Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis is a rare, chronic cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, may have benefit as a treatment for primary biliary cholangitis is unknown. METHODS: In this multinational, phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients with primary biliary cholangitis who had had an inadequate response to or unacceptable side effects with ursodeoxycholic acid to receive once-daily elafibranor, at a dose of 80 mg, or placebo. The primary end point was a biochemical response (defined as an alkaline phosphatase level of <1.67 times the upper limit of the normal range, with a reduction of ≥15% from baseline, and normal total bilirubin levels) at week 52. Key secondary end points were normalization of the alkaline phosphatase level at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24, as measured on the Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]). RESULTS: A total of 161 patients underwent randomization. A biochemical response (the primary end point) was observed in 51% of the patients (55 of 108) who received elafibranor and in 4% (2 of 53) who received placebo, for a difference of 47 percentage points (95% confidence interval [CI], 32 to 57; P<0.001). The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group at week 52 (difference, 15 percentage points; 95% CI, 6 to 23; P = 0.002). Among patients who had moderate-to-severe pruritus (44 patients in the elafibranor group and 22 in the placebo group), the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (-1.93 vs. -1.15; difference, -0.78; 95% CI, -1.99 to 0.42; P = 0.20). Adverse events that occurred more frequently with elafibranor than with placebo included abdominal pain, diarrhea, nausea, and vomiting. CONCLUSIONS: Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo. (Funded by GENFIT and Ipsen; ELATIVE ClinicalTrials.gov number, NCT04526665.).

RETROSPECTIVE STUDY OF GLYCEMIC CONTROL FOLLOWING TRANSITION FROM THE INTENSIVE CARE UNIT IN A NATIONAL SAMPLE OF U.S. HOSPITALS.

OBJECTIVE: Retrospective study to evaluate glycemic control outcomes after transition from the intensive care unit (ICU) to a non-ICU area in a national sample of U.S. hospitals. METHODS: Mean point-of-care blood glucose (POC-BG) data were assessed overall and at 24 hours before and up to 72 hours after the transition. Comparisons in glucose variability (standard deviation of POC-BG data) were assessed. Impact on glycemic control was evaluated after accounting for hospital characteristics through logistic regression analysis. RESULTS: POC-BG data were obtained from 576 hospitals. Overall mean (SD) POC-BG values in ICU versus non-ICU areas were 176 (24) versus 169 (21) mg/dL (P<.01). Mean (SD) of the ICU POC-BG data were 76 (16) versus 73 (16) mg/dL in the non-ICU data (P<.01). However, when comparing values of POC-BG in the last 24-hour ICU period with those from up to 72 hours posttransition, we found no differences, indicative of overall stable glycemic control and variability after transition. Any deterioration of glucose control following the transition was significantly associated with hospital size (P<.01): the smallest hospitals had the highest percentage of these cases. In addition, geographic region showed significant variability (P = .04), with hospitals in the Midwest and West having the highest proportion of cases in which glycemic control worsened following the transition. CONCLUSION: Glycemic control and variability did not change after transition from the ICU, but outcomes may depend on certain hospital characteristics. Inpatient glycemic control assessment should move beyond just cross-sectional studies and consider the impact of transitioning across inpatient areas. Other statistical approaches to studying this question should be evaluated.

Benchmarking glycemic control in u.s. Hospitals.

OBJECTIVE: Report data on glucose control from 635 U.S. hospitals. METHODS: Point-of-care blood glucose (POC-BG) test data from January through December 2012 from 635 facilities were extracted. Glucose control was evaluated using patient-day-weighted mean POC-BG values. We calculated hypoglycemia and hyperglycemia rates, stratified by presence or absence of intensive care unit (ICU) admission, and we evaluated the relationship between glycemic control and hospital characteristics. RESULTS: In total, 51,375,764 POC-BG measurements (non-ICU, 39,197,762; ICU, 12,178,002) from 2,612,966 patients (non-ICU, 2,415,209; ICU, 575,084) were analyzed. The mean POC-BG was 167 mg/dL for non-ICU patients and 170 mg/dL for ICU patients. The prevalence of hyperglycemia (defined as glucose value >180 mg/dL) was 32.3 and 28.2% in non-ICU and ICU patients, respectively. The prevalence of hypoglycemia (defined as glucose value <70 mg/dL) was 6.1 and 5.6% in non-ICU and ICU patients, respectively. In non-ICU and ICU settings, the patient-day-weighted mean glucose was highest in the smallest hospitals, in rural hospitals, and in hospitals located in the Northeast (all P<.01). For non-ICU patients, we observed a significant difference in the percentage of patient days with hypoglycemia by geographic region only (P<.001). In ICU patients, the prevalence of hypoglycemia varied significantly by hospital type (P<.03) and geographic region (P<.01). CONCLUSION: In this largest POC-BG data set analysis conducted to date, glycemic control varied according to hospital characteristics. Our findings remain consistent with previous reports. Among other variables, national benchmarking of inpatient glucose data will need to consider differences in hospital characteristics.

