Comparative effectiveness of non-compounded polidocanol 1% endovenous microfoam (Varithena) ablation versus endovenous thermal ablation utilizing a systematic review and network meta-analysis.

OBJECTIVE: We compared the effectiveness and safety of polidocanol 1% endovenous microfoam ablation vs endovenous thermal ablation with radiofrequency or laser energy for treatment of venous insufficiency caused by lower extremity truncal vein incompetence via network meta-analysis of published comparative evidence. METHODS: We conducted a systematic literature review following best practices, including a prospective protocol. We screened studies published in English from 2000 to 2023 for randomized and nonrandomized studies reporting direct or indirect comparisons between polidocanol 1% endovenous microfoam and endovenous thermal ablation. Thirteen studies met our eligibility criteria for the network meta-analysis. The co-primary effectiveness outcomes were the closure rate ≥3 months after procedure and the average change in the Venous Clinical Severity Score. For the subgroup of venous ulcer patients, the ulcer healing rate was the primary effectiveness outcome. The secondary outcomes included safety and patient-reported outcomes. Network meta-analyses were conducted on outcomes having sufficient data. Categorical outcomes were summarized using odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity tests and estimates of network inconsistency were used to investigate the robustness of our meta-analysis. RESULTS: We found that polidocanol 1% endovenous microfoam was not significantly different statistically from endovenous thermal ablation for venous closure (OR, 0.65; 95% CI, 0.36-1.18; P = .16). Although not the primary aim of the study, the network meta-analysis also provided evidence to confirm our supposition that polidocanol 1% endovenous microfoam was significantly differentiated statistically from physician-compounded foam, with higher odds for vein closure (OR, 2.91; 95% CI, 1.58-5.37; P < .01). A sensitivity analysis using the longest available time point for closure in each study, with a minimum of 12 months of follow-up (median, 48 months; range, 12-72 months), showed results similar to those of the main analysis. No association was found between the risk of deep vein thrombosis and the treatment received. The available data were insufficient for a network meta-analysis of Venous Clinical Severity Score improvement and ulcer healing rates. CONCLUSIONS: Polidocanol 1% endovenous microfoam was not significantly different statistically from endovenous thermal ablation for venous closure and deep vein thrombosis risk for chronic venous insufficiency treatment, based on a network meta-analysis of published evidence. Polidocanol 1% endovenous microfoam was significantly differentiated statistically from physician-compounded foam, with higher odds of vein closure. A sensitivity analysis found venous closure findings were robust at follow-up intervals of 12 months or greater and for up to 6 years. New evidence meeting the inclusion criteria for this review will be incorporated at regular intervals into a living network meta-analysis.

Cost-effectiveness of catheter ablation versus medical therapy for the treatment of atrial fibrillation in the United Kingdom.

INTRODUCTION: Research evidence has shown that catheter ablation is a safe and superior treatment for atrial fibrillation (AF) compared to medical therapy, but real-world practice has been slow to adopt an early interventional approach. This study aims to determine the cost effectiveness of catheter ablation compared to medical therapy from the perspective of the United Kingdom. METHODS: A patient-level Markov health-state transition model was used to conduct a cost-utility analysis. The population included patients previously treated for AF with medical therapy, including those with heart failure (HF), simulated over a lifetime horizon. Data sources included published literature on utilization and cardiovascular event rates in real world patients, a systematic literature review and meta-analysis of randomized controlled trials for AF recurrence, and publicly available government data/reports on costs. RESULTS: Catheter ablation resulted in a favorable incremental cost-effectiveness ratio (ICER) of £8614 per additional quality adjusted life years (QALY) gained when compared to medical therapy. More patients in the medical therapy group failed rhythm control at any point compared to catheter ablation (72% vs. 24%) and at a faster rate (median time to treatment failure: 3.8 vs. 10 years). Additionally, catheter ablation was estimated to be more cost-effective in patients with AF and HF (ICER = £6438) and remained cost-effective over all tested time horizons (10, 15, and 20 years), with the ICER ranging from £9047-£15 737 per QALY gained. CONCLUSION: Catheter ablation is a cost-effective treatment for atrial fibrillation, compared to medical therapy, from the perspective of the UK National Health Service.

