bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relapse-Related Molecular Signature in Lung Adenocarcinomas Identifies Patients With Dismal Prognosis
Authors: Tomida Shuta , Takeuchi Toshiyuki , Shimada Yukako , Arima Chinatsu , Matsuo Keitaro , Mitsudomi Tetsuya , Yatabe Yasushi , Takahashi Takashi 
Published: May 2009

Purpose In order to aid the development of patient-tailored therapeutics, we attempted to identify a relapse-related signature that allows selection of a group of adenocarcinoma patients with a high probability of relapse. Patients and Methods Whole-genome expression profiles were analyzed in 117 lung adenocarcinoma samples using microarrays consisting of 41,000 probes. A weighted voting classifier for identifying patients with a relapse-related signature was constructed with an approach that allowed no information leakage during each training step, using 10-fold cross-validation and 100 random partitioning procedures. Results We identified a relapse-related molecular signature represented by 82 probes (RRS-82) through genome-wide expression profiling analysis of a training set of 60 patients. The robustness of RRS-82 in the selection of patients with a high probability of relapse was then validated with a completely blinded test set of 27 adenocarcinoma patients, showing a clear association of high risk RRS-82 with very poor patient prognosis regardless of disease stage. The discriminatory power of RRS-82 was further validated using an additional independent cohort of 30 stage I patients who underwent surgery at a distinct period of time as well as with the Duke data set on a different platform. Furthermore, completely separate training and validation procedures using another data set recently reported by the Director's Challenge Consortium also successfully confirmed the predictive power of the genes comprising RRS-82. Conclusion RRS-82 may be useful for identifying adenocarcinoma patients at very high risk for relapse, even those with cancer in the early stage.
BRAF Mutation Testing of Thyroid Fine-Needle Aspiration Biopsy Specimens for Preoperative Risk Stratification in Papillary Thyroid Cancer
Authors: Xing Mingzhao , Clark Douglas , Guan Haixia , Ji Meiju , Dackiw Alan , Carson Kathryn A. , Kim Matthew , Tufaro Anthony , Ladenson Paul , Zeiger Martha , Tufano Ralph 
Published: May 2009

Purpose This study investigated the utility of BRAF mutation testing of thyroid fine-needle aspiration biopsy (FNAB) specimens for preoperative risk stratification in papillary thyroid cancer (PTC). Patients and Methods We assessed the T1799A BRAF mutation status in thyroid FNAB specimens obtained from 190 patients before thyroidectomy for PTC and its association with clinicopathologic characteristics of the tumor revealed postoperatively. Results We observed a significant association of BRAF mutation in preoperative FNAB specimens with poorer clinicopathologic outcomes of PTC. In comparison with the wild-type allele, BRAF mutation strongly predicted extrathyroidal extension (23% v 11%; P = .039), thyroid capsular invasion (29% v 16%; P = .045), and lymph node metastasis (38% v 18%; P = .002). During a median follow-up of 3 years (range, 0.6 to 10 years), PTC persistence/recurrence was seen in 36% of BRAF mutation–positive patients versus 12% of BRAF mutation–negative patients, with an odds ratio of 4.16 (95% CI, 1.70 to 10.17; P = .002). The positive and negative predictive values for preoperative FNAB-detected BRAF mutation to predict PTC persistence/recurrence were 36% and 88% for overall PTC and 34% and 92% for conventional PTC, respectively. Conclusion Preoperative BRAF mutation testing of FNAB specimens provides a novel tool to preoperatively identify PTC patients at higher risk for extensive disease (extrathyroidal extension and lymph node metastases) and those who are more likely to manifest disease persistence/recurrence. BRAF mutation, as a powerful risk prognostic marker, may therefore be useful in appropriately tailoring the initial surgical extent for patients with PTC.
Phase II Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With Hairy Cell Leukemia
Authors: Kreitman Robert J. , Stetler-Stevenson Maryalice , Margulies Inger , Noel Pierre , FitzGerald David J.P. , Wilson Wyndham H. , Pastan Ira 
Published: May 2009