Trends in glycemic control over a 2-year period in 126 US hospitals.

BACKGROUND: Cross-sectional data on inpatient glucose control in a large sample of US hospitals are now available, but little is known about changes in glycemic control over time in these institutions. OBJECTIVE: To evaluate trends in glycemic control in US hospitals over 2 years. DESIGN: Retrospective analysis. METHODS: Point-of-care blood glucose (POC-BG) test results at 126 hospitals during January to December 2007 and January to December 2009 were extracted using the Remote Automated Laboratory System-Plus (Medical Automation Systems, Charlottesville, VA), and patient-day-weighted mean glucose levels were compared. SETTING/PATIENTS: Hospitalized patients. RESULTS: A total of 12,541,929 POC-BG measurements from 1,010,705 patients were analyzed for 2007, and 10,659,418 POC-BG measurements from 656,206 patients were analyzed for 2009. Patient-day-weighted mean POC-BG in 2009 decreased by 5 mg/dL in the non-intensive care unit (non-ICU) data compared with that in 2007 (154 mg/dL vs 159 mg/dL, respectively; P < 0.001). However, POC-BG values were clinically unchanged in intensive care unit (ICU) data from 2009 vs 2007 (167 mg/dL vs 166 mg/dL; P < 0.001). From 2007 to 2009, the proportion of patient-day-weighted mean POC-BGs that were >180 mg/dL declined from 28% to 25% in non-ICU patients (P < 0.001), but not in ICU. Decreases in patient-day-weighted mean POC-BG values in non-ICU patients were significant regardless of hospital size, type, and geographic region (all P < 0.001), but similar decreases were not found in ICU data. CONCLUSIONS: In this first analysis of glucose changes in US hospitals, improvements over 2 years occurred in non-ICU patients. Ongoing analysis will determine whether this trend continues.

Insights into mentorship for endocrinologists.

CONTEXT: Effective mentorship is considered a prerequisite for success during medical training and an ensuing professional career in academic medicine. The Endocrine Society established sessions on mentorship at the Trainee Day during several annual meetings. These requests motivated a group of endocrinologists at the University of Virginia to assess prior literature on mentorship and collect opinions on the importance of the various characteristics of mentorship from endocrinologists, general faculty, and trainees. This information served as the basis for in-depth reflection and discussions on mentorship. OBJECTIVE: The goal was to identify and prioritize the quintessential elements involved in mentorship and to reach practical conclusions that would be beneficial to academic endocrinologists. COMMENTARY: A multigenerational mentorship tree emphasizes that successful mentors can influence generations of mentees and that this represents a multiplier effect. The authors propose that trainees who are informed about the most important characteristics of an effective mentor can make better choices of a mentor. On the other hand, mentors can best define expectations when mentees know what to expect from a mentor, based on key characteristics. CONCLUSIONS: Similarities and differences in expectation about mentorship can be leveraged for better communication between mentor and mentee and for the development of stage-appropriate educational curricula on academic mentorship.

Assessing inpatient glycemic control: what are the next steps?

Despite the emergence of glucometrics (i.e., systematic analysis of data on blood glucose levels of inpatients) as a subject of high interest, there remains a lack of standardization on how glucose parameters are measured and reported. This dilemma must be resolved before a national benchmarking process can be developed that will allow institutions to track and compare inpatient glucose control performance against established guidelines and that can also be supported by quality care organizations. In this article, we review some of the questions that need to be resolved through consensus and review of the evidence, and discuss some of the limitations in analyzing and reporting inpatient glucose data that must be addressed (or at least accepted as limitations) before hospitals can commit resources to gathering, compiling, and presenting inpatient glucose statistics as a health care quality measure. Standards must include consensus on which measures to report, the unit of analysis, definitions of targets for hyperglycemia treatment, a definition of hypoglycemia, determination of how data should be gathered (from chart review or from laboratory information systems), and which type of sample (blood or point of care) should be used for analysis of glycemic control. Hospitals and/or their representatives should be included in the discussion. For inpatient glucose control to remain a focus of interest, further dialogue and consensus on the topic are needed.

