Screening disability insurance applications

This paper investigates the effects of stricter screening of disability insurance applications. A large-scale experiment was setup where in two of the 26 Dutch regions case workers of the disability insurance administration were instructed to screen applications more stringently. The empirical results show that stricter screening reduces long-term sickness absenteeism and disability insurance applications. We find evidence for direct effects of stricter screening on work resumption during the period of sickness absence and for self-screening by potential disability insurance applicants. Stricter screening seems to improve targeting efficiency, without inducing negative spillover effects to the inflow into unemployment insurance. The costs of stricter screening are only a small fraction of the monetary benefits.Disability insurance; experiment; policy evaluation; sickness absenteeism; self-screening

Platelet-derived growth factor applications in periodontal and peri-implant bone regeneration

Introduction: Achieving successful tissue regeneration following traditional therapeutic protocols, combining bone grafts and barrier membranes, may be challenging in certain clinical scenarios. A deeper understanding of periodontal and peri-implant wound healing and recent advances in the field of tissue engineering have provided clinicians with novel means to obtain predictable clinical outcomes. The use of growth factors such as recombinant human platelet-derived growth factor-BB (rhPDGF) with biocompatible matrices to promote tissue regeneration represents a promising approach in the disciplines of periodontology and implantology. Areas covered: This review covers the basic principles of bone and periodontal regeneration, and provides an overview of the biology of PDGF and its potential to predictably and reproducibly promote bone regeneration in regular clinical practice. The results of preclinical and clinical human studies evaluating the effectiveness of growth-factor-enhanced matrices are analyzed and discussed. Expert opinion: Current available evidence supports the use of rhPDGF-enhanced matrices to promote periodontal and peri-implant bone regeneration

Minimal invasive horizontal ridge augmentation using subperiosteal tunneling technique

BACKGROUND: The goal of this study was to retrospectively evaluate the prognosis of minimal invasive horizontal ridge augmentation (MIHRA) technique using small incision and subperiosteal tunneling technique. METHODS: This study targeted 25 partially edentulous patients (10 males and 15 females, mean age 48.8 ± 19.7 years) who needed bone graft for installation of the implants due to alveolar bone deficiency. The patients took the radiographic exam, panoramic and periapical view at first visit, and had implant fixture installation surgery. All patients received immediate or delayed implant surgery with bone graft using U-shaped incision and tunneling technique. After an average of 2.8 months, the prosthesis was connected and functioned. The clinical prognosis was recorded by observation of the peri-implant tissue at every visit. A year after restoration, the crestal bone loss around the implant was measured by taking the follow-up radiographs. One patient took 3D-CT before bone graft, after bone graft, and 2 years after restoration to compare and analyze change of alveolar bone width. RESULTS: This study included 25 patients and 39 implants. Thirty eight implants (97.4 %) survived. As for postoperative complications, five patients showed minor infection symptoms, like swelling and tenderness after bone graft. The other one had buccal fenestration, and secondary bone graft was done by the same technique. No complications related with bone graft were found except in these patients. The mean crestal bone loss around the implants was 0.03 mm 1 year after restoration, and this was an adequate clinical prognosis. A patient took 3D-CT after bone graft, and the width of alveolar bone increased 4.32 mm added to 4.6 mm of former alveolar bone width. Two years after bone graft, the width of alveolar bone was 8.13 mm, and this suggested that the resorption rate of bone graft material was 18.29 % during 2 years. CONCLUSIONS: The bone graft material retained within a pouch formed using U-shaped incision and tunneling technique resulted with a few complications, and the prognosis of the implants placed above the alveolar bone was adequate

Predictors of mortality of patients with acute respiratory failure secondary to chronic obstructive pulmonary disease admitted to an intensive care unit: A one year study

BACKGROUND: Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) commonly require hospitalization and admission to intensive care unit (ICU). It is useful to identify patients at the time of admission who are likely to have poor outcome. This study was carried out to define the predictors of mortality in patients with acute exacerbation of COPD and to device a scoring system using the baseline physiological variables for prognosticating these patients. METHODS: Eighty-two patients with acute respiratory failure secondary to COPD admitted to medical ICU over a one-year period were included. Clinical and demographic profile at the time of admission to ICU including APACHE II score and Glasgow coma scale were recorded at the time of admission to ICU. In addition, acid base disorders, renal functions, liver functions and serum albumin, were recorded at the time of presentation. Primary outcome measure was hospital mortality. RESULTS: Invasive ventilation was required in 69 patients (84.1%). Fifty-two patients survived to hospital discharge (63.4%). APACHE II score at the time of admission to ICU {odds ratio (95 % CI): 1.32 (1.138–1.532); p < 0.001} and serum albumin (done within 24 hours of admission) {odds ratio (95 % CI): 0.114 (0.03-0.432); p = 0.001}. An equation, constructed using the adjusted odds ratio for the two parameters, had an area under the ROC curve of 91.3%. For the choice of cut-off, sensitivity, specificity, positive and negative predictive value for predicting outcome was 90%, 86.5%, 79.4% and 93.7%. CONCLUSION: APACHE II score at admission and SA levels with in 24 hrs after admission are independent predictors of mortality for patients with COPD admitted to ICU. The equation derived from these two parameters is useful for predicting outcome of these patients

