Cost-effectiveness of Mediterranean diet and physical activity in secondary cardiovascular disease prevention: results from the UCC-SMART cohort study.

AIMS: The efficacy of a healthy lifestyle in secondary prevention of cardiovascular disease (CVD) is well established and a first-line recommendation in CVD prevention guidelines. The aim of this study was to assess whether Mediterranean diet and physical activity are also cost-effective in patients with established CVD. METHODS AND RESULTS: A cost-utility analysis (CUA) was performed comparing a combined Mediterranean diet and physical activity intervention to usual care in patients with CVD. The CUA had a healthcare perspective and lifetime horizon. Costs and utilities were estimated using a microsimulation on a cohort of 100 000 patients with CVD sampled from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease study (n = 8947, mean age 62 ± 8.7 years, and 74% male). Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Mediterranean diet and physical activity yielded 2.0 incremental quality-adjusted life years (QALYs) and cost reductions of €1236 per person compared with usual care, resulting in an ICER of €-626/QALY [95% confidence interval (CI) -1929 to 2673]. At a willingness-to-pay of €20 000/QALY, INHB was 2.04 (95% CI 0.99-3.58) QALYs and INMB was €40 757 (95% CI 19 819-71 605). The interventions remained cost-effective in a wide range of sensitivity analyses, including worst-case scenarios and scenarios with reimbursement for food and physical activity costs. CONCLUSION: In patients with established CVD, a combined Mediterranean diet and physical activity intervention was cost-saving and highly cost-effective compared with usual care. These findings strongly advocate for the incorporation of lifestyle interventions as integral components of care for all patients with CVD.

Lifestyle optimization, including physical activity and healthy diet, is a central recommendation for preventing recurrent cardiovascular events. In this study, we assessed whether improving physical activity habits and adherence to a heart-healthy Mediterranean diet would also be a cost-effective option. The results were remarkable­following the Mediterranean diet and engaging in physical activity were expected to result in an increase of 2.0 quality-adjusted life years (QALYs, equal to a life year in perfect health) and cost savings. This means that lifestyle optimization in secondary cardiovascular disease (CVD) prevention improves population health, while reducing overall healthcare costs. These findings underscore the importance of implementing lifestyle changes in the care for all individuals with CVD. A healthy lifestyle is not only effective in improving health but also a prudent financial decision.A combined Mediterranean diet and physical activity intervention is expected to result in two additional QALYs and three additional life years free of recurrent cardiovascular events per patient with established CVD.Targeting a healthy lifestyle is expected to lead to cost savings compared with usual care, due to the low costs of the intervention and the high efficacy in preventing recurrent cardiovascular events.Lifestyle optimization in secondary CVD prevention was shown to result in a dominant incremental cost-effectiveness ratio of €−626/QALY, which strongly advocates for healthy policy targeted at implementing lifestyle interventions in regular care for patients with CVD.

Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment.

Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia.

ABSTRACT: The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. Across the entire study population, a 20% reduction in nerve fibers on the PHN-affected side compared with that in the contralateral side was noted; however, the reduction was much higher in older individuals, approaching 40% in those aged 70 years or older. There was a decrease in contralateral fiber counts as well, also noted in prior biopsy studies, the mechanism of which is not fully clear. Nav1.7-positive immunolabeling was present in approximately one-third of subepidermal nerve fibers and did not differ on the PHN-affected vs contralateral sides. Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.

The development and efficacy of a paediatric cardiology fellowship online preparatory course.

