The cost-effectiveness of an early interventional strategy in non-ST-elevation acute coronary syndrome based on the RITA 3 trial

The published version of the aritcle can be found at the link below.Background: Evidence suggests that an early interventional strategy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) can improve health outcomes but also increase costs when compared with a conservative strategy.Objective: The aim of this study was to assess the cost-effectiveness of an early interventional strategy in different risk groups from a UK health-service perspective.Design: Decision-analytic model based on randomised clinical trial data.Main outcome measures: Costs in UK Sterling at 2003/2004 prices and quality-adjusted life years (QALYs) combined into an incremental cost-effectiveness ratio.Methods: Data from the third Randomised Intervention Trial of unstable Angina (RITA 3) was employed to estimate rates of cardiovascular death and myocardial infarction, costs and health-related quality of life. Cost-effectiveness was estimated over patients' lifetimes within the decision-analytic model.Results: The mean incremental cost per QALY gained for an early interventional strategy was approximately £55000, £22000 and £12000 for patients at low, intermediate and high risk, respectively. The early interventional strategy is approximately 1%, 35% and 95% likely to be cost-effective for patients at low, intermediate and high risk, respectively, at a threshold of £20000 per QALY. The cost-effectiveness of early intervention in low-risk patients is sensitive to assumptions about the duration of the treatment effect.Conclusion: An early interventional strategy in patients presenting with NSTE-ACS is likely to be considered cost-effective for patients at high and intermediate risk, but this is less likely to be the case for patients at low risk

The New ‘Coimbra Method’: A Biologically Appropriate Method for Recording Specific Features of Fibrocartilaginous Entheseal Changes

A working group was established in 2009 during a workshop in Coimbra, Portugal to review the various methodologies used to record entheseal changes (EC), and develop a standardized system to facilitate comparisons across studies. This paper presents the first results of the “Coimbra method”; a new qualitative method for recording fibrocartilaginous entheses based on the types of changes observed. Materials and Methods: The new method divides the enthesis into a margin (only the area opposite the acute angle of fibre attachment) and surface (which also includes the remaining margin). Five features are recorded: bone formation, erosion, fine porosity, macroporosity, and cavitation. A total of 67 male skeletons from the identified SIMON collection, Geneva, Switzerland all of whom were manual workers and aged between 20 and 79 years, were used for this study. Six skeletons were used by the authors as exemplars to determine standard criteria for recording each change. Thirty male skeletons were selected to test intra- and inter-observer error of the new method. An additional 31 skeletons were used for a preliminary test of the relationship between EC and age, using exploratory statistics and ordinal regression. Results: Intra- and inter-observer error had a similar percentage agreement of around 70%. The exploratory statistics indicated a general trend for increased scores of each feature with age, but ordinal regression demonstrated that this was not statistically significant (p<0.05) for all features. Discussion: The recording method is repeatable for some entheses. The effect of the ageing process is dependent on enthesis and EC feature. Unlike most methods, the “Coimbra method” records EC features in detail; this has the advantage of allowing studies of the relationship between different EC and age, as well as sex and occupation. Further studies on larger identified skeletal collections are needed to test the effect of age, sex and occupation.

Enhancing outcomes of low-intensity parenting groups through sufficient exemplar training: a randomized control trial

Low-intensity parenting groups, such as the Triple P-Positive Parenting Program Discussion Groups, appear to be a cost-effective intervention for child conduct problems. Several studies evaluating a Triple P Discussion Group on disobedience found promising results for improving child and parent outcomes. However, a sufficient exemplar training approach that incorporates generalization promotion strategies may assist parents to more flexibly apply positive parenting principles to a broader range of child target behaviors and settings, leading to greater change. We compared the effects of sufficient exemplar training to an existing narrowly focused low-intensity intervention. Participants were 78 families with a 5–8 year-old child. Sufficient exemplar training resulted in more robust changes in child behavior and superior outcomes for mothers on measures of parenting behavior, parenting self-efficacy, mental health, and perceptions of partner support at post-intervention and 6-month follow-up. These results indicate that teaching sufficient exemplars may promote generalization leading to enhanced intervention outcomes

The Economics of Cruel and Unusual Punishment

Abstract It has sometimes been argued that one way to reduce the costs of law enforcement would be to reduce the probability of detection and conviction (hence saving those costs), while at the same time increasing the size of the punishment. Following this strategy would keep the expected costs (to a risk neutral criminal) of committing a crime constant and hence keep the deterrence level constant; it would have the benefit, though, of reducing costs to the rest of society. There are some well-known objections to such a policy. One such objection deals with marginal deterrence: A convicted murderer serving a life sentence with no chance of parole in a jurisdiction which bans capital punishment has nothing to lose from killing a prison guard-there is no marginal deterrence to the commission of a more serious crime or any additional crime for that matter. In fact, so long as there remains any upper limit to the amount of punishment that can be inflicted upon a convicted criminal, the only ways to create some type of marginal deterrence are to reduce the punishments for less serious crimes, which will either reduce the deterrence of those less serious crimes, or alternatively to require the use of more of society&apos;s scarce resources to increase the probabilities of apprehension and conviction. It is possible to reduce this marginal deterrence problem, however, by practicing cruel and unusual punishment on perpetrators of serious crimes, i.e. by raising the limits of allowable punishment. Anecdotal evidence suggests this practice is followed unofficially with child molesters and killers of prison guards and hence provides some additional deterrence against these crimes. Despite the theoretical validity of this argument, our society has chosen to impose a constitutional ban on cruel and unusual punishment. Furthermore, over time we seem to have lowered the threshold of what is considered cruel and unusual. Following Dr. Pangloss, the concluding section of the paper examines why rational maximizers would choose to give up this additional potential deterrence. The explanations depend upon an assumed positive income elasticity of demand for humanitarianism or for insurance against the costs of punishing the innocent. While there are some reasons to accept the humanitarianism argument, the insurance argument seems more persuasive

