Hybrid epicardial-endocardial ablation for long-standing persistent atrial fibrillation: A subanalysis of the CONVERGE Trial.

Background: Favorable clinical outcomes are difficult to achieve in long-standing persistent atrial fibrillation (LSPAF) with catheter ablation (CA). The CONVERGE (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent Atrial FIbrillation) trial evaluated the effectiveness of hybrid convergent (HC) ablation vs endocardial CA. Objective: The study sought to evaluate the safety and effectiveness of HC vs CA in the LSPAF subgroup from the CONVERGE trial. Methods: The CONVERGE trial was a prospective, multicenter, randomized trial that enrolled 153 patients at 27 sites. A post hoc analysis was performed on LSPAF patients. The primary effectiveness was freedom from atrial arrhythmias off new or increased dose of previously failed or intolerant antiarrhythmic drugs (AADs) through 12 months. The primary safety endpoint was major adverse event incidence through 30 days with HC. Key secondary effectiveness measures included (1) percent of patients achieving ≥90% AF burden reduction vs baseline and (2) AF freedom. Results: Sixty-five patients (42.5% of total enrollment) had LSPAF; 38 in HC and 27 in CA. Primary effectiveness was 65.8% (95% confidence interval [CI] 50.7%-80.9%) with HC vs 37.0% (95% CI 5.1%-52.4%) with CA (P = .022). Through 18 months, these rates were 60.5% (95% CI 50.0%-76.1%) with HC vs 25.9% (95% CI 9.4%-42.5%) with CA (P = .006). Secondary effectiveness rates were higher than CA with HC at 12 and 18 months. Freedom from atrial arrhythmias off AADs was 52.6% (95% CI 36.8%-68.5%) and 47.4% (95% CI 31.5%-63.2%) with HC at 12 and 18 months vs 25.9% (95% CI 9.4%-42.5%) and 22.2% (95% CI 6.5%-37.9%) with CA, respectively (12 months: P = .031; 18 months: P = .038). Three (7.9%) major adverse events occurred within 30 days of HC. Conclusion: Post hoc analysis demonstrated effectiveness and acceptable safety of HC compared with CA in LSPAF.

Cost-effectiveness of ranibizumab and aflibercept to treat diabetic macular edema from a US perspective: analysis of 2-year Protocol T data.

Aims: Protocol T (NCT01627249) was a head-to-head study conducted by the Diabetic Retinopathy Clinical Research Network that compared intravitreal aflibercept, bevacizumab, and ranibizumab for the treatment of diabetic macular edema (DME). A cost-effectiveness analysis accompanying the 1-year data of Protocol T revealed that aflibercept was not cost-effective vs ranibizumab for all patients, but could have been cost-effective in certain patient sub-groups if the 1-year results were extrapolated out to 10 years. The present study evaluated the cost-effectiveness of US Food and Drug Administration-approved anti-vascular endothelial growth factor agents (ranibizumab, aflibercept) for treatment of DME using the 2-year data from Protocol T.Methods: Costs of aflibercept 2.0 mg or ranibizumab 0.3 mg, visual acuity (VA)-related medical costs, and quality-adjusted life-years (QALYs) were simulated for eight VA health states. Treatment, adverse event management, and VA-related healthcare resource costs (2016 US dollars) were based on Medicare reimbursement and published literature. VA-related health utilities were determined using a published algorithm. Patients were stratified by baseline VA: 20/40 or better; 20/50 or worse.Results: Total 2-year costs were higher, and QALYs similar, for aflibercept vs ranibizumab in the full cohort ($44,423 vs $34,529; 1.476 vs 1.466), 20/40 or better VA sub-group ($40,854 vs $31,897; 1.517 vs 1.519), and 20/50 or worse VA sub-group ($48,214 vs $37,246; 1.433 vs 1.412), respectively. Incremental cost-effectiveness ratios in the full cohort and 20/50 or worse VA sub-group were $986,159/QALY and $523,377/QALY, respectively. These decreased to $711,301 and $246,978 when analyses were extrapolated to 10 years.Limitations: Key potential limitations include the fact that VA was the only QALY parameter analyzed and the uncertainty surrounding the role of better- and worse-seeing eye VA in overall functional impairment.Conclusions: This analysis suggests that aflibercept is not cost-effective vs ranibizumab for patients with DME, regardless of baseline vision.

Cost of managing meningitis and encephalitis among infants and children in the United States.

