Partitioned Survival and State Transition Models for Healthcare Decision Making in Oncology: Where Are We Now?

OBJECTIVES: Partitioned survival models (PSMs) are routinely used to inform reimbursement decisions for oncology drugs. We discuss the appropriateness of PSMs compared to the most common alternative, state transition models (STMs). METHODS: In 2017, we published a National Institute for Health and Care Excellence (NICE) Technical Support Document (TSD 19) describing and critically reviewing PSMs. This article summarizes findings from TSD 19, reviews new evidence comparing PSMs and STMs, and reviews recent NICE appraisals to understand current practice. RESULTS: PSMs evaluate state membership differently from STMs and do not include a structural link between intermediate clinical endpoints (eg, disease progression) and survival. PSMs directly consider clinical trial endpoints and can be developed without access to individual patient data, but limit the scope for sensitivity analyses to explore clinical uncertainties in the extrapolation period. STMs facilitate these sensitivity analyses but require development of robust survival models for individual health-state transitions. Recent work has shown PSMs and STMs can produce substantively different survival extrapolations and that extrapolations from STMs are heavily influenced by specification of the underlying survival models. Recent NICE appraisals have not generally included both model types, reviewed individual clinical event data, or scrutinized life-years accrued in individual health states. CONCLUSIONS: The credibility of survival predictions from PSMs and STMs, including life-years accrued in individual health states, should be assessed using trial data on individual clinical events, external data, and expert opinion. STMs should be used alongside PSMs to support assessment of clinical uncertainties in the extrapolation period, such as uncertainty in post-progression survival.

An overview of current and emerging devices for percutaneous left atrial appendage closure.

Atrial fibrillation (AF) is common and is a prominent risk factor for ischemic stroke. Oral anticoagulant (OAC) therapy has been the main strategy for stroke prevention in AF patients; however, OAC therapy carries a bleeding risk and is not tolerated by all patients. Left atrial appendage (LAA) closure offers a non-pharmacological alternative for stroke prevention in patients with non-valvular AF. In this update, an overview of current and emerging LAA occluders is given - with special attention to the key design features of every single device and, if available, preclinical or clinical data.

Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness.

BACKGROUND: Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources. OBJECTIVE: To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting. DESIGN, SETTING, AND PARTICIPANTS: We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. INTERVENTION: SOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75mg/m2) was administered alongside SOC for six three-weekly cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS AND LIMITATIONS: The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled. CONCLUSIONS: Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. PATIENT SUMMARY: Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.

Cost-effectiveness of adjunct non-pharmacological interventions for osteoarthritis of the knee.

BACKGROUND: There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. METHODS: Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). RESULTS: When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. CONCLUSIONS: Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture is cost-effective at this threshold, and thresholds down to £14,000 per QALY.

The Clinical and Cost Effectiveness of Apremilast for Treating Active Psoriatic Arthritis: A Critique of the Evidence.

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of apremilast was invited to submit evidence for its clinical and cost effectiveness for the treatment of active psoriatic arthritis (PsA) for whom disease-modifying anti-rheumatic drugs (DMARDs) have been inadequately effective, not tolerated or contraindicated. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This paper provides a description of the ERG review of the company's submission, the ERG report and submission and summarises the NICE Appraisal Committee's subsequent guidance (December 2015). In the company's initial submission, the base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of £14,683 per quality-adjusted life-year (QALY) gained for the sequence including apremilast (positioned before tumour necrosis factor [TNF]-α inhibitors) versus a comparator sequence without apremilast. However, the ERG considered that the base-case sequence proposed by the company represented a limited set of potentially relevant treatment sequences and positions for apremilast. The company's base-case results were therefore not a sufficient basis to inform the most efficient use and position of apremilast. The exploratory ERG analyses indicated that apremilast is more effective (i.e. produces higher health gains) when positioned after TNF-α inhibitor therapies. Furthermore, assumptions made regarding a potential beneficial effect of apremilast on long-term Health Assessment Questionnaire (HAQ) progression, which cannot be substantiated, have a very significant impact on results. The NICE Appraisal Committee (AC), when taking into account their preferred assumptions for HAQ progression for patients on treatment with apremilast, placebo response and monitoring costs for apremilast, concluded that the addition of apremilast resulted in cost savings but also a QALY loss. These cost savings were not high enough to compensate for the clinical effectiveness that would be lost. The AC thus decided that apremilast alone or in combination with DMARD therapy is not recommended for treating adults with active PsA that has not responded to prior DMARD therapy, or where such therapy is not tolerated.

