A note on Youden's J and its cost ratio

<p>Abstract</p> <p>Background</p> <p>The Youden index, the sum of sensitivity and specificity minus one, is an index used for setting optimal thresholds on medical tests.</p> <p>Discussion</p> <p>When using this index, one implicitly uses decision theory with a ratio of misclassification costs which is equal to one minus the prevalence proportion of the disease. It is doubtful whether this cost ratio truly represents the decision maker's preferences. Moreover, in populations with a different prevalence, a selected threshold is optimal with reference to a different cost ratio.</p> <p>Summary</p> <p>The Youden index is not a truly optimal decision rule for setting thresholds because its cost ratio varies with prevalence. Researchers should look into their cost ratio and employ it in a decision theoretic framework to obtain genuinely optimal thresholds.</p

The effects of knee joint angle on neuromuscular activity during electrostimulation in healthy older adults

Introduction Electrostimulation devices stimulate the common peroneal nerve, producing a calf muscle-pump action to promote venous circulation. Whether knee joint angle influences calf neuromuscular activity remains unclear. Our aim was to determine the effects of knee joint angle on lower limb neuromuscular activity during electrostimulation. Methods Fifteen healthy, older adults underwent 60 min of electrostimulation, with the knee joint at three different angles (0°, 45° or 90° flexion; random order; 20 min each). Outcome variables included electromyography of the peroneus longus, tibialis anterior and gastrocnemius medialis and lateralis and discomfort. Results Knee angle did not influence tibialis anterior and peroneus longus neuromuscular activity during electrostimulation. Neuromuscular activity was greater in the gastrocnemius medialis (p = 0.002) and lateralis (p = 0.002) at 90°, than 0° knee angle. Electrostimulation intensity was positively related to neuromuscular activity for each muscle, with a knee angle effect for the gastrocnemius medialis (p = 0.05). Conclusion Results suggest that during electrostimulation, knee joint angle influenced gastrocnemii neuromuscular activity; increased gastrocnemius medialis activity across all intensities (at 90°), when compared to 0° and 45° flexion; and did not influence peroneus longus and tibialis anterior activity. Greater electrostimulation-evoked gastrocnemii activity has implications for producing a more forceful calf muscle-pump action, potentially further improving venous flow

Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates

Symptomatic oesophageal cancer is usually advanced and the prognosis poor. Lethality of symptomatic oesophageal cancer has motivated screening for these diseases earlier in their evolution, but reliable methods for early diagnosis remain elusive. We have demonstrated that dysregulated expression of minichromosome maintenance (MCM) proteins 2–7 is characteristic of early epithelial carcinogenesis, and that these key DNA replication initiation factors can be used as diagnostic markers for cervical and genito-urinary tract cancer. In this study, we investigated whether minichromosome maintenance protein 5 (Mcm5) can be used to detect oesophageal cancer cells in gastric aspirates. Two monoclonal antibodies raised against His-tagged human Mcm5 were used in a time-resolved immunofluorometric assay to measure Mcm5 levels in cells isolated from gastric aspirates of 40 patients undergoing gastroscopy for suspected or known oesophageal carcinoma or symptoms of dyspepsia. The test discriminated with high specificity and sensitivity between patients with and without oesophageal cancer (85% sensitivity (95% confidence interval (CI)=62–97%), 85% specificity (CI=66–96%)), as demonstrated by the large area under the receiver operating characteristics curve (0.93 (95% CI=0.85–0.99)). Elevated levels of Mcm5 in gastric aspirates are highly predictive of oesophageal cancer. This simple test for oesophageal cancer is readily automated with potential applications in primary diagnosis, surveillance and screening

The way that you do it? An elaborate test of procedural invariance of TTO, using a choice-based design

The time tradeoff (TTO) method is often used to derive Quality-Adjusted Life Year health state valuations. An important problem with this method is that results have been found to be responsive to the procedure used to elicit preferences. In particular, fixing the duration in the health state to be valued and inferring the duration in full health that renders an individual indifferent, causes valuations to be higher than when the duration in full health is fixed and the duration in the health state to be valued is elicited. This paper presents a new test of procedural invariance for a broad range of time horizons, while using a choice-based design and adjusting for discounting. As one of the known problems with the conventional procedure is the violation of constant proportional tradeoffs (CPTO), we also investigate CPTO for the alternative TTO procedure. Our findings concerning procedural invariance are rather supportive for the TTO procedure. We find no violations of procedural invariance except for the shortest gauge duration. The results for CPTO are more troublesome: TTO scores depend on gauge duration, reinforcing the evidence reported when using the conventional procedure

