 1.43-7.49; P = .002). In multivariate analysis, high PRA does not impact survival when controlling for each of the factors shown in univariable analysis to be associated with long-term survival. The Kaplan-Meier method provided the following survival estimates at 1 year (95% CI) and 5 years (95% CI) after cardiac transplantation: All patients, 93.6% (89.9%-97.3%) and 85.8% (80.0%-92.1%); PRA <10%, 96.6% (93.4%-99.9%) and 86.7% (79.6%-94.3%); and PRA >10%, 86.7% (78.0%-96.4%) and 83.8% (74.0%-95.0%). Despite high PRA being associated with higher mortality at 1 year (14.9% vs 3.8%, P = .035), no significant difference exists in Kaplan-Meier overall survival at 5 years posttransplant in patients with and without high PRA (log-rank P = .4). CONCLUSIONS: In our cohort, 5-year survival in patients with high PRA (PRA >10%) is similar to that in patients without high PRA (PRA <10%), despite the presence of more risk factors in those with high PRA. Individualized immunomodulatory strategies can potentially mitigate the risk of high PRA.

Economic evaluation of surgical treatments for women with stress urinary incontinence: a cost-utility and value of information analysis.

OBJECTIVES: Stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MUI) are common conditions that can have a negative impact on the quality of life of patients and serious cost implications for healthcare providers. The objective of this study was to assess the cost-effectiveness of nine different surgical interventions for treatment of SUI and stress-predominant MUI from a National Health Service and personal social services perspective in the UK. METHODS: A Markov microsimulation model was developed to compare the costs and effectiveness of nine surgical interventions. The model was informed by undertaking a systematic review of clinical effectiveness and network meta-analysis. The main clinical parameters in the model were the cure and incidence rates of complications after different interventions. The outcomes from the model were expressed in terms of cost per quality-adjusted life-years (QALYs) gained. In addition, expected value of perfect information (EVPI) analyses were conducted to quantify the main uncertainties facing decision-makers. RESULTS: The base-case results suggest that retropubic mid-urethral sling (retro-MUS) is the most cost-effective surgical intervention over a 10-year and lifetime time horizon. The probabilistic results show that retro-MUS and traditional sling are the interventions with the highest probability of being cost-effective across all willingness-to-pay thresholds over a lifetime time horizon. The value of information analysis results suggest that the largest value appears to be in removing uncertainty around the incidence rates of complications, the relative treatment effectiveness and health utility values. CONCLUSIONS: Although retro-MUS appears, at this stage, to be a cost-effective intervention, research is needed on possible long-term complications of all surgical treatments to provide reassurance of safety, or earlier warning of unanticipated adverse effects. The value of information analysis supports the need, as a first step, for further research to improve our knowledge of the actual incidence of complications.

Surgical treatments for women with stress urinary incontinence: a systematic review of economic evidence.

BACKGROUND: Surgical interventions for the treatment of stress urinary incontinence (SUI) in women are commonly employed following the failure of minimally invasive therapies. Due to the limited information available on the relative cost-effectiveness of available surgeries for treating SUI, a de novo economic analysis was conducted to assess costs and effects of all relevant surgeries. To inform the economic analysis, the objective of this review was to identify and assess the quality of existing economic evaluation studies on different surgical interventions for the treatment of SUI in women. METHODS: The following databases were searched during the review process: Medical Literature Analysis and Retrieval System Online (MEDLINE), MEDLINE In-Process, Excerpta Medica Database (Embase), National Health Service Economic Evaluation Database (NHS EED), and Health Management Information Consortium and Cost-Effectiveness Analysis Registry (CEA registry). The key criteria for inclusion were that the study population included women with SUI and that the surgical interventions considered were utilised as either a primary or a follow-up surgery. The review included only full economic evaluations. Studies were quality assessed using the Drummond checklist for economic evaluations. No quantitative synthesis of the results by meta-analysis was conducted due to the high methodological heterogeneity. RESULTS: Twenty-six economic evaluations were included, of which 13 were model-based analyses. Surgical treatments assessed most frequently were mid-urethral slings and open and laparoscopic colposuspension. There were some differences in the methodological approaches taken, including differences in type of economic analysis, perspective, time horizon, types of resource use, and costs and outcomes that were included in the analysis. The majority of studies conducted a cost-utility analysis from a health system perspective and applied a time horizon of between 1 and 5 years. The cost-effectiveness results suggest that single-incision mini-sling and mid-urethral slings are among the most cost-effective options. CONCLUSIONS: The review has shown that methods used for the economic evaluation of surgical treatments for SUI vary widely in terms of study design, analysis type, compared alternatives, time horizon, costing methodologies and effect outcomes. Future economic evaluation studies on surgical treatments for SUI may be improved by the application of available guidelines. SYSTEMATIC REVIEW REGISTRATION: Registered in PROSPERO in 2016, CRD42016049339.