Tumour necrosis factor-α inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and economic evaluation.

BACKGROUND: Tumour necrosis factor (TNF)-α inhibitors (anti-TNFs) are typically used when the inflammatory rheumatologic diseases ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-AxSpA) have not responded adequately to conventional therapy. Current National Institute for Health and Care Excellence (NICE) guidance recommends treatment with adalimumab, etanercept and golimumab in adults with active (severe) AS only if certain criteria are fulfilled but it does not recommend infliximab for AS. Anti-TNFs for patients with nr-AxSpA have not previously been appraised by NICE. OBJECTIVE: To determine the clinical effectiveness, safety and cost-effectiveness within the NHS of adalimumab, certolizumab pegol, etanercept, golimumab and infliximab, within their licensed indications, for the treatment of severe active AS or severe nr-AxSpA (but with objective signs of inflammation). DESIGN: Systematic review and economic model. DATA SOURCES: Fifteen databases were searched for relevant studies in July 2014. REVIEW METHODS: Clinical effectiveness data from randomised controlled trials (RCTs) were synthesised using Bayesian network meta-analysis methods. Results from other studies were summarised narratively. Only full economic evaluations that compared two or more options and considered both costs and consequences were included in the systematic review of cost-effectiveness studies. The differences in the approaches and assumptions used across the studies, and also those in the manufacturer's submissions, were examined in order to explain any discrepancies in the findings and to identify key areas of uncertainty. A de novo decision model was developed with a generalised framework for evidence synthesis that pooled change in disease activity (BASDAI and BASDAI 50) and simultaneously synthesised information on function (BASFI) to determine the long-term quality-adjusted life-year and cost burden of the disease in the economic model. The decision model was developed in accordance with the NICE reference case. The model has a lifetime horizon (60 years) and considers costs from the perspective of the NHS and personal social services. Health effects were expressed in terms of quality-adjusted life-years. RESULTS: In total, 28 eligible RCTs were identified and 26 were placebo controlled (mostly up to 12 weeks); 17 extended into open-label active treatment-only phases. Most RCTs were judged to have a low risk of bias overall. In both AS and nr-AxSpA populations, anti-TNFs produced clinically important benefits to patients in terms of improving function and reducing disease activity; for AS, the relative risks for ASAS 40 ranged from 2.53 to 3.42. The efficacy estimates were consistently slightly smaller for nr-AxSpA than for AS. Statistical (and clinical) heterogeneity was more apparent in the nr-AxSpA analyses than in the AS analyses; both the reliability of the nr-AxSpA meta-analysis results and their true relevance to patients seen in clinical practice are questionable. In AS, anti-TNFs are approximately equally effective. Effectiveness appears to be maintained over time, with around 50% of patients still responding at 2 years. Evidence for an effect of anti-TNFs delaying disease progression was limited; results from ongoing long-term studies should help to clarify this issue. Sequential treatment with anti-TNFs can be worthwhile but the drug survival response rates and benefits are reduced with second and third anti-TNFs. The de novo model, which addressed many of the issues of earlier evaluations, generated incremental cost-effectiveness ratios ranging from £19,240 to £66,529 depending on anti-TNF and modelling assumptions. CONCLUSIONS: In both AS and nr-AxSpA populations anti-TNFs are clinically effective, although more so in AS than in nr-AxSpA. Anti-TNFs may be an effective use of NHS resources depending on which assumptions are considered appropriate. FUTURE WORK RECOMMENDATIONS: Randomised trials are needed to identify the nr-AxSpA population who will benefit the most from anti-TNFs. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014010182. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Graduated compression stockings for the prevention of deep-vein thrombosis in postoperative surgical patients: a systematic review and economic model with a value of information analysis.