Association between TNF-alpha and Entamoeba histolytica diarrhea.

An association between tumor necrosis factor alpha (TNF-alpha) and Entamoeba histolytica diarrhea was assessed in a cohort of 138 non-related Bangladeshi children who have been prospectively followed since 2001. Peripheral blood mononuclear cells (PBMCs) obtained at study entry were purified, cultured, and stimulated with soluble amebic antigen before cytokine measurement from supernatant. Higher levels of TNF-alpha were associated with increased risk of first (P = 0.01) and recurrent E. histolytica-related diarrheal episodes (P = 0.005). Children who developed E. histolytica diarrhea had significantly higher TNF-alpha protein levels than those who experienced asymptomatic E. histolytica infection (P value = 0.027) or no infection (P value = 0.017). Microarray studies performed using RNA isolated from acute and convalescent whole blood and colon biopsy samples revealed higher but non-significant TNF-alpha messenger RNA (mRNA) levels in subjects with acute E. histolytica diarrhea compared with convalescence. We conclude that there is an association between higher TNF-alpha production and E. histolytica diarrhea.

Phase I trial of intrapleural docetaxel administered through an implantable catheter in subjects with a malignant pleural effusion.

INTRODUCTION: Malignant pleural effusion (MPE) is a common complication in patients with advanced malignancy. This dose escalation phase I study was designed to determine the maximum tolerated dose of intrapleural docetaxel administered through an implantable catheter in subjects with MPE. METHODS: Subjects with MPE (n = 15) with median age of 64.6 years and an Eastern Cooperative Oncology Group performance status of 0 to 2 at baseline were enrolled into four single dose levels of docetaxel administered intrapleurally after drainage of the pleural effusion and insertion of an intrapleural catheter. The study determined the pharmacokinetic properties, clinical response, and toxicity profile of intrapleural docetaxel. RESULTS: All patients tolerated the therapy well and there were no significant toxicities. The majority of patients had a complete radiographic response. All patients receiving dose 100 mg/m2 or higher had a complete radiographic response. One dose-limiting toxicity was encountered in the dose 50 mg/m2. Pharmacokinetic data demonstrated peak plasma concentration of docetaxel between 30 minutes and 6 hours after infusion. Pleural exposure to docetaxel was 1000 times higher than systemic exposure. CONCLUSIONS: Single-dose intrapleural administration of doxetaxel is well tolerated in patients with MPE with minimal toxicity. The excellent clinical responses in this study after treatment with intrapleural doxetaxel suggest that further investigation is warranted.

A pilot study evaluating the safety and efficacy of modafinal for cancer-related fatigue.

BACKGROUND: Fatigue is a common symptom that lowers the quality of life of patients with cancer, affecting between 60% and 90% of patients. Relatively few options are available for the treatment of this debilitating condition. Modafinal, a psychostimulant developed for the treatment of narcolepsy, has been used to treat fatigue in other diseases such as multiple sclerosis, but little data support its use in cancer patients. OBJECTIVE AND DESIGN: The primary objective of this open-label pilot study was to evaluate the safety, and efficacy of modafinil in improving cancer-related fatigue (CRF) as measured by the Brief Fatigue Inventory (BFI). The effect of this agent on depression, quality of life, functional status, and cognitive function was also assessed. Modafinal was self-administered at a dose of 100 mg/d during weeks 1-2, and 200 mg during weeks 3-4. Assessments were performed at baseline, 2, and 4 weeks. RESULTS: BFI score was improved in 46% of patients at 2 weeks and 75% at 4 weeks (p = 0.025). Hospital Anxiety and Depression Scale scores declined at 2 and 4 weeks (p < 0.001). Most scales for neurocognitive function were unchanged. Score for all Functional Assessment of Cancer Therapy-Brain (FACT-BR) subscales (measuring quality of life), except social/family well-being, were improved (p < 0.05) at 2 and 4 weeks. Significant changes in Eastern Cooperative Oncology Group (ECOG) performance status were noted, with 40% of patients improving at least one level. Modafinil was well-tolerated with only one patient discontinuing treatment due to drug-related toxicity. CONCLUSION: In this pilot study modafinil was well-tolerated and effective for fatigue in patients with cancer. Improvements were also seen in mood, quality of life, and functional status.