Surgical interventions for women with stress urinary incontinence: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVES: To compare the effectiveness and safety of surgical interventions for women with stress urinary incontinence. DESIGN: Systematic review and network meta-analysis. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials evaluating surgical interventions for the treatment of stress urinary incontinence in women. METHODS: Identification of relevant randomised controlled trials from Cochrane reviews and the Cochrane Incontinence Specialised Register (searched May 2017), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Medline In-Process, Medline Epub Ahead of Print, CINAHL, ClinicalTrials.gov, and WHO ICTRP. The reference lists of relevant articles were also searched. Primary outcomes were "cure" and "improvement" at 12 months, analysed by means of network meta-analyses, with results presented as the surface under the cumulative ranking curve (SUCRA). Adverse events were analysed using pairwise meta-analyses. Risk of bias was assessed using the Cochrane risk of bias tool. The quality of evidence for network meta-analysis was assessed using the GRADE approach. RESULTS: 175 randomised controlled trials assessing a total of 21 598 women were included. Most studies had high or unclear risk across all risk of bias domains. Network meta-analyses were based on data from 105 trials that reported cure and 120 trials that reported improvement of incontinence symptoms. Results showed that the interventions with highest cure rates were traditional sling, retropubic midurethral sling (MUS), open colposuspension, and transobturator MUS, with rankings of 89.4%, 89.1%, 76.7%, and 64.1%, respectively. Compared with retropubic MUS, the odds ratio of cure for traditional sling was 1.06 (95% credible interval 0.62 to 1.85), for open colposuspension was 0.85 (0.54 to 1.33), and for transobtrurator MUS was 0.74 (0.59 to 0.92). Women were also more likely to experience an improvement in their incontinence symptoms after receiving retropubic MUS or transobturator MUS compared with other surgical procedures. In particular, compared with retropubic MUS, the odds ratio of improvement for transobturator MUS was 0.76 (95% credible interval 0.59 to 0.98), for traditional sling was 0.69 (0.39 to 1.26), and for open colposuspension was 0.65 (0.41 to 1.02). Quality of evidence was moderate for retropubic MUS versus transobturator MUS and low or very low for retropubic MUS versus the other two interventions. Data on adverse events were available mainly for mesh procedures, indicating a higher rate of repeat surgery and groin pain but a lower rate of suprapubic pain, vascular complications, bladder or urethral perforation, and voiding difficulties after transobturator MUS compared with retropubic MUS. Data on adverse events for non-MUS procedures were sparse and showed wide confidence intervals. Long term data were limited. CONCLUSIONS: Retropubic MUS, transobturator MUS, traditional sling, and open colposuspension are more effective than other procedures for stress urinary incontinence in the short to medium term. Data on long term effectiveness and adverse events are, however, limited, especially around the comparative adverse events profiles of MUS and non-MUS procedures. A better understanding of complications after surgery for stress urinary incontinence is imperative. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049339.

Surgical treatments for women with stress urinary incontinence: the ESTER systematic review and economic evaluation.