A retrospective cohort study design was used to assess the use and costs of diagnostic tests, medication, and total hospitalization costs for pediatric patients with suspected meningitis/encephalitis who received a lumbar puncture (LP) procedure. Related costs were calculated by timing of LP performed and infectious etiology for infants (<1 year) and children (1-17 years). A total of 3030 infants and 3635 children with suspected ME diagnosed between 2011 and 2014 were included in the study. The mean hospitalization cost for infants and children was $12,759 and $11,119, respectively, with medication and laboratory test costs of $834 and $1771 for infants and $825 and $855 for children, respectively. Total visit cost increased with delayed LP procedure, ICU stay, and if the etiology was viral (other than enterovirus or arbovirus) or bacterial. Higher diagnostic and treatment costs were associated with delayed LP procedure, etiologic agent, and ICU stay.

Cost of managing meningitis and encephalitis among adult patients in the United States of America.

OBJECTIVE: To determine the associated costs related to the diagnosis and treatment of meningitis and encephalitis (ME) in adult patients in the USA. METHODS: A retrospective observational study design was used to assess the use and costs of diagnostic tests and antimicrobial treatment and the total hospitalization costs for adult patients with suspected ME, who received a lumbar puncture procedure during an emergency department visit or during the first two service days of an inpatient stay. Related costs were calculated by timing of lumbar puncture performed and infectious etiology. RESULTS: A total 26429 adult patients with suspected ME diagnosed between 2011 and 2014 were included in the study. The mean hospitalization cost was $15 572±27168, with antimicrobial medication cost of $1144±4052 and laboratory test cost of $210±244. The total visit cost increased with delayed lumbar puncture procedure, intensive care unit stay, and if the etiology was fungi, arbovirus, or bacteria. CONCLUSIONS: Higher diagnostic and treatment costs are associated with a delayed lumbar puncture procedure, the etiological agent, and the requirement for an intensive care unit stay.

Establishment of a reference standard database for use in the qualitative and semi-quantitative analysis of pharmaceutical contact materials within an extractables survey by GC-MS.

The analysis of reference standards may be performed to enhance the qualitative and quantitative data generated by non-specific screening methods utilized in extractables studies performed on pharmaceutical contact materials. However, the establishment of a database containing relative response factor and retention index values obtained from these standards has not been published. In this study, the establishment of such a database for GC-MS, a methodology commonly included in extractables studies, on an intra-lab basis was investigated. A set of 154 organic compounds representing a diverse range of chemical functionalities and properties was analyzed at eight time points on four GC-MS instruments that represent the diversity of age and model at our laboratory. The results of this study have shown that any variance in relative response factor between instruments was not significant from a practical perspective as supported by the coefficient of variation values (n = 32), which were ≤15% and ≤10% for 75% and 45% of the compounds tested, respectively. Furthermore, the retention index of the compounds, as expressed by retention time and relative retention time, did not have more than a 2% coefficient of variation between instruments or columns in most cases. It was concluded that a database of these values could be established for future use in extractables studies on an intra-laboratory basis.

A Case of Spontaneous Transdiaphragmatic Intercostal Hernia with Contralateral Injury, and Review of the Literature.

This case report discusses the diagnosis and management of a 67-year-old male presenting with a spontaneous transdiaphragmatic intercostal hernia with contralateral intercostal hernia. The patient had a history of chronic obstructive pulmonary disease (COPD) exacerbations requiring multiple prolonged courses of steroids. The patient was ultimately diagnosed with computed tomography (CT) and underwent surgical repair via thoracotomy with primary repair of the diaphragmatic defect. The patient's postoperative course was uncomplicated. A review of the literature since the first similar case in 1977 recognizes the propensity of this injury to be found in patients with COPD and chronic steroid usage, as well as its diagnosis and management. The case reviewed is the second documented case of a concurrent abdominal wall herniation and the first one with a contralateral injury. It is important for clinicians to be aware of this pathology when evaluating patients with COPD and chronic steroid usage.

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. OBJECTIVE: To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. PATIENTS AND METHODS: A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. RESULTS: Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6-10.5 for intermediate-risk patients and 7.8-9.3 for high-risk patients. There were no statistically significant differences among surgical methods, which tended to be more effective than RT methods, with the exception of combined external beam + brachytherapy for high-risk disease. RT methods were consistently more expensive than surgical methods; costs ranged from $19 901 (robot-assisted prostatectomy for low-risk disease) to $50 276 (combined RT for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. CONCLUSIONS: Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions about strategies to improve efficiency of treatment selection for localised prostate cancer.

A clinical outcomes and cost analysis comparing photoselective vaporization of the prostate to alternative minimally invasive therapies and transurethral prostate resection for the treatment of benign prostatic hyperplasia.

