Veterans Administration Readjustment Counseling Service Counselors' Training Needs: Results of a National Needs Assessment.

The Department of Veteran Affairs established Readjustment Counseling Service (RCS) to meet the mental health needs of active-duty service members, veterans, and their families. A diverse therapeutic skill set is needed to serve this complex population. To assess training needs, a national mixed-methods needs assessment consisting of a survey for RCS counselors and focus groups among counselors, RCS educational trainers, and national leadership was conducted. Survey results (n = 681) showed that RCS counselors were most interested in trainings on moral injury, acceptance and commitment therapy, and military sexual trauma (MST). Desired trainings aligned with populations served. Themes from focus groups revealed the need for foundational trainings so that all RCS counselors are adept in treating MST, moral injury, and posttraumatic disorder and proficient in caring for couples. Additionally, counselors desired advanced trainings tailored to individual counselors' needs. RCS counselors identified multiple trainings to help them treat those they serve.

Effectiveness and cost-effectiveness of a web-based cardiac rehabilitation programme for people with chronic stable angina: protocol for the ACTIVATE (Angina Controlled Trial Investigating the Value of the 'Activate your heart' Therapeutic E-intervention) randomised controlled trial.

INTRODUCTION: Chronic stable angina is common and disabling. Cardiac rehabilitation is routinely offered to people following myocardial infarction or revascularisation procedures and has the potential to help people with chronic stable angina. However, there is insufficient evidence of effectiveness and cost-effectiveness for its routine use in this patient group. The objectives of this study are to compare the effectiveness and cost-effectiveness of the 'Activate Your Heart' cardiac rehabilitation programme for people with chronic stable angina compared with usual care. METHODS AND ANALYSIS: ACTIVATE is a multicentre, parallel-group, two-arm, superiority, pragmatic randomised controlled trial, with recruitment from primary and secondary care centres in England and Wales and a target sample size of 518 (1:1 allocation; allocation sequence by minimisation programme with built-in random element). The study uses secure web-based allocation concealment. The two treatments will be optimal usual care (control) and optimal usual care plus the 'Activate Your Heart' web-based cardiac rehabilitation programme (intervention). Outcome assessment and statistical analysis will be performed blinded; participants will be unblinded. Outcomes will be measured at baseline and at 6 and 12 months' follow-up. Primary outcome will be the UK version of Seattle Angina Questionnaire (SAQ-UK), physical limitations domain at 12 months' follow-up. Secondary outcomes will be the remaining two domains of SAQ-UK, dyspnoea, anxiety and depression, health utility, self-efficacy, physical activity and the incremental shuttle walk test. All safety events will be recorded, and serious adverse events assessed to determine whether they are related to the intervention and expected. Concurrent economic evaluation will be cost-utility analysis from health service perspective. An embedded process evaluation will determine the mechanisms and processes that explain the implementation and impacts of the cardiac rehabilitation programme. ETHICS AND DISSEMINATION: North of Scotland National Health Service Research Ethics Committee approval, reference 21/NS/0115. Participants will provide written informed consent. Results will be disseminated by peer-reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN10054455.

Potential endpoints for assessment of bone health in persons with neurofibromatosis type 1.

Neurofibromatosis type 1 is a genetic syndrome characterized by a wide variety of tumor and non-tumor manifestations. Bone-related issues, such as scoliosis, tibial dysplasia, and low bone mineral density, are a significant source of morbidity for this population with limited treatment options. Some of the challenges to developing such treatments include the lack of consensus regarding the optimal methods to assess bone health in neurofibromatosis type 1 and limited data regarding the natural history of these manifestations. In this review, the Functional Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration: (1) presents the available techniques for measuring overall bone health and metabolism in persons with neurofibromatosis type 1, (2) reviews data for use of each of these measures in the neurofibromatosis type 1 population, and (3) describes the strengths and limitations for each method as they might be used in clinical trials targeting neurofibromatosis type 1 bone manifestations. The Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration supports the development of a prospective, longitudinal natural history study focusing on the bone-related manifestations and relevant biomarkers of neurofibromatosis type 1. In addition, we suggest that the neurofibromatosis type 1 research community consider adding the less burdensome measurements of bone health as exploratory endpoints in ongoing or planned clinical trials for other neurofibromatosis type 1 manifestations to expand knowledge in the field.

Review of imaging recommendations from Response Assessment in Pediatric Neuro-Oncology (RAPNO).