Predictive value of atrial fibrillation during the postradiofrequency ablation blanking period.

BACKGROUND: Recurrent arrhythmia following catheter ablation of atrial fibrillation (AF) may present early, during a standard 3-month blanking period. Early recurrence has been correlated to late recurrence, but the degree to which its absence predicts longer-term success has not been quantified. OBJECTIVE: The purpose of this study was to explore and quantify the relationship between early and late arrhythmia recurrence, specifically the negative predictive value, that is, the degree to which absence of blanking period recurrence predicts absence of late recurrence. METHODS: A systematic literature review and meta-analysis were conducted using statistical methods of a diagnostic test accuracy review. Studies of AF ablation using point-by-point radiofrequency, with repeated monitoring of arrhythmia recurrence including asymptomatic recurrence, and with separate data by AF type, were eligible. RESULTS: Nine studies met the prespecified eligibility criteria. For paroxysmal AF, 89% (confidence interval [CI] 82%-94%) of patients free from early recurrence remained free from late recurrence. The estimate for persistent AF was similar (91%; CI 75%-97%). This finding was robust in sensitivity analyses. Patients with early recurrence had a wider range of likely outcomes with longer-term follow-up. CONCLUSION: Freedom from AF recurrence during the blanking period is highly predictive of longer-term success in catheter ablation. Clinical trials in this area may be able to leverage these findings to more quickly assess the potential utility of new ablation technologies and methods, for example, by using early surrogate measures of success.

How safe and effective are flow diverters for the treatment of unruptured small/medium intracranial aneurysms of the internal carotid artery? Meta-analysis for evidence-based performance goals.

BACKGROUND: The objective of this meta-analysis was to establish safety and effectiveness benchmarks for endovascular therapy of unruptured small-to-medium internal carotid artery (ICA) aneurysms using flow diverters. METHODS: A systematic literature review and subsequent meta-analysis were performed using best research methods. Studies of any design with at least 10 patients treated with flow diverters for predominantly (≥90%) unruptured small/medium ICA aneurysms and ≥6 month follow-up were included. The primary effectiveness endpoint was complete aneurysm occlusion rate at 12 months. The primary safety endpoint was a composite measure of cumulative events that could indicate a stroke or neurologic death: any death, stroke, intracranial hemorrhage, or worsening on the modified Rankin Scale. RESULTS: 41 studies (2614 patients) met eligibility criteria for the meta-analysis. The core lab adjusted complete occlusion rate was 74.9% (95% CI 69.6% to 79.8%) at 12 months for studies using any flow diverter. With an aim of generating performance goals for a US Investigational Device Exemption (IDE) study, a pre-specified analysis was conducted using only studies with flow diverters commercially available in the USA. In this cohort, 12 month complete occlusion was 74.6% (95% CI 66.8% to 81.7%). The primary safety event rate for flow diverters commercially available in the USA was 7.8% (95% CI 4.8% to 11.4%). CONCLUSIONS: The treatment of small and medium-sized aneurysms with flow diverters is effective in achieving curative reconstruction in most cases and is associated with low rates of morbidity and mortality. This meta-analysis informs robust performance goals for evaluating new flow diverters in small/medium unruptured carotid aneurysms.

The use of intracardiac echocardiography catheters in endocardial ablation of cardiac arrhythmia: Meta-analysis of efficiency, effectiveness, and safety outcomes.