The use of a Psoroptes ovis serodiagnostic test for the analysis of a natural outbreak of sheep scab

<p>Abstract</p> <p>Background</p> <p>Sheep scab is a highly contagious disease of sheep caused by the ectoparasitic mite <it>Psoroptes ovis</it>. The disease is endemic in the UK and has significant economic impact through its effects on performance and welfare. Diagnosis of sheep scab is achieved through observation of clinical signs e.g. itching, pruritis and wool loss and ultimately through the detection of mites in skin scrapings. Early stages of infestation are often difficult to diagnose and sub-clinical animals can be a major factor in disease spread. The development of a diagnostic assay would enable farmers and veterinarians to detect disease at an early stage, reducing the risk of developing clinical disease and limiting spread.</p> <p>Methods</p> <p>Serum samples were obtained from an outbreak of sheep scab within an experimental flock (n = 480 (3 samples each from 160 sheep)) allowing the assessment, by ELISA of sheep scab specific antibody prior to infestation, mid-outbreak (combined with clinical assessment) and post-treatment.</p> <p>Results</p> <p>Analysis of pre-infestation samples demonstrated low levels of potential false positives (3.8%). Of the 27 animals with clinical or behavioural signs of disease 25 tested positive at the mid-outbreak sampling period, however, the remaining 2 sheep tested positive at the subsequent sampling period. Clinical assessment revealed the absence of clinical or behavioural signs of disease in 132 sheep, whilst analysis of mid-outbreak samples showed that 105 of these clinically negative animals were serologically positive, representing potential sub-clinical infestations.</p> <p>Conclusions</p> <p>This study demonstrates that this ELISA test can effectively diagnose sheep scab in a natural outbreak of disease, and more importantly, highlights its ability to detect sub-clinically infested animals. This ELISA, employing a single recombinant antigen, represents a major step forward in the diagnosis of sheep scab and may prove to be critical in any future control program.</p

A Comprehensive and Universal Method for Assessing the Performance of Differential Gene Expression Analyses

The number of methods for pre-processing and analysis of gene expression data continues to increase, often making it difficult to select the most appropriate approach. We present a simple procedure for comparative estimation of a variety of methods for microarray data pre-processing and analysis. Our approach is based on the use of real microarray data in which controlled fold changes are introduced into 20% of the data to provide a metric for comparison with the unmodified data. The data modifications can be easily applied to raw data measured with any technological platform and retains all the complex structures and statistical characteristics of the real-world data. The power of the method is illustrated by its application to the quantitative comparison of different methods of normalization and analysis of microarray data. Our results demonstrate that the method of controlled modifications of real experimental data provides a simple tool for assessing the performance of data preprocessing and analysis methods

Use of 16S ribosomal RNA gene analyses to characterize the bacterial signature associated with poor oral health in West Virginia

<p>Abstract</p> <p>Background</p> <p>West Virginia has the worst oral health in the United States, but the reasons for this are unclear. This pilot study explored the etiology of this disparity using culture-independent analyses to identify bacterial species associated with oral disease.</p> <p>Methods</p> <p>Bacteria in subgingival plaque samples from twelve participants in two independent West Virginia dental-related studies were characterized using 16S rRNA gene sequencing and Human Oral Microbe Identification Microarray (HOMIM) analysis. Unifrac analysis was used to characterize phylogenetic differences between bacterial communities obtained from plaque of participants with low or high oral disease, which was further evaluated using clustering and Principal Coordinate Analysis.</p> <p>Results</p> <p>Statistically different bacterial signatures (<it>P </it>< 0.001) were identified in subgingival plaque of individuals with low or high oral disease in West Virginia based on 16S rRNA gene sequencing. Low disease contained a high frequency of <it>Veillonella </it>and <it>Streptococcus</it>, with a moderate number of <it>Capnocytophaga</it>. High disease exhibited substantially increased bacterial diversity and included a large proportion of Clostridiales cluster bacteria (<it>Selenomonas</it>, <it>Eubacterium, Dialister</it>). Phylogenetic trees constructed using 16S rRNA gene sequencing revealed that Clostridiales were repeated colonizers in plaque associated with high oral disease, providing evidence that the oral environment is somehow influencing the bacterial signature linked to disease.</p> <p>Conclusions</p> <p>Culture-independent analyses identified an atypical bacterial signature associated with high oral disease in West Virginians and provided evidence that the oral environment influenced this signature. Both findings provide insight into the etiology of the oral disparity in West Virginia.</p

