Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy

OBJECTIVES: To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment. METHODS: Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/microl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements > or =10 0000 copies/ml (higher threshold) or > or =500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated. RESULTS: A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6-33.6%) for the higher and 12.6% (6.7-21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3-97.8%) and 97.3% (96.5-98.0%), for positive predictive value 9.5% (3.6-19.6%) and 19.0% (10.2-30.9%) and for negative predictive value 98.5% (97.9-99.0%) and 95.7% (94.7-96.6%). CONCLUSIONS: The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings.

Is a change in patient-reported dysphagia after induction chemotherapy in locally advanced esophageal cancer a predictive factor for pathological response to neoadjuvant chemoradiation?

GOALS OF WORK: In patients with locally advanced esophageal cancer, only those responding to the treatment ultimately benefit from preoperative chemoradiation. We investigated whether changes in subjective dysphagia or eating restrictions after two cycles of induction chemotherapy can predict histopathological tumor response observed after chemoradiation. In addition, we examined general long-term quality of life (QoL) and, in particular, eating restrictions after esophagectomy. MATERIALS AND METHODS: Patients with resectable, locally advanced squamous cell- or adenocarcinoma of the esophagus were treated with two cycles of chemotherapy followed by chemoradiation and surgery. They were asked to complete the EORTC oesophageal-specific QoL module (EORTC QLQ-OES24), and linear analogue self-assessment QoL indicators, before and during neoadjuvant therapy and quarterly until 1 year postoperatively. A median change of at least eight points was considered as clinically meaningful. MAIN RESULTS: Clinically meaningful improvements in the median scores for dysphagia and eating restrictions were found during induction chemotherapy. These improvements were not associated with a histopathological response observed after chemoradiation, but enhanced treatment compliance. Postoperatively, dysphagia scores remained low at 1 year, while eating restrictions persisted more frequently in patients with extended transthoracic resection compared to those with limited transhiatal resection. CONCLUSIONS: The improvement of dysphagia and eating restrictions after induction chemotherapy did not predict tumor response observed after chemoradiation. One year after esophagectomy, dysphagia was a minor problem, and global QoL was rather good. Eating restrictions persisted depending on the surgical technique used.

Admission blood glucose is an independent predictive factor for hospital mortality in polytraumatised patients

PURPOSE: The goal of this study was to analyse a possible association of admission blood glucose with hospital mortality of polytraumatised patients and to develop an outcome prediction model for this patient group. METHODS: The outcome of adult polytraumatised patients admitted to the University Hospital of Berne, Switzerland, between 2002 and 2004 with an ISS > or = 17, and more than one severely injured organ system was retrospectively analysed. RESULTS: The inclusion criteria were met by 555 patients, of which 108 (19.5%) died. Hyperglycaemia proved to be an independent predictor for hospital mortality (P < 0.0001), following multiple regression analysis. After inclusion of admission blood glucose, the calculated mortality prediction model performed better than currently described models (P < 0.0001, AUC 0.924). CONCLUSION: In this retrospective, single-centre study in polytraumatised patients, admission blood glucose proved to be an independent predictor of hospital mortality following regression analysis controlling for age, gender, injury severity and other laboratory parameters. A reliable admission blood glucose-based mortality prediction model for polytraumatised patients could be established. This observation may be helpful in improving the precision of future outcome prediction models for polytraumatised patients. These observations warrant further prospective evaluation.

Limited predictive value of FDG-PET for response assessment in the preoperative treatment of esophageal cancer: results of a prospective multi-center trial (SAKK 75/02)