BACKGROUND: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship. METHODS: The Online Preparatory Course contained 18 online learning modules covering basic concepts in anatomy, auscultation, echocardiography, catheterisation, cardiovascular intensive care, electrophysiology, pulmonary hypertension, heart failure, and cardiac surgery. Each online learning module included an instructional video with pre-and post-video tests. Participants completed pre- and post-Online Preparatory Course knowledge-based exams and surveys. Pre- and post-Online Preparatory Course survey and knowledge-based examination results were compared via Wilcoxon sign and paired t-tests. RESULTS: 151 incoming paediatric cardiology fellows from programmes across the USA participated in the 3 months prior to starting fellowship training between 2017 and 2019. There was significant improvement between pre- and post-video test scores for all 18 online learning modules. There was also significant improvement between pre- and post-Online Preparatory Course exam scores (PRE 43.6 ± 11% versus POST 60.3 ± 10%, p < 0.001). Comparing pre- and post-Online Preparatory Course surveys, there was a statistically significant improvement in the participants' comfort level in 35 of 36 (97%) assessment areas. Nearly all participants (98%) agreed or strongly agreed that the Online Preparatory Course was a valuable learning experience and helped alleviate some anxieties (77% agreed or strongly agreed) related to starting fellowship. CONCLUSION: An Online Preparatory Course prior to starting fellowship can provide a foundation of knowledge, decrease anxiety, and serve as an effective educational springboard for paediatric cardiology fellows.

Time and Distance Cost of Longer Acting Anti-VEGF Therapies for Macular Degeneration: Contributions to Drug Cost Comparisons.

Purpose: To evaluate the holistic cost of longer acting anti-VEGF therapy for macular degeneration when considering the associated costs of travel to the retina clinic. Design: Theoretical evaluation of cost using publicly available pricing data and reimbursements at the Veterans Affairs (VA) Medical Center. Patients and Methods: Setting: VA Medical Center. Study population: Patients with age related macular degeneration. Main outcome measures: Three-year cost of therapy when considering medication as well as travel costs and time spent in transit. Results: Based on cost data derived purely from wholesale acquisition cost and projected injection frequency over the first three years of treatment, faricimab is less expensive than ranibizumab and aflibercept by $37,709 and $6359, respectively. Aflibercept is less expensive ranibizumab by $31,350 over the first 3 years of treatment. When considering even small distances traveled by patients, these cost differences grow, amplified at even larger distances: at 25 miles, ranibizumab becomes $38,814 and $32,133 more expensive than faricimab and aflibercept, respectively. Aflibercept becomes $6681 more expensive than faricimab. At 100 miles, ranibizumab becomes $41,502 and $34,038 more expensive than faricimab and aflibercept, respectively. Aflibercept becomes $7464 more expensive than faricimab. Conclusion: Longer acting anti-VEGF therapies may differ not only in their wholesale acquisition cost, but also in the frequency of per label injections and associated clinic visits. Taking into account distance and time cost of travel may contribute to a more holistic view of cost differences among these therapies.

The readiness of public primary health care (PUSKESMAS) for cardiovascular services in Makasar city, Indonesia.

BACKGROUNDS: The increasing burden of cardiovascular disease (CVD) has become a major challenge globally, including in Indonesia. Understanding the readiness of primary health care facilities is necessary to confront the challenge of providing access to quality CVD health care services. Our study aimed to provide information regarding readiness to deliver CVD health services in public primary health care namely Puskesmas. METHODS: The study questionnaire was adapted from the World Health Organization (WHO) Service Availability and Readiness Assessment (SARA), modified based on the package of essentials for non-communicable disease (PEN) and the Indonesian Ministry of health regulation. Data were collected from all Puskesmas facilities (N = 47) located in Makassar city. We analysed relevant data following the WHO-SARA manual to assess the readiness of Puskesmas to deliver CVD services. Human resources, diagnostic capacity, supporting equipment, essential medication, infrastructure and guidelines, and ambulatory services domain were assessed based on the availability of each tracer item in a particular domain. The mean domain score was calculated based on the availability of tracer items within each domain. Furthermore, the means of all domains' scores are expressed as an overall readiness index. Higher scores indicate greater readiness of Puskesmas to deliver CVD-related health care. RESULTS: Puskesmas delivers health promotion, disease prevention, and prompt diagnosis for cardiovascular-related diseases, including hypertension, diabetes, coronary heart disease (CHD), and stroke. Meanwhile, basic treatments were observed in the majority of the Puskesmas. Long-term care for hypertension and diabetes patients and rehabilitation for CHD and stroke were only observed in a few Puskesmas. The readiness score of Puskesmas to deliver CVD health care ranged from 60 to 86 for. Furthermore, there were 11 Puskesmas (23.4%) with a score below 75, indicating a sub-optimal readiness for delivering CVD health services. A shortage of essential medicines and a low capacity for diagnostic testing were the most noticeable shortcomings leading to suboptimal readiness for high-quality CVD health services. CONCLUSION: Close cooperation with the government and other related stakeholders is required to tackle the identified shortcomings, especially the continuous monitoring of adequate supplies of medicines and diagnostic tools to achieve better CVD care for patients in Indonesia.