BACKGROUND: Deep-vein thrombosis (DVT) can occur in surgical patients. Routine prophylaxis can be pharmacological and/or mechanical [e.g. graduated compression stockings (GCSs)]. GCSs are available in knee length or thigh length. OBJECTIVE: To establish the expected value of undertaking additional research addressing the relative effectiveness of thigh-length GCSs versus knee-length GCSs, in addition to pharmacoprophylaxis, for prevention of DVT in surgical patients. DESIGN: Systematic review and economic model, including value of information (VOI) analysis. REVIEW METHODS: Randomised controlled trials (RCTs) assessing thigh- or knee-length GCSs in surgical patients were eligible for inclusion. The primary outcome was incidence of DVT. DVT complications and GCSs adverse events were assessed. Random-effects meta-analysis was performed. To draw on a wider evidence base, a random-effects network meta-analysis (NMA) was undertaken for the outcome DVT. A review of trials and observational studies of patient adherence was also conducted. A decision-analytic model was developed to assess the cost-effectiveness of thigh- and knee-length GCSs and the VOI. RESULTS: Twenty-three RCTs were included in the review of effectiveness. There was substantial variation between trials in terms of the patient characteristics, interventions and methods of outcome assessment. Five trials comparing knee-length with thigh-length GCSs with or without pharmacoprophylaxis were pooled; the summary estimate of effect indicated a non-significant trend favouring thigh-length GCSs [odds ratio (OR) 1.48, 95% confidence interval (CI) 0.80 to 2.73]. Thirteen trials were included in the NMA. In the base-case analysis, thigh-length GCSs with pharmacoprophylaxis were more effective than knee-length GCSs with pharmacoprophylaxis (knee vs. thigh OR 1.76, 95% credible interval 0.82 to 3.53). Overall, thigh-length stockings with pharmacoprophylaxis was the most effective treatment, with a 0.73 probability of being the most effective treatment in a new trial of all the treatments. Patient adherence was generally higher with knee-length GCSs, and patients preferred knee-length GCSs. Thigh-length GCSs were found to be cost-effective in all but the subgroup with the lowest baseline risk, although the absolute differences in costs and effects were relatively small. The expected value of perfect information ranged from £0.2M to £178.0M depending on the scenario and subgroup. The relative effect parameters had the highest expected value of partial perfect information and ranged from £2.0M to £39.4M. The value of further research was most evident in the high-risk subgroups. LIMITATIONS: There was substantial variation across the included trials in terms of patient and intervention characteristics. Many of the included trials were old and poorly reported, which reduces the reliability of the results of the review. CONCLUSIONS: Given that the results from both the standard meta-analysis and the NMA lacked precision (CIs were wide) owing to the heterogeneous evidence base, a new definitive trial in high-risk patients may be warranted. However, the efficiency of any further research (i.e. whether this represents value for money) is dependent on several factors, including the acquisition price of GCSs, expected compliance with thigh-length GCSs wear, and whether or not uncertainty can be resolved around possible effect modifiers, as well as the feasibility and actual cost of undertaking the proposed research. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014007202. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Ipilimumab for Previously Untreated Unresectable Malignant Melanoma: A Critique of the Evidence.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ipilimumab (Bristol-Myers Squibb Pharmaceuticals Limited) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents a summary of the manufacturer's submission of ipilimumab, the ERG review and the resulting NICE guidance TA319, issued in July 2014. Ipilimumab at a recommended dose of 3 mg/kg monotherapy was previously granted marketing authorisation by the European Medicines Agency in adult patients who had received prior therapy and was recommended by NICE in guidance TA268. In October 2013, the EMA approved the extension of this indication to previously untreated advanced melanoma patients. NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the NICE Appraisal Committee was whether ipilimumab at a recommended dose of 3 mg/kg monotherapy was effective and cost effective compared with first-line standard of care involving dacarbazine (DTIC) and vemurafenib (for BRAF V600 mutation-positive patients). The CA184-024 trial was the primary source of clinical evidence for ipilimumab. However, this was based on a dose of 10 mg/kg with concomitant DTIC. The results over a 5-year period indicated that ipilimumab 10 mg/kg plus DTIC demonstrated a significant increase in median overall survival (OS) of 2.1 months compared with DTIC plus placebo (11.2 vs. 9.1 months). The BRIM-3 trial, which was an open-label randomised controlled trial (RCT) in BRAF V600 mutation-positive patients, was the primary source of evidence for an indirect comparison with vemurafenib. The results showed that vemurafenib increased median OS by 3.6 months compared with DTIC (13.2 vs. 9.6 months). The economic evaluation compared the costs and outcomes of ipilimumab by assuming that the 3 mg/kg dosing regimen was clinically equivalent in efficacy to an ipilimumab 10 mg/kg dosing regimen plus DTIC and by using a treatment sequencing approach that incorporated second-line active therapy and third-line best supportive care (BSC). In the first appraisal meeting, the committee recommended ipilimumab only in the context of research as part of a clinical study. This was primarily based on the lack of robust evidence to support the assumption of clinical equivalence between dosages and the absence of evidence available to inform the sequential use of treatments. Following the consultation, the manufacturer submitted additional analyses and evidence to support the cost effectiveness of ipilimumab at first line. The manufacturer's response was based on concerns relating to uncertainty surrounding the relative efficacy of ipilimumab 3 mg/kg monotherapy compared with DTIC and vemurafenib, comparability of the patient populations at first and second line, and the effects of concomitant DTIC. These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) was £ 47,900 per quality-adjusted life-year (QALY) gained for ipilimumab compared with DTIC and £ 28,600 per QALY gained for ipilimumab compared with vemurafenib. Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended ipilimumab as an option for adults with previously untreated advanced melanoma.