BACKGROUND: Urinary incontinence in women is a distressing condition that restricts quality of life and results in a large economic burden to both the NHS and women themselves. OBJECTIVE: To evaluate the clinical effectiveness, safety and cost-effectiveness of surgical treatment for stress urinary incontinence (SUI) in women and explore women's preferences. DESIGN: An evidence synthesis, a discrete choice experiment (DCE) and an economic decision model, with a value-of-information (VOI) analysis. Nine surgical interventions were compared. Previous Cochrane reviews for each were identified and updated to include additional studies. Systematic review methods were applied. The outcomes of interest were 'cure' and 'improvement'. Both a pairwise and a network meta-analysis (NMA) were conducted for all available surgical comparisons. A DCE was undertaken to assess the preferences of women for treatment outcomes. An economic model assessed the cost-effectiveness of alternative surgeries and a VOI analysis was undertaken. RESULTS: Data from 175 studies were included in the effectiveness review. The majority of included studies were rated as being at high or unclear risk of bias across all risk-of-bias domains. The NMA, which included 120 studies that reported data on 'cure' or 'improvement', showed that retropubic mid-urethral sling (MUS), transobturator MUS, traditional sling and open colposuspension were more effective than other surgical procedures for both primary outcomes. The results for other interventions were variable. In general, rate of tape and mesh exposure was higher after transobturator MUS than after retropubic MUS or single-incision sling, whereas the rate of tape or mesh erosion/extrusion was similar between transobturator MUS and retropubic MUS. The results of the DCE, in which 789 women completed an anonymous online questionnaire, indicate that women tend to prefer surgical treatments associated with no pain or mild chronic pain and shorter length of hospital stay as well as those treatments that have a smaller risk for urinary symptoms to reoccur after surgery. The cost-effectiveness results suggest that, over a lifetime, retropubic MUS is, on average, the least costly and most effective surgery. However, the high level of uncertainty makes robust estimates difficult to ascertain. The VOI analysis highlighted that further research around the incidence rates of complications would be of most value. LIMITATIONS: Overall, the quality of the clinical evidence was low, with limited data available for the assessment of complications. Furthermore, there is a lack of robust evidence and significant uncertainty around some parameters in the economic modelling. CONCLUSIONS: To our knowledge, this is the most comprehensive assessment of published evidence for the treatment of SUI. There is some evidence that retropubic MUS, transobturator MUS and traditional sling are effective in the short to medium term and that retropubic MUS is cost-effective in the medium to long term. The VOI analysis highlights the value of further research to reduce the uncertainty around the incidence rates of complications. There is a need to obtain robust clinical data in future work, particularly around long-term complication rates. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016049339. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Urinary incontinence, defined as involuntary leakage of urine, is a common condition that varies in type and severity and can have a huge impact on the quality of life of women. The aim of this project was to summarise the evidence on the clinical effectiveness, safety and cost-effectiveness of nine surgical operations for stress urinary incontinence in women and assess the need for further research. Women's preferences for surgery were also explored. Currently there is no agreement among decision-makers, doctors and patients about which of the available surgical operations is best. Based on previous Cochrane reviews, the effects and safety of each operation were systematically reviewed and analysed. Their cost-effectiveness and the value of conducting further research were also evaluated. To better understand the preference of women, an online survey containing a discrete choice experiment was conducted. Finally, patient representatives were consulted to help us to understand the consequences of the findings from a patient's perspective. The evidence on surgical operations was predominantly short to medium term (up to 12 months). This analysis found that the quality of the evidence varied, with the majority of trials being subject to high or unclear risk of bias, making the conclusions that can be drawn less robust. The findings of the clinical evidence review suggest that retropubic sling procedures, transobturator sling procedures and traditional sling procedures are more effective than other surgical procedures for both 'cure' and 'improvement' of stress urinary incontinence. The results of the economic analyses support these findings, suggesting that retropubic mid-urethral sling is the most cost-effective surgical operation. However, data on complications were lacking, limiting any strong conclusions. The results suggest that there is value in undertaking further research to reduce the uncertainty around the medium- to long-term complications of all surgical treatments and this was reflected in patients' views.