Assessment of the safety of the cationic arginine-rich peptides (CARPs) poly-arginine-18 (R18 and R18D) in ex vivo models of mast cell degranulation and red blood cell hemolysis.

Our laboratory focuses on the development of novel neuroprotective cationic peptides, such poly-arginine-18 (R18: 18-mer of l-arginine; net charge +18) and its d-enantiomer R18D in stroke and other brain injuries. In the clinical development of R18/R18D, their cationic property raises potential safety concerns on their non-specific effects to induce mast cell degranulation and hemolysis. To address this, we first utilised primary human cultured mast cells (HCMCs) to examine anaphylactoid effects. We also included as controls, the well-characterised neuroprotective TAT-NR2B9c peptide and the widely used heparin reversal peptide, protamine. Degranulation assay based on ß-hexosaminidase release demonstrated that R18 and R18D did not induce significant mast cell degranulation in both untreated (naïve) and IgE-sensitised HCMCs in a dose-response study to a maximum peptide concentration of 16 µM. Similarly, TAT-NR2B9c and protamine did not induce significant mast cell degranulation. To examine hemolytic effects, red blood cells (RBCs), were incubated with the peptides at a concentration range of 1-16 µM in the absence or presence of 2% plasma. Measurement of hemoglobin absorbance revealed that only R18 induced a modest, but significant degree of hemolysis at the 16 µM concentration, and only in the absence of plasma. This study addressed the potential safety concern of the application of the cationic neuroprotective peptides, especially, R18D, on anaphylactoid responses and hemolysis. The findings indicate that R18, R18D, TAT-NR2B9c and protamine are unlikely to induce histamine mediated anaphylactoid reactions or RBC hemolysis when administered intravenously to patients.

Proton magnetic resonance spectroscopy assessment of neonatal brain metabolism during cardiopulmonary bypass surgery.

Here, we report on the development and performance of a robust 3-T single-voxel proton magnetic resonance spectroscopy (1 H MRS) experimental protocol and data analysis pipeline for quantifying brain metabolism during cardiopulmonary bypass (CPB) surgery in a neonatal porcine model, with the overall goal of elucidating primary mechanisms of brain injury associated with these procedures. The specific aims were to assess which metabolic processes can be reliably interrogated by 1 H MRS on a 3-T clinical scanner and to provide an initial assessment of brain metabolism during deep hypothermia cardiac arrest (DHCA) surgery and recovery. Fourteen neonatal pigs underwent CPB surgery while placed in a 3-T MRI scanner for 18, 28, and 37°C DHCA studies under hyperglycemic, euglycemic, and hypoglycemic conditions. Total imaging times, including baseline measurements, circulatory arrest (CA), and recovery averaged 3 h/animal, during which 30-40 single-voxel 1 H MRS spectra (sLASER pulse sequence, TR/TE = 2000/30 ms, 64 or 128 averages) were acquired from a 2.2-cc right midbrain voxel. 1 H MRS at 3 T was able to reliably quantify (1) anaerobic metabolism via depletion of brain glucose and the associated build-up of lactate during CA, (2) phosphocreatine (PCr) to creatine (Cr) conversion during CA and subsequent recovery upon reperfusion, (3) a robust increase in the glutamine-to-glutamate (Gln/Glu) ratio during the post-CA recovery period, and (4) a broadening of the water peak during CA. In vivo 1 H MRS at 3 T can reliably quantify subtle metabolic brain changes previously deemed challenging to interrogate, including brain glucose concentrations even under hypoglycemic conditions, ATP usage via the conversion of PCr to Cr, and differential changes in Glu and Gln. Observed metabolic changes during CPB surgery of a neonatal porcine model provide new insights into possible mechanisms for prevention of neuronal injury.