The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group includes neuroradiologists, neuro-oncologists, neurosurgeons, radiation oncologists, and clinicians in various additional specialties. This review paper will summarize the imaging recommendations from RAPNO for the six RAPNO publications to date covering pediatric low-grade glioma, pediatric high-grade glioma, medulloblastoma and other leptomeningeal seeding tumors, diffuse intrinsic pontine glioma, ependymoma, and craniopharyngioma.

Evaluation of "Caserotek" a low cost and effective artificial blood-feeding device for mosquitoes.

Entomological research studies on mosquito vector biology, vector competence, insecticide resistance, dispersal, and survival (using mark-release-recapture techniques) often rely on laboratory-reared mosquito colonies to produce large numbers of consistently reared, aged, and sized mosquitoes. We developed a low-cost blood feeding apparatus that supports temperatures consistent with warm blooded animals, using commonly available materials found in low resource environments. We compare our system ("Caserotek") to Hemotek and glass/membrane feeding methods. Two experiments were conducted with Aedes aegypti (Linnaeus 1762) and one with Anopheles darlingi (Root 1926) (Diptera: Culicidae); 3 replicates were conducted for each experiment. Aedes aegypti female mosquitoes were provided chicken blood once per week for 30 min (Experiment #1) for 14 days or 1 hour (Experiment #2) for 21 days. Anopheles darlingi were fed once for 1 hour (Experiment #3). Blood-feeding rates, survival rates, and egg production were calculated across replicates. Caserotek had a significantly higher 30-min engorgement rate (91.1%) than Hemotek (47.7%), and the glass feeder (29.3%) whereas for 1-hour feeding, Hemotek had a significantly lower engorgement rate than either of the other two devices (78% versus 91%). Thirty-day survival was similar among the feeding devices, ranging from 86% to 99%. Mean egg production was highest for the Caserotek feeder (32 eggs per female) compared to the glass feeder and Hemotek device (21-22 eggs per female). Our new artificial feeding system had significantly higher blood feeding rates than for more expensive artificial systems and was equivalent to other fitness parameters. Caserotek only requires the ability to boil water to maintain blood temperatures using a Styrofoam liner. It can be easily scaled up to large production facilities and used under austere conditions.

Arterial spin labeling as an ancillary assessment to postoperative conventional angiogram in pediatric moyamoya disease.

OBJECTIVE: Digital subtraction angiography (DSA) is commonly performed after pial synangiosis surgery for pediatric moyamoya disease to assess the degree of neovascularization. However, angiography is invasive, and the risk of ionizing radiation is a concern in children. In this study, the authors aimed to identify whether arterial spin labeling (ASL) can predict postoperative angiogram grading. In addition, they sought to determine whether patients who underwent ASL imaging without DSA had similar postoperative outcomes when compared with patients who received ASL imaging and postoperative DSA. METHODS: The medical records of pediatric patients who underwent pial synangiosis for moyamoya disease at a quaternary children's hospital were reviewed during a 10-year period. ASL-only and ASL+DSA cohorts were analyzed. The frequency of preoperative and postoperative symptoms was analyzed within each cohort. Three neuroradiologists assigned a visual ASL grade for each patient indicating the change from the preoperative to postoperative ASL perfusion sequences. A postoperative neovascularization grade was also assigned for patients who underwent DSA. RESULTS: Overall, 21 hemispheres of 14 patients with ASL only and 14 hemispheres of 8 patients with ASL+DSA were analyzed. The groups had similar rates of MRI evidence of acute or chronic stroke preoperatively (61.9% in the ASL-only group and 64.3% in the ASL+DSA group). In the entire cohort, transient ischemic attack (TIA) (p = 0.027), TIA composite (TIA or unexplained neurological symptoms; p = 0.0006), chronic headaches (p = 0.035), aphasia (p = 0.019), and weakness (p = 0.001) all had decreased frequency after intervention. The authors found a positive association between revascularization observed on DSA and the visual ASL grading (p = 0.048). The visual ASL grades in patients with an angiogram indicating robust neovascularization demonstrated improved perfusion when compared with the ASL grades of patients with a poor neovascularization. CONCLUSIONS: Noninvasive ASL perfusion imaging had an association with postoperative DSA neoangiogenesis following pial synangiosis surgery in children. There were no significant postoperative stroke differences between the ASL-only and ASL+DSA cohorts. Both cohorts demonstrated significant improvement in preoperative symptoms after surgery. Further study in larger cohorts is necessary to determine whether the results of this study are validated in order to circumvent the invasive catheter angiogram.