A clinical and biological comparison between malignant mixed müllerian tumors and grade 3 endometrioid endometrial carcinomas.

OBJECTIVE: To examine the clinicopathologic features, progression-free interval, and survival of patients with grade 3 endometrioid endometrial cancer (G3 EEC) and malignant mixed müllerian tumors (MMMTs). Akt, epidermal growth factor receptor (EGFR), and HER-2/neu expression in these histologic subtypes was also investigated. Associations between phosphorylated Akt and clinicopathologic features were tested. METHODS: One hundred nineteen women whose conditions were diagnosed with MMMT or G3 EEC from January 1, 1990, to December 31, 2003, met inclusion criteria. Retrospective data review was performed. In addition, Akt and EGFR protein expression was measured in tissue samples using Western blotting and immunohistochemistry. Fluorescence in situ hybridization was used to assay HER-2/neu gene amplification. RESULTS: Fifty-nine patients with MMMT and 60 patients with G3 EEC were identified. Patients with MMMT were older (P = 0.055), more likely to be African American (P = 0.049), have a family history of breast cancer (P = 0.039), have disease involving the uterine cervix (P = 0.007), and experience postoperative complications (P = 0.012). Patients with MMMT had a significantly shorter progression-free interval (23 vs 57 months, P = 0.001) and survival (55 vs 92 months, P = 0.001) than patients with G3 EEC.Grade 3 EEC and MMMT have significantly higher phospho-Akt levels than grade 1 EEC and normal controls. Phospho-Akt was associated with depth of myometrial invasion (r = 0.46, P = 0.05), but not with stage, lymph-vascular space invasion, or tumor size. The mesenchymal component of MMMT preferentially demonstrated EGFR expression relative to the epithelial component (45% vs 13%, P = 0.06). HER-2/neu amplification was observed in 1 of 37 samples. CONCLUSIONS: Improved therapy is warranted for both poorly differentiated EEC and MMMT. Recognition of similarities and differences between MMMT and other high-grade histologic types of uterine cancer may provide rationale for new treatment approaches possibly incorporating targeted biological therapies.

Dose-escalation designs in oncology: ADEPT and the CRM.

The ADEPT software package is not a statistical method in its own right as implied by Gerke and Siedentop (Statist. Med. 2008; DOI: 10.1002/sim.3037). ADEPT implements two-parameter CRM models as described in O'Quigley et al. (Biometrics 1990; 46(1):33-48). All of the basic ideas (use of a two-parameter logistic model, use of a two-dimensional prior for the unknown slope and intercept parameters, sequential estimation and subsequent patient allocation based on minimization of some loss function, flexibility to use cohorts instead of one by one inclusion) are strictly identical. The only, and quite trivial, difference arises in the setting of the prior. O'Quigley et al. (Biometrics 1990; 46(1):33-48) used priors having an analytic expression whereas Whitehead and Brunier (Statist. Med. 1995; 14:33-48) use pseudo-data to play the role of the prior. The question of interest is whether two-parameter CRM works as well, or better, than the one-parameter CRM recommended in O'Quigley et al. (Biometrics 1990; 46(1):33-48). Gerke and Siedentop argue that it does. The published literature suggests otherwise. The conclusions of Gerke and Siedentop stem from three highly particular, and somewhat contrived, situations. Unlike one-parameter CRM (Biometrika 1996; 83:395-405; J. Statist. Plann. Inference 2006; 136:1765-1780; Biometrika 2005; 92:863-873), no statistical properties appear to have been studied for two-parameter CRM. In particular, for two-parameter CRM, the parameter estimates are inconsistent. This ought to be a source of major concern to those proposing its use. Worse still, for finite samples the behavior of estimates can be quite wild despite having incorporated the kind of dampening priors discussed by Gerke and Siedentop. An example in which we illustrate this behavior describes a single patient included at level 1 of 6 levels and experiencing a dose limiting toxicity. The subsequent recommendation is to experiment at level 6! Such problematic behavior is not common. Even so, we show that the allocation behavior of two-parameter CRM is very much less stable than that of one-parameter CRM.

