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Alan K Sears,
Sonia A Perez,
Guy T Clifton,
Linda C Benavides,
Jeremy D Gates,
Kevin S Clive,
Jarrod P Holmes, Nathan M Shumway,
David C Van Echo,
Mark G Carmichael,
Sathibalan Ponniah,
Constantin N Baxevanis,
Elizabeth A Mittendorf,
Michael Papamichail,
George E Peoples
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ABSTRACT: INTRODUCTION: Immunotherapy, including vaccines targeting the human EGFR2 (HER-2/neu) protein, is an active area of investigation in combatting breast cancer. Several vaccines are currently undergoing clinical trials, most of which are CD8(+) T-cell-eliciting vaccines. AE37 is a promising primarily CD4(+) T-cell-eliciting HER-2/neu breast cancer vaccine currently in clinical trials. AREAS COVERED: This article reviews preclinical investigations as well as findings from completed and ongoing Phase I and Phase II clinical trials of the AE37 vaccine. EXPERT OPINION: Clinical trials have shown the AE37 vaccine to be safe and capable of generating peptide-specific, durable immune responses. This has been shown in patients with any level of HER-2/neu expression. Early clinical findings suggest there may be benefit to AE37 vaccination in preventing breast cancer recurrence.
Expert opinion on biological therapy 09/2011; 11(11):1543-50. · 3.22 Impact Factor
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ABSTRACT: Multiple formats of journal club exist but data is lacking regarding which model is most effective. Many residents are dissatisfied with their current format, which was the case at our institution.
This article discusses a resident run model, residents' perceptions following its implementation, and recommendations for running a successful journal club. Practice points Journal club formats vary extensively without a clearly superior method. Defining goals is the first step to a successful journal club. Structured review instruments for articles enhance journal club. The presence of subspecialty staff may augment learning. Resident-run models of journal club can be successfully implemented.
A resident run model of journal club was developed based on Adult Learning Theory. A 30-question survey was created to assess residents' attitudes and satisfaction with the new model.
All respondents preferred the new model compared to the old model. Residents reported the new model increased their medical knowledge (88%) and they were able to apply the methods learned in journal club to actual patients (82%).
A resident run model of journal club may be a viable option for those attempting to start or improve their current club.
Medical Teacher 05/2009; 31(4):e156-61. · 1.22 Impact Factor
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ABSTRACT: Treatment of breast cancer in the adjuvant setting has changed rapidly over the last few years. In addition to improvements in chemotherapy, radiation, hormone manipulation, and surgery, immunotherapy has emerged as an effective adjunct for the treatment of breast cancer. Passive immunotherapeutic agents such as trastuzumab have been widely adopted as the standard of care for HER-2/neu overexpressing breast cancer. Vaccine therapy in the metastatic setting has yet to demonstrate clinical significance in a phase III testing. This may be due to the enhanced immunosuppressive effects demonstrated in the tumor microenvironment. Lack of co-stimulatory molecules, activation of the cytotoxic T-lymphocyte antigen-4 (CTLA-4), increased T regulatory cells as well as soluble immunosuppressive factors produced by the tumor contribute to the ineffectiveness of vaccine therapy. Based on these observations, there has been a shift towards treating patients with minimal residual disease and a high risk of relapse. In this adjuvant setting, immune mechanisms of tumor evasion are less formidable, and the use of vaccine therapy in these patients may offer a higher chance of clinical benefit. There are several different vaccine approaches, including the use of cell-based vaccines (autologous, allogeneic, or dendritic cell-based), tumor-associated peptide or protein vaccines, DNA vaccines, heat shock proteins, and recombinant technology using viral or bacterial vectors to enhance immunogenicity of vaccine preparations. This review summarizes principles involving vaccine formulation and antigen selection, followed by a brief synopsis of therapeutic vaccines given in the metastatic setting and possible reasons for their lack of efficacy. The current literature regarding vaccine development for the treatment of breast cancer in the adjuvant setting is also reviewed.
