bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing Patterns of Resistance to Ampicillin/Sulbactam
Authors: Yasuda Sally Usdin , Kumar Princy N , Young Mary A , Timpone Joseph G , Turner Helen C , Pierce Phillip F 
Published: July 2017

Objective: To report on methods to halt the increasing resistance of gram-negative organisms to ampicillin/sulbactam. Design: A before-after observational design was used to evaluate susceptibility of organisms to ampicillin/sulbactam. Setting: A university teaching hospital. Interventions: An educational program regarding appropriate prescribing of ampicillin/sulbactam and restriction of the use of ampicillin/sulbactam. Main Outcome Measures: Antimicrobial susceptibility to ampicillin/sulbactam. Results: The trend in increasing resistance was halted for Escherichia coli and Enterobacter. Emerging resistance of other organisms was not observed. Conclusions: The trend in increasing resistance was halted by restrictions on prescribing and by providing education regarding rational prescribing of ampicillin/sulbactam. We recommend that this combination not be used empirically to treat nosocomial infections or for bacteria against which ampicillin alone is effective.
Improving Medication Compliance: A Practical Intervention
Authors: Perri Matthew , Martin Bradley C , Pritchard Franklin L 
Published: July 2017

Objective: To examine the effect of a device specifically designed to improve patient medication compliance. This device, the Counter Cap (CC), is a prescription vial closure that mechanically indicates when the bottle was last opened, presumably to take a dose of medication. The primary objective was to assess the effect of the CC on patient compliance as measured by refill behavior. Method: An experimental pretest-posttest control group design was used to study the effect of the CC on patient compliance. A systematic sampling technique was used to assign subjects to the experimental and control groups. Patient compliance was assessed through prescription refill behaviors measured over a six-month period (three months pre-CC and three months post-CC). Results: A full six months of prescription refill data were analyzed for 186 of 337 patients from 21 pharmacies. Patients in the experimental group (n = 88) demonstrated significantly improved (F = 4.44, p = 0.0366) medication compliance and less variability in the number of days of departure from the ideal compliance rate (F = 6.89, p = 0.009) over the control group (n = 98) as measured by refill behavior. Conclusions: The CC proved to be an inexpensive means to improve medication compliance as defined by this investigation.
Atypical Neuroleptic Malignant Syndrome Presenting as Rhabdomyolysis, Altered Consciousness, and Leukocytosis
Authors: Azaz-Livshits Tanya L , Symmer Lev I , Fraenkel Yehuda M 
Published: July 2017

Objective: To provide a clinically accurate description of an atypical form of neuroleptic malignant syndrome (NMS) induced by perphenazine, to underline the importance of early diagnosis of this atypical form of NMS, and to stimulate discussion of possible mechanisms of this adverse drug event. Case Summary: A 61-year-old man had received perphenazine for 5 years for treatment of schizophrenia. He presented with progressive muscle rigidity, difficulty walking, and lower back pain. He was found to be disoriented and confused with tardive dyskinesia and muscle weakness. The patient was afebrile and normotensive. Clinical workup and laboratory test results were consistent with a diagnosis of rhabdomyolysis. The patient was treated with rehydration and sodium bicarbonate. Perphenazine therapy was discontinued and the symptoms resolved within 3 days. Discussion: Rhabdomyolysis has been reported in patients receiving psychotropic drugs, but the frequency of the occurrence is not known. The most frequent cause of rhabdomyolysis in psychiatric patients is NMS; however, this patient had only part of the classical picture of NMS. Other cases of atypical presentation are reviewed. Conclusions: Muscle injury in the presence of psychotropic drugs can manifest in many different ways. This suggests a complex mechanism of injury, involving central mechanisms as well as direct injury to the muscle.
Eosinophilia Possibly Associated with Intravenous Levofloxacin
Authors: LeDuc Andrea G , Zimmermann Anthony E 
Published: July 2017