Transcatheter patch closure of an atrial septal defect of sinus venosus type using the immediate release patch.

Following promising preclinical studies, we report our first clinical experience with transcatheter closure of an atrial septal defect of sinus venosus type in a 65-year-old patient using the Immediate Release Patch.

Closure of interatrial defects by immediate-release patch.

The Immediate-Release Patch is the newest version of the Transcatheter Patch, which is a bioabsorbable device for the closure of cardiac defects. Closure of 12 atrial septal defects and 1 fenestration was attempted using this device. Of the 13 devices used, 12 were implanted successfully (including that for the fenestration), whereas 1 device moved from the original position and was retrieved percutaneously. No other major adverse events occurred. After a median follow-up period of 11 months, trivial (≤ 2-mm) residual shunts remained in two patients, and a significant residual defect (7 mm) remained in 1 patient. The major advantages of this device include its wirelessness, its bioabsorbablity, potential application for defects up to 30 mm using only three sizes, its easier retrieval, and its ability to occlude defects with a deficient rim and some ostium primum and sinus venosus type defects. In contrast to the metal devices, it is bulkier and has a different application method requiring operator familiarity, and it sometimes leaves residual shunts.

Transcatheter patch occlusion of the left atrial appendage using surgical adhesives in high-risk patients with atrial fibrillation.

OBJECTIVES: The efficacy of left atrial appendage (LAA) occlusion using the Transcatheter Patch (TP) (Custom Medical Devices, Athens, Greece) in conjunction with surgical adhesives was assessed. BACKGROUND: The TP is a bioabsorbable device that can be adjusted for the shape and size of the LAA without the risk of perforation. It is attached by a surgical adhesive and is released in 45 min. METHODS: Occlusion of the LAA was performed in 20 high-risk patients, 59 to 89 years of age, with atrial fibrillation. A 2-stage polyethylene glycol surgical adhesive was applied to the distal half of the device. Activation of the adhesive was achieved by direct injection of alkaline solution. Fluoroscopy and transesophageal echocardiography only were used for device placement in 17 patients. In 3 patients, angiography was used as well. Follow-up transesophageal echocardiography was performed upon discharge. RESULTS: The procedure was successful in 17 cases. In the 3 patients in whom angiography was performed, the patch did not attach and was retrieved. In 1 case, the patch was placed beyond the mouth of the appendage, resulting in a residual opening. There was further improvement of the occlusion rate on the follow-up transesophageal echocardiography. There was 1 complication related to the procedure, namely, thrombus was released from the long sheath in the left atrium upon withdrawal and required treatment to be dissolved. No recurrent strokes were reported. CONCLUSIONS: Occlusion of the LAA by the TP is feasible and effective in most patients with atrial fibrillation at high risk for embolic stroke. Angiography before placement probably affects patch adhesion and is contraindicated.

Transcatheter patch occlusion of ventricular septal defect in Down syndrome.

Closure of perimembranous ventricular septal defects in patients with Down syndrome, either surgically or by Amplatzer occluders, carries a high risk of complete heart block. We report 5 closures using the transcatheter patch, a wireless bioabsorbable device without any reported heart block to date. The median defect size was 11 mm. Small devices were used in 4 patients and a medium size in 1. The patch was released after 48 hours in 3 patients and immediately in the other 2. Of the 5 patients, 3 were followed up for >5 years and 2 for 1 year. None of these patients had atrioventricular block during their follow-up. In conclusion, the transcatheter patch might be superior in terms of cardiac conduction system protection in patients with Down syndrome after ventricular septal defect closure.

The immediate release patch in the correction of experimental atrial septal defects.

