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Abstract The initiation of transcription and replication of influenza A virus requires the 5' and 3' ends of vRNA. Here, the role of segment-specific non-coding sequences of influenza A virus on viral RNA synthesis was studied. Recombinant viruses, with the nonstructural protein (NS) segment-specific non-coding sequences replaced by the corresponding sequences of the neuraminidase (NA) segment, were characterized. The NS and NA vRNA levels in cells infected with these mutants were much higher than those of the wild type, whereas the NS and NA mRNA levels of the mutants were comparable to the wild-type levels. By contrast, the PB2 vRNA and mRNA levels of all the tested viruses were similar, indicating that vRNA with heterologous segment-specific non-coding sequences was not affected by the mutations. The observations suggested that, with the cooperation between the homologous 5' and 3'segment-specific sequences, the introduced mutations could specifically enhance the replication of NA and NS vRNA.

Background: Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer., Objectives: To describe patient characteristics, periprocedural management, and clinical outcomes in DOAC-treated patients with AF according to active cancer status., Methods: We conducted descriptive and comparative analyses using data from the PAUSE study. Multivariable logistic regression was used to determine whether active cancer status was an independent risk factor for bleeding outcomes. Covariates were selected a priori based on biological rationale and preexisting knowledge., Results: Patients with active cancer were older (P < .001), more likely to be thrombocytopenic (P = .026), have moderate renal dysfunction (P = .005), and more likely to receive low-dose DOAC therapy (P < .001). A greater proportion of patients with active cancer underwent a high-bleed-risk procedure (P < .001), with longer periprocedural DOAC-interruption intervals (P <.001) and lower preprocedural residual DOAC levels (P = .002). Active cancer was an independent predictor for surgical major bleeding (OR = 2.45; 95% CI, 1.08-5.14) after adjusting for study center, procedure category and bleed risk, thrombocytopenia, hypertension, and the use of a P2Y12 inhibitor., Conclusions: Active cancer status is associated with an increased risk of surgical major bleeding among DOAC-treated patients with AF undergoing interruption of anticoagulation for elective invasive procedures., Competing Interests: Declaration of competing interests J.R. Shaw has received in-kind laboratory support from Diagnostica Stago. T-F. Wang reports research funding from Leo Pharma and advisory honoraria from Valeo Pharma. Dr. Spyropoulos has received research support from Boehringer Ingelheim and Janssen, and consulting fees from Janssen, Bristol-Meyer Squibb/Pfizer Alliance, Sanofi, Alexion, Boehringer Ingelheim, Bayer, Roche Diagnostics. M. Carrier has received research funding from Leo Pharma and Pfizer, in addition to honoraria from BMS, Valeo Pharma, Leo Pharma, Sanofi, and Servier. J. Douketis has conducted consultancy/advisory board work for AstraZeneca, Cytosorb, PhaseBio, Servier, Leo Pharma and Pfizer. N. Li, J. Abdulrehman, S. Frosi Stella, M. St John, J. Nixon and S. Schulman declare no relevant conflicts of interest., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: The ideal approach to managing parastomal and small bowel ectopic varices (EVs) is yet to be established., Purpose: To evaluate outcomes following percutaneous antegrade transhepatic venous obliteration (PATVO) in patients presenting with bleeding from parastomal or small bowel EVs., Material and Methods: A case series of 12 patients presenting with active or recurrent bleeding from parastomal or small bowel EVs who underwent 17 PATVO interventions at our tertiary care institution was performed. Data extraction from electronic medical records included baseline characteristics and procedural details. Endpoints included technical success, early clinical success, and re-bleeding., Results: Technical success was 100% ( n = 17), and early clinical success was 82.3% ( n = 14). No patient experienced any intra- or post-operative complications. Rebleed rates after initial PATVO in patients who achieved early clinical success was as follows: 3-month, 0% ( n = 0); 6-month, 20% ( n = 2); 12-month, 20% ( n = 2). Rebleed rates after all PATVO procedures (including patients undergoing repeat procedures) that achieved early clinical success were as follows: 3-month, 0% ( n = 0); 6-month, 14% ( n = 2; 12-month, 14% ( n = 2). All patients with re-bleeding required reintervention with either PATVO, transjugular intrahepatic portosystemic shunt (TIPS) or both., Conclusion: PATVO can be safely performed to treat bleeding from parastomal and small bowel EVs. In patients who present with recurrent bleeding despite PATVO, TIPS with/without embolization of bleeding varices remains a valid option as described by the literature., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