Purpose To conduct a phase II trial in chemoresistant hairy cell leukemia (HCL) with BL22, a recombinant anti-CD22 immunotoxin which showed phase I activity in HCL. Patients and Methods Eligible patients had relapsed/refractory HCL and needed treatment based on blood counts. Patients were stratified into three groups: response to cladribine less than 1 year, those with a response lasting 1 to 4 years, or no response and uncontrolled infection. Patients received BL22 40 μg/kg every other day for three doses on cycle 1. Those achieving hematologic remission (HR), defined as neutrophils ≥ 1,500/mm3, hemoglobin ≥ 11 g/dL, and platelets ≥ 100,000/mm3, were observed. Patients without HR were re-treated at 30 μg/kg every other day for three doses every 4 weeks beginning at least 8 weeks after cycle 1. Results Thirty-six patients were enrolled including 26, nine, and one in groups 1 to 3. The response after one cycle (CR, 25%; PR, 25%) improved when 56% were re-treated (CR, 47%; PR, 25%). CR rate was similar in groups 1 and 2 (P = .7). Twenty-two with baseline spleen height lower than 200 mm had higher CR (64% v 21%; P = .019) and OR rates (95% v 36%; P = .0002) compared to 14 with spleens either absent or higher than 200 mm. The only serious toxicity was reversible grade 3 hemolytic uremic syndrome, not requiring plasmapheresis, in two patients (6%). High neutralizing antibodies were observed in four patients (11%) and prevented re-treatment. Conclusion BL22 activity in HCL is confirmed. Best responses to BL22 after cladribine failure are achieved before the patients develop massive splenomegaly or undergo splenectomy.
Outcome in a Prospective Phase II Trial of Medically Inoperable Stage I Non–Small-Cell Lung Cancer Patients Treated With Stereotactic Body Radiotherapy
Authors: Baumann Pia , Nyman Jan , Hoyer Morten , Wennberg Berit , Gagliardi Giovanna , Lax Ingmar , Drugge Ninni , Ekberg Lars , Friesland Signe , Johansson Karl-Axel , Lund Jo-Åsmund , Morhed Elisabeth , Nilsson Kristina , Levin Nina , Paludan Merete , Sederholm Christer , Traberg Anders , Wittgren Lena , Lewensohn Rolf 
Published: May 2009

Purpose The impact of stereotactic body radiotherapy (SBRT) on 3-year progression-free survival of medically inoperable patients with stage I non–small-cell lung cancer (NSCLC) was analyzed in a prospective phase II study. Patients and Methods Fifty-seven patients with T1NOMO (70%) and T2N0M0 (30%) were included between August 2003 and September 2005 at seven different centers in Sweden, Norway, and Denmark and observed up to 36 months. SBRT was delivered with 15 Gy times three at the 67% isodose of the planning target volume. Results Progression-free survival at 3 years was 52%. Overall- and cancer-specific survival at 1, 2, and 3 years was 86%, 65%, 60%, and 93%, 88%, 88%, respectively. There was no statistically significant difference in survival between patients with T1 or T2 tumors. At a median follow-up of 35 months (range, 4 to 47 months), 27 patients (47%) were deceased, seven as a result of lung cancer and 20 as a result of concurrent disease. Kaplan-Meier estimated local control at 3 years was 92%. Local relapse was observed in four patients (7%). Regional relapse was observed in three patients (5%). Nine patients (16%) developed distant metastases. The estimated risk of all failure (local, regional, or distant metastases) was increased in patients with T2 (41%) compared with those with T1 (18%) tumors (P = .027). Conclusion With a 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances.
Effects of Angiotensin-Converting Enzyme Inhibitor Versus Valsartan on Cellular Signaling Events in Heart Transplant
Authors: White Michel , Ross Heather , Levesque Sylvie , Whittom Lucette , Pelletier Guy B , Racine Normand , Meloche Sylvain , Voisin Laure 
Published: May 2009