Sympathomimetic increases resting energy expenditure following bariatric surgery: A randomized controlled clinical trial.

OBJECTIVE: The aim of this study was to test the hypothesis that ephedrine + caffeine (EC) reduces the fall in resting energy expenditure (REE) following bariatric surgery. METHODS: This 32-week, randomized, double-blinded, placebo-controlled trial included 142 patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery. Participants were randomized to either EC or placebo for 27 weeks, beginning 5 weeks post surgery. The primary end points were change in REE (measured), percentage of predicted REE ([measured REE/Harris-Benedict equation-predicted REE] × 100), and body composition. Secondary outcomes included change in percentage of weight. Adverse events (AEs) were recorded. RESULTS: The reduction in REE was smaller in the EC versus the placebo group, but it was not significant. Percentage of predicted REE was increased in the EC versus the placebo group (difference, mean [SE]: 5.82 [2.29], p = 0.013). Percentage of weight (difference: -3.83 [1.39], p = 0.007) was reduced in the EC versus the placebo group. Percentage of predicted REE was increased and body weight decreased in the EC-treated participants who underwent SG compared with those who underwent SG and were treated with placebo (difference in percentage of predicted REE = 8.06 [2.83], p = 0.006; difference in weight percentage = -4.37 [1.92], p = 0.025). Percentage of fat-free mass was increased in the SG participants treated with EC versus placebo (difference: 1.31 [0.63], p = 0.042). The most common AEs were anxiety, dizziness, insomnia, and tremors. Most AEs were not different from placebo by Week 32. CONCLUSIONS: EC enhances weight loss and reduces the fall in REE following bariatric surgery. Adrenergic symptoms mostly resolve over time.

Residual cardiovascular risk reduction guided by lifetime benefit estimation in patients with symptomatic atherosclerotic disease: effectiveness and cost-effectiveness.

AIMS: To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease. METHODS AND RESULTS: For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996-2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following: low-density lipoprotein cholesterol (LDL-c) < 1.8 mmol/L, systolic blood pressure <140 mmHg, and antithrombotic medication. Outcomes were evaluated for the total cohort using a microsimulation model. Effectiveness was evaluated as total gain in CVD-free life and events avoided, cost-effectiveness as incremental cost-effectivity ratio (ICER). In comparison to baseline treatment, treatment according to lifetime benefit would lead to an increase of 24 243 CVD-free life years [95% confidence interval (CI) 19 980-29 909] and would avoid 940 (95% CI 742-1140) events in the next 10 years. For risk-factor based treatment, this would be an increase of 18 564 CVD-free life years (95% CI 14 225-20 456) and decrease of 857 (95% CI 661-1057) events. The ICER of lifetime benefit-based treatment with a treatment threshold of ≥1 year additional CVD-free life per therapy was €15 092/QALY gained and of risk factor-based treatment €9933/QALY gained. In a direct comparison, lifetime benefit-based treatment compared to risk factor-based treatment results in 1871 additional QALYs for the price of €36 538/QALY gained. CONCLUSION: Residual risk reduction guided by lifetime benefit estimation results in more CVD-free life years and more CVD events avoided compared to the conventional risk factor-based strategy. Lifetime benefit-based treatment is an effective and potentially cost-effective strategy for reducing residual CVD risk in patients with clinical manifest vascular disease.

Transit Use and Health Care Costs: A Cross-sectional Analysis.