This study assessed the safety profile of high-volume (>10 mL) 3% sodium tetradecyl sulfate (STS) sclerotherapy for the treatment of renal cysts in patients with autosomal dominant polycystic kidney disease. A total of 211 sclerotherapy treatments were performed in 169 patients over a 5-year period, with a comparison of 2 patient cohorts based on the STS volumes used. The first cohort (n = 112) received a high volume (greater than 10 mL) of STS, and the second cohort (n = 57) received a low volume (less than 10 mL). The minor adverse event rate for the cohorts was 14.5% and 9.6%, respectively (P = .310), with postprocedure pain being the most common event. One major adverse event occurred, for which the patient required hospitalization for infection after low-volume STS treatment. Doses of STS higher than those currently recommended by the Food and Drug Administration for intravascular use allow large renal cysts to be treated safely in the setting of autosomal dominant polycystic kidney disease., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to assess the midterm outcomes and safety of prostate artery embolization (PAE) for the treatment of benign prostatic hyperplasia (BPH)., Methods: A single-center, retrospective review of PAE performed for BPH was performed. Validated International Prostate Symptom Score (IPSS), quality of life (QoL) index, and International Index for Erectile Function (IIEF-5) questionnaires were completed at baseline and at least 12 months post-procedure. Prostate imaging was performed preprocedure as well as 3 months and 12 months post-procedure to assess prostate volume (PV). Uroflowmetry was also performed at baseline and 12 months post-procedure to assess urine flow rate (Q max ) and post-void residual (PVR) volume. Adverse events were graded according to Society of Interventional Radiology (SIR) guidelines., Results: Eighty male patients underwent the PAE procedure (mean age 69 years). Prostate volume decreased significantly from a mean volume 156 to 107 mL after 12 months post-procedure, commensurate with a mean reduction of 27.5% ( P < .05). Significant improvements were seen in IPSS (21.8 vs 10.5) and QoL (4.5 vs 2.0) from baseline to 12 months post-procedure ( P < .05). There was no significant change in IIEF-5 score. There was a significant reduction in PVR (202 vs 105 mL) and improvement in Q max (5.9 vs 10.0 mL/s) between baseline and 12 months post-procedure ( P < .05). No major complications occurred; 4 minor complications occurred (SIR grade A or B)., Conclusion: Prostate artery embolization achieved a clinically and statistically significant prostate volume reduction, symptom and QoL improvement, and enhanced uroflowmetry parameters in patients with BPH.