BACKGROUND: Only responding patients benefit from preoperative therapy for locally advanced esophageal carcinoma. Early detection of non-responders may avoid futile treatment and delayed surgery. PATIENTS AND METHODS: In a multi-center phase ll trial, patients with resectable, locally advanced esophageal carcinoma were treated with 2 cycles of induction chemotherapy followed by chemoradiotherapy (CRT) and surgery. Positron emission tomography with 2[fluorine-18]fluoro-2-deoxy-d-glucose (FDG-PET) was performed at baseline and after induction chemotherapy. The metabolic response was correlated with tumor regression grade (TRG). A decrease in FDG tumor uptake of less than 40% was prospectively hypothesized as a predictor for histopathological non-response (TRG > 2) after CRT. RESULTS: 45 patients were included. The median decrease in FDG tumor uptake after chemotherapy correlated well with TRG after completion of CRT (p = 0.021). For an individual patient, less than 40% decrease in FDG tumor uptake after induction chemotherapy predicted histopathological non-response after completion of CRT, with a sensitivity of 68% and a specificity of 52% (positive predictive value 58%, negative predictive value 63%). CONCLUSIONS: Metabolic response correlated with histopathology after preoperative therapy. However, FDG-PET did not predict non-response after induction chemotherapy with sufficient clinical accuracy to justify withdrawal of subsequent CRT and selection of patients to proceed directly to surgery.

Quantifying the periodicty of Inter Movement Intervals of Leg Movements

ims: Periodic leg movements in sleep (PLMS) are a frequent finding in polysomnography. Most patients with restless legs syndrome (RLS) display PLMS. However, since PLMS are also often recorded in healthy elderly subjects, the clinical significance of PLMS is still discussed controversially. Leg movements are seen concurrently with arousals in obstructive sleep apnoea (OSA) may also appear periodically. Quantitative assessment of the periodicity of LM/PLM as measured by inter movement intervals (IMI) is difficult. This is mainly due to influencing factors like sleep architecture and sleep stage, medication, inter and intra patient variability, the arbitrary amplitude and sequence criteria which tend to broaden the IMI distributions or make them even multi-modal. Methods: Here a statistical method is presented that enables eliminating such effects from the raw data before analysing the statistics of IMI. Rather than studying the absolute size of IMI (measured in seconds) we focus on the shape of their distribution (suitably normalized IMI). To this end we employ methods developed in Random Matrix Theory (RMT). Patients: The periodicity of leg movements (LM) of four patient groups (10 to 15 each) showing LM without PLMS (group 1), OSA without PLMS (group 2), PLMS and OSA (group 3) as well as PLMS without OSA (group 4) are compared. Results: The IMI of patients without PLMS (groups 1 and 2) and with PLMS (groups 3 and 4) are statistically different. In patients without PLMS the distribution of normalized IMI resembles closely the one of random events. In contrary IMI of PLMS patients show features of periodic systems (e.g. a pendulum) when studied in normalized manner. Conclusions: For quantifying PLMS periodicity proper normalization of the IMI is crucial. Without this procedure important features are hidden when grouping LM/PLM over whole nights or across patients. The clinical significance of PLMS might be eluded when properly separating random LM from LM that show features of periodic systems.

An insulin infusion advisory system for type 1 diabetes patients based on non-linear model predictive control methods

In this paper, an Insulin Infusion Advisory System (IIAS) for Type 1 diabetes patients, which use insulin pumps for the Continuous Subcutaneous Insulin Infusion (CSII) is presented. The purpose of the system is to estimate the appropriate insulin infusion rates. The system is based on a Non-Linear Model Predictive Controller (NMPC) which uses a hybrid model. The model comprises a Compartmental Model (CM), which simulates the absorption of the glucose to the blood due to meal intakes, and a Neural Network (NN), which simulates the glucose-insulin kinetics. The NN is a Recurrent NN (RNN) trained with the Real Time Recurrent Learning (RTRL) algorithm. The output of the model consists of short term glucose predictions and provides input to the NMPC, in order for the latter to estimate the optimum insulin infusion rates. For the development and the evaluation of the IIAS, data generated from a Mathematical Model (MM) of a Type 1 diabetes patient have been used. The proposed control strategy is evaluated at multiple meal disturbances, various noise levels and additional time delays. The results indicate that the implemented IIAS is capable of handling multiple meals, which correspond to realistic meal profiles, large noise levels and time delays.