Serial assessment of measurable residual disease in medulloblastoma liquid biopsies.

Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.

Imaging Evaluation of Plexiform Neurofibromas in Neurofibromatosis Type 1: A Survey-Based Assessment.

OBJECTIVE: To assess imaging utilization practices across clinical specialists in neurofibromatosis type 1 (NF1) for the evaluation of symptomatic and asymptomatic children and adults with or without plexiform neurofibromas (PN). METHODS: An institutional review board-exempt survey was administered to medical practitioners caring for individuals with NF1 at the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) meeting in September 2019. The survey included questions on respondent demographic data (9 questions), type of imaging obtained for asymptomatic (4 questions) and symptomatic (4 questions) people with and without PN, and utilization of diffusion-weighted imaging (2 questions). RESULTS: Thirty practitioners participated in the survey. Most were academic neuro-oncologists at high-volume (>10 patients/week) NF1 centers. Of 30 respondents, 26 had access to whole-body MRI (WB-MRI). The most common approach to an asymptomatic person without PN was no imaging (adults: 57% [17/30]; children: 50% [15/30]), followed by a screening WB-MRI (adults: 20% [6/30]; children: 26.7% [8/30]). The most common approach to a person with symptoms or known PN was regional MRI (adults: 90% [27/30]; children: 93% [28/30]), followed by WB-MRI (adults: 20% [6/30]; children: 36.7% [11/30]). WB-MRI was most often obtained to evaluate a symptomatic child with PN (37% [11/30]). CONCLUSIONS: More than 90% of practitioners indicated they would obtain a regional MRI in a symptomatic patient without known or visible PN. Otherwise, there was little consensus on imaging practices. Given the high prevalence of PN and risk of malignant conversion in this patient population, there is a need to define imaging-based guidelines for optimal clinical care and the design of future clinical trials.

Children drinking private well water have higher blood lead than those with city water.

Although the Flint, Michigan, water crisis renewed concerns about lead (Pb) in city drinking water, little attention has been paid to Pb in private wells, which provide drinking water for 13% of the US population. This study evaluates the risk of Pb exposure in children in households relying on private wells. It is based on a curated dataset of blood Pb records from 59,483 North Carolina children matched with household water source information. We analyze the dataset for statistical associations between children's blood Pb and household drinking water source. The analysis shows that children in homes relying on private wells have 25% increased odds (95% CI 6.2 to 48%, P < 0.01) of elevated blood Pb, compared with children in houses served by a community water system that is regulated under the Safe Drinking Water Act. This increased Pb exposure is likely a result of corrosion of household plumbing and well components, because homes relying on private wells rarely treat their water to prevent corrosion. In contrast, corrosion control is required in regulated community water systems. These findings highlight the need for targeted outreach to prevent Pb exposure for the 42.5 million Americans depending on private wells for their drinking water.

Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Paediatric low-grade gliomas (also known as pLGG) are the most common type of CNS tumours in children. In general, paediatric low-grade gliomas show clinical and biological features that are distinct from adult low-grade gliomas, and the developing paediatric brain is more susceptible to toxic late effects of the tumour and its treatment. Therefore, response assessment in children requires additional considerations compared with the adult Response Assessment in Neuro-Oncology criteria. There are no standardised response criteria in paediatric clinical trials, which makes it more difficult to compare responses across studies. The Response Assessment in Pediatric Neuro-Oncology working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop consensus recommendations for response assessment in paediatric low-grade gliomas. Final recommendations were based on literature review, current practice, and expert opinion of working group members. Consensus recommendations include imaging response assessments, with additional guidelines for visual functional outcomes in patients with optic pathway tumours. As with previous consensus recommendations, these recommendations will need to be validated in prospective clinical trials.

Energy access in Malawian healthcare facilities: consequences for health service delivery and environmental health conditions.

Many healthcare facilities (HCFs) in low-income countries experience unreliable connectivity to energy sources, which adversely impacts the quality of health service delivery and provision of adequate environmental health services. This assessment explores the status and consequences of energy access through interviews and surveys with administrators and healthcare workers from 44 HCFs (central hospitals, district hospitals, health centres and health posts) in Malawi. Most HCFs are connected to the electrical grid but experience weekly power interruptions averaging 10 h; less than one-third of facilities have a functional back-up source. Inadequate energy availability is associated with irregular water supply and poor medical equipment sterilization; it adversely affects provider safety and contributes to poor lighting and working conditions. Some challenges, such as poor availability and maintenance of back-up energy sources, disproportionately affect smaller HCFs. Policymakers, health system actors and third-party organizations seeking to improve energy access and quality of care in Malawi and similar settings should address these challenges in a way that prioritizes the specific needs of different facility types.