Background: Acute cholecystitis in nonsurgical candidates is often managed with cholecystostomy tube drainage. After symptom resolution, management options include cholecystectomy, long-term tube drainage, or tube removal. Percutaneous cholecystolithotomy (PCCL) can offer another therapeutic option for patients who are poor operative candidates., Study Design: A retrospective study of PCCL performed between December 2000 and September 2017 was conducted. Demographic characteristics, procedure details, gallstone-related complications, procedure-related complications, readmission, and mortality data were collected., Results: Seventy-five patients were identified (52.0% male, 48.0% female, mean ± SD age 75.6 ± 13.9 years). Mean ± SD follow-up time was 2.8 ± 3.7 years. Most of the patients (90.7%) had an American Society of Anesthesiologists physical status classification of 3 or 4. Eleven patients (14.7%) had failed earlier cholecystectomy. A total of 96 PCCL procedures were performed, and complete gallstone removal was achieved in 68 of 75 patients (90.7%), including all patients with previously aborted cholecystectomy. The 30-day and 90-day readmission rates were 4% and 8%, respectively. Three patients (3.9%) subsequently underwent cholecystectomy after PCCL. Ten (10.4%) procedure-related complications (Clavien-Dindo grade I and II) and 17 (22.7%) gallstone-related complications occurred during the follow-up period. Postprocedural choledocholithiasis occurred in 6 patients (8.0%). Recurrent gallstones developed in 5 patients (6.3%) (3 patients undergoing cholecystectomy and 2 patients treated with cholecystostomy tube)., Conclusions: PCCL is a viable option for management of symptomatic gallbladder stones in high-risk surgical patients. There is a high technical success rate, even in patients with earlier failed cholecystectomy. Most patients (77.3%) avoided gallstone-related complications after the procedure., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: This pilot study aims to evaluate the effect of hepatic intraarterial norepinephrine injection in vasculature modulation for hepatocellular carcinoma (HCC) tumors., Materials and Methods: This is a single-center prospective study of patients with HCC with proven single-lobe tumors > 3 cm. Eight patients were included, with a mean age of 63 y ± 8. All patients had Barcelona Clinic Liver Cancer stage B HCC and an Eastern Cooperative Oncology Group performance status of 0. Mean tumor size was 6.1 cm ± 1.8; all tumors were hypervascular. Patients underwent CT hepatic perfusion before and after injection of 24 μg of norepinephrine intraarterially (4 μg/mL; total 6 mL injected at a rate of 1 mL/s). Color-coded perfusion maps were used to assess the effects of local therapy on hepatic perfusion values. Tumor-to-liver ratio (TLR) was calculated from the ratio of tumor perfusion to background liver perfusion value., Results: Seven of 8 patents had significant (P = .04) absolute increase in tumor perfusion vs background liver, varying from incremental (-2 mL/min/100 mL) to 290 mL/min/100 mL. There was a nonsignificant increase in TLR from 2.7 ± 1.3 to 2.9 ± 1.4 after norepinephrine injection (P = .8). Mean peak time to maximal increase in tumor perfusion after injection was 6.1 s (range, 4.5-9.1 s). Norepinephrine injection was well tolerated without major adverse events., Conclusions: Norepinephrine causes increased blood flow toward HCC tumors, but with a corresponding smaller increase in blood flow to noncancerous liver tissue, with no observed systemic side effects., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Objective: The fractional flow reserve (FFR) versus angiography for multivessel evaluation (FAME) study has demonstrated that FFR substantially reduces major adverse cardiac events and resource utilization in coronary artery disease (CAD) patients. We aimed to assess the cost utility of FFR in percutaneous coronary interventions (PCI) from the perspective of the Brazilian Public Health System (SUS)., Design: Patient-level cost-utility analysis along the FAME study., Participants: Multivessel coronary artery disease patients., Intervention: PCI, either guided by FFR or by angiography alone., Setting: The procedure costs were based on the mean amount of unitary resource utilization multiplied by the costs from SUS reimbursement list. The utilities were derived using Brazilian weights for time trade-off European Quality of Life-5 Dimensions. The World Health Organization recommendation based on gross domestic product per capita (international dollars [I$] 35 876/quality-adjusted life year [QALY]) was used as willingness-to-pay threshold., Main Outcome Measure: We determined the incremental cost-utility ratio (ICUR) in I$ per QALY gained during the 1-year time horizon., Results: One-year costs were I$ 8931 for the angiography-guided PCI and I$ 8968 for the FFR-guided PCI, resulting in an incremental cost of I$ 37. Effectiveness during 1 year was 0.798 QALYs for angiography-guided PCI and 0.811 for FFR-guided PCI, resulting in an incremental effectiveness of 0.013 QALYs. The base-case ICUR of FFR versus angiography-guided PCI was 2780 I$/QALY. Cost-saving results are achieved with a FFR price reduction of at least 2.2%., Conclusions: Developing countries should give attention to strategies proven to be cost-effective in other health systems. In our analysis, FFR-guided PCI is very cost-effective in the Brazilian SUS and with a minimal price reduction of the device, FFR could be cost saving., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale & Objective: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. Progressive increase in cyst number and size leads to kidney failure in a majority of patients. Large kidney cysts, although few, can be especially deleterious by impeding kidney blood flow and obstructing urine flow over a large region. Foam sclerotherapy is a minimally invasive procedure that may be used to ablate large cysts. We examined the effectiveness and safety of foam sclerotherapy for kidney volume reduction in patients with ADPKD., Study Design: Prospective cohort study., Setting & Participants: Adults with ADPKD at a tertiary referral center in Toronto., Predictor: Foam sclerotherapy., Outcomes: Volume of treated kidneys and adverse events., Analytical Approach: Treated and nontreated kidney volume, kidney function, tolerability, and symptoms were analyzed within each patient., Results: We performed 77 foam sclerotherapy treatment sessions in 66 patients. Foam sclerotherapy was associated with a 21.8% volume reduction of the treated kidneys (n = 95; median, 1,138 [IQR, 801-1,582] mL before vs 891 [IQR, 548-1,450] mL after; P  < 0.001), while the volume of the nontreated kidneys increased by 3.4% during the same time frame (n = 37; median, 655 [IQR, 352-998] mL before vs 677 [IQR, 371-1,164] mL after; P  < 0.001). 4 (6%) patients had a higher measured creatinine clearance by at least 10 mL/min at least 12 months after foam sclerotherapy. 9 (14%) patients experienced self-limiting pain at the procedure site and 2 (3%) had cyst or urinary tract infection. Most patients with flank/back pain, abdominal pain, and abdominal distension had improvement in their symptoms., Limitations: Small sample, observational data., Conclusions: Foam sclerotherapy is a safe and effective procedure for kidney volume reduction and amelioration of compressive symptoms in select patients with ADPKD. Further studies are needed to assess its effects on kidney blood flow and kidney function and determine the subgroups of patients most likely to benefit., (© 2019 Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.)

