Background: To support decision-making in aortic valve replacement in children and adults, we provide a comprehensive overview of outcome after the Ross procedure. Methods and Results: A systematic search was conducted for publications reporting clinical outcome after the Ross procedure, published between January 1, 2000, and November 22, 2017. Reported event rates and time-to-event data were pooled and entered into a microsimulation model to calculate life expectancy and lifetime event risk. Ninety-nine publications were included (13 129 patients; total follow-up: 93 408 patient-years, pooled mean follow-up: 7.9±5.3 years). Pooled mean age at surgery was 9.4±5.5 years for children and 41.9±11.4 for adults. For children and adults, respectively, pooled early mortality risk was 4.19% (95% CI, 3.21–5.46) and 2.01% (95% CI, 1.44–2.82), late mortality rate was 0.54%/y (95% CI, 0.42–0.70) and 0.59%/y (95% CI, 0.46–0.76), autograft reintervention 1.28%/y (95% CI, 0.99–1.66) and 0.83%/y (95% CI, 0.68–1.01), and right ventricular outflow tract reintervention 1.97%/y (95% CI, 1.64–2.36) and 0.47%/y (95% CI, 0.37–0.59). Pooled thromboembolism and bleeding rates were low and comparable to the general population. Lifetime risks of autograft and right ventricular outflow tract reintervention were, respectively, 94% and 100% for children and 49% and 19% for a 45-year-old. Estimated life expectancy after surgery was 59 years for children (general population: 64 years) and 30 years for a 45 years old (general population: 31 years). Conclusions: Through excellent survival and avoidance of the burden of anticoagulation, the Ross procedure provides a unique opportunity for patients whose preferences do not align with the outcome provided by mechanical valve replacement and for growing children who also benefit from autograft diameter increase along with somatic growth. On the downside, almost all pediatric and many adult Ross patients will require a reintervention in their lifetime.

ObjectiveIncontinence is an important health problem. Effectively treating incontinence could lead to important health gains in patients and caregivers. Management of incontinence is currently suboptimal, especially in elderly patients. To optimise the provision of incontinence care a global optimum continence service specification (OCSS) was developed. The current study evaluates the costs and effects of implementing this OCSS for community-dwelling patients older than 65 years with four or more chronic diseases in the Netherlands.MethodA decision analytic model was developed comparing the current care pathway for urinary incontinence in the Netherlands with the pathway as described in the OCSS. The new care strategy was operationalised as the appointment of a continence nurse specialist (NS) located with the general practitioner (GP). This was assumed to increase case detection and to include initial assessment and treatment by the NS. The analysis used a societal perspective, including medical costs, containment products (out-of-pocket and paid by insurer), home care, informal care, and implementation costs.ResultsWith the new care strategy a QALY gain of 0.005 per patient is achieved while saving €402 per patient over a 3 year period from a societal perspective. In interpreting these findings it is important to realise that many patients are undetected, even in the new care situation (36%), or receive care for containment only. In both of these groups no health gains were achieved.ConclusionImplementing the OCSS in the Netherlands by locating a NS in the GP practice is likely to reduce incontinence, improve quality of life, and reduce costs. Furthermore, the study also highlighted that various areas of the continence care process lack data, which would be valuable to collect through the introduction of the NS in a study setting.

Background: To support decision-making in aortic valve replacement in nonelderly adults, we aim to provide a comprehensive overview of reported outcome after bioprosthetic aortic valve replacement and to translate this to age-specific patient outcome estimates. Methods and Results: A systematic review was conducted for papers reporting clinical outcome after aortic valve replacement with currently available bioprostheses in patients with a mean age <55 years, published between January 1, 2000, and January 9, 2016. Pooled reported event rates and time-to-event data were pooled and entered into a microsimulation model to calculate life expectancy and lifetime event risk for the ages of 25, 35, 45, and 55 years at surgery. Nineteen publications were included, encompassing a total of 2686 patients with 21 117 patient-years of follow-up (pooled mean follow-up: 7.9±4.2 years). Pooled mean age at surgery was 50.7±11.0 years. Pooled early mortality risk was 3.30% (95% CI, 2.39–4.55), late mortality rate was 2.39%/y (95% CI, 1.13–2.94), reintervention 1.82%/y (95% CI, 1.31–2.52), structural valve deterioration 1.59%/y (95% CI, 1.21–2.10), thromboembolism 0.53%/y (95% CI, 0.42–0.67), bleeding 0.22%/y (95% CI, 0.16–0.32), endocarditis 0.48%/y (95% CI, 0.37–0.62), and 20-year pooled actuarial survival was 58.7% and freedom from reintervention was 29.0%. Median time to structural valve deterioration was 17.3 years and median time to all-cause first reintervention was 16.9 years. For a 45-year-old adult, for example, this translated to a microsimulation-based estimated life expectancy of 21 years (general population: 32 years) and lifetime risk of reintervention of 78%, structural valve deterioration 71%, thromboembolism 12%, bleeding 5%, and endocarditis 9%. Conclusions: Aortic valve replacement with bioprostheses in young adults is associated with high structural valve deterioration and reintervention rates and low, though not absent, hazards of thromboembolism and bleeding. Foremostly, most patients will require one or more reinterventions during their lifetime and survival is impaired in comparison with the age- and sex-matched general population. Prosthesis durability remains the main concern in nonelderly patients.