Assessment of community hospital disaster preparedness in New York State.

OBJECTIVE: The intent of this study was to assess disaster preparedness in community hospitals across New York. DESIGN: Descriptive and analytical cross-sectional survey study. The survey instrument consisted of 35 questions that examined six elements of disaster preparedness: disaster plan development, onsite surge capacity, available materials and resources, disaster education and training, disaster preparedness funding levels, and perception of disaster preparedness. SETTING: Community hospitals in New York. SUBJECTS: Contact information was obtained for 207 of 208 community hospitals. Email invitations to participate in the survey were sent to hospital CEOs and disaster preparedness coordinators. Completed surveys were received from 80 hospitals. MAIN OUTCOME MEASURES: Hospital responses to questions related to the six elements of disaster preparedness. RESULTS: Most (87.5 percent) hospitals had experienced a disaster event during the past 5 years (2012-2016). Eighty percent had disaster plans that addressed all of six major types of disasters. Only 17.5 percent believed their disaster plans were "very sufficient" and did not require any revisions. Nearly three-quarters (73.3 percent) of hospitals could continue operations for less than a week without external resources. Less than half (49.4 percent) reported being satisfied or very satisfied with the level of funding that they received from the Hospital Preparedness Program. Most (88.8 percent) respondents felt that barriers to disaster preparedness exist for their organizations. CONCLUSIONS: The results demonstrate the current level of disaster preparedness among New York hospitals. The study's approach is discussed as a model that will enable hospitals to identify focus areas for improvement and opportunities for legislation and advocacy.

Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology committee.

Lack of standard response criteria in clinical trials for medulloblastoma and other seeding tumors complicates assessment of therapeutic efficacy and comparisons across studies. An international working group was established to develop consensus recommendations for response assessment. The aim is that these recommendations be prospectively evaluated in clinical trials, with the goal of achieving more reliable risk stratification and uniformity across clinical trials. Current practices and literature review were performed to identify major confounding issues and justify subsequently developed recommendations; in areas lacking scientific investigations, recommendations were based on experience of committee members and consensus was reached after discussion. Recommendations apply to both adult and pediatric patients with medulloblastoma and other seeding tumors. Response should be assessed using MR imaging (brain and spine), CSF cytology, and neurologic examination. Clinical imaging standards with minimum mandatory sequence acquisition that optimizes detection of leptomeningeal metastases are defined. We recommend central review prior to inclusion in treatment cohorts to ensure appropriate risk stratification and cohort inclusion. Consensus recommendations and response definitions for patients with medulloblastomas and other seeding tumors have been established; as with other Response Assessment in Neuro-Oncology recommendations, these need to now be prospectively validated in clinical trials.

Biological characterization of a novel in vitro cell irradiator.

To evaluate the overall robustness of a novel cellular irradiator we performed a series of well-characterized, dose-responsive assays to assess the consequences of DNA damage. We used a previously described novel irradiation system and a traditional 137Cs source to irradiate a cell line. The generation of reactive oxygen species was assessed using chloromethyl-H2DCFDA dye, the induction of DNA DSBs was observed using the comet assay, and the initiation of DNA break repair was assessed through γH2AX image cytometry. A high correlation between physical absorbed dose and biologic dose was seen for the production of intracellular reactive oxygen species, physical DNA double strand breaks, and modulation of the cellular double stand break pathway. The results compared favorably to irradiation with a traditional 137Cs source. The rapid, straightforward tests described form a reasonable approach for biologic characterization of novel irradiators. These additional testing metrics go beyond standard physics testing such as Monte Carlo simulation and thermo-luminescent dosimeter evaluation to confirm that a novel irradiator can produce the desired dose effects in vitro. Further, assessment of these biological metrics confirms that the physical handling of the cells during the irradiation process results in biologic effects that scale appropriately with dose.

Emissions and Economics of Behind-the-Meter Electricity Storage.