Introduction: Image-guided biopsy is an important tool in the diagnosis of solid pancreatic masses. This study aims to evaluate the accuracy and complications associated with this procedure., Methods: We conducted a retrospective cohort study of all patients referred to interventional radiology for pancreatic biopsy at our institution from July 2004-July 2015. Two radiologists independently reviewed the images, technical aspects, and clinical characteristics., Results: A total of 82 patients underwent pancreatic biopsy using a combination of computed tomography (CT) and/or ultrasound guidance. Mean age was 67.8 years with 56% males. Most lesions were located in the head (63.4%), followed by the tail (19.5%), and the body (17.1%). The procedures were performed using the anterior (79.3%), lateral (7.3%), or posterior (13.4%) approach, with direct access in 85.4% of the patients and indirect access (transgastric or transhepatic) in 14.6% of cases. Core biopsies were obtained in 81.7% of cases, and fine needle aspiration was performed in 18.3% of cases. Needle size varied from 18-22 gauge (median 20 gauge). The median number of samples collected was 3 (range 1-8). A conclusive result was obtained in 82.9% of cases. There were 9 (11%) patients with minor complications: minor bleeding, pain, and inadvertent bowel puncture with no clinical repercussion. There were no deaths or major complications., Conclusion: Percutaneous image-guided pancreatic mass biopsy can be performed safely with excellent accuracy. Our results are comparable with endoscopic biopsy/aspiration, and percutaneous biopsy may be used as an alternative, particularly at institutions where endoscopy facilities are limited., (Copyright © 2018 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.)

The original version of this article published previously contained an error.

Purpose: Minimally invasive alternatives to transurethral resection of the prostate (TURP) such as prostate arterial embolization (PAE) and photoselective vaporization of the prostate (PVP) are being explored as adjuncts in the care of patients with benign prostatic hyperplasia. However, there are conflicting reports of the costs of these procedures. The purpose of this study was to compare the direct and indirect hospital costs of TURP, PAE and PVP., Materials and Methods: A chart review was performed in patients who underwent TURP, PVP and PAE from April 2015 to March 2017. All hospital costs were collected in accordance with the Ontario Case Costing Initiative, a standardized medical case costing system. Costs were characterized as direct or indirect and fixed or variable. Probabilistic sensitivity analysis was conducted to study cost uncertainty., Results: During the study period, a total of 209 men underwent TURP, 28 PVP and 21 PAE. Mean age (years) was as follows: TURP 71.43; PVP 73.66; PAE 70.77 (p = 0.366). Mean length of stay (days) was as follows: TURP 1.63; PVP 1.55; PAE 1 (p = 0.076). Total costs of the PAE group ($3829, SD $1582) were less than both PVP ($5719, SD $1515) and TURP groups ($5034, SD $1997, p < 0.001). There was no significant difference in direct costs between the groups. Monte Carlo simulation demonstrated that PAE was the least costly alternative majority of the time., Conclusions: The total hospital costs of PAE at our institution are significantly lower than those of PVP and TURP.

Introduction: Pulled or dislodged gastrostomy catheters represent a common complication associated with percutaneous gastrostomy and are a common cause of recurrent visits in patients with altered mental status. We intended to perform an experiment to compare the pull forces required to dislodge different commonly used gastrostomy catheters., Materials and Methods: We used a digital force gauge device to measure the pull forces required to dislodge three types of 20 French gastrostomy catheters in double-layer skin models. These included the Flow 20 Pull Method (Cook Medical, Bloomington, IN, USA), Entuit Gastrostomy BR Balloon Retention feeding tube (Cook Medical, Bloomington, IN, USA), and Ponsky Non-Balloon Replacement Gastrostomy Tube (CR Bard Inc, Salt Lake City, Utah, USA). The catheters were inserted into the skin model using the same technique as would be utilized in a patient., Results: The mean forces measured to dislodge the per-oral Flow 20 Pull Method, Entuit Thrive Balloon Retention, and button-type retention Ponsky replacement catheters were 35.6, 22.8, and 20.6 Newtons, respectively. The pull method per-oral gastrostomy catheter required significantly more pull force to dislodge than both the Ponsky button-type retention catheter and the Entuit balloon retention catheters. There was no significant difference in the pull force required to dislodge the Ponsky replacement catheter and the Entuit balloon retention catheter., Conclusions: Per-oral image-guided gastrostomy with pull-method button-type retention catheters may be the ideal choice in patients at high risk of tube dislodgment.