Crystal structures of K2[XSi5O12] (X = Fe2+, Co, Zn) and Rb2[XSi5O12] (X = Mn) leucites: comparison of monoclinic P21/c and Iad polymorph structures and inverse relationship between tetrahedral cation (T = Si and X)—O bond distances and intertetrahedral T—O—T angles

The leucite tectosilicate mineral analogues K X Si O (X = Fe , Co, Zn) and Rb X Si O (X = Mn) have been synthesized at elevated temperatures both dry at atmospheric pressure and at controlled water vapour pressure; for X = Co and Zn both dry and hydrothermally synthesized samples are available. Rietveld refinement of X-ray data for hydrothermal K X Si O (X = Fe , Co, Zn) samples shows that they crystallize in the monoclinic space group P2 /c and have tetrahedral cations (Si and X) ordered onto distinct framework sites [cf. hydrothermal K MgSi O ; Bell et al. (1994a), Acta Cryst. B50, 560-566]. Dry-synthesized K X Si O (X = Co, Zn) and Rb X Si O (X = Mn) samples crystallize in the cubic space group Ia{\overline 3}d and with Si and X cations disordered in the tetrahedral framework sites as typified by dry K MgSi O . Both structure types have tetrahedrally coordinated SiO and XO sharing corners to form a partially substituted silicate framework. Extraframework K and Rb cations occupy large channels in the framework. Structural data for the ordered samples show that mean tetrahedral Si-O and X-O bond lengths cover the ranges 1.60 Å (Si-O) to 2.24 Å (Fe -O) and show an inverse relationship with the intertetrahedral angles (T-O-T) which range from 144.7° (Si-O-Si) to 124.6° (Si-O-Fe ). For the compositions with both disordered and ordered tetrahedral cation structures (K MgSi O , K CoSi O , K ZnSi O , Rb MnSi O and Cs CuSi O leucites) the disordered polymorphs always have larger unit-cell volumes, larger intertetrahedral T-O-T angles and smaller mean T-O distances than their isochemical ordered polymorphs. The ordered samples clearly have more flexible frameworks than the disordered structures which allow the former to undergo a greater degree of tetrahedral collapse around the interframework cavity cations. Multivariant linear regression has been used to develop equations to predict intertetrahedral T-O-T angle variation depending on the independent variables Si-O and X-O bond lengths, cavity cation ideal radius, intratetrahedral (O-T-O) angle variance, and X cation electronegativity

Active cooling control of the CLEO detector using a hydrocarbon coolant farm

We describe a novel approach to particle-detector cooling in which a modular farm of active coolant-control platforms provides independent and regulated heat removal from four recently upgraded subsystems of the CLEO detector: the ring-imaging Cherenkov detector, the drift chamber, the silicon vertex detector, and the beryllium beam pipe. We report on several aspects of the system: the suitability of using the aliphatic-hydrocarbon solvent PF(TM)-200IG as a heat-transfer fluid, the sensor elements and the mechanical design of the farm platforms, a control system that is founded upon a commercial programmable logic controller employed in industrial process-control applications, and a diagnostic system based on virtual instrumentation. We summarize the system's performance and point out the potential application of the design to future high-energy physics apparatus.Comment: 21 pages, LaTeX, 5 PostScript figures; version accepted for publication in Nuclear Instruments and Methods in Physics Research

Screening of candidate substrates and coupling ions of transporters by thermostability shift assays

Substrates of most transport proteins have not been identified, limiting our understanding of their role in physiology and disease. Traditional identification methods use transport assays with radioactive compounds, but they are technically challenging and many compounds are unavailable in radioactive form or are prohibitively expensive, precluding large-scale trials. Here, we present a high-throughput screening method that can identify candidate substrates from libraries of unlabeled compounds. The assay is based on the principle that transport proteins recognize substrates through specific interactions, which lead to enhanced stabilization of the transporter population in thermostability shift assays. Representatives of three different transporter (super)families were tested, which differ in structure as well as transport and ion coupling mechanisms. In each case, the substrates were identified correctly from a large set of chemically related compounds, including stereo-isoforms. In some cases, stabilization by substrate binding was enhanced further by ions, providing testable hypotheses on energy coupling mechanisms

An outbreak of Salmonella Saintpaul in a Scottish childcare facility: the influence of parental under-reporting