Background Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) provide similar biologic effects in model systems and similar clinical impacts in humans. The changes in the cardiac angiotensin system signaling pathways in the human heart in response to ACE inhibitors versus ARBs have been incompletely studied. Objective To investigate the effects of ACE inhibitors versus valsartan on the angiotensin II signal transduction pathways in the transplanted human heart. Methods Twenty-seven stable cardiac transplant recipients were randomized to remain on ACE inhibitor therapy (n = 8) or to receive valsartan (n = 19). Two additional endomyocardial biopsy samples were obtained at baseline and after 9 months of therapy. The expression of cardiac angiotensin type I and II receptors and atrial natriuretic factor (ANF) was measured by quantitative polymerase chain reaction. The expression and phosphorylation levels of selected signal transduction pathways were analyzed by immunoblotting. Results The mean dose of valsartan was 114 ± 41 mg/day. The use of valsartan resulted in a similar impact on blood pressure and biochemistry profile. There were no significant changes in the expression of angiotensin type I and II receptors and ANF with valsartan. Similarly, no significant changes in the expression and phosphorylation of Jun N-terminal kinase, extracellular signal–regulated kinase 1 and 2, and p38 mitogen-activated protein kinases or AKT, and mammalian target of rapamycin was observed in the valsartan-treated group. Conclusions Valsartan use is associated with similar clinical and molecular cardiac effects as ACE inhibitor therapy in stable long-term cardiac transplant recipients.
Community Pharmacist–Provided Extended Diabetes Care
Authors: Doucette William R , Witry Matthew J , Farris Karen B , Mcdonough Randal P 
Published: May 2009

Background Pharmacists in various settings have been effective in initiating diabetes treatment. Patients with diabetes require ongoing disease management, and community pharmacists are in a strategic position to provide such extended care. Little is known, however, about the effects of community pharmacist–provided interventions beyond the initial treatment period. Objective To evaluate the effect of community pharmacist–provided extended diabetes care service on primary clinical outcomes, including hemoglobin A1c (A1C), low-density lipoprotein cholesterol (LDL-C), and blood pressure, and on patients' reported self-care activities. Methods A randomized controlled trial was conducted in patients with diabetes. Participants had already completed at least 2 diabetes education sessions at a local diabetes education center. Nine specially trained pharmacists administered interventions during up to 4 quarterly visits per patient. Interventions included discussing medications, clinical goals, and self-care activities with patients and recommending medication changes to physicians when appropriate. The main outcome measures were 12-month changes in A1C, LDL-C, blood pressure, and self-report of self-care activities. Results Seventy-eight patients participated in the study (36 intervention, 42 control); 66 were included in the final analysis (31 intervention, 35 control). Compared with changes in the control group, patients who received interventions significantly increased the number of days per week that they engaged in a set of diet and diabetes self-care activities (1.25 and 0.73 more days/wk, respectively). The mean 12-month changes for A1C, LDL-C, and blood pressure were not significantly different between the 2 study groups. Conclusions Although pharmacist-provided interventions did not demonstrate statistically significant improvements in clinical outcomes over the study period, study results did show that pharmacists were effective at increasing the number of days that patients spent engaging in healthy diet and diabetes self-care activities. Addressing lifestyle and self-care behaviors can be a beneficial component of a pharmacist-provided extended diabetes care service.
Evaluating the Incidence of Leukopenia and Neutropenia with Valproate, Quetiapine, or the Combination in Children and Adolescents
Authors: Rahman Aminur , Mican Lisa M , Fischer Charles , Campbell Angela H 
Published: May 2009