Annual installations of behind-the-meter (BTM) electric storage capacity are forecast to eclipse grid-side electrochemical storage by the end of the decade. Here, we characterize the economic payoff and regional emission consequences of BTM storage without colocated generation under different tariff conditions, battery characteristics, and ownership scenarios using metered loads for several hundred commercial and industrial customers. Net emissions are calculated as increased system emissions from charging minus avoided emissions from discharging. Net CO2 emissions range from 75 to 270 kg/MWh of delivered energy depending on location and ownership perspective, though in New York, these emissions can be reduced with careful tariff design. Net NOx emissions range from -0.13 to 0.24 kg/MWh, and net SO2 emissions range from -0.01 to 0.58 kg/MWh. Emission rates are driven primarily by energy losses, not by the difference between marginal emission rates during battery charging and discharging. Economics are favorable for many buildings in regions with high demand charges like California and New York, even without subsidies. Future penetration into regions with average charges like Pennsylvania will depend greatly on installation cost reductions and wholesale prices for ancillary services.

The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway.

The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation-arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders. This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field. © 2016 Wiley Periodicals, Inc.

A review of the peri-operative risk stratification assessment tools used for the prediction of cardiovascular complications in non-cardiac surgery.

The development of atherosclerosis is a complex process that involves several inflammatory mechanisms. The evolution of a fatty streak to a mature occlusive atheromatous plaque occurs over several decades. However, during acute plaque rupture, to a varying degree, these same inflammatory systems are involved.Evidence exists that suggests a relationship between the activated inflammatory pathways; in the setting of lower respiratory tract or urinary tract infections and cardiac events such as unstable angina or myocardial infarctions.Peripheral vascular disease patients demonstrate atheromatous disease throughout their arterial tree, with coronary artery involvement in a significant proportion of individuals. The stress that a surgical intervention creates may be the catalyst for an acute coronary syndrome through the activation of these inflammatory pathways. Individual responses to the surgical insult are unpredictable and the extent to which the inflammatory mechanisms are stimulated is variable. The measurements of inflammatory biomarkers, such as C-reactive protein, have been associated with adverse short- and long-term mortality in patients who experience an acute coronary syndrome.This review article looks at the previous assessment tools that have been developed over time to try and predict the peri-operative risk of patients undergoing non-cardiac surgery, based on traditional patient parameters. We also explore the use of bio-markers in addition to these characteristics and how future work is being developed to look at the potential use of these to improve individual risk profiles.

The impact of social deprivation on coronary revascularisation treatment outcomes within the National Health Service in England and Wales.

BACKGROUND: There is strong evidence to suggest that social deprivation is linked to health inequalities. In the UK, concerns have been raised regarding disparities in the outcomes of acute cardiac services within the National Health Service (NHS). This study explored whether differences exist in (a) elective hospital presentation time (b) indicators of severity and disease burden and (c) treatment outcomes (hospital stay and mortality) on the basis of the index of multiple deprivation (IMD) status. DESIGN: This study was a retrospective analysis of data from NHS databases for 13,758 patients that had undergone cardiac revascularisation interventions at the Liverpool Heart and Chest Hospital between April 2007-March 2012. METHODS: The data was analysed by descriptive, univariate and multivariate statistics to explore the association between the IMD quintiles (Q1-Q5) and revascularisation type, elective presentation time, hospital length of stay and mortality. RESULTS AND CONCLUSIONS: Univariate analysis indicated that there were significant differences between patients from the most deprived areas (Q5) compared with patients from the least deprived areas (Q1), these included admission volumes, time before presentation to hospital and proportion of non-elective cases. After risk-adjustments, percutaneous coronary intervention patients from Q5 compared with Q1 had significantly greater length of hospital stay and risk of in-hospital major acute cardiovascular events. After multivariate adjustment for baseline risk factors, patients from Q5 were associated with significantly worse five-year survival as compared with Q1 (hazard ratio (HR) 1.52, 95% confidence interval (CI): 1.36-1.71; p < 0.001). In conclusion, there is evidence to suggest that inequalities in cardiac revascularisation choices and outcomes in the UK may be associated with social deprivation.

Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis.