INTRODUCTION: Greater transit use is associated with higher levels of physical activity, which is associated with lower health risks and better health outcomes. However, there is scant evidence about whether health care costs differ based on level of transit ridership. METHODS: A sample (n=947) of members of Kaiser Permanente in the Portland, Oregon area were surveyed in 2015 about their typical use of various modes of travel including transit. Electronic medical record-derived health care costs were obtained among these members for the prior three years. Analysis examined proportional costs between High transit users (3+ days/week), Low transit users (1-2 days/week), and Non-users adjusting for age and sex, and then individually (base models) and together for demographic and health status variables. RESULTS: In separate base models across individual covariates, High transit users had lower total health care costs (59-69% of Non-user's costs) and medication costs (31-37% of Non-users' costs) than Non-users. Low transit users also had lower total health care (69%-76% of Non-users' costs) and medication costs (43-57% transit of Non-user's costs) than Non-users. High transit users' outpatient costs were also lower (77-82% of Non-users). In fully-adjusted models, total health care and medication costs were lower among High transit users' (67% and 39%) and Low transit users' (75% and 48%) compared to Non-users, but outpatient costs did not differ by transit use. CONCLUSIONS: Findings have implications for the potential cost benefit of encouraging and supporting more transit use, although controlled longitudinal and experimental evidence is needed to confirm findings and understand mechanisms.

Longitudinal Assessment of Right Ventricular Function in Hypoplastic Left Heart Syndrome.

Overall survival of patients with hypoplastic left heart syndrome (HLHS) has shown continued improvement. Right ventricular (RV) dysfunction, in the long term, adversely affects prognosis in these patients. This study examines changes in echocardiographic markers of RV function in a longitudinal cohort. We retrospectively reviewed patients with HLHS managed at our institution from 7/1994 to 1/2016. Follow-up included surgical and clinical data, and echocardiographic measures. Measures of RV function preceding and following all three stages of single ventricular palliation were collected. Freedom from transplant-free survival was assessed by Kaplan-Meier analysis. Multivariable associations with time to death or transplant were explored using the Cox proportional hazards model. A total of 120 patients with HLHS were identified. Norwood operation was performed in all patients. The probability of survival for the cohort was 71 ± 4.4%, 69 ± 4.5% and 66 ± 4.7% at 1, 2 and 5 years respectively after stage I Norwood operation. RV fractional area change (FAC), compared to post-Norwood was decreased at all subsequent stages with the greatest change noted post-superior cavo-pulmonary shunt from 40.7 ± 9.3% to 31.1 ± 8.3% (p < 0.001). Similarly, tricuspid valve annular systolic excursion (TAPSE) Z-score declined from -2.9 ± 1.3 to -9.7 ± 1.3 (p < 0.001) with a decrement at every stage of evaluation. In comparison to patients with post-Norwood RV FAC >35% and TAPSE Z-score > -5, patients with RV FAC ≤ 35% and TAPSE Z-score ≤ -5 had a significantly lower transplant-free survival (p < 0.0001). In patients with HLHS undergoing staged palliation, decrement in RV function manifests longitudinally. Post-Norwood RV FAC and TAPSE Z-score appear to be early markers of poor outcome in this population.

Plasma Trough Concentrations of Antihypertensive Drugs for the Assessment of Treatment Adherence: A Meta-Analysis.

Biochemical drug screening by liquid chromatography-tandem mass spectrometry in plasma is an accurate method for the quantification of plasma concentrations of antihypertensive medications in patients with hypertension. Trough concentrations could possibly be used as drug-specific cutoff values in the biochemical assessment of (non-)adherence. We performed a literature review and meta-analysis of pharmacokinetic studies to determine plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan. PubMed was searched for pharmacokinetic studies up to September 2020. Eligible studies reported steady-state mean trough concentration and their variance. Pooled trough concentrations were estimated using a three-level random effects meta-analytic model. Moderator analyses were performed to explore sources of heterogeneity. One thousand three hundred eighteen potentially relevant articles were identified of which 45 were eligible for inclusion. The pooled mean trough concentration was 9.2 ng/mL (95% CI, 7.5-10.8) for amlodipine, 41.0 ng/mL (95% CI, 17.4-64.7) for hydrochlorothiazide, and 352.9 ng/mL (95% CI, 243.5-462.3) for valsartan. Substantial heterogeneity was present for all 3 pooled estimates. Moderator analyses identified dosage as a significant moderator for the pooled trough concentration of amlodipine (ß1=0.9; P<0.05), mean age, and mean body weight for the mean trough concentration of hydrochlorothiazide (ß1=2.2, P<0.05, respectively, ß1=-4.0, P<0.05) and no significant moderators for valsartan. Plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan, measured with liquid chromatography-tandem mass spectrometry, are highly heterogeneous over the different studies. Use of the pooled trough concentration as a cutoff in the biochemical assessment of adherence can result in inaccurate diagnosis of (non-)adherence, which may seriously harm the patient-physician relationship, and is therefore not recommended.