Objective: To report the first published case of eosinophilia following the administration of intravenous levofloxacin. Case Summary: An 84-year-old white man was admitted for community-acquired pneumonia, for which he received intravenous levofloxacin therapy. The absolute eosinophil count on admission was 120 cells/mm3 (differential 3.5%). On day 6 of admission and therapy, the absolute eosinophil count peaked at 957 cells/mm3 (differential 16.8%) and then returned to a normal value of 1.2% on day 7, one day after discontinuation of levofloxacin. Discussion: Fluoroquinolones are broad-spectrum antimicrobials used frequently to treat a variety of infections. A review of MEDLINE (1996-May 1999) did not yield any previous reports of eosinophilia associated with intravenous levofloxacin therapy. However, many quinolones have been associated with eosinophilia, occasionally with significant associated morbidity. This patient's eosinophilia developed within one day of initiating levofloxacin and resolved within one day of discontinuation of the drug. To our knowledge, this is the first reported case of eosinophilia related to intravenous levofloxacin therapy. Conclusions: The temporal relationship of events in this case suggests that levofloxacin was the cause of this patient's eosinophilia. We report this case to alert clinicians to the possibility of eosinophilia associated with levofloxacin.
Dominant hand, non-dominant hand, or both? The effect of pre-training in hand-eye coordination upon the learning curve of laparoscopic intra-corporeal knot tying
Authors: Molinas Carlos Roger , Binda Maria Mercedes , Campo Rudi 
Published: July 2017

Abstract
Background
Training of basic laparoscopic psychomotor skills improves both acquisition and retention of more advanced laparoscopic tasks, such as laparoscopic intra-corporeal knot tying (LICK). This randomized controlled trial (RCT) was performed to evaluate the effect of different pre-training programs in hand-eye coordination (HEC) upon the learning curve of LICK.

Results
The study was performed in a private center in Asunción, Paraguay, by 60 residents/specialists in gynaecology with no experience in laparoscopic surgery. Participants were allocated in three groups. In phase 1, a baseline test was performed (T1, three repetitions). In phase 2, participants underwent different training programs for HEC (60 repetitions): G1 with both the dominant hand (DH) and the non-dominant hand (NDH), G2 with the DH only, G3 none. In phase 3, a post HEC/pre LICK training test was performed (T2, three repetitions). In phase 4, participants underwent a standardized training program for LICK (60 repetitions). In phase 5, a final test was performed (T3, three repetitions). The score was based on the time taken for task completion system. The scores were plotted and non-linear regression models were used to fit the learning curves to one- and two-phase exponential decay models for each participant (individual curves) and for each group (group curves). For both HEC and LICK, the group learning curves fitted better to the two-phase exponential decay model. For HEC with the DH, G1 and G2 started from a similar point, but G1 reached a lower plateau at a higher speed. In G1, the DH curve started from a lower point than the NDH curve, but both curves reached a similar plateau at comparable speeds. For LICK, all groups started from a similar point, but immediately after HEC training and before LICK training, G1 scored better than the others. All groups reached a similar plateau but with a different decay, G1 reaching this plateau faster than the others groups.

Conclusions
This study demonstrates that pre-training in HEC with both the DH and the NDH shortens the LICK learning curve.
Analysis of Adjuvant Endocrine Therapy in Practice From Electronic Health Record Data of Patients With Breast Cancer
Authors: Harrell Morgan , Fabbri Daniel , Levy Mia 
Published: July 2017

Purpose Adjuvant endocrine therapy is a long-term drug therapy prescribed to prevent recurrence of hormone receptor–positive breast cancer. Data on adjuvant endocrine therapy are reported though clinical trials, which may differ from treatment practice and outcomes in the general population of patients with breast cancer. With secondary use of electronic health record (EHR) data, we summarize adjuvant endocrine treatment practice and outcomes in real-world settings. Methods We analyzed treatment data derived from EHR data on 1,587 patients with stage I to III breast cancer at a National Cancer Institute–designated comprehensive cancer center to learn the frequencies of real-world adjuvant endocrine drug switches and discontinuation and to explore the potential cause for drug switches and discontinuation from medical records. We measured rates of drug use, drug switches, early drug discontinuation, adverse events, recurrence, and death. We also measured adverse events and change in menopause status as potential causes for drug switch and discontinuation. Results Within the study population, approximately 49% of patients were lost to follow-up or did not complete adjuvant treatment through 5 years. Fifty-two percent of patients switched to a different endocrine therapy drug