PURPOSE: We critically evaluated the clinical outcomes and cost characteristics of alternative procedural treatment options for symptomatic benign prostatic hyperplasia. MATERIALS AND METHODS: An outcomes and cost analysis was performed for benign prostatic hyperplasia treatments, including photoselective vaporization, microwave thermotherapy, transurethral needle ablation, interstitial laser coagulation and transurethral resection. Clinical outcomes were measured by the percent improvement in American Urological Association/International Prostate Symptom Score, the maximum uroflowmetry rate and quality of life score. An economic simulation model was constructed to estimate the expected cost of benign prostatic hyperplasia procedural therapies from a payer perspective. The model included costs of initial treatment, followup care, adverse events and re-treatment. Sensitivity and threshold analyses tested the impact of changing model inputs on base case results. RESULTS: Ablative therapies showed better improvement in symptom score, flow rate and quality of life score compared to thermotherapy procedures. Photoselective vaporization resulted in the largest beneficial changes in American Urological Association/International Prostate Symptom Score, the maximum uroflowmetry rate and the quality of life score at all time points evaluated, followed by transurethral resection and then interstitial laser coagulation. The estimated cost was lower for photoselective vaporization than for any other procedural option at any interval studied. Sensitivity analyses indicated that the results of baseline analyses were robust to reasonable changes in clinical and economic inputs to the model. CONCLUSIONS: Compared to alternative treatment options photoselective vaporization of the prostate is a clinically efficacious and cost-effective treatment for symptomatic benign prostatic hyperplasia.

Evaluation of the complexity of open abdominal aneurysm repair in the era of endovascular stent grafting.

OBJECTIVE: Endovascular repair has proven to be an effective treatment for many abdominal aortic aneurysms (AAA). Aneurysms that require open repair have usually been disqualified from an endovascular approach as a result of a variety of anatomic constraints, which may also make open repair more difficult. Our purpose was to review open AAA repair and assess the complexity of the operative procedure and associated morbidity and mortality data in the era of endovascular stent grafting. METHODS: We retrospectively reviewed the records of 606 patients undergoing elective open AAA repair at a single tertiary care community hospital from January 1, 1996, to December 31, 2004. Patients with ruptured aneurysms and all endovascular repairs were excluded. Patients were grouped into two categories. Group 1 included 301 patients who underwent open repair before the initiation of an endovascular stent grafting program in November 1999. Group 2 included 305 patients who underwent open repair after the initiation of the stent graft program. Operative reports were reviewed to determine the location of the proximal aortic cross clamp, management of the renal vein, associated iliac aneurysmal or occlusive disease, and type of surgical reconstruction. Morbidity, mortality, and disposition data were compared for the two groups and subjected to chi2 analysis. RESULTS: Suprarenal aortic cross-clamp placement was required in 6% of group 1 patients and 20% of group 2 patients (P < .05). Division of the renal vein was necessary in 11% of group 1 patients and 18% of group 2 patients (P < .05). Iliac aneurysms were present in 25% of group 1 patients and 42% of group 2 patients (P < .05). The incidence of associated iliac occlusive disease was 12% in group 1 and 20% in group 2 (P < .05). The type of reconstruction required (aortoaorto, aortoiliac, aortofemoral) was not found to be statistically significant. All major sources of morbidity, including renal insufficiency, myocardial infarction, stroke, and intubation times, were similar between the two groups. The length of stay was 9.2 days in both groups, and 11.3% of group 1 patients and 26% of group 2 patients were discharged to an extended-care facility rather than directly home. The overall mortality rate was 2.0% for patients in group 1 and 3.8% for group 2 patients. This was not a statistically significant difference. CONCLUSIONS: Surgeons performing open repair of AAA in the era of endovascular stent grafting are operating on patients who require more complex repairs, including a greater frequency of suprarenal cross clamping, renal vein division, and management of associated iliac aneurysmal and occlusive disease. Despite this, morbidity and mortality rates are similar to those in patients operated on before the initiation of an endovascular stent grafting program.

Cost effectiveness of bortezomib in the treatment of advanced multiple myeloma.

This study evaluated the cost effectiveness of bortezomib in relapsed, refractory myeloma, relative to best supportive care (BSC) and thalidomide. Data were derived from the phase 2 pivotal study of bortezomib, a Delphi panel of six myeloma thought leaders, and published literature. Objective assumptions regarding treatment choices and consequences (response and complications), and actual cost data were used. Bortezomib was found to be cost effective relative to BSC and thalidomide. Sensitivity analyses demonstrated the robustness of the results. These data suggest that bortezomib provides a cost-effective treatment option and the best value (in terms of cost/life-yr gained) among the currently available therapeutic options for relapsed, refractory myeloma.