Within-Trial Cost-Effectiveness of a Structured Lifestyle Intervention in Adults With Overweight/Obesity and Type 2 Diabetes: Results From the Action for Health in Diabetes (Look AHEAD) Study.

OBJECTIVE: To assess the cost-effectiveness (CE) of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, as implemented in the Action for Health in Diabetes study. RESEARCH DESIGN AND METHODS: Data were from 4,827 participants during their first 9 years of study participation from 2001 to 2012. Information on Health Utilities Index Mark 2 (HUI-2) and HUI-3, Short-Form 6D (SF-6D), and Feeling Thermometer (FT), cost of delivering the interventions, and health expenditures was collected during the study. CE was measured by incremental CE ratios (ICERs) in costs per quality-adjusted life year (QALY). Future costs and QALYs were discounted at 3% annually. Costs were in 2012 U.S. dollars. RESULTS: Over the 9 years studied, the mean cumulative intervention costs and mean cumulative health care expenditures were $11,275 and $64,453 per person for ILI and $887 and $68,174 for DSE. Thus, ILI cost $6,666 more per person than DSE. Additional QALYs gained by ILI were not statistically significant measured by the HUIs and were 0.07 and 0.15, respectively, measured by SF-6D and FT. The ICERs ranged from no health benefit with a higher cost based on HUIs to $96,458/QALY and $43,169/QALY, respectively, based on SF-6D and FT. CONCLUSIONS: Whether ILI was cost-effective over the 9-year period is unclear because different health utility measures led to different conclusions.

Forensic tracers of exposure to produced water in freshwater mussels: a preliminary assessment of Ba, Sr, and cyclic hydrocarbons.

Hydraulic fracturing is often criticized due in part to the potential degradation of ground and surface water quality by high-salinity produced water generated during well stimulation and production. This preliminary study evaluated the response of the freshwater mussel, Elliptio complanata, after exposure to produced water. A limited number of adult mussels were grown over an 8-week period in tanks dosed with produced water collected from a hydraulically fractured well. The fatty tissue and carbonate shells were assessed for accumulation of both inorganic and organic pollutants. Ba, Sr, and cyclic hydrocarbons indicated the potential to accumulate in the soft tissue of freshwater mussels following exposure to diluted oil and gas produced water. Exposed mussels showed accumulation of Ba in the soft tissue several hundred times above background water concentrations and increased concentrations of Sr. Cyclic hydrocarbons were detected in dosed mussels and principle component analysis of gas chromatograph time-of-flight mass spectrometer results could be a novel tool to help identify areas where aquatic organisms are impacted by oil and gas produced water, but larger studies with greater replication are necessary to confirm these results.

Neuroprotective Cationic Arginine-Rich Peptides (CARPs): An Assessment of Their Clinical Safety.