An open cohort study of bone metastasis incidence following surgery in breast cancer patients

Background: To help design clinical trials of adjuvant bisphosphonate therapy for breast cancer, the temporal incidence of bone metastasis was investigated in a cohort of patients. We have tried to draw the criteria to use adjuvant bisphosphonate.Methods: Consecutive breast cancer patients undergoing surgery between 1988 and 1998 (5459 patients) were followed up regarding bone metastasis until December 2006. Patients characteristics at the time of surgery were analyzed by Cox method, with bone metastasis as events. Patient groups were assigned according to Cox analysis, and were judged either to require the adjuvant bisphosphonate or not, using the tentative criteria: high risk (>3% person-year), medium risk (1-3%), and low risk (3% per person-year, patients with stage I <1% per person-year, andthose with stages II were between 1 and 3%. Further analysis with histology in stage II patients showed that stage IIB with high risk histology also had a high incidence (3% person year), whereas stage IIA with medium risk histology were <1%.Conclusions: Bone metastasis incidence remained constant for many years. Using pN, T, and histopathology, patients could be classified into high, medium, and low risk groups

Lung tumour markers in oncology practice: a study of TPA and CA125

Several substances mark the course of lung cancer and may reliably help the clinician in decision-making. This is the first clinical study specifically designed to compare tissue polypeptide antigen and CA 125 tumour associated antigen. Three hundred and eighty-four new lung cancer patients (309 males) were studied at their first clinical presentation and then strictly followed-up. Anthropometric, clinical and laboratory data – including tissue polypeptide antigen and CA 125 tumour associated antigen serum levels – were prospectively recorded. A total of 1000 tissue polypeptide antigen and CA 125 tumour associated antigen serum assays (384 pre-treatment and 616 posttreatment assays) were performed. Both tissue polypeptide antigen and CA 125 tumour associated antigen correlated significantly with the T, N and M stage descriptors at diagnosis (Rho: 0.200, 0.203, 0.263 and 0.181, 0.240, 0.276, respectively), and then with the objective response to treatment (Rho: 0.388 and 0.207, respectively). A pleural neoplastic involvement was mainly associated to an increase of CA 125 tumour associated antigen (Rho: 0.397). Both tissue polypeptide antigen and CA 125 tumour associated antigen were strongly predictive of the patients' outcome, as assessed by the univariate analysis of survival (log-rank test: 37.24 and 29.01) and several Cox' proportional hazards regression models. The two marker tests are similarly helpful and appear complementary, given the low inter-marker correlation and their independent prognostic capability

Time esophageal pH < 4 overestimates the prevalence of pathologic esophageal reflux in subjects with gastroesophageal reflux disease treated with proton pump inhibitors

<p>Abstract</p> <p>Background</p> <p>A Stanford University study reported that in asymptomatic GERD patients who were being treated with a proton pump inhibitor (PPI), 50% had pathologic esophageal acid exposure.</p> <p>Aim</p> <p>We considered the possibility that the high prevalence of pathologic esophageal reflux might simply have resulted from calculating acidity as time pH < 4.</p> <p>Methods</p> <p>We calculated integrated acidity and time pH < 4 from the 49 recordings of 24-hour gastric and esophageal pH from the Stanford study as well as from another study of 57 GERD subjects, 26 of whom were treated for 8 days with 20 mg omeprazole or 20 mg rabeprazole in a 2-way crossover fashion.</p> <p>Results</p> <p>The prevalence of pathologic 24-hour esophageal reflux in both studies was significantly higher when measured as time pH < 4 than when measured as integrated acidity. This difference was entirely attributable to a difference between the two measures during the nocturnal period. Nocturnal gastric acid breakthrough was not a useful predictor of pathologic nocturnal esophageal reflux.</p> <p>Conclusion</p> <p>In GERD subjects treated with a PPI, measuring time esophageal pH < 4 will significantly overestimate the prevalence of pathologic esophageal acid exposure over 24 hours and during the nocturnal period.</p