BACKGROUND: Acute coronary syndromes (ACSs) are life-threatening conditions associated with acute myocardial ischaemia. There are three main types of ACS: ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). One treatment for ACS is percutaneous coronary intervention (PCI) plus adjunctive treatment with antiplatelet drugs. Dual therapy antiplatelet treatment [aspirin plus either prasugrel (Efient(®), Daiichi Sankyo Company Ltd UK/Eli Lilly and Company Ltd), clopidogrel or ticagrelor (Brilique(®), AstraZeneca)] is standard in UK clinical practice. Prasugrel is the focus of this review. OBJECTIVES: The remit is to appraise the clinical effectiveness and cost-effectiveness of prasugrel within its licensed indication for the treatment of ACS with PCI and is a review of National Institute for Health and Care Excellence technology appraisal TA182. DATA SOURCES: Four electronic databases (MEDLINE, EMBASE, The Cochrane Library, PubMed) were searched from database inception to June 2013 for randomised controlled trials (RCTs) and to August 2013 for economic evaluations comparing prasugrel with clopidogrel or ticagrelor in ACS patients undergoing PCI. METHODS: Clinical outcomes included non-fatal and fatal cardiovascular (CV) events, adverse effects of treatment and health-related quality of life (HRQoL). Cost-effectiveness outcomes included incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. An independent economic model assessed four mutually exclusive subgroups: ACS patients treated with PCI for STEMI and with and without diabetes mellitus and ACS patients treated with PCI for UA or NSTEMI and with and without diabetes mellitus. RESULTS: No new RCTs were identified beyond that reported in TA182. TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38) compared prasugrel with clopidogrel in ACS patients scheduled for PCI. No relevant economic evaluations were identified. Our analyses focused on a key subgroup of patients: those aged < 75 years who weighed > 60 kg (no previous stroke or transient ischaemic attack). For the primary composite end point (death from CV causes, non-fatal myocardial infarction or non-fatal stroke) statistically significantly fewer events occurred in the prasugrel arm (8.3%) than in the clopidogrel arm (11%). No statistically significant difference in major bleeding events was noted. However, there was a significant difference in favour of clopidogrel when major and minor bleeding events were combined (3.0 vs. 3.9%). No conclusions could be drawn regarding HRQoL. The results of sensitivity analyses confirmed that it is likely that, for all four ACS subgroups, within 5-10 years prasugrel is a cost-effective treatment option compared with clopidogrel at a willingness-to-pay threshold of £20,000 to £30,000 per QALY gained. At the full 40-year time horizon, all estimates are < £10,000 per QALY gained. LIMITATIONS: Lack of data precluded a clinical comparison of prasugrel with ticagrelor; the comparative effectiveness of prasugrel compared with ticagrelor therefore remains unknown. The long-term modelling exercise is vulnerable to major assumptions about the continuation of early health outcome gains. CONCLUSION: A key strength of the review is that it demonstrates the cost-effectiveness of prasugrel compared with clopidogrel using the generic price of clopidogrel. Although the report demonstrates the cost-effectiveness of prasugrel compared with clopidogrel at a threshold of £20,000 to £30,000 per QALY gained, the long-term modelling is vulnerable to major assumptions regarding long-term gains. Lack of data precluded a clinical comparison of prasugrel with ticagrelor; the comparative effectiveness of prasugrel compared with ticagrelor therefore remains unknown. Well-audited data are needed from a long-term UK clinical registry on defined ACS patient groups treated with PCI who receive prasugrel, ticagrelor and clopidogrel. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005047. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A prospective, randomized, single-blind study evaluating the effectiveness, tolerability, and cost of colonoscopy bowel preparations.

Colorectal cancer, the third most common cancer in U.S. adults, can be detected early through colonoscopy. Thorough bowel preparation facilitates successful colonoscopy. Effectiveness, tolerability, and costs of 3 bowel preparations were compared in patients undergoing outpatient screening colonoscopy. In this prospective, randomized, single-blind study, comparing three preparation protocols, 209 of 276 consented subjects completed (Protocol [N = 67] = HalfLytely© 1 L × 2 doses and bisacodyl 5 mg delayed release tablets × 2 tablets; Protocol 2 [N = 74] = MiraLAX® 5 tablespoons × 2 doses and bisacodyl 5 mg tablets × 2 tablets; and Protocol 3 [N = 68] = MoviPrep 1 L × 2 doses). Patients completed symptom diaries and a gastroenterologist rated effectiveness. Most subjects were White females, aged 59 years (mean). Protocol 1 was the most effective regimen, but Protocol 2 was the most tolerable and cost-effective. While the three bowel protocol differences were not statistically significant for all outcomes measured, there were clinically meaningful differences. As Protocol 1 was most effective, HalfLytely© and bisacodyl is recommended for patients prior to colonoscopy. For patients who cannot tolerate HalfLytely© or MoviPrep, or with financial concerns, Protocol 2 (MiraLAX® & bisacodyl) is alternatively recommended.