Economic burden of illness of acute coronary syndromes: medical and productivity costs

<p>Abstract</p> <p>Background</p> <p>The significant economic burden associated with acute coronary syndromes (ACS) provides a need to evaluate both medical costs and productivity costs, according to evolving guideline-driven ACS treatment strategies, medical management (MM), percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG).</p> <p>Methods</p> <p>Commercially insured individuals, aged 18-64, with an emergency room (ER) visit or hospitalization accompanied by an ACS diagnosis (index event) were identified from a large claims database between 01/2004 and 12/2005 with a 1-year follow-up period. Patients who had an ACS diagnosis in the 12 months prior to their index event were excluded. Patients were divided into 3 groups according to treatment strategies during the index event: MM, PCI, or CABG. A subset of patients was identified for the productivity cost analysis exploring short-term disability and absenteeism costs. Multivariate generalized linear models were performed to examine the ACS costs by 3 different treatment strategies.</p> <p>Results</p> <p>A total of 10,487 patients were identified for the medical cost analysis. The total 1-year medical costs (index event costs plus the 1-year follow-up costs) were lowest for MM patients ($34,087), followed by PCI patients ($52,673) and CABG patients ($86,914). Of the 3,080 patients in the productivity costs analysis, 2,454 patients were identified in the short-term disability cohort and 626 patients were identified in the absenteeism cohort. Both the estimated mean total 1-year short-term disability and absenteeism costs were highest for CABG patients ($17,335, $14,960, respectively) compared to MM patients ($6,048, $9,826, respectively) and PCI patients ($9,221, $9,460, respectively).</p> <p>Conclusions</p> <p>Both total 1-year medical costs and 1-year productivity costs are substantial for working-aged individuals with ACS. These costs differ according to the type of treatment strategy, with CABG having higher costs compared to either PCI or MM.</p

Accuracy and quality assessment of 454 GS-FLX Titanium pyrosequencing

<p>Abstract</p> <p>Background</p> <p>The rapid evolution of 454 GS-FLX sequencing technology has not been accompanied by a reassessment of the quality and accuracy of the sequences obtained. Current strategies for decision-making and error-correction are based on an initial analysis by Huse <it>et al. </it>in 2007, for the older GS20 system based on experimental sequences. We analyze here the quality of 454 sequencing data and identify factors playing a role in sequencing error, through the use of an extensive dataset for Roche control DNA fragments.</p> <p>Results</p> <p>We obtained a mean error rate for 454 sequences of 1.07%. More importantly, the error rate is not randomly distributed; it occasionally rose to more than 50% in certain positions, and its distribution was linked to several experimental variables. The main factors related to error are the presence of homopolymers, position in the sequence, size of the sequence and spatial localization in PT plates for insertion and deletion errors. These factors can be described by considering seven variables. No single variable can account for the error rate distribution, but most of the variation is explained by the combination of all seven variables.</p> <p>Conclusions</p> <p>The pattern identified here calls for the use of internal controls and error-correcting base callers, to correct for errors, when available (e.g. when sequencing amplicons). For shotgun libraries, the use of both sequencing primers and deep coverage, combined with the use of random sequencing primer sites should partly compensate for even high error rates, although it may prove more difficult than previous thought to distinguish between low-frequency alleles and errors.</p

Bayesian Markov Random Field Analysis for Protein Function Prediction Based on Network Data

Inference of protein functions is one of the most important aims of modern biology. To fully exploit the large volumes of genomic data typically produced in modern-day genomic experiments, automated computational methods for protein function prediction are urgently needed. Established methods use sequence or structure similarity to infer functions but those types of data do not suffice to determine the biological context in which proteins act. Current high-throughput biological experiments produce large amounts of data on the interactions between proteins. Such data can be used to infer interaction networks and to predict the biological process that the protein is involved in. Here, we develop a probabilistic approach for protein function prediction using network data, such as protein-protein interaction measurements. We take a Bayesian approach to an existing Markov Random Field method by performing simultaneous estimation of the model parameters and prediction of protein functions. We use an adaptive Markov Chain Monte Carlo algorithm that leads to more accurate parameter estimates and consequently to improved prediction performance compared to the standard Markov Random Fields method. We tested our method using a high quality S.cereviciae validation network with 1622 proteins against 90 Gene Ontology terms of different levels of abstraction. Compared to three other protein function prediction methods, our approach shows very good prediction performance. Our method can be directly applied to protein-protein interaction or coexpression networks, but also can be extended to use multiple data sources. We apply our method to physical protein interaction data from S. cerevisiae and provide novel predictions, using 340 Gene Ontology terms, for 1170 unannotated proteins and we evaluate the predictions using the available literature