Aims  This study aims to provide a contemporary overview of outcomes after tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR). Methods and results  The literature was systematically searched for papers published between January 2005 and December 2017 reporting on clinical/echocardiographic outcomes after TV surgery for functional TR. A random effects meta-analysis was conducted for outcome variables, and late outcomes are visualized by pooled Kaplan–Meier curves. Subgroup analyses were performed for studies with a within-study comparison of suture vs. ring repair and flexible vs. rigid ring repair. Eighty-seven publications were included, encompassing 13 184 patients (mean age: 62.1 ± 11.8 years, 55% females). A mitral valve procedure was performed in 92% of patients. Pooled mean follow-up was 4.0 ± 2.8 years. Pooled early mortality was 3.9% (95% CI: 3.2–4.6), and late mortality rate was 2.7%/year (95% CI: 2.0–3.5), of which approximately half was cardiac-related 1.2%/year (95% CI: 0.8–1.9). Pooled risk of early moderate-to-severe TR at discharge was 9.4% (95% CI: 7.0–12.1). Late moderate-to-severe TR rate after discharge was 1.9%/year (95% CI: 1.0–3.5). Late reintervention rate was 0.3%/year (95% CI: 0.2–0.4). Mortality and overall (early and late) TR rate were comparable between suture vs. ring annuloplasty (14 studies), whereas overall TR rate was higher after flexible ring vs. rigid ring annuloplasty (6 studies) (7.5%/year vs. 3.9%/year, P = 0.002). Conclusion  This study shows that patients undergoing surgery for functional tricuspid regurgitation (FTR) have an acceptable early and late mortality. However, TR remains prevalent after surgery. The results of this study can be used to inform patients and clinicians about the expected outcome after surgery for FTR and can results serve as a benchmark for the performance of emerging transcatheter TV interventions.

Objective The objective of this study was to develop guidance contributing to improved consistency and quality in economic evaluations of personalised medicine (PM), given current ambiguity about how to measure the value of PM as well as considerable variation in the methodology and reporting in economic evaluations of PM. Methods A targeted literature review of methodological papers was performed for an overview of modelling challenges in PM. Expert interviews were held to discuss best modelling practice. A systematic literature review of economic evaluations of PM was conducted to gain insight into current modelling practice. The findings were synthesised and used to develop a set of draft recommendations. The draft recommendations were discussed at a stakeholder workshop and subsequently finalised. Results Twenty-two methodological papers were identified. Some argued that the challenges in modelling PM can be addressed within existing methodological frameworks, others disagreed. Eighteen experts were interviewed. They believed large uncertainty to be a key concern. Out of 195 economic evaluations of PM identified, 56% addressed none of the identified modelling challenges. A set of 23 recommendations was developed. Eight recommendations focus on the modelling of test-treatment pathways. The use of non-randomised controlled trial data is discouraged but several recommendations are provided in case randomised controlled trial data are unavailable. The parameterisation of structural uncertainty is recommended. Other recommendations consider perspective and discounting; premature survival data; additional value elements; patient and clinician compliance; and managed entry agreements. Conclusions This study provides a comprehensive list of recommendations to modellers of PM and to evaluators and reviewers of PM models. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01010-z.