AIMS: The optimal use of intracardiac echocardiography (ICE) may reduce fluoroscopy time and procedural complications during endocardial ablation of cardiac arrhythmias. Due to limited evidence in this area, we conducted the first systematic literature review and meta-analysis to evaluate outcomes associated with the use of ICE. METHODS AND RESULTS: Studies reporting the use of ICE during ablation procedures vs without ICE were searched using PubMed/MEDLINE. A meta-analysis was performed on the 19 studies (2186 patients) meeting inclusion criteria, collectively representing a broad range of arrhythmia mechanisms. Use of ICE was associated with significant reductions in fluoroscopy time (Hedges' g -1.06; 95% confidence interval [CI] -1.81 to -0.32; P < .01), fluoroscopy dose (Hedges' g -1.27; 95% CI -1.91 to -0.62; P < .01), and procedure time (Hedges' g -0.35; 95% CI -0.64 to -0.05; P = .02) vs ablation without ICE. A 6.95 minute reduction in fluoroscopy time and a 15.2 minute reduction in procedure time was observed between the ICE vs non-ICE groups. These efficiency gains were not associated with any decreased effectiveness or safety. Sensitivity analyses limiting studies to an atrial fibrillation (AF) only population yielded similar results to the main analysis. CONCLUSION: The use of ICE in the ablation of cardiac arrhythmias is associated with significantly lower fluoroscopy time, fluoroscopy dose, and shorter procedure time vs ablation without ICE. These efficiency improvements did not compromise the clinical effectiveness or safety of the procedure.

Burden of mild haemophilia A: Systematic literature review.

INTRODUCTION: Although the clinical manifestations of severe haemophilia A (HA) are well studied, the challenges, if any, of living with mild HA are not clearly delineated to date. AIM: To assess available evidence of clinical risks and societal/economic impacts of disease in adult patients with mild HA using a systematic literature review. METHODS: Prespecified study selection criteria were applied in a comprehensive literature search. Included studies varied in design and reported outcomes of interest for adults (≥13 years of age) with mild HA. RESULTS: Seventeen studies with a total of 3213 patients met eligibility criteria (published or presented in English, 1966-2017). Most studies were observational, and the outcomes reported were too sparse and dissimilar to support a formal meta-analysis. Mean annual bleeding rates ranged from 0.44 to 4.5 episodes per patient per year. Quality of life (QoL; SF-36 General Health) was impacted compared to healthy controls. Health care costs and productivity were seldom assessed and no robust comparisons to healthy controls were available. CONCLUSION: Quantifying outcomes for adult patients with mild HA remains challenging, with estimates of key QoL and cost data often based on small data sets and without comparison to population norms. Therefore, the clinical impact of mild haemophilia may be under-represented and unmet needs may remain unaddressed. As paradigm-changing therapies for HA emerge, stronger knowledge of mild HA can guide the development of care options that minimize burden and enhance the QoL for this segment of the haemophilia community, and for the haemophilia community in totality.

Atrial fibrillation ablation with a spring sensor-irrigated contact force-sensing catheter compared with other ablation catheters: systematic literature review and meta-analysis.

OBJECTIVES: The objective of our review was to systematically assess available evidence on the effectiveness, safety and efficiency of a spring sensor-irrigated contact force (CF) catheter (THERMOCOOL SMARTTOUCH Catheter (ST)) for percutaneous ablation of paroxysmal or persistent atrial fibrillation (AF), compared with other ablation catheters, or with the ST with the operator blinded to CF data. DESIGN: Systematic literature review and meta-analysis. BACKGROUND: Emerging evidence suggests improved clinical outcomes of AF ablation using CF-sensing catheters; however, reviews to date have included data from multiple, distinct CF technologies. METHODS: We conducted a systematic review and meta-analysis of published studies comparing the use of ST versus other ablation catheters for the treatment of AF. A comprehensive search of electronic and manual sources was conducted. The primary endpoint was freedom from recurrent atrial tachyarrhythmia (AT) at 12 months. Procedural and safety data were also analysed. RESULTS: Thirty-four studies enrolling 5004 patients were eligible. The use of ST was associated with increased odds of freedom from AT at 12 months (71.0%vs60.8%; OR 1.454, 95% CI 1.12 to 1.88, p=0.004) over the comparator group, and the effect size was most evident in paroxysmal AF patients (75.6%vs64.7%; OR 1.560, 95% CI 1.09 to 2.24, p=0.015). Procedure and fluoroscopy times were shorter with ST (p=0.05 and p<0.01, respectively, vs comparator groups). The reduction in procedure time is estimated at 15.5 min (9.0%), and fluoroscopy time 4.8 min (18.7%). Complication rates, including cardiac tamponade, did not differ between groups. CONCLUSIONS: Compared with the use of other catheters, AF ablation using the CF-sensing ST catheter for AF is associated with improved success rates, shorter procedure and fluoroscopy times and similar safety profile.