Predictive-DCT Coding for 3D Mesh Sequences Compression

This paper proposes a new compression algorithm for dynamic 3d meshes. In such a sequence of meshes, neighboring vertices have a strong tendency to behave similarly and the degree of dependencies between their locations in two successive frames is very large which can be efficiently exploited using a combination of Predictive and DCT coders (PDCT). Our strategy gathers mesh vertices of similar motions into clusters, establish a local coordinate frame (LCF) for each cluster and encodes frame by frame and each cluster separately. The vertices of each cluster have small variation over a time relative to the LCF. Therefore, the location of each new vertex is well predicted from its location in the previous frame relative to the LCF of its cluster. The difference between the original and the predicted local coordinates are then transformed into frequency domain using DCT. The resulting DCT coefficients are quantized and compressed with entropy coding. The original sequence of meshes can be reconstructed from only a few non-zero DCT coefficients without significant loss in visual quality. Experimental results show that our strategy outperforms or comes close to other coders.

The Costs and Predictive Factors of Bovine Respiratory Disease in Standardized Steer Tests

A retrospective study of 2,146 feedlot cattle in 17 feedlot tests from 1988 to 1997 was conducted to determine the impact of bovine respiratory disease (BRD) on veterinary treatment costs, average daily gain, carcass traits, mortality, and net profit. Morbidity caused by BRD was 20.6%. The average cost to treat each case of BRD was $12.39. Mortality rate of calves diagnosed and treated for BRD was 5.9% vs. .35% for those not diagnosed with BRD. Average daily gain differed between treated and non-treated steers during the first 28 days on feed but did not differ from 28 days to harvest. Net profit was $57.48 lower for treated steers. Eighty-two percent of this difference was due to a combination of mortality and treatment costs. Eighteen percent of the net profit difference was due to improved performance and carcass value of the non-treated steers. Data from 496 steers and heifers in nine feedlot tests were used to determine the effects of age, weaning, and use of modified live virus or killed vaccines prior to the test to predict BRD. Younger calves, non-weaned calves, and calves vaccinated with killed vaccines prior to the test had higher BRD morbidity than those that were older, weaned, or vaccinated with modified live virus vaccines, respectively. Treatment regimes that precluded relapse resulting in re-treatment prevented reduced performance and loss of carcass value. Using modified live virus vaccines and weaning calves 30 days prior to shipment reduced the incidence of BRD.

Mid-term results in relation to age and analysis of predictive factors after fixation of acetabular fractures using the modified Stoppa approach.

INTRODUCTION Data concerning outcome after management of acetabular fractures by anterior approaches with focus on age and fractures associated with roof impaction, central dislocation and/or quadrilateral plate displacement are rare. METHODS Between October 2005 and April 2009 a series of 59 patients (mean age 57 years, range 13-91) with fractures involving the anterior column was treated using the modified Stoppa approach alone or for reduction of displaced iliac wing or low anterior column fractures in combination with the 1st window of the ilioinguinal approach or the modified Smith-Petersen approach, respectively. Surgical data, accuracy of reduction, clinical and radiographic outcome at mid-term and the need for endoprosthetic replacement in the postoperative course (defined as failure) were assessed; uni- and multivariate regression analysis were performed to identify independent predictive factors (e.g. age, nonanatomical reduction, acetabular roof impaction, central dislocation, quadrilateral plate displacement) for a failure. Outcome was assessed for all patients in general and in accordance to age in particular; patients were subdivided into two groups according to their age (group "<60yrs", group "≥60yrs"). RESULTS Forty-three of 59 patients (mean age 54yrs, 13-89) were available for evaluation. Of these, anatomic reduction was achieved in 72% of cases. Nonanatomical reduction was identified as being the only multivariate predictor for subsequent total hip replacement (Adjusted Hazard Ratio 23.5; p<0.01). A statistically significant higher rate of nonanatomical reduction was observed in the presence of acetabular roof impaction (p=0.01). In 16% of all patients, total hip replacement was performed and in 69% of patients with preserved hips the clinical results were excellent or good at a mean follow up of 35±10 months (range: 24-55). No statistical significant differences were observed between both groups. CONCLUSION Nonanatomical reconstruction of the articular surfaces is at risk for failure of joint-preserving management of acetabular fractures through an isolated or combined modified Stoppa approach resulting in total joint replacement at mid-term. In the elderly, joint-preserving surgery is worth considering as promising clinical and radiographic results might be obtained at mid-term.