Hepatic Arterial Blood Flow Modulation in Patients with Hepatocellular Carcinoma: A Pilot Study of the Influence of Intraarterial Norepinephrine Assessed with CT Perfusion.

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.

Initial Canadian Experience of Prostate Artery Embolization for Symptomatic Benign Prostatic Hyperplasia: Midterm Outcomes.

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 (Qmax) 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 Qmax (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.

Correction to: Minimally Invasive Treatment for Benign Prostatic Hyperplasia: Economic Evaluation from a Standardized Hospital Case Costing System.

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

Foam Sclerotherapy for Cyst Volume Reduction in Autosomal Dominant Polycystic Kidney Disease: A Prospective Cohort Study.

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.

Minimally Invasive Treatment for Benign Prostatic Hyperplasia: Economic Evaluation from a Standardized Hospital Case Costing System.

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.

Long-term Cost-Effectiveness of Diagnostic Tests for Assessing Stable Chest Pain: Modeled Analysis of Anatomical and Functional Strategies.

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.

Cost-utility analysis of methylphenidate treatment for children and adolescents with ADHD in Brazil

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.

Cost-utility analysis of methylphenidate treatment for children and adolescents with ADHD in Brazil.

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.

The Brazilian policy of withholding treatment for ADHD is probably increasing health and social costs.

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.

Serial analyses of C-reactive protein and myeloperoxidase in acute coronary syndrome.

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.

Association of anemia with clinical outcomes in stable coronary artery disease.

BACKGROUND: Although anemia is pathophysiologically associated with myocardial ischemia, there are scarce data on its clinical impact in patients with stable coronary artery disease on contemporary treatment. This study aims to describe the prevalence of anemia, and its association with symptoms and outcomes in this population. METHODS: We conducted a prospective cohort study in stable documented coronary artery disease patients. Anemia criteria was hemoglobin (Hb) <12 g/dl in women and <13 g/dl in men. Hemoglobin levels were divided in quartiles (Q) adjusted for sex. Major events included acute coronary syndromes, stroke and cardiovascular deaths. Secondary outcomes were presence of angina and chronic use of nitrates. Cox regression models were used to evaluate the independent effect of anemia on clinical outcomes. RESULTS: Among 310 patients, 71 (23%) met criteria for anemia. After a mean follow-up of 44+/-23 months, hemoglobin levels had a marked association with occurrence of major events (27% in Q1, 7% in Q2, 8% in Q3 and 12% in Q4; P<0.01). In multivariate analysis, anemia was independently associated with an increased risk of death [hazard ratio (HR) 6.5, 95% confidence interval (1.7-24.2)], major events [HR 3.3 (1.7-6.5)] and revascularization procedures [HR 2.3 (1.3-4.1)]. Persistent of angina symptoms (32 vs. 18%, P=0.01) and chronic use of nitrates (35 vs. 21%, P=0.02) were also more frequent among patients with anemia at baseline. CONCLUSIONS: In patients with stable ischemic heart disease, presence of anemia, even mild, is associated with a worse prognosis. Strategies aiming at identifying reversible causes of anemia or new treatments should be evaluated in prospective clinical trials.