Phenylalanine blood levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis.

Blood phenylalanine (Phe) levels provide a practical and reliable method for the diagnosis and monitoring of metabolic status in patients with phenylketonuria (PKU). To assess the reliability of blood Phe levels as a predictive biomarker of clinical outcomes in the development of treatments for PKU, a systematic literature review and meta-analysis of published trials of PKU, which included Phe level and neurological and dietary compliance outcome measures, was conducted. Within-study correlations between Phe level and intelligence quotient (IQ) were extracted from 40 studies. Significant, proportional correlations were found during critical periods (from 0 to 12 years of age) for early-treated patients with PKU (r=-0.35; 95% confidence interval [CI]: -0.44 to -0.27), where each 100 micromol/l increase in Phe predicted a 1.3- to 3.1-point reduction in IQ. Similar significant correlations were observed between IQ and mean lifetime Phe level for early-treated patients (r=0.34; 95% CI: -0.42 to -0.25), where each 100 micromol/l increase in Phe predicted a 1.9- to 4.1-point reduction in IQ. Moderate correlations were found between concurrent Phe level and IQ for early-treated patients. In conclusion, these results confirm a significant correlation between blood Phe level and IQ in patients with PKU, and support the use of Phe as a predictive biomarker for IQ in clinical trials.

A systematic review of the economic burden of chronic angina.

BACKGROUND: Chronic angina carries an economic burden because of symptom management, the risk of major cardiovascular events, and lost productivity. The level of these costs has not been systematically quantified. OBJECTIVE: This study sought to assemble best evidence on the economic burden of chronic angina, including both the direct costs of healthcare and the indirect costs of lost productivity. METHODS: Studies published in English from January 1990 to June 2003 were located via electronic and manual searches and systematically reviewed. Eligible studies included those with information on cost of illness, cost of treatment, employment status, and/or work productivity and/or limitations for a population of patients with chronic angina. RESULTS: Seventeen studies assessed the healthcare cost of managing chronic angina. Cost estimates varied widely because of differing patient populations, healthcare settings, countries of origin, and year(s) of data collection. The most critical determinant of healthcare costs appeared to be the use of revascularization procedures. Twenty studies reported work limitations, 5 of which quantified productivity loss in monetary terms. Interventions for chronic angina resulted in some improvement in employment and work limitations over the short term. However, the positive effect of revascularization procedures tended to erode over the long term (3 years and beyond) in a substantial number of patients. CONCLUSIONS: Chronic angina carries substantial healthcare costs caused by frequent medical visits, medications, and expensive revascularization procedures. Workplace productivity loss because of angina is also substantial, but lasting long-term improvement in work status has been difficult to achieve.

Disability and chronic fatigue syndrome: a focus on function.

