62 research outputs found

    Cost-effectiveness of In-home Automated External Defibrillators for Individuals at Increased Risk of Sudden Cardiac Death

    Full text link
    In-home automated external defibrillators (AEDs) are increasingly recommended as a means for improving survival of cardiac arrests that occur at home. The current study was conducted to explore the relationship between individuals' risk of cardiac arrest and cost-effectiveness of in-home AED deployment. Design : Markov decision model employing a societal perspective. Patients : Four hypothetical cohorts of American adults 60 years of age at progressively greater risk for sudden cardiac death (SCD): 1) all adults (annual probability of SCD 0.4%); 2) adults with multiple SCD risk factors (probability 2%); 3) adults with previous myocardial infarction (probability 4%); and 4) adults with ischemic cardiomyopathy unable to receive an implantable defibrillator (probability 6%). Intervention : Strategy 1: individuals suffering an in-home cardiac arrest were treated with emergency medical services equipped with AEDs (EMS-D). Strategy 2: individuals suffering an in-home cardiac arrest received initial treatment with an in-home AED, followed by EMS. Results : Assuming cardiac arrest survival rates of 15% with EMS-D and 30% with AEDs, the cost per quality-adjusted life-year gained (QALY) of providing in-home AEDs to all adults 60 years of age is 216,000.CostsofprovidinginhomeAEDstoadultswithmultipleriskfactors(2216,000. Costs of providing in-home AEDs to adults with multiple risk factors (2% probability of SCD), previous myocardial infarction (4% probability), and ischemic cardiomyopathy (6% probability) are 132,000, 104,000,and104,000, and 88,000, respectively. Conclusions : The cost-effectiveness of in-home AEDs is intimately linked to individuals' risk of SCD. However, providing in-home AEDs to all adults over age 60 appears relatively expensive.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72168/1/j.1525-1497.2005.40247.x.pd

    The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

    Get PDF
    Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions

    Science-Driven Optimization of the LSST Observing Strategy

    Get PDF
    The Large Synoptic Survey Telescope is designed to provide an unprecedented optical imaging dataset that will support investigations of our Solar System, Galaxy and Universe, across half the sky and over ten years of repeated observation. However, exactly how the LSST observations will be taken (the observing strategy or "cadence") is not yet finalized. In this dynamically-evolving community white paper, we explore how the detailed performance of the anticipated science investigations is expected to depend on small changes to the LSST observing strategy. Using realistic simulations of the LSST schedule and observation properties, we design and compute diagnostic metrics and Figures of Merit that provide quantitative evaluations of different observing strategies, analyzing their impact on a wide range of proposed science projects. This is work in progress: we are using this white paper to communicate to each other the relative merits of the observing strategy choices that could be made, in an effort to maximize the scientific value of the survey. The investigation of some science cases leads to suggestions for new strategies that could be simulated and potentially adopted. Notably, we find motivation for exploring departures from a spatially uniform annual tiling of the sky: focusing instead on different parts of the survey area in different years in a "rolling cadence" is likely to have significant benefits for a number of time domain and moving object astronomy projects. The communal assembly of a suite of quantified and homogeneously coded metrics is the vital first step towards an automated, systematic, science-based assessment of any given cadence simulation, that will enable the scheduling of the LSST to be as well-informed as possible

    Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems

    Get PDF
    Rodent models of focal cerebral ischemia are essential tools in experimental stroke research. They have added tremendously to our understanding of injury mechanisms in stroke and have helped to identify potential therapeutic targets. A plethora of substances, however, in particular an overwhelming number of putative neuroprotective agents, have been shown to be effective in preclinical stroke research, but have failed in clinical trials. A lot of factors may have contributed to this failure of translation from bench to bedside. Often, deficits in the quality of experimental stroke research seem to be involved. In this article, we review the commonest rodent models of focal cerebral ischemia - middle cerebral artery occlusion, photothrombosis, and embolic stroke models - with their respective advantages and problems, and we address the issue of quality in preclinical stroke modeling as well as potential reasons for translational failure

    A 'snip' in time: what is the best age to circumcise?

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves.</p> <p>Discussion</p> <p>We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used.</p> <p>Summary</p> <p>Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.</p

    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

    Get PDF
    Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
    corecore