Human melanoma cytolysis by combined inhibition of mammalian target of rapamycin and vascular endothelial growth factor/vascular endothelial growth factor receptor-2.

Vascular endothelial growth factor (VEGF) plays a vital role in tumor angiogenesis. VEGF is produced by human melanomas, and the VEGF receptor 2 (VEGFR-2) is expressed by most advanced stage melanomas, suggesting the possibility of an autocrine loop. Here, we show that bevacizumab, an anti-VEGF antibody, inhibits proliferation of VEGFR-2(+) melanoma cell lines by an average of 41%; however, it failed to inhibit proliferation of VEGFR-2(neg) melanoma cell lines. The growth inhibitory effect of bevacizumab was eliminated by VEGFR-2 knockdown with small interfering RNA, showing that VEGF autocrine growth in melanoma is mediated through VEGFR-2. However, bevacizumab inhibition of autocrine signals did not completely inhibit cell proliferation nor cause cell death. Cell survival is mediated partially through mammalian target of rapamycin (mTOR), which is inhibited by rapamycin. Combination of bevacizumab with rapamycin caused loss of half of the VEGFR-2(+) melanoma cells, but no reduction in the number of VEGFR-2(neg) melanoma cells. The results show (a) an autocrine growth loop active in VEGFR-2(+) melanoma, (b) a nonangiogenic mechanism for inhibition of melanoma by blocking autocrine VEGFR-2 activation, and (c) a possible therapeutic role for combination of inhibitors of mTOR plus VEGF in selected melanomas.

Correlation of interferon-gamma production by peripheral blood mononuclear cells with childhood malnutrition and susceptibility to amebiasis.

The contribution of interferon-gamma (IFN-gamma) to immunity from amebiasis was assessed in a three-year prospective study of children 2-5 years of age in an urban slum of Dhaka, Bangladesh. IFN-gamma produced by peripheral blood mononuclear cells stimulated with soluble amebic antigen was measured upon enrollment. Thirty-one of the 209 enrolled children had Entamoeba histolytica-associated diarrhea. Children who produced higher than the median level of IFN-gamma (median = 580 pg/mL) had longer survival without E. histolytica diarrhea/dysentery (log rank test P = 0.03) and a reduction in the risk of E. histolytica diarrhea/dysentery by more than half (Cox proportional hazard regression = 0.45, P = 0.04). When adjusted for stunting, the association between IFN-gamma and the time to the first episode of E. histolytica-associated diarrhea remained marginally significant (Cox proportional hazard regression = 0.49, P = 0.07). We conclude that production of IFN-gamma is linked to nutritional status and predicts future susceptibility to symptomatic amebiasis.

Relemed: sentence-level search engine with relevance score for the MEDLINE database of biomedical articles.

BACKGROUND: Receiving extraneous articles in response to a query submitted to MEDLINE/PubMed is common. When submitting a multi-word query (which is the majority of queries submitted), the presence of all query words within each article may be a necessary condition for retrieving relevant articles, but not sufficient. Ideally a relationship between the query words in the article is also required. We propose that if two words occur within an article, the probability that a relation between them is explained is higher when the words occur within adjacent sentences versus remote sentences. Therefore, sentence-level concurrence can be used as a surrogate for existence of the relationship between the words. In order to avoid the irrelevant articles, one solution would be to increase the search specificity. Another solution is to estimate a relevance score to sort the retrieved articles. However among the >30 retrieval services available for MEDLINE, only a few estimate a relevance score, and none detects and incorporates the relation between the query words as part of the relevance score. RESULTS: We have developed "Relemed", a search engine for MEDLINE. Relemed increases specificity and precision of retrieval by searching for query words within sentences rather than the whole article. It uses sentence-level concurrence as a statistical surrogate for the existence of relationship between the words. It also estimates a relevance score and sorts the results on this basis, thus shifting irrelevant articles lower down the list. In two case studies, we demonstrate that the most relevant articles appear at the top of the Relemed results, while this is not necessarily the case with a PubMed search. We have also shown that a Relemed search includes not only all the articles retrieved by PubMed, but potentially additional relevant articles, due to the extended 'automatic term mapping' and text-word searching features implemented in Relemed. CONCLUSION: By using sentence-level matching, Relemed can deliver higher specificity, thus eliminating more false-positive articles. By introducing an appropriate relevance metric, the most relevant articles on which the user wishes to focus are listed first. Relemed also shrinks the displayed text, and hence the time spent scanning the articles.