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of the Immediate Release Patch (IRP) in the occlusion of experimental Atrial Septal Defects (ASDs). BACKGROUND: The IRP consists of a polyurethane foam patch, supported by a balloon catheter which incorporates a detaching mechanism. This mechanism allows for withdrawal of the catheter from the balloon/patch complex. After release, the device is held in position using a bioabsorbable safety thread, which is sutured subcutaneously at the groin. METHODS: Experimental ASDs, 10-14 mm in diameter, were created in ten piglets. The ASDs were then corrected using IRPs 12-16 mm in diameter, under fluoroscopy and echocardiography. The animals were followed for one to four months, and were then euthanized and autopsied. A RAST test, which detects the presence of IgE antibodies for latex, was performed in seven animals. RESULTS: All procedures, except for one, resulted in full occlusion of the defects, without serious complications. No devices embolized, and in less than two months, the balloons had deflated and the area of the device had decreased significantly. The autopsies revealed complete endothelialization as well as no thrombus formation on the device or the thread. The thread was absorbed after one month. In a single case, infection was detected on the right side of the device. Latex antibodies were not detected. CONCLUSION: The IRP was effective and safe in the animal model of an ASD. There was evidence of bio-absorption of the complete device over time, without adverse reaction to latex. Clinical application is justified.

Transcatheter patch occlusion of perimembranous ventricular septal defects.

Sixteen surgical candidates for ventricular septal defect correction were brought to the catheterization laboratory for transcatheter patch occlusion. There were 3 cases of nonrestrictive ventricular septal defects, including 2 with malalignment (tetralogy of Fallot). All patients, except those with tetralogy of Fallot who were cyanotic, had large left-right shunts. They were all corrected through the femoral vein. All defects with the exception of 2 were successfully occluded (12 full occlusions, 2 residual shunts). On follow-up, there were no embolizations, aortic insufficiency, or other complications. The method appears effective and relatively safe, and could challenge the current surgical standard of treatment.

Transcatheter patch occlusion of experimental atrial septal defects.

The effectiveness and safety of transcatheter patch atrial septal defect (ASD) occlusion were studied in 20 piglets. Experimental atrial septal defects were created by foramen ovale dilation. ASDs were corrected by polyurethane patches of two types (flat and sleeve). Specially made balloon catheters supported the patches for periods varying from 1 to 6 days; after this period, the supporting catheters were withdrawn and the patches were released. All transcatheter patches were safely embedded in the atrial septum 48 hr or more after implantation. All defects were fully occluded. One patch became infected. The transcatheter patch experimental ASD occlusion method was found effective and safe, potentially applicable in the occlusion of human ASDs.

Transcatheter patch correction of secundum atrial septal defects.

The efficacy and safety of the transcatheter patch (TP) correction of a secundum atrial septal defect (ASD) was studied acutely and on short-term follow-up in 20 patients, successfully implanted with the device. TPs are made of polyurethane foam and require temporary balloon catheter immobilization on the atrial septum for 48 hours. Eighteen patients were not suitable for disk-device repair. The patient median age and ASD diameter were 37 years and 26 mm, respectively. Eighteen patients had immediate effective ASD occlusion; 2 patients had significant residual shunts. Premature leaks of the supportive balloons were responsible for the residual shunts. One of the patients with residual shunt received a second patch 6 months later with full occlusion. All patients with implants were doing well up to 24 months after implantation. Existing symptoms improved although residual shunts remained; septal anatomy was normalized, with the patched area becoming progressively indistinguishable from the rest of the septum. In conclusion, TP occlusion of secundum ASD is feasible and effective even for defects unsuitable for disk-device repair. The method appears safe acutely and on short-term follow-up, with symptomatic improvement and normalization of septal anatomy.

Buttoned Device Occlusion of Patent Ductus Arteriosus.

Buttoned device, consisting of a square-shaped occluder and a rhomboid-shaped counter-occluder can be implanted across patent ductus arteriosus (PDA) via relatively small sheaths. In a large multi-institutional study, successful device implantation was achieved in 98% of patients. Decrease in the pulmonary-to-systemic flow ratio occurred. Effective occlusion was demonstrated in 88% of patients. PDAs could be occluded irrespective of their shape (conical, tubular, or short), length (short or long), or diameter (small or large). During follow-up for 1 to 60 months, 3% of patients required reintervention to treat residual shunts with (1%) or without (2%) hemolysis. There was gradual reduction and disappearance of the residual shunt during follow-up. Despite these encouraging results, patients with residual shunts are at risk for developing bacterial endocarditis. Therefore, the device was modified by incorporating a folding plug over the button loop, which resulted in complete occlusion of PDA at implantation.