Background: Salmonella outbreaks in childcare facilities are relatively rare, most often occurring secondary to contaminated food products or poor infection control practices. We report an outbreak of Salmonella Saintpaul at a pre-school facility in Ayrshire, Scotland with atypical clinical and epidemiological features. Methods: Following notification of the initial two cases, the multi-disciplinary Incident Management Team initiated enhanced active case finding and two environmental inspections of the site, including food preparation areas. Parent and staff interviews were conducted by the Public Health department covering attendance, symptomatology and risk factors for all probable and confirmed cases. Microbiological testing of stool samples and the facility water tank was conducted. Whole Genome Sequencing (WGS) was performed for positive stool samples at the national reference laboratory. Infection control measures were introduced iteratively due to the atypical progression of the outbreak. Results: There were 15 confirmed cases and 3 children admitted to hospital during the outbreak. However, 35.7% of cases reported extremely mild symptoms. The attack rate was 15.2%, and age of affected children ranged from 18 to 58 months (mean 35 months). All cases were the same Multilocus Sequence Type (MLST50). Epidemiological investigation strongly suggested person-to-person spread within the facility. Existing infection control practices were found to be of a high standard, but introduction of additional evidence-based control measures was inadequate in halting transmission. Facility staff reported concerns about lack of parental disclosure of gastrointestinal symptoms, particularly where these were mild, with 50.0% of cases having attended while symptomatic against public health advice. Voluntary two-week closure of the facility was implemented to halt transmission, following which there were no new cases. WGS results were unavailable until after the decision was taken to close the facility. Conclusions: This is the first reported instance of a Salmonella Saintpaul outbreak at a childcare facility, or where person-to-person transmission is indicated. Clinicians should consider the influence of parental under-reporting on gastrointestinal outbreaks in childcare settings, particularly where perceived severity is low and financial or social pressures to attend work may reduce compliance. WGS cannot yet replace conventional microbiological techniques during short, localised outbreaks due to delays receiving results

"When you haven't got much of a voice": An evaluation of the quality of Independent Mental Health Advocate (IMHA) Services in England

Advocacy serves to promote the voice of service users, represent their interests and enable participation in decision-making. Given the context of increasing numbers of people detained under the Mental Health Act and heightened awareness of the potential for neglect and abuse in human services, statutory advocacy is an important safeguard supporting human rights and democratising the social relationships of care. This article reports findings from a national review of Independent Mental Health Advocate (IMHA) provision in England. A qualitative study used a two-stage design to define quality and assess the experience and impact of IMHA provision in eight study sites. A sample of 289 participants – 75 focus group participants and 214 individuals interviewed – including 90 people eligible for IMHA services, as well as advocates, a range of hospital and community-based mental health professionals, and commissioners. The research team included people with experience of compulsion. Findings indicate that the experience of compulsion can be profoundly disempowering, confirming the need for IMHA. However, access was highly variable and more problematic for people with specific needs relating to ethnicity, age and disability. Uptake of IMHA services was influenced by available resources, attitude and understanding of mental health professionals, as well as the organisation of IMHA provision. Access could be improved through a system of opt-out as opposed to opt-in. Service user satisfaction was most frequently reported in terms of positive experiences of the process of advocacy rather than tangible impacts on care and treatment under the Mental Health Act. IMHA has the potential to significantly shift the dynamic so that service users have more of a voice in their care and treatment. However, a shift is needed from a narrow conception of statutory advocacy as safeguarding rights to one emphasising self-determination and participation in decisions about care and treatment

Intradialytic hypotension: Frequency, sources of variation and correlation with clinical outcome

Intradialytic hypotension ( IH ) is a frequent complication of hemodialysis ( HD ) and is associated with increased patient mortality and cardiovascular events. We studied IH to determine its variability, correlates, and clinical impact in 13 outpatient HD facilities. Blood pressure was captured by machine download. IH was defined as >30  mmHg decrease in systolic blood pressure to 20 HD treatments. We studied IH in 44,801 treatments ( T x) in 1137 patients. IH was frequent (17.2% of treatments) and highly variable by patient (0–100% T x) and dialysis facility (11.1–25.8% T x). 25.1% of patients had no IH (0% T x) and 16.2% had IH on >35% T x. Increased IH frequency was associated with age, female gender, diabetes, H ispanic origin, longer end stage renal disease vintage, higher body mass index, higher ultrafiltration volume, the second and third weekly T x, lower pre‐ HD systolic blood pressure, higher difference between prescribed and achieved post‐ HD weight, and higher dialysate temperature. Dialysis facility was an independent predictor of IH frequency. Patients with >35% IH treatments had poorer survival ( P  = 0.036), and more frequent and longer hospitalization ( P  = 0.04, P  = 0.002, respectively) than patients without IH . In conclusion, IH frequency was highly variable, associated with individual facilities, patient and treatment characteristics, and correlated with mortality and hospitalization. Identifying practice patterns associated with IH coupled with routine reporting of IH will facilitate medical management and may result in the prevention of IH , decreased mortality, and decreased hospitalization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106860/1/hdi12138.pd