Mutual Mate Choice: When it Pays Both Sexes to Avoid Inbreeding

Theoretical models of sexual selection predict that both males and females of many species should benefit by selecting their mating partners. However, empirical evidence testing and validating this prediction is scarce. In particular, whereas inbreeding avoidance is expected to induce sexual conflicts, in some cases both partners could benefit by acting in concert and exerting mutual mate choice for non-assortative pairings. We tested this prediction with the gregarious cockroach Blattella germanica (L.). We demonstrated that males and females base their mate choice on different criteria and that choice occurs at different steps during the mating sequence. Males assess their relatedness to females through antennal contacts before deciding to court preferentially non-siblings. Conversely, females biased their choice towards the most vigorously courting males that happened to be non-siblings. This study is the first to demonstrate mutual mate choice leading to close inbreeding avoidance. The fact that outbred pairs were more fertile than inbred pairs strongly supports the adaptive value of this mating system, which includes no “best phenotype” as the quality of two mating partners is primarily linked to their relatedness. We discuss the implications of our results in the light of inbreeding conflict models

The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC) trial in elderly hypertensives with early cognitive impairment: Role of the renin angiotensin system inhibition

<p>Abstract</p> <p>Background</p> <p>Prior evidence suggests that the renin angiotensin system and antihypertensives that inhibit this system play a role in cognitive, central vascular, and endothelial function. Our objective is to conduct a double-blind randomized controlled clinical trial, the antihypertensives and vascular, endothelial, and cognitive function (AVEC), to compare 1 year treatment of 3 antihypertensives (lisinopril, candesartan, or hydrochlorothiazide) in their effect on memory and executive function, cerebral blood flow, and central endothelial function of seniors with hypertension and early objective evidence of executive or memory impairments.</p> <p>Methods/Design</p> <p>The overall experimental design of the AVEC trial is a 3-arm double blind randomized controlled clinical trial. A total of 100 community eligible individuals (60 years or older) with hypertension and early cognitive impairment are being recruited from the greater Boston area and randomized to lisinopril, candesartan, or hydrochlorothiazide ("active control") for 12 months. The goal of the intervention is to achieve blood pressure control defined as SBP < 140 mm Hg and DBP < 90 mm Hg. Additional antihypertensives are added to achieve this goal if needed. Eligible participants are those with hypertension, defined as a blood pressure 140/90 mm Hg or greater, early cognitive impairment without dementia defined (10 or less out of 15 on the executive clock draw test or 1 standard deviation below the mean on the immediate memory subtest of the repeatable battery for the assessment of neuropsychological status and Mini-Mental-Status-exam >20 and without clinical diagnosis of dementia or Alzheimer's disease). Individuals who are currently receiving antihypertensives are eligible to participate if the participants and the primary care providers are willing to taper their antihypertensives. Participants undergo cognitive assessment, measurements of cerebral blood flow using Transcranial Doppler, and central endothelial function by measuring changes in cerebral blood flow in response to changes in end tidal carbon dioxide at baseline (off antihypertensives), 6, and 12 months. Our outcomes are change in cognitive function score (executive and memory), cerebral blood flow, and carbon dioxide cerebral vasoreactivity.</p> <p>Discussion</p> <p>The AVEC trial is the first study to explore impact of antihypertensives in those who are showing early evidence of cognitive difficulties that did not reach the threshold of dementia. Success of this trial will offer new therapeutic application of antihypertensives that inhibit the renin angiotensin system and new insights in the role of this system in aging.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov NCT00605072</p

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

A comparison of methods for temporal analysis of aoristic crime

Objectives: To test the accuracy of various methods previously proposed (and one new method) to estimate offence times where the actual time of the event is not known. Methods: For 303 thefts of pedal cycles from railway stations, the actual offence time was determined from closed-circuit television and the resulting temporal distribution compared against commonly-used estimated distributions using circular statistics and analysis of residuals. Results: Aoristic analysis and allocation of a random time to each offence allow accurate estimation of peak offence times. Commonly-used deterministic methods were found to be inaccurate and to produce misleading results. Conclusions: It is important that analysts use the most accurate methods for temporal distribution approximation to ensure any resource decisions made on the basis of peak times are reliable