Background At the Austin State Hospital, Austin, TX, a number of cases of neutropenia and leukopenia have been observed in children and adolescents who were treated with the combination of valproate and quetiapine. Use of this combination has raised concerns regarding an increased risk of hematologic toxicity. Objective To evaluate the incidence of leukopenia and neutropenia associated with the use of valproate, quetiapine, or the combination in the child and adolescent population. Methods This study was a retrospective evaluation of patients from the child and adolescent psychiatric service of the Austin State Hospital who were treated with valproate, quetiapine, or the combination. Subjects were selected from patients discharged between August 1, 2004, and August 31, 2007. Laboratory data were evaluated to determine the incidence and severity of leukopenia and neutropenia associated with valproate, quetiapine, and a combination of the 2. Results A total of 131 patients were included in the study. Analysis of the laboratory data revealed a combined incidence of neutropenia and/or leukopenia of 44%, 26%, and 6% in the combination group, valproate monotherapy group, and quetiapine monotherapy group, respectively. Differences in the incidence of neutropenia and/or leukopenia between the quetiapine monotherapy group and valproate monotherapy group, as well as the quetiapine monotherapy group and the combination group reached statistical significance. A significant difference was found among groups based on absolute neutrophil count Common Toxicity Criteria severity (p < 0.001). The combination group differed significantly in incidence of moderate-to-severe neutropenia (14 cases) from both the valproate (5 cases) and quetiapine (0 cases) monotherapy groups, A significantly greater number (44%) of African American patients experienced neutropenia and/or leukopenia than white (not Hispanic or Latino; 29%) or Hispanic or Latino (11%) patients. Conclusions Patients treated with valproate or the combination of valproate and quetiapine should be monitored for the occurrence of leukopenia and neutropenia. Controlled studies are warranted to examine possible pharmacokinetic and pharmacodynamic interactions with the combination of valproate and quetiapine to further evaluate the hematologic findings of this study.
Clinical Evidence of Interaction Between Itraconazole and Nonnucleoside Reverse Transcriptase Inhibitors in HIV-Infected Patients with Disseminated Histoplasmosis
Authors: Andrade Roberto A , Evans Richard T , Hamill Richard J , Zerai Teddy , Giordano Thomas P 
Published: May 2009

Background Itraconazole is the preferred drug for chronic maintenance therapy in HIV-infected patients with disseminated histoplasmosis. Unfortunately, few clinical data exist confirming a presumed interaction between itraconazole and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Objective To determine whether serum itraconazole concentrations are affected by the type of antiretroviral therapy (NNRTI or protease inhibitor [PI]) being taken concomitantly. Methods This retrospective cohort identified patients on antiretroviral therapy and itraconazole for disseminated histoplasmosis between January 2003 and December 2006 at a large HIV clinic in Houston, TX. Available laboratory values were abstracted from medical records. Results Thirteen itraconazole concentrations from 10 patients were avaitable for analysis: 7 patients were on concomitant Pls, 4 on concomitant NNRTIs, and 2 on antiretroviral regimens containing both Pls and NNRTIs. Six of the itraconazole concentrations during concomitant PI treatment were therapeutic (>1.0 μg/mL). in contrast with none in patients taking an NNRTI. All patients taking concomitant NNRTIs had undetectable serum itraconazole concentrations (<0.05 μg/mL). Two patients switched from NNRTI-based to PI-based antiretroviral regimens and subsequently reached therapeutic itraconazole concentrations. Although limited by small sample size, this study provides the largest clinical data among HIV-infected patients demonstrating that coadministration of an NNRTI and itraconazole results in significant decreases in itraconazole blood concentrations, likely by inducing the CYP3A4 enzyme system. Conclusions Itraconazole concentrations should be monitored in patients taking concomitant NNRTIs. PI-based highly active antiretroviral therapy (HAART) may be preferred over NNRTI-based HAART when itraconazole is used to treat HIV-infected patients with disseminated histoplasmosis.
Prevalence of Use and the Risk of Adverse Effects Associated with Complementary and Alternative Medicine in a Cohort of Patients Receiving Warfarin
Authors: Leung Vivian Wy , Shalansky Stephen J , Lo Melissa K , Jadusingh Esther A 
Published: May 2009

Background The use of complementary and alternative medicine (CAM), including orally administered herbals, botanicals, vitamins, and supplements, may pose a risk to patients on warfarin therapy. Objective To estimate the prevalence of CAM use among patients taking warfarin and evaluate the impact of CAM exposure on the risk of warfarin-related adverse effects. Methods A survey was administered to hospital inpatients and clinic outpatients on drug exposure (including CAM) over the previous month, self-reported bleeding events, use of alcohol and vitamin K–rich foods, and medical conditions. Prescription medication use was verified, and laboratory records were checked for out-of-range international normalized ratios (INRs) (defined as INR >4 or <2). The use of CAM, including products with reported or theoretical interactions with warfarin, was compared between patients with and without self-reported bleeding or out-of-range INR. Results Among the 314 patients who completed the survey, 44.3% reported using CAM at least weekly. Potentially interacting CAM was used by 34.1% of all patients, or 18.2% if vitamin E was excluded as an interacting CAM. Vitamin E was used by 24.2% of all patients and 71.0% of those who used potentially interacting CAM. There was no significant difference in CAM use or consumption of vitamin K–rich foods between patients with and without INRs greater than 4 or for patients with and without INRs less than 2. Conclusions The use of potentially interacting CAM in this cohort was higher than the use previously reported among patients on warfarin therapy. However, exposure to CAM was not associated with an increase in the risk of self-reported bleeding or out-of-range INR.
New Drug Approvals: Romiplostim Management of Immune Thrombocytopenic Purpura
Authors: Ipema Heather J , Jung Michelle Y , Lodolce Amy E 
Published: May 2009