Chronic type B aortic dissection with aneurysmal degeneration requiring intervention presents significant therapeutic challenges. Thoracic endovascular aortic repair with a fenestrated endograft is a feasible option, but false lumen branches without an adjacent re-entry or perforation in the septum can pose a significant challenge. We present two cases of fenestrated endovascular aneurysm repair for chronic type B aortic dissection in which a renal artery from the false lumen was cannulated by creating a "neofenestration" through the dissection flap using a radiofrequency PowerWire (Baylis Medical Inc, Montreal, Quebec, Canada) technique (Toronto PowerWire fenestration technique)., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this research is to evaluate the relative cost-effectiveness of functional and anatomical strategies for diagnosing stable coronary artery disease (CAD), using exercise (Ex)-ECG, stress echocardiogram (ECHO), single-photon emission CT (SPECT), coronary CT angiography (CTA) or stress cardiacmagnetic resonance (C-MRI)., Setting: Decision-analytical model, comparing strategies of sequential tests for evaluating patients with possible stable angina in low, intermediate and high pretest probability of CAD, from the perspective of a developing nation's public healthcare system., Participants: Hypothetical cohort of patients with pretest probability of CAD between 20% and 70%., Primary and Secondary Outcome Measures: The primary outcome is cost per correct diagnosis of CAD. Proportion of false-positive or false-negative tests and number of unnecessary tests performed were also evaluated., Results: Strategies using Ex-ECG as initial test were the least costly alternatives but generated more frequent false-positive initial tests and false-negative final diagnosis. Strategies based on CTA or ECHO as initial test were the most attractive and resulted in similar cost-effectiveness ratios (I$ 286 and I$ 305 per correct diagnosis, respectively). A strategy based on C-MRI was highly effective for diagnosing stable CAD, but its high cost resulted in unfavourable incremental cost-effectiveness (ICER) in moderate-risk and high-risk scenarios. Non-invasive strategies based on SPECT have been dominated., Conclusions: An anatomical diagnostic strategy based on CTA is a cost-effective option for CAD diagnosis. Functional strategies performed equally well when based on ECHO. C-MRI yielded acceptable ICER only at low pretest probability, and SPECT was not cost-effective in our analysis., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Although drug-eluting stents (DES) have been widely incorporated into clinical practice in developed countries, several countries restrict their use mainly because of their high cost and unfavorable incremental cost-effectiveness ratios (ICER)., Objective: To evaluate the cost-effectiveness of DES in comparison with bare-metal stents (BMS) for treatment of coronary artery disease (CAD)., Design: Markov model., Data Sources: Published literature, government database, and CAD patient cohort., Target Population: Single-vessel CAD patients., Time Horizon: One year and lifetime., Perspective: Brazilian Public Health System (SUS)., Intervention: Six strategies composed of percutaneous intervention with a BMS or 1 of 5 DES (paclitaxel, sirolimus, everolimus, zotarolimus, and zotarolimus resolute)., Outcome Measures: Cost for target vessel revascularization avoided and cost for quality-adjusted life year gained., Base Case Analysis: In the short-term analysis, sirolimus was the most effective and least costly among DES (ICER of I$20,642 per target vessel revascularization avoided), with all others DES dominated by sirolimus. Lifetime cumulative costs ranged from I$18,765 to I$21,400. In the base case analysis, zotarolimus resolute had the most favorable ICER among the DES (ICER I$62,761), with sirolimus, paclitaxel, and zotarolimus being absolute dominated and everolimus extended dominated by zotarolimus resolute, although all the results were above the willingness-to-pay threshold of 3 times the gross domestic product per capita (I$35,307)., Sensitivity Analysis: In deterministic sensitivity analysis, results were sensitive to cost of DES, number of stents used per patient, baseline probability, and duration of stent thrombosis risk. The probabilistic sensitivity analysis demonstrated a probability of 81% for BMS being the strategy of choice, with 9% for everolimus and 9% zotarolimus resolute, at the willingness-to-pay threshold., Conclusion: DES is not a good value for money in SUS perspective, despite its benefit in reducing target vessel revascularization. Since the cost-effectiveness of DES is mainly driven by the stents' cost difference, they should cost less than twice the BMS price to become a cost-effective alternative., (© The Author(s) 2016.)

Several tests exist for diagnosing coronary artery disease, with varying accuracy and cost. We sought to provide cost-effectiveness information to aid physicians and decision-makers in selecting the most appropriate testing strategy. We used the state-transitions (Markov) model from the Brazilian public health system perspective with a lifetime horizon. Diagnostic strategies were based on exercise electrocardiography (Ex-ECG), stress echocardiography (ECHO), single-photon emission computed tomography (SPECT), computed tomography coronary angiography (CTA), or stress cardiac magnetic resonance imaging (C-MRI) as the initial test. Systematic review provided input data for test accuracy and long-term prognosis. Cost data were derived from the Brazilian public health system. Diagnostic test strategy had a small but measurable impact in quality-adjusted life-years gained. Switching from Ex-ECG to CTA-based strategies improved outcomes at an incremental cost-effectiveness ratio of 3100 international dollars per quality-adjusted life-year. ECHO-based strategies resulted in cost and effectiveness almost identical to CTA, and SPECT-based strategies were dominated because of their much higher cost. Strategies based on stress C-MRI were most effective, but the incremental cost-effectiveness ratio vs CTA was higher than the proposed willingness-to-pay threshold. Invasive strategies were dominant in the high pretest probability setting. Sensitivity analysis showed that results were sensitive to costs of CTA, ECHO, and C-MRI. Coronary CT is cost-effective for the diagnosis of coronary artery disease and should be included in the Brazilian public health system. Stress ECHO has a similar performance and is an acceptable alternative for most patients, but invasive strategies should be reserved for patients at high risk., (© 2016 Wiley Periodicals, Inc.)

Objective: To perform a cost-utility analysis on the treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate immediate-release (MPH-IR) in children and adolescents from Brazil., Method: A Markov model was constructed to compare MPH-IR vs. no treatment. A 24-week naturalistic study was conducted to collect transition probabilities and utility data. Effectiveness was expressed as quality-adjusted life-years (QALY), and costs reported in 2014 international dollars (I$). The perspective was the Brazilian Unified Health System as payer, and the time horizon was 6 years., Results: Of 171 patients, 73 provided information at baseline, and 56 at week 24. Considering the MPH-IR monthly cost of I$ 38, the incremental cost-effectiveness ratio (ICER) of treatment was I$ 9,103/QALY for children and I$ 11,883/QALY for adolescents. In two-way sensitivity analysis, considering one Gross National Product per capita (I$ 11,530) as willingness-to-pay, a cost of no-treatment lower than I$ 45/month would render MPH-IR a cost-saving strategy., Discussion: MPH-IR treatment of children and adolescents is cost-effective for ADHD patients from the Brazilian public health system perspective. Both patients and the healthcare system might benefit from such a strategy., Trial Registration Number: NCT01705613.

Aim: To investigate the survival rates after transarterial embolization (TAE)., Methods: One hundred third six hepatocellular carcinoma (HCC) patients [90 barcelona clinic liver cancer (BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test., Results: The overall mean survival was 35.8 mo (95%CI: 25.1-52.0). The survival rates of the BCLC A patients (33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo (95%CI: 27.5-52.0). The survival rates of the BCLC B patients (66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo (95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo (95%CI: 32.8-34.3), 28.6 mo (95%CI: 27.5-29.8), 19.0 mo (95%CI: 17.2-20.9) and 13 mo, respectively (P = 0.013)., Conclusion: The BCLC sub-staging system could add additional prognosis information for post-embolization survival rates in HCC patients.

Background: Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial., Objective: To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective., Methods: We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40 mg), intermediate dose; and above 40% (atorvastatin 20-80 mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied., Results: Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios., Conclusions: Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil.

Transarterial chemoembolization (TACE) and transarterial embolization (TAE) have improved the survival rates of patients with unresectable hepatocellular carcinoma (HCC); however, the optimal TACE/TAE embolic agent has not yet been identified. The aim of this study was to compare the effect of two different embolic agents such as microspheres (ME) and polyvinyl alcohol (PVA) on survival, tumor response, and complications in patients with HCC submitted to transarterial embolization (TAE). Eighty HCC patients who underwent TAE between June 2008 and December 2012 at a single center were retrospectively studied. A total of 48 and 32 patients were treated with PVA and ME, respectively. There were no significant differences in survival (P = 0.679) or tumoral response (P = 0.369) between groups (PVA or ME). Overall survival rates at 12, 18, 24, 36, and 48 months were 97.9, 88.8, 78.9, 53.4, and 21.4% in the PVA-TAE group and 100, 92.9, 76.6, 58.8, and 58% in the ME-TAE group (P = 0.734). Patients submitted to TAE with ME presented postembolization syndrome more frequently when compared with the PVA group (P = 0.02). According to our cohort, the choice of ME or PVA as embolizing agent had no significant impact on overall survival.