ObjectiveIn the era of limited healthcare budgets, healthcare costs of heart valve implantations need to be considered to inform cost-effectiveness analyses. We aimed to provide age group-specific costs estimates of heart valve implantations, related complications and other healthcare utilisation following the intervention.MethodsWe performed retrospective analyses of healthcare costs of patients who had undergone heart valve implantations in 2010–2013 and controls using claims data from Dutch health insurers. Heart valve implantations included surgical valve replacement and transcatheter valve implantation in all heart valve positions. Patients were divided in four age groups. Control groups were created by taking random samples of the Dutch population stratified by age, gender, socioeconomic status and comorbidities. We applied non-parametric bootstrapping to address uncertainty of the cost estimates. The association of patient and intervention characteristics with costs was determined by (multilevel) generalised linear models.ResultsThe baseline characteristics of 18 903 patients and 188 925 controls were comparable. The annual healthcare costs were substantially higher for surgical heart valve replacement patients than for controls, especially in the year of heart valve implantation. Factors associated with increased annual healthcare costs for patients were older age, female gender, comorbidities, low socioeconomic status and complications.ConclusionsWe provided a comprehensive overview of age group-specific incidence of heart valve implantations, subsequent survival and complications as well as associated healthcare costs of all patients in the Netherlands. Our results provide real-world costs estimates that can be used as a benchmark for costs of future innovative heart valve implantations.

Background The number of healthcare interventions described as ‘personalised medicine’ (PM) is increasing rapidly. As healthcare systems struggle to decide whether to fund PM innovations, it is unclear what models for financing and reimbursement are appropriate to apply in this context. Objective To review financing and reimbursement models for PM, summarise their key characteristics, and describe whether they can influence the development and uptake of PM. Methods A literature review was conducted in Medline, Embase, Web of Science, and Econlit to identify studies published in English between 2009 and 2021, and reviews published before 2009. Grey literature was identified through Google Scholar, Google and subject-specific webpages. Articles that described financing and reimbursement of PM, and financing of non-PM were included. Data were extracted and synthesised narratively to report on the models, as well as facilitators, incentives, barriers and disincentives that could influence PM development and uptake. Results One hundred and fifty-three papers were included. Research and development of PM was financed through both public and private sources and reimbursed largely through traditional models such as single fees, Diagnosis-Related Groups, and bundled payments. Financial-based reimbursement, including rebates and price-volume agreements, was mainly applied to targeted therapies. Performance-based reimbursement was identified mainly for gene and targeted therapies, and some companion diagnostics. Gene therapy manufacturers offered outcome-based rebates for treatment failure for interventions including Luxturna ® , Kymriah ® , Yescarta ® , Zynteglo ®, Zolgensma ® and Strimvelis ® , and coverage with evidence development for Kymriah ® and Yescarta ® . Targeted testing with OncotypeDX ® was granted value-based reimbursement through initial coverage with evidence development. The main barriers and disincentives to PM financing and reimbursement were the lack of strong links between stakeholders and the lack of demonstrable benefit and value of PM. Conclusions Public-private financing agreements and performance-based reimbursement models could help facilitate the development and uptake of PM interventions with proven clinical benefit. Supplementary Information The online version contains supplementary material available at 10.1007/s40258-021-00714-9.

This study aims to (1) examine the variation in implementation of a 2-year chronic obstructive pulmonary disease (COPD) management programme called RECODE, (2) analyse the facilitators and barriers to implementation and (3) investigate the influence of this variation on health outcomes. Implementation variation among the 20 primary-care teams was measured directly using a self-developed scale and indirectly through the level of care integration as measured with the Patient Assessment of Chronic Illness Care (PACIC) and the Assessment of Chronic Illness Care (ACIC). Interviews were held to obtain detailed information regarding the facilitators and barriers to implementation. Multilevel models were used to investigate the association between variation in implementation and change in outcomes. The teams implemented, on average, eight of the 19 interventions, and the specific package of interventions varied widely. Important barriers and facilitators of implementation were (in)sufficient motivation of healthcare provider and patient, the high starting level of COPD care, the small size of the COPD population per team, the mild COPD population, practicalities of the information and communication technology (ICT) system, and hurdles in reimbursement. Level of implementation as measured with our own scale and the ACIC was not associated with health outcomes. A higher level of implementation measured with the PACIC was positively associated with improved self-management capabilities, but this association was not found for other outcomes. There was a wide variety in the implementation of RECODE, associated with barriers at individual, social, organisational and societal level. There was little association between extent of implementation and health outcomes.