Cationic arginine-rich peptides represent a novel class of peptides being developed as neuroprotective agents for stroke and other acute and chronic neurological disorders. As a group, cationic arginine-rich peptides have a diverse range of other biological properties including the ability to traverse cell membranes, modulate immune responses, antagonise ion channel receptor function, as well as possessing cardioprotective, anti-nociceptive, anti-microbial and anti-cancer properties. A sound understanding of their safety profile is essential for the design of future clinical trials and for ensuring translational success with these compounds. At present, while many neuroprotective cationic arginine-rich peptides have been examined in preclinical animal neuroprotection studies, few have been assessed in human safety studies. Despite this, the safety of the prototypical cationic arginine-rich peptide, protamine, which has been in clinical use for over 70 years to reverse the anticoagulant effects of heparin and as an excipient in certain insulin preparations, is well established. In addition, the poly-arginine peptide R9 (ALX40-4C) was developed as an anti-human inmmunodeficiency virus therapeutic in the mid-1990s, and more recently, the neuroprotective cationic arginine-rich peptides TAT-NR2B9c (NA-1), CN-105 and RD2 are being evaluated for the treatment of ischaemic stroke, haemorrhagic stroke and Alzheimer's disease, respectively. Based on the available clinical data, cationic arginine-rich peptides as a group appear to be safe when administered at therapeutic doses by a slow intravenous infusion. While protamine, owing to its isolation from salmon milt and homology with human sperm protamine, can trigger anaphylactic and anaphylactoid reactions in a small proportion of patients previously exposed to the peptide (e.g. diabetic patients), who are allergic to fish or have undergone a vasectomy, such reactions are unlikely to be triggered in individuals exposed to non-protamine cationic arginine-rich peptides.

Would treatment decisions about secondary prevention of CVD based on estimated lifetime benefit rather than 10-year risk reduction be cost-effective?

OBJECTIVE: To test the hypothesis that treatment decisions (treatment with a PCSK9-mAb versus no treatment) are both more effective and more cost-effective when based on estimated lifetime benefit than when based on estimated risk reduction over 10 years. METHODS: A microsimulation model was constructed for 10,000 patients with stable cardiovascular disease (CVD). Costs and quality-adjusted life years (QALYs) due to recurrent cardiovascular events and (non)vascular death were estimated for lifetime benefit-based compared to 10-year risk-based treatment, with PCSK9 inhibition as an illustration example. Lifetime benefit in months gained and 10-year absolute risk reduction were estimated using the SMART-REACH model, including an individualized treatment effect of PCSK9 inhibitors based on baseline low-density lipoprotein cholesterol. For the different numbers of patients treated (i.e. the 5%, 10%, and 20% of patients with the highest estimated benefit of both strategies), cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER), indicating additional costs per QALY gain. RESULTS: Lifetime benefit-based treatment of 5%, 10%, and 20% of patients with the highest estimated benefit resulted in an ICER of €36,440/QALY, €39,650/QALY, or €41,426/QALY. Ten-year risk-based treatment decisions of 5%, 10%, and 20% of patients with the highest estimated risk reduction resulted in an ICER of €48,187/QALY, €53,368/QALY, or €52,390/QALY. CONCLUSION: Treatment decisions (treatment with a PCSK9-mAb versus no treatment) are both more effective and more cost-effective when based on estimated lifetime benefit than when based on estimated risk reduction over 10 years.

Geographic Access to Stroke Care Services in Rural Communities in Ontario, Canada.

BACKGROUND: Optimal stroke care requires access to resources such as neuroimaging, acute revascularization, rehabilitation, and stroke prevention services, which may not be available in rural areas. We aimed to determine geographic access to stroke care for residents of rural communities in the province of Ontario, Canada. METHODS: We used the Ontario Road Network File database linked with the 2016 Ontario Acute Stroke Care Resource Inventory to estimate the proportion of people in rural communities, defined as those with a population size <10,000, who were within 30, 60, and 240 minutes of travel time by car from stroke care services, including brain imaging, thrombolysis treatment centers, stroke units, stroke prevention clinics, inpatient rehabilitation facilities, and endovascular treatment centers. RESULTS: Of the 1,496,262 people residing in rural communities, the majority resided within 60 minutes of driving time to a center with computed tomography (85%), thrombolysis (81%), a stroke unit (68%), a stroke prevention clinic (74%), or inpatient rehabilitation (77.0%), but a much lower proportion (32%) were within 60 minutes of driving time to a center capable of providing endovascular thrombectomy (EVT). CONCLUSIONS: Most rural Ontario residents have appropriate geographic access to stroke services, with the exception of EVT. This information may be useful for jurisdictions seeking to optimize the regional organization of stroke care services.