BioDrugs 01/2009; 23(5):277-87. · 3.44 Impact Factor
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ABSTRACT: Air hunger at end-of-life poses challenges to providers who attempt to comfort while not diminishing mental capacities. We examined the presence, methods of assessment, and treatment of air hunger. This observational study prospectively screened 198 consecutive medicine admissions for increased risk of near-term death. These patients in turn were screened for dyspnea. Patients screening positive were assessed on admission and the next day with the Visual Analog Scale (VAS), modified Borg Scale, and the American Thoracic Society (ATS) Shortness of Breath Scale. Additionally, resident physician opinions of patient dyspnea level were assessed using the same tools. Treatments focused on alleviating air hunger were recorded. Thirty-nine percent of patients were at risk for near-term death and of these, 53% (95% CI: 41-65%) reported air hunger. All dyspnea scales improved to a statistically and clinically significant degree (Borg p=0.007, VAS p<0.0005, ATS p=0.008). There was statistically significant agreement between Borg-VAS and between Borg-ATS with a trend toward significance with ATS-VAS. Physician assessment of dyspnea showed poor agreement with patients. A median of three treatments were received by patients but dyspnea improvement did not correlate with the type, number, or specific combination of therapies. Dyspnea is common near end-of-life. Borg or VAS scales appear useful in assessing terminal dyspnea and can be employed in assessing terminal air hunger. No individual treatment or combination of treatments significantly improved patients' dyspnea. However, air hunger significantly improved with hospitalization.
Respiratory Medicine 01/2008; 102(1):27-31. · 2.47 Impact Factor
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ABSTRACT: The objective of this study was to discuss the appropriate diagnostic and treatment approach to an active duty patient presenting with recurrent kidney stones. A 37-year-old active duty infantryman, stationed in Iraq, was evacuated by air to Waiter Reed Army Medical Center for workup of recurrent kidney stones and hypercalcemia. A diagnosis was made and the definitive treatment was performed. During this report, we will illustrate the various aspects of diagnosis that are involved with the workup of kidney stones and hypercalcemia as well as discuss the available treatment options. Relevant military issues include proceeding with the initial management regimen and recognition of appropriate reasons for initiation of referral consultation.
Military medicine 08/2006; 171(7):684-6. · 0.92 Impact Factor
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ABSTRACT: The objective of this study was to discuss the appropriate diagnostic and treatment approach to an active duty patient presenting with recurrent kidney stones. A 37-year-old active duty infantryman, stationed in Iraq, was evacuated by air to Walter Reed Army Medical Center for workup of recurrent kidney stones and hypercalcemia. A diagnosis was made and the definitive treatment was performed. During this report, we will illustrate the various aspects of diagnosis that are involved with the workup of kidney stones and hypercalcemia as well as discuss the available treatment options. Relevant military issues include proceeding with the initial management regimen and recognition of appropriate reasons for initiation of referral consultation.
Military medicine 06/2006; 171(7):684-686. · 0.92 Impact Factor
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ABSTRACT: Patients taking oral anticoagulants with an international normalized ratio (INR) greater than 4.0 are at increased risk for bleeding. We performed a meta-analysis to determine the effectiveness of phytonadione (vitamin K) in treating excessive anticoagulation.
The MEDLINE, EMBASE, and Cochrane Library databases were searched (without language restrictions) for articles published between January 1985 and September 2004. Randomized controlled trials or prospective, nonrandomized trials that used vitamin K to treat patients without major hemorrhage with an INR greater than 4.0 due to oral anticoagulant use were included. The primary outcome was achievement of the target INR (1.8-4.0) at 24 hours after vitamin K administration. Summary estimates were calculated using a random effects model.
Twenty-one studies (10 randomized and 11 prospective trials) were included. Among oral vitamin K treatment arms (4, n = 75), the proportion with a target INR at 24 hours was 82% (95% confidence interval [CI], 70%-93%), which was similar to intravenous vitamin K treatment arms (6, n = 69; target INR, 77%; 95% CI, 60%-95%). Treatment arms of subcutaneous vitamin K (3, n = 58; 31%; 95% CI, 7%-55%) and placebo/observation (2, n = 27; 20%; 95% CI, 0%-47%) were less likely to achieve target INR at 24 hours. Only 1 of 21 trials appropriately assessed for adverse events, so a summary estimate for bleeding risk could not be generated.
Limited evidence suggests that oral and intravenous vitamin K are equivalent and more effective for excessive anticoagulation than simply withholding warfarin sodium. Subcutaneous vitamin K, however, is inferior to oral and intravenous vitamin K for this indication and is similar to placebo. Whether treatment with vitamin K decreases hemorrhagic events cannot be determined from the published literature.
Archives of Internal Medicine 03/2006; 166(4):391-7. · 11.46 Impact Factor
