Archive for October 16, 2010

Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer

N Engl J of Medicine Published at June 7, 2010

K. Kian Ang, M.D., Ph.D., Jonathan Harris, M.S., Richard Wheeler, M.D., Randal Weber, M.D., David I. Rosenthal, M.D., Phuc Felix Nguyen-Tân, M.D., William H. Westra, M.D., Christine H. Chung, M.D., Richard C. Jordan, D.D.S., Ph.D., Charles Lu, M.D., Harold Kim, M.D., Rita Axelrod, M.D., C. Craig Silverman, M.D., Kevin P. Redmond, M.D., and Maura L. Gillison, M.D., Ph.D.


Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.


We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer.


The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage.


Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer.

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Prognostic Implications of HPV in Oropharyngeal Cancer

Douglas R. Lowy, M.D., and Karl Munger, Ph.D.

Identification of human papillomavirus (HPV) as the etiologic agent of cervical cancer has led to its identification in other cancers, with oropharyngeal squamous-cell carcinoma the most common of these.1,2 In this issue of the Journal, Ang and colleagues3 report findings from their study ( number, NCT00047008 [] ) that contribute to the growing body of evidence that HPV-positive oropharyngeal squamous-cell carcinoma represents a distinct clinicopathological entity associated with a better prognosis than HPV-negative oropharyngeal squamous-cell carcinoma.4,5 In a randomized trial of patients with oropharyngeal squamous-cell carcinoma, the overall survival was substantially better among patients with HPV-positive cancer than among patients with HPV-negative cancer. The size of the sample — 323 patients with oropharyngeal squamous-cell carcinoma and known HPV status, of whom 64% had HPV-positive tumors — enabled the authors to control for many variables and to conclude that HPV status was a critical independent prognostic determinant….

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October 16, 2010 at 7:53 pm Leave a comment

Rapid Influenza Antigen Test for Diagnosis of Pandemic (H1N1) 2009

Emerging Infectious Diseases May 2010  V.16  N.5  p.824-826

Janice K. Louie,  Hugo Guevara, Erica Boston, Melissa Dahlke, Maria Nevarez, Tong Kong, Robert Schechter, Carol A. Glaser, and David P. Schnurr

California Department of Public Health, Richmond, California, USA


We compared the QuickVue Influenza test with PCR for diagnosing pandemic (H1N1) 2009 in 404 persons with influenza-like illness. Overall sensitivity, specificity, and positive and negative predictive values were 66%, 84%, 84%, and 64%, respectively. Rapid test results should be interpreted cautiously when pandemic (H1N1) 2009 virus is suspected.

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October 16, 2010 at 7:52 pm Leave a comment

New Delhi metallo-beta-lactamase (NDM-1): towards a new pandemia?

Clinical Microbiology and Infection Sept. 2010

Jean Marc Rolain1,*, Philippe Parola1,2, Giuseppe Cornaglia3

1. URMITE UMR CNRS-IRD 6236, IFR48, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France

2. EuroTravNet, The ECDC collaborative Network for Tropical and Travel Medicine

3. Department of Pathology and Diagnostics, University of Verona, Italy

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October 16, 2010 at 7:49 pm Leave a comment

Efficacy and Safety of Intravenous Peramivir for Treatment of Seasonal Influenza Virus Infection

Antimicrob. Agents Chemother. 1 November 2010 V.54 N.11 p.4568-4574

Shigeru Kohno,1* Hiroshi Kida,2 Masashi Mizuguchi,3 Jingoro Shimada,4 for the S-021812 Clinical Study Group

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan,1 Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan,2 Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, Tokyo, Japan,3 St. Marianna University School of Medicine, Kawasaki, Japan4

Peramivir, a sialic acid analogue, is a selective inhibitor of neuraminidases produced by influenza A and B viruses. We evaluated the efficacy and safety of a single intravenous dose of peramivir in outpatients with uncomplicated seasonal influenza virus infection. A total of 300 previously healthy adult subjects aged 20 to 64 years with a positive influenza virus rapid antigen test were recruited within 48 h of the onset of influenza symptoms and randomized to three groups: single intravenous infusion of either 300 mg peramivir per kg of body weight, 600 mg peramivir, or matching placebo on study day 1. Influenza symptoms and body temperature were self-assessed for 14 days. Nasal and pharyngeal swabs were collected to determine the viral titer. The primary endpoint was the time to alleviation of symptoms. Of the 300 subjects, 296 were included in the intent-to-treat infected population (300 mg peramivir, n = 99; 600 mg peramivir, n = 97; and placebo, n = 100). Peramivir significantly reduced the time to alleviation of symptoms at both 300 mg (hazard ratio, 0.681) and 600 mg (hazard ratio, 0.666) compared with placebo (adjusted P value, 0.0092 for both comparisons). No serious adverse events were reported. Peramivir was well tolerated, and its adverse-event profile was similar to that of placebo. A single intravenous dose of peramivir is effective and well tolerated in subjects with uncomplicated seasonal influenza virus infection.