Automated CT Perfusion Imaging Versus Non-contrast CT for Ischemic Core Assessment in Large Vessel Occlusion.

PURPOSE: There is increasing use of automated computed tomography perfusion (CTP) to aid thrombectomy decision in emergent large vessel occlusion. It is important to understand the performance of these software packages in predicting ischemic core and tissue-at-risk in the real-world setting. The aim of this study was to evaluate whether ischemic core on non-contrast CT (NCCT) and automated CTP correspond and predict infarct extent after thrombectomy for ischemic stroke. METHODS: Consecutive patients with acute anterior circulation large vessel occlusion undergoing successful thrombectomy (TICI 2b/3) were studied. All patients had baseline CT, CTP with RAPID post-processing software (RAPID-CTP), and post-thrombectomy 24 h CT. Ischemic cores were assessed by two blinded raters independently using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on each modality. The interrater agreement for ASPECTS, and correlation between baseline CT-ASPECTS, RAPID-CTP-ASPECTS, and 24h CT-ASPECTS were calculated. RESULTS: A total of 86 patients with a mean age of 70.3 years (SD 16.5) were studied. The median baseline CT-ASPECTS was 9.5 (interquartile range, IQR 8-10), median RAPID-CTP-ASPECTS was 9 (IQR 8-10), and mean RAPID-CTP-ischemic core volume was 14.4 ml (SD 27.9 ml). The mean mismatch volume (difference of Tmax > 6s and cerebral blood flow (CBF) < 30%) was 128.6 ml (SD 126.0 ml). There was substantial correlation between baseline and 24h CT-ASPECTS (rs: 0.62; p < 0.001), but poor correlation between RAPID-CTP-ASPECTS and RAPID-CTP ischemic core volume with 24h NCCT-ASPECTS (rs: 0.21; p = 0.06 and -0.16; p = 0.15 respectively). The positive predictive value of any established infarct for baseline CT-ASPECTS was 81%, while that of RAPID-CTP-ASPECTS was 64%. CONCLUSION: In this series of successfully revascularized patients, ischemic core as estimated by RAPID-CTP-ASPECTS did not correlate with the baseline CT and tended to depict a larger infarct core than the infarct extent as assessed by 24h CT-ASPECTS.

A Descriptive Revenue Analysis of a Wound-Center IR Collaboration to Treat Lower Extremity Venous Ulcers.

PURPOSE: To describe the revenue from a collaboration between a dedicated wound care center and an interventional radiology (IR) practice for venous leg ulcer (VLU) management at a tertiary care center. MATERIALS AND METHODS: This retrospective study included 36 patients with VLU referred from a wound care center to an IR division during the 10-month active study period (April 2017 to January 2018) with a 6-month surveillance period (January 2018 to June 2018). A total of 15 patients underwent endovascular therapy (intervention group), whereas 21 patients did not (nonintervention group). Work relative value units (wRVUs) and dollar revenue were calculated using the Centers for Medicare and Medicaid Services Physician Fee Schedule. RESULTS: Three sources of revenue were identified: evaluation and management (E&M), diagnostic imaging, and procedures. The pathway generated 518.15 wRVUs, translating to $37,522. Procedures contributed the most revenue (342.27 wRVUs, $18,042), followed by E&M (124.23 wRVUs, $8,881), and diagnostic imaging (51.65 wRVUs, $10,599). Intervention patients accounted for 86.7% of wRVUs (449.48) and 80.0% of the revenue ($30,010). An average of 33 minutes (38.3 hours total) and 2.06 hours (36.8 hours total) were spent on E&M visits and procedures, respectively. CONCLUSIONS: In this collaboration between the wound center and IR undertaken to treat VLU, IR and E&M visits generated revenue and enabled procedural and downstream imaging revenue.