BACKGROUND: Evidence was sought in the published literature on how best to measure, monitor, and treat disability in patients with chronic fatigue syndrome (CFS). METHODS: A systematic review was performed of English-language literature published between January 1, 1988, and November 15, 2001. Interventional and observational studies of adults with CFS were eligible if they reported measures of disability and employment. A qualitative synthesis of results relating impairment measures to employment was performed. RESULTS: Of 3840 studies identified, 37 reported employment status and some measure of mental or physical impairment associated with disability. Most patients with CFS in these studies were unemployed. In 22 studies, the employment status of control subjects was also available. Only depression seemed to be associated with unemployment in patients with CFS. No other measurable impairment seemed to be consistently associated with disability or work outcomes. Only cognitive behavior therapy, rehabilitation, and exercise therapy interventions were associated with restoring the ability to work. No specific patient characteristics were identified as best predictors of positive employment outcomes. No quantitative syntheses of results were performed. CONCLUSIONS: For questions of disability and employment in CFS, the limitations inherent in the current literature are extensive. Methodologically rigorous, longitudinal, and interventional studies are needed to determine baseline characteristics that are associated with the inability to work and interventions that are effective in restoring the ability to work in the CFS population. Simple and consistent evaluations of functional capacity in patients with CFS are needed.

Efficacy of selected treatments of HIV wasting: a systematic review and meta-analysis.

PURPOSE: To assess the efficacy of recombinant human growth hormone (rhGH), testosterone, and anabolic steroids in the treatment of HIV wasting. METHODS: A systematic review and meta-analysis of studies published in English since 1996 was conducted. Studies of anabolic steroids, testosterone, and rhGH in treatment of HIV wasting reporting the efficacy outcomes of body composition measures, work output, or health-related quality of life (QoL) were eligible. Meta-analyses were performed for mean pre-post change in lean body mass (LBM), the within-study mean difference in pre-post change for LBM, and of odds ratios for certain safety events. RESULTS: A total of 18 studies met inclusion criteria for this review. CONCLUSION: The 3 treatments for HIV wasting assessed--rhGH, testosterone, and anabolic steroids--all demonstrated significant efficacy in increasing LBM as compared with placebo. Although meta-analysis did not indicate any statistically significant differences between these agents in the degree of efficacy in this outcome, the Food and Drug Administration-approved dose of rhGH may have advantages over the other 2 therapies in terms of improvements in functional capacity and QoL.

The effect of anemia treatment on selected health-related quality-of-life domains: a systematic review.

BACKGROUND: Anemia is a reduction in the oxygen-carrying capacity of red blood cells that results in a variety of symptoms, including dyspnea, headaches, light-headedness, and fatigue. Although anemia has been associated with reduced health-related quality of life (HRQoL), its treatment has not yet been consistently shown to improve HRQoL. OBJECTIVE: This systematic review of the literature was conducted to determine whether the treatment of anemia improves HRQoL domains, regardless of the type of underlying disease. METHODS: Data for this review were drawn from the clinical trial databases from 2 previous systematic literature reviews of erythropoiesis-stimulating protein treatment for renal insufficiency- and cancer-related anemia, both spanning the period January 1, 1980, through December 31, 2001. MEDLINE, Cancerlit, and Current Contents/Clinical Medicine were searched using the combined terms erythropoietin, kidney failure, neoplasms, and anemia. The reference lists of all identified articles were searched manually for additional relevant papers. The review included prospective studies that reported both HRQoL and hematocrit (Hct) in patients with cancer or renal insufficiency who received treatment for anemia with an erythropoiesis-stimulating protein. HRQoL was categorized by domain (overall, energy/fatigue, physical, activity); changes in HRQoL domains were expressed as effect sizes and meta-analyzed, as were correlation coefficients. The effects on HRQoL of dropout rate, study duration, baseline Hct, and change in Hct were examined in meta-regression analyses. RESULTS: Sixteen studies each were identified in patients with renal insufficiency (N = 2253) and patients with cancer (N = 10,695). The treated groups included 11,710 patients, and the control groups included 1238 patients. The baseline Hct in all treated groups averaged 26.0%: 28.3% in the group with cancer and 24.4% in the group with renal insufficiency. The mean improvement in Hct from baseline to the end of treatment was 8.3% (range, 1.0%-16.5%) in treated patients and 1.0% (range, 0.0%-3.3%) in controls. The Hct changes were similar in treated patients with cancer and treated patients with renal insufficiency, as was the HRQoL effect size (0.43). Dropout rate and study duration were not significant predictors of HRQoL changes, but change in Hct was a significant predictor in both conditions. Meta-analysis of the correlation coefficients, adjusting for HRQoL domains, showed a consistent and significant positive correlation between change in Hct and change in HRQoL (P < 0.001). CONCLUSION: The consistency in both direction and magnitude of effect across many studies and thousands of patients supports the hypothesis that treatment of anemia with erythropoiesis-stimulating protein improves selected HRQoL domains in patients with renal insufficiency- or cancer-related anemia.

Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review.

BACKGROUND AND PURPOSE: To determine the frequency of mucositis and associated outcomes in patients receiving radiotherapy (RT) for head and neck cancer through a systematic review of recently published literature. MATERIALS AND METHODS: According to the study protocol, databases were searched for randomized clinical trials (English only, 1996-1999) of patients with head and neck cancer receiving RT with or without chemotherapy that reported one or more outcomes of interest. RESULTS: Thirty-three studies (n=6181 patients) met inclusion criteria. Mucositis was defined using a variety of scoring systems. The mean incidence was 80%. Over one-half of patients (56%) who received altered fractionation RT (RT-AF) experienced severe mucositis (grades 3-4) compared to 34% of patients who received conventional RT. Rates of hospitalization due to mucositis, reported in three studies (n=700), were 16% overall and 32% for RT-AF patients. Eleven percent of patients had RT regimens interrupted or modified because of mucositis in five studies (n=1267) reporting this outcome. Data insufficiency or heterogeneity prohibited analysis of mucositis severity and other associated outcomes, such as oral pain, dysphagia and opioid use. CONCLUSIONS: Mucositis is a frequent, severe toxicity in patients treated with RT for head and neck cancer. While it appears that mucositis may lead to hospitalization and treatment interruptions, its overall impact on outcomes has not been adequately investigated.

Effect of amlodipine on systolic blood pressure.

BACKGROUND: Systolic hypertension is the most common form of hypertension, particularly in people aged >60 years. Caused by decreased compliance of large arteries, systolic hypertension is an independent risk factor for cardiovascular disease. Recent studies have demonstrated that it is more important to control systolic blood pressure (SBP) than diastolic blood pressure (DBP). OBJECTIVE: The objective of this study was to perform a systematic literature review to examine the effectiveness of amlodipine in lowering SBP in a variety of patient subgroups and clinical settings. METHODS: The literature review methodology included identifying, selecting, appraising, extracting, and synthesizing primary research studies. Following an a priori protocol, published literature was searched from 1980 to 2001 using 3 electronic databases. A manual review of the reference lists of recent review articles and all accepted studies was performed. Parallel-group, randomized, controlled trials that included at least 10 adults with baseline hypertension (SBP>or=140 mm Hg, DBP>or=90 mm Hg, or both), included at least 1 arm randomized to initial treatment with amlodipine monotherapy, had a minimum treatment duration of 8 weeks, and reported baseline and end-point blood pressure were included. RESULTS: Of 696 citations identified, 85 primary studies met all inclusion criteria. Comparable treatment arms were pooled, and weightd mean SBP was calculated. In the amlodipine monotherapy arms, which included >5000 patients, SBP decreased by a mean of 17.5 mm Hg from baseline. The effect of amlodipine in reducing SBP was greater in elderly patients (age>or=60 years) and patients with author-defined isolated systolic hypertension. The dose was titrated to achieve the target blood pressure in 73 of 89 amlodipine treatment arms, whereas 16 treatment arms reported fixed doses. The median daily dose was 5 mg (range, 1.25-15 mg) in both the fixed-dose and dose-titration groups. CONCLUSIONS: In this review of the published literature, amlodipine monotherapy was effective in reducing SBP. Antihypertensive agents such as amlodipine warrant consideration for the management of patients with inadequately controlled SBP.