October 16, 2010 at 3:00 pm Leave a comment

Amikacin Monotherapy for Sepsis Caused by Panresistant Pseudomonas aeruginosa

Antimicrob. Agents Chemother. 1 November 2010 V.54 N.11 p.4939-4941

Brice Layeux,1 Fabio Silvio Taccone,2 David Fagnoul,2 Jean-Louis Vincent,2 and Frédérique Jacobs1*

Department of Infectious Diseases,1 Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium2

Two patients with severe sepsis due to panresistant Pseudomonas aeruginosa, deteriorating despite therapy with colistin and β-lactams, were cured with a high daily dose (25 to 50 mg/kg) of amikacin to obtain a peak/MIC ratio of at least 8 to 10 (MIC = 16 µg/ml). Concomitant use of continuous venovenous hemodiafiltration (CVVHDF) provided no deterioration in renal function after treatment. High dosage of aminoglycosides combined with CVVHDF may represent a valuable therapeutic option for infection due to multiresistant pathogens.


October 16, 2010 at 2:58 pm Leave a comment

Systematic Review and Meta-Analysis of the Efficacy of Appropriate Empiric Antibiotic Therapy for Sepsis

Antimicrob. Agents Chemother. 1 November 2010 V.54 N.11 p.4851-4863

Mical Paul,1* Vered Shani,2 Eli Muchtar,2 Galia Kariv,2 Eyal Robenshtok,2 and Leonard Leibovici2

Unit of Infectious Diseases,1 Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel2

Quantifying the benefit of early antibiotic treatment is crucial for decision making and can be assessed only in observational studies. We performed a systematic review of prospective studies reporting the effect of appropriate empirical antibiotic treatment on all-cause mortality among adult inpatients with sepsis. Two reviewers independently extracted data. Risk of bias was assessed using the Newcastle-Ottawa score. We calculated unadjusted odds ratios (ORs) with 95% confidence intervals for each study and extracted adjusted ORs, with variance, methods, and covariates being used for adjustment. ORs were pooled using random-effects meta-analysis. We examined the effects of methodological and clinical confounders on results through subgroup analysis or mixed-effect meta-regression. Seventy studies were included, of which 48 provided an adjusted OR for inappropriate empirical antibiotic treatment. Inappropriate empirical antibiotic treatment was associated with significantly higher mortality in the unadjusted and adjusted comparisons, with considerable heterogeneity occurring in both analyses (I2 > 70%). Study design, time of mortality assessment, the reporting methods of the multivariable models, and the covariates used for adjustment were significantly associated with effect size. Septic shock was the only clinical variable significantly affecting results (it was associated with higher ORs). Studies adjusting for background conditions and sepsis severity reported a pooled adjusted OR of 1.60 (95% confidence interval = 1.37 to 1.86; 26 studies; number needed to treat to prevent one fatal outcome, 10 patients [95% confidence interval = 8 to 15]; I2 = 46.3%) given 34% mortality with inappropriate empirical treatment. Appropriate empirical antibiotic treatment is associated with a significant reduction in all-cause mortality. However, the methods used in the observational studies significantly affect the effect size reported. Methods of observational studies assessing the effects of antibiotic treatment should be improved and standardized.


October 16, 2010 at 2:56 pm Leave a comment

Standard Care Impact on Effects of Highly Active Antiretroviral Therapy Adherence Interventions

Arch Int Med February 8, 2010; Vol. 170, No. 3  p.240-250

A Meta-analysis of Randomized Controlled Trials

Marijn de Bruin, PhD; Wolfgang Viechtbauer, PhD; Herman P. Schaalma, PhD; Gerjo Kok, PhD; Charles Abraham, PhD; Harm J. Hospers, PhD

Faculty of Psychology, Department of Work and Social Psychology, (Drs de Bruin, Schaalma, Kok, and Hospers) and Faculty of Health, Medicine, and Life Sciences, Department of Methodology and Statistics (Dr Viechtbauer), Maastricht University, Maastricht, the Netherlands; Department of Communication Science, Wageningen University, Wageningen, the Netherlands (Dr de Bruin); and School of Psychology, University of Sussex, Falmer, England (Dr Abraham). Died July 25, 2009.


Poor adherence to medication limits the effectiveness of treatment for human immunodeficiency virus. Systematic reviews can identify practical and effective interventions. Meta-analyses that control for variability in standard care provided to control groups may produce more accurate estimates of intervention effects.


To examine whether viral load and adherence success rates could be accurately explained by the active content of highly active antiretroviral therapy (HAART) adherence interventions when controlling for variability in care delivered to controls, databases were searched for randomized controlled trials of HAART adherence interventions published from 1996 to January 2009. A total of 1342 records were retrieved, and 52 articles were examined in detail. Directly observed therapy and interventions targeting specific patient groups (ie, psychiatric or addicted patients, patients <18 years) were excluded, yielding a final sample of 31 trials. Two coders independently retrieved study details. Authors were contacted to complete missing data.


Twenty studies were included in the analyses. The content of adherence care provided to control and intervention groups predicted viral load and adherence success rates in both conditions (P < .001 for all comparisons), with an estimated impact of optimal adherence care of 55 percentage points. After controlling for variability in care provided to controls, the capacity of the interventions accurately predicted viral load and adherence effect sizes (R2 = 0.78, P = .02; R2 = 0.28, P < .01). Although interventions were generally beneficial, their effectiveness reduced noticeably with increasing levels of standard care.


Intervention and control patients were exposed to effective adherence care. Future meta-analyses of (behavior change) interventions should control for variability in care delivered to active controls. Clinical practice may be best served by implementing current best practice.


October 16, 2010 at 2:55 pm Leave a comment


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