Cognitive effects of diarrhea, malnutrition, and Entamoeba histolytica infection on school age children in Dhaka, Bangladesh.

Cognitive function was assessed in 191 Bangladeshi children 6-9 years of age using verbal and nonverbal tests. These scores were added to a health surveillance database that was compiled over the four previous years that includes incidence of diarrhea and Entamoeba histolytica infection and nutritional status. The associations of diarrhea, malnutrition, and social factors with cognitive scores were analyzed statistically, and associations between diarrhea and test scores were controlled for the influence of social factors. Cognitive scores were negatively associated with stunting during school age, as well as the height-for-age and weight-for-age scores at study enrollment. Incidence of diarrhea was associated with nonverbal test scores before, but not after, controlling for socioeconomic factors. Generally E. histolytica infection was not found to independently influence scores, except that E. histolytica-associated dysentery was associated with lower test scores while dysentery of any etiology was not. Thus, malnutrition during the school age years, but not diarrhea or E. histolytica infection, was associated with a lower level of cognitive functioning. This suggested that intervention during school age years may be able to mitigate the cognitive deficiencies associated with malnutrition.

Pap testing among Vietnamese women: health care system and physician factors.

Cervical cancer occurs more frequently among Vietnamese Americans than women of any other race/ethnicity. In addition, previous studies in California have documented low Papanicolaou (Pap) testing rates in Vietnamese communities. This study focused on health care system factors and physician characteristics associated with recent cervical cancer screening among Vietnamese women. A population-based survey was conducted in Seattle during 2002. In-person interviews were conducted by bilingual, bicultural female survey workers. The survey response rate was 82% and 518 women were included in the analysis. Seventy-four percent of the respondents reported having been screened for cervical cancer on at least one occasion, and 64% reported a Pap smear within the previous 2 years. Women with a regular doctor were more likely to have been recently screened than those without a regular doctor (OR = 2.33, 95% CI = 1.45-3.74). Among those with a regular doctor, having a male physician, receiving care at a private doctor's office (rather than a community, hospital, or multi-specialty clinic), and concern about the cost of health care were independently associated with lower screening rates. Physician ethnicity was not associated with recent Pap smear receipt. The findings support targeted interventions for Vietnamese women without a regular physician and private doctors' offices that serve Vietnamese Americans. The availability of low cost screening services should be publicized in Vietnamese communities.

Proportional odds ratio model for comparison of diagnostic tests in meta-analysis.

BACKGROUND: Consider a meta-analysis where a 'head-to-head' comparison of diagnostic tests for a disease of interest is intended. Assume there are two or more tests available for the disease, where each test has been studied in one or more papers. Some of the papers may have studied more than one test, hence the results are not independent. Also the collection of tests studied may change from one paper to the other, hence incomplete matched groups. METHODS: We propose a model, the proportional odds ratio (POR) model, which makes no assumptions about the shape of ORp, a baseline function capturing the way OR changes across papers. The POR model does not assume homogeneity of ORs, but merely specifies a relationship between the ORs of the two tests. One may expand the domain of the POR model to cover dependent studies, multiple outcomes, multiple thresholds, multi-category or continuous tests, and individual-level data. RESULTS: In the paper we demonstrate how to formulate the model for a few real examples, and how to use widely available or popular statistical software (like SAS, R or S-Plus, and Stata) to fit the models, and estimate the discrimination accuracy of tests. Furthermore, we provide code for converting ORs into other measures of test performance like predictive values, post-test probabilities, and likelihood ratios, under mild conditions. Also we provide code to convert numerical results into graphical ones, like forest plots, heterogeneous ROC curves, and post test probability difference graphs. CONCLUSIONS: The flexibility of POR model, coupled with ease with which it can be estimated in familiar software, suits the daily practice of meta-analysis and improves clinical decision-making.

CXC chemokine receptor 3 expression by activated CD8+ T cells is associated with survival in melanoma patients with stage III disease.