Objective: To estimate the economic consequences of the current Brazilian government policy for attention-deficit/hyperactivity disorder (ADHD) treatment and how much the country would save if treatment with immediate-release methylphenidate (MPH-IR), as suggested by the World Health Organization (WHO), was offered to patients with ADHD., Method: Based on conservative previous analyses, we assumed that 257,662 patients aged 5 to 19 years are not receiving ADHD treatment in Brazil. We estimated the direct costs and savings of treating and not treating ADHD on the basis of the following data: a) spending on ADHD patients directly attributable to grade retention and emergency department visits; and b) savings due to impact of ADHD treatment on these outcomes., Results: Considering outcomes for which data on the impact of MPH-IR treatment are available, Brazil is probably wasting approximately R$ 1.841 billion/year on the direct consequences of not treating ADHD in this age range alone. On the other hand, treating ADHD in accordance with WHO recommendations would save approximately R$ 1.163 billion/year., Conclusions: By increasing investments on MPH-IR treatment for ADHD to around R$ 377 million/year, the country would save approximately 3.1 times more than is currently spent on the consequences of not treating ADHD in patients aged 5 to 19 years.

Objective: To analyze the expenses of HIV/AIDS and acute myocardial infarction (AMI) treatment in Brazil., Methods: A search in the Brazilian epidemiological database (DATASUS) on AMI and AIDS hospitalizations and their costs was done from January 1998 to December 2011. The number of HIV/AIDS cases and antiretroviral treatment (ART) costs was obtained from public Brazilian databases., Results: In 5 years, HIV/AIDS cases increased 38.5%, mainly in patients aged 25-49. There were 180,640 patients in ART in 2007 at a cost of R$ 3,920 per patient/year. The hospitalizations due to AIDS were stable over the last 13 years; however, the hospitalizations due to AMI have increased 78%. In 2007, the expenses with hospitalizations for HIV/AIDS and AMI (25-49 years) were approximately 0.12 and 1.52% of the Ministry of Health budget allocated to reimburse inpatient costs. The expenses on ART totaled 1.5% of the total budget (all age groups)., Conclusion: The prevalence of HIV/AIDS is still increasing in Brazil. There are scientific evidences suggesting an increased incidence of AIM in this population. Considering the high costs for the treatment of both diseases, an economic analysis is important to alert health managers to strengthen the preventive measures to guarantee the financial sustainability of such treatment.

Background: The benefit of statins in the reduction of cardiovascular events was demonstrated in several placebo-controlled trials. More intensive therapy seems to be associated with greater benefit. Our objective was to compare different statin doses in the reduction of cardiovascular events and deaths, combining direct and indirect evidence, through mixed treatment comparisons (MTC)., Methods: We conducted a systematic review in MEDLINE and Cochrane CENTRAL. A random-effects Bayesian MTC model was used to combine placebo-controlled and direct statin comparison trials. Intensity of statin doses was classified according to expected LDL-cholesterol reduction effect: ≤30% as low; 30-40%, intermediate, and ≥40%, high. Outcomes evaluated were non-fatal myocardial infarction (MI), stroke, coronary revascularization and coronary, cardiovascular and all-cause death. Inconsistency was assessed with split-node methodology., Results: 47 trials (11 with direct statin comparisons) were included. High doses reduced non-fatal MI by 28% (95% CI: 18%-36%) and by 14% (7%-21%) when compared to low and intermediate doses, respectively. High doses also diminished revascularization [RR versus low and intermediate doses of 0.81 (0.69-0.95) and 0.88 (0.77-0.99), respectively] and stroke [RR of 0.83 (0.68-0.99) against low doses]. Regimen intensity did not change death rates (e.g., for all-cause mortality, RRs of 0.93 (0.80-1.06) and 0.98 (0.87-1.08) for high vs. low and intermediate doses, respectively). No statistical inconsistencies were found in the analyses., Conclusions: In this study, in which all available evidence from statin trials was simultaneously analyzed, the benefit of more intensive therapy was restricted to non-fatal events., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Many randomized clinical trials have demonstrated the effectiveness of the implantable cardioverter-defibrillator (ICDs) in death reduction of chronic heart failure (CHF) patients. Some developed countries studies have evaluated its cost-effectiveness, but these data are not applicable to Brazil., Objective: To evaluate the cost-effectiveness of ICD in CHF patients under two perspectives in Brazil: public and supplementary health systems., Methods: A Markov model was developed to analyze the incremental cost-effectiveness ratio (ICER) of ICD compared to conventional therapy in patients with CHF. Effectiveness was measured in quality-adjusted life years (QALYs). We searched the literature for data regarding effectiveness and complications. Costs were retrieved from public and health insurances reimbursement codebooks and from mean cost of admissions from a public and a private hospital. One-way sensitivity analysis was performed in all variables of the model., Results: ICER was R$ 68,318/QALY in the public and R$ 90,942/QALY in the private perspective. These values are much higher than the one suggested by the World Health Organization of 3 times the gross domestic product per head (R$ 40,545 in Brazil). The results were sensitive to the cost of the device, battery replacement interval and ICD effectiveness. In a simulation resembling MADIT-I population survival and ICD benefit, ICER was R$ R$ 23,739/QALY in the public and R$ 33,592/QALY in the private perspective., Conclusion: The ICER of ICD is elevated in the general ICC population, in either the public or private perspective. A more favorable result occurs in patients with a high sudden death risk.