Objective To review the pharmacology, pharmacokinetics, efficacy, and safety of romiplostim, the first drug approved for use in patients with immune thrombocytopenic purpura (ITP). Data Sources Articles were identified through searches of MEDLINE (1966–January 2009) and International Pharmaceutical Abstracts (1970–January 2009) using the key words romiplostim and AMG 531. Searches were limited to articles published in English. The manufacturer was contacted for additional data. Study Selection And Data Extraction Clinical trials and pharmacokinetic data were selected for review. Data Synthesis Romiplostim is a second-generation thrombopoietic receptor agonist that exerts its therapeutic effect by stimulating megakaryopoiesis. Subcutaneous therapy results in a dose-dependent increase in platelets; however, interindividual variability exists. Time to peak concentration is approximately 14 hours, and the elimination half-life is approximately 3.5 days (range 1–34). Romiplostim undergoes endothelial recirculation and is eliminated by the reticuloendothelial system. The results of 2 Phase 3, randomized, double-blind, placebo-con trolled trials have demonstrated the efficacy of romiplostim for increasing platelet counts in patients with ITP refractory to other therapies, including splenectomy. Effects on platelets were transient and decreased within 2 weeks of discontinuing the drug. Interim results of an open-label extension study revealed that romiplostim has sustained efficacy and tolerability for up to 156 weeks at a dosage range of 1–17 μg/kg/wk (mean 5.9 ± 3.9). The most common adverse effects include headache, fatigue, epistaxis, and contusion. Romiplostim is also under investigation for treatment of thrombocytopenia associated with myelodysplastic syndrome. The drug must be ordered directly from the manufacturer through a limited access program, and weekly subcutaneous injections are given in the clinic setting. Conclusions Romiplostim is effective for the management of ITP in adults refractory to other therapies, including splenectomy.
Self-Medication of Upper Gastrointestinal Symptoms: A Community Pharmacy Study
Authors: Mehuys Els , Bortel Luc Van , Bolle Leen De , Tongelen Inge Van , Remon Jean-Paul , Looze Danny De 
Published: May 2009

Background Upper gastrointestinal (GI) symptoms are a common reason for self-treatment with over-the-counter (OTC) medication. However, data are scarce on the typology of GI complaints for which individuals seek self-medication and, more importantly, on the prevalence of alarm symptoms in this population. Objective To investigate: (1) the nature of GI symptoms that people intend to self-medicate, (2) prevalence of alarm symptoms, (3) adherence to referral advice given by the pharmacist, and (4) self-reported efficacy and frequency of use of OTC medication for minor complaints. Methods This descriptive study was performed in 63 community pharmacies. Participants (N = 592, aged 18–82 y) completed a questionnaire to assess symptom characteristics and previous medical consulting. Based on this information, the pharmacist referred subjects to a physician or advised self-treatment. Four weeks later, participants were presented a follow-up questionnaire evaluating their adherence to referral advice or efficacy of self-treatment. Results The most frequently reported GI symptoms were burning retrosternal discomfort (49.2%), acid regurgitation (53.2%), and bothersome postprandial fullness (51.2%). At least one alarm symptom was present in 22.4% of the individuals, with difficulty in swallowing being the most prevalent (15.4%). Although 21% of the customers were referred, only 51.7% of these contacted a physician. Almost all (95.1%) of the remaining customers who were advised self-treatment reported symptom relief with the OTC drug obtained. Conclusions Mild GI symptoms will mostly resolve with self-treatment. Yet, the value of pharmacist counseling on OTC treatment should be recognized, as community pharmacists can play an important role in distinguishing symptoms that warrant further medical examination.