Despite the presence of tumor Ag-specific CD8(+) T cells in the peripheral blood, metastatic melanoma often evades immune-mediated destruction. Even after therapeutic efforts to expand Ag-specific T-cell populations, the correlation between magnitude of response and clinical efficacy has been weak. Because the migratory phenotype of tumor Ag-specific effector T cells may determine their ability for tumor control, we hypothesized that the expression of CC or CXC chemokine receptor (CCR) molecules on activated CD8(+) T cells may define phenotypes associated with more effective control of melanoma progression and prolonged survival. In a retrospective evaluation of patient isolates, CCR expression was determined for activated CD8(+) T cells derived from the peripheral blood or tumor-involved lymph nodes of 52 patients with stage III or IV metastatic melanoma. In patients with stage III disease, expression of CXCR3 by CD8(+)CD45RO(+) cells was significantly associated with enhanced survival. This was a stage-specific effect, because it was not observed in patients with stage IV disease. In addition, CCR4 and CXCR3 were highly coexpressed and associated with enhanced survival in stage III patients; however, CXCR3 seems to be the dominant receptor associated with clinical outcome. These findings support the hypothesis that the host immune system affects cancer progression and control, and that measures of CCR status of circulating lymphocytes may have prognostic value.

Pap screening and knowledge of risk factors for cervical cancer in Chinese women in British Columbia, Canada.

OBJECTIVE: Cervical cancer is a significant cause of mortality and morbidity for Chinese Canadian women, due in part to inadequate Pap screening. A community-based survey was conducted involving 528 Chinese immigrant women residing in British Columbia, Canada, in order to identify barriers and facilitators to Pap testing. This paper addresses the relationship between knowledge level about cervical cancer risk factors and Pap screening practices. DESIGN: Female trilingual Chinese interviewers conducted personal at-home interviews about knowledge of cervical cancer risk factors, history of Pap screening, sociodemographic and acculturation factors. RESULTS: The average summary score for knowledge about cervical cancer risk factors was 5.2/10, and knowledge level was significantly associated with the woman's educational level and the gender of the doctor providing usual care. Seventy-four per cent of respondents reported ever having received a Pap test, and 56% reported having received a test within the last two years. Respondents with the highest knowledge were more likely to have ever received a Pap test (OR 6.4, 95% CI: 2.6, 15.9), and to have recently received a test (OR 3.1, 95% CI: 1.4, 6.7). CONCLUSION: The average knowledge level about cervical cancer risk factors is low in Chinese Canadian women, especially among those with less education and who receive their usual care from a male doctor. Knowledge of these risk factors influences Pap screening behaviour. Culturally and linguistically appropriate education interventions addressing Pap testing and risk factors for cervical cancer are needed in the Canadian Chinese community. Educational resources are also needed for their primary care givers.

Serious health consequences associated with alcohol use among college students: demographic and clinical characteristics of patients seen in an emergency department.

OBJECTIVE: Heavy episodic alcohol use has been associated with numerous consequences among college students. However, neither the incidence nor the demographic and clinical characteristics of serious health consequences have been clearly defined in this population. This study is conducted to better understand clinical outcomes associated with alcohol use in college students. METHOD: In a prospective observational study, medical records of students presenting to a large university medical center emergency department were examined. Demographic and clinical features of alcohol-related visits were gathered on patients who were enrolled as undergraduates at a 4-year public institution during 2 academic years from July 2000 through June 2002. Enrollment was approximately 12,500 undergraduates per year. RESULTS: Of all emergency visits, 13% were alcohol related; and of all undergraduate students, 0.7% presented with alcohol-related medical conditions each year. Injuries accounted for 53% of all visits, and acute intoxication accounted for 34%. Nine of 185 patients were hospitalized. Men aged 21 years and older had the highest odds of visiting the emergency department. Trauma occurred more frequently among men, students > 18 years of age and white students. Accidents (84%) and fights (16%) were the sources of injuries. Acute intoxication occurred more frequently among women, students < or = 18 years of age and nonwhite students. CONCLUSIONS: Alcohol use contributes to a small yet significant proportion of emergency room visits for college students. Distinctive subgroups of college students, including legal-age drinkers, experience patterns of serious health consequences as a result of problem use of alcohol.