Background: Several studies have demonstrated the effectiveness and cost-effectiveness of implantable cardioverter-defibrillators (ICDs) in chronic heart failure (CHF) patients. Despite its widespread use in developing countries, limited data exist on its cost-effectiveness in these settings., Objective: To evaluate the cost-effectiveness of ICD in CHF patients under the perspective of the Brazilian Public Healthcare System (PHS)., Methods: We developed a Markov model to evaluate the incremental cost-effectiveness ratio (ICER) of ICD compared with conventional therapy in patients with CHF and New York Heart Association class II and III. Effectiveness was evaluated in quality-adjusted life years (QALYs) and time horizon was 20 years. We searched MEDLINE for clinical trials and cohort studies to estimate data from effectiveness, complications, mortality, and utilities. Costs from the PHS were retrieved from national administrative databases. The model's robustness was assessed through Monte Carlo simulation and one-way sensitivity analysis. Costs were expressed as international dollars, applying the purchasing power parity conversion rate (PPP US$)., Results: ICD therapy was more costly and more effective, with incremental cost-effectiveness estimates of PPP US$ 50,345/QALY. Results were more sensitive to costs related to the device, generator replacement frequency and ICD effectiveness. In a simulation resembling the MADIT-I population survival and ICD benefit, the ICER was PPP US$ 17,494/QALY and PPP US$ 15,394/life years., Conclusions: In a Brazilian scenario, where ICD cost is proportionally more elevated than in developed countries, ICD therapy was associated with a high cost-effectiveness ratio. The results were more favorable for a patient subgroup at increased risk of sudden death.

Background: C-reactive protein (CRP) and myeloperoxidase (MPO) are involved in the pathogenesis of atherosclerosis, mainly during periods of instabilization. This study aims to test the hypothesis that patients with acute coronary syndrome (ACS) maintain a persistent inflammatory state, and that this is associated with long-term mortality., Hypothesis: We hypothesized that serum C-reactive protein and myeloperoxidase collected at the index event and later, could add to the prognostic information in patients with ACS., Methods: In a prospective cohort of 115 consecutive patients with ACS, myeloperoxidase and C-reactive protein were measured at admission and 2 y later. Patients were followed-up for the occurrence of cardiac death and other major cardiac events., Results: Levels of CRP decreased from 26 +/- 34 mg/L in the acute phase to 6 +/- 8 mg/L in the chronic phase (p < 0.001), and MPO levels decreased from 86 +/- 43 pM to 27 +/- 32 pM (p < 0.001). After 29 +/- 12 mo, 27% patients died, 39% had new episode of ACS, and 30% underwent revascularization procedures. Initial CRP levels above 10 mg/L were associated with higher long-term mortality (hazard ratio [HR]: 2.43; 95% confidence interval [CI]: 0.98 to 6.07; p = 0.048). MPO levels were not associated with death or other major events., Conclusions: Changes over time or absolute values in the chronic phase of both markers were not associated with clinical outcomes. CRP levels, but not MPO levels, in the index event were predictive of long-term cardiovascular mortality.