Cost-effectiveness of a targeted disinfection program in household kitchens to prevent foodborne illnesses in the United States, Canada, and the United Kingdom.

Foodborne illnesses impose a substantial economic and quality-of-life burden on society by way of acute morbidity and chronic sequelae. We developed an economic model to evaluate the potential cost-effectiveness of a disinfection program that targets high-risk food preparation activities in household kitchens. For the United States, Canada, and the United Kingdom, we used published literature and expert opinion to estimate the cost of the program (excluding the educational component); the number of cases of Salmonella, Campylobacter, and Escherichia coli O157:H7 infections prevented; and the economic and quality-of-life outcomes. In our primary analysis, the model estimated that approximately 80,000 infections could be prevented annually in U.S. households, resulting in 138 million dollars in direct medical cost savings (e.g., physician office visits and hospitalizations avoided), 15,845 quality-adjusted life-years (QALYs) gained, 788 million dollars in program costs, and a favorable cost-effectiveness ratio of 41,021 dollars/QALY gained. Results were similar for households in Canada and the United Kingdom (21,950 dollars Can/QALY gained and 86,341 pounds sterling/QALY gained, respectively). When we evaluated implementing the program only in U.S. households with high-risk members (those less than 5 years of age, greater than 65 years of age, or immunocompromised), the cost-effectiveness ratio was more favorable (10,163 dollars/QALY gained). Results were similar for high-risk households in Canada and the United Kingdom (1,915 dollars Can/QALY gained and 28,158 pounds sterling/QALY gained, respectively). Implementing a targeted disinfection program in household kitchens in the United States, Canada, and the United Kingdom appears to be a cost-effective strategy, falling within the range generally considered to warrant adoption and diffusion (<100,000 dollars/QALY gained).

Implantation techniques and chronic lead parameters of biventricular pacing dual-chamber defibrillators.

INTRODUCTION: The aim of this study is to describe implantation techniques and lead performance for biventricular pacing, dual-chamber implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: A dual-chamber ICD with biventricular pacing was implanted in 87 patients with congestive heart failure (ejection fraction: 0.21 +/- 0.09), prolonged QRS duration (161 +/- 22 msec), and an indication for ICD therapy. Left ventricular pacing was achieved with a thoracotomy approach (n = 21) or a nonthoracotomy approach (n = 66). With a thoracotomy, biventricular devices were implanted successfully in all patients. During follow-up (17 +/- 11 months), 9 patients died (43%), 2 underwent transplantation, and 2 required left ventricular lead revision. At last follow-up, biventricular sensing and capture threshold were 11 +/- 5 mV and 1.5 +/- 0.8 V, respectively. For nonthoracotomy procedures, two types of coronary sinus (CS) leads were implanted: an over-the-wire lead (n = 45) and a shaped lead (n = 21). The rate of successful implantation (overall: 89%) (over-the-wire 93% vs shaped 81%; P = 0.1) and durations for CS lead placement (66 +/- 50 vs 58 +/- 34 min, P = 0.6) and the procedure (133 +/- 58 vs 129 +/- 33 min, P = 0.8) were not different between the two CS leads. During follow-up (11 +/- 9 months), 9 patients died (14%), and the shaped CS lead dislodged in 3 patients (3 shaped vs 0 over-the-wire, P = 0.01). At last follow-up, biventricular sensing and capture threshold were 10 +/- 4 mV and 1.8 +/- 0.7 V, respectively, and there was no difference between over-the-wire and shaped leads. By multivariate analysis, mortality was associated with absence of spironolactone therapy but not procedural features. CONCLUSION: Nonthoracotomy CS lead implantation is feasible, with a success rate of about 90% and few adverse events. For the remaining 10%, a thoracotomy approach can be completed safely in these ill patients without increased risk for death.

Strategies for assessing health economic and quality of life outcomes in multiple sclerosis.

Multiple sclerosis is a disabling disease that, until recently, had few effective treatment options. With the advent of new medical technologies to treat multiple sclerosis has come the need to assess the long-term clinical, economic and quality of life trade-offs associated with these treatments to inform medical decision-making, as well as equitable resource allocation. Assessing these trade-offs in multiple sclerosis is particularly challenging. Therefore, considering an appropriate evaluation strategy prior to initiating a health outcomes study in multiple sclerosis is essential. This review presents an overview of multiple sclerosis, the challenges facing researchers and offers strategies and a framework for assessing economic and quality of life outcomes in patients with multiple sclerosis.