Clinical presentation and predictors of outcome in patients with severe acute exacerbation of chronic obstructive pulmonary disease requiring admission to intensive care unit

BACKGROUND: Severe acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is a common reason for emergency room (ER) visit about which little has been documented from India. METHODS: Prospective study of the clinical presentation and predictors of outcome in 116 patients presenting with severe AE-COPD requiring admission to the medical intensive care unit between January 2000 and December 2004. RESULTS: Their mean age was 62.1 ± 9.8 years. There were 102 males. Mean duration of COPD was 7.2 ± 5.8 years. All males were smokers (22.3 ± 11.2 pack years); 35.2% smoked cigarettes and 64.8% smoked bidis. All women were exposed to domestic fuel. Associated co-morbid illnesses were present in 81 patients (69.8%); 53(45.7%) had one co-morbid illness and the remaining 28 (54.3%) had two or more co-morbid illnesses. Evidence of past pulmonary tuberculosis (PTB) was present in 28.4% patients; 5 patients who also had type II diabetes mellitus had active PTB. Arterial blood gas analysis revealed respiratory failure in 40 (33.8%) patients (type I 17.5% and type II 82.5%). Invasive mechanical ventilation was required in 18 patients. Sixteen (13.7%) patients died. Stepwise multivariate logistic regression analysis revealed need for invasive ventilation (OR 45.809, 95%CI 607.46 to 3.009;p < 0.001); presence of co-morbid illness (OR 0.126, 95%CI 0.428 to 0.037;p < 0.01) and hypercapnia (OR 0.114, 95%CI 1.324 to 0.010;p < 0.05) were predictors of death. CONCLUSION: Co-morbid conditions and metabolic abnormalities render the diagnosis of AE-COPD difficult and also contribute to mortality. High prevalence of past PTB and active PTB in patients with AE-COPD suggests an intriguing relationship between smoking, PTB and COPD which merits further study

SIGNATURE: A workbench for gene expression signature analysis

<p>Abstract</p> <p>Background</p> <p>The biological phenotype of a cell, such as a characteristic visual image or behavior, reflects activities derived from the expression of collections of genes. As such, an ability to measure the expression of these genes provides an opportunity to develop more precise and varied sets of phenotypes. However, to use this approach requires computational methods that are difficult to implement and apply, and thus there is a critical need for intelligent software tools that can reduce the technical burden of the analysis. Tools for gene expression analyses are unusually difficult to implement in a user-friendly way because their application requires a combination of biological data curation, statistical computational methods, and database expertise.</p> <p>Results</p> <p>We have developed SIGNATURE, a web-based resource that simplifies gene expression signature analysis by providing software, data, and protocols to perform the analysis successfully. This resource uses Bayesian methods for processing gene expression data coupled with a curated database of gene expression signatures, all carried out within a GenePattern web interface for easy use and access.</p> <p>Conclusions</p> <p>SIGNATURE is available for public use at <url>http://genepattern.genome.duke.edu/signature/</url>.</p

An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer

INTRODUCTION. Perhaps the major challenge in developing more effective therapeutic strategies for the treatment of breast cancer patients is confronting the heterogeneity of the disease, recognizing that breast cancer is not one disease but multiple disorders with distinct underlying mechanisms. Gene-expression profiling studies have been used to dissect this complexity, and our previous studies identified a series of intrinsic subtypes of breast cancer that define distinct populations of patients with respect to survival. Additional work has also used signatures of oncogenic pathway deregulation to dissect breast cancer heterogeneity as well as to suggest therapeutic opportunities linked to pathway activation. METHODS. We used genomic analyses to identify relations between breast cancer subtypes, pathway deregulation, and drug sensitivity. For these studies, we use three independent breast cancer gene-expression data sets to measure an individual tumor phenotype. Correlation between pathway status and subtype are examined and linked to predictions for response to conventional chemotherapies. RESULTS. We reveal patterns of pathway activation characteristic of each molecular breast cancer subtype, including within the more aggressive subtypes in which novel therapeutic opportunities are critically needed. Whereas some oncogenic pathways have high correlations to breast cancer subtype (RAS, CTNNB1, p53, HER1), others have high variability of activity within a specific subtype (MYC, E2F3, SRC), reflecting biology independent of common clinical factors. Additionally, we combined these analyses with predictions of sensitivity to commonly used cytotoxic chemotherapies to provide additional opportunities for therapeutics specific to the intrinsic subtype that might be better aligned with the characteristics of the individual patient. CONCLUSIONS. Genomic analyses can be used to dissect the heterogeneity of breast cancer. We use an integrated analysis of breast cancer that combines independent methods of genomic analyses to highlight the complexity of signaling pathways underlying different breast cancer phenotypes and to identify optimal therapeutic opportunities.V Foundation for Cancer Research (Partners in Excellence grant

The Genomic Analysis of Lactic Acidosis and Acidosis Response in Human Cancers

The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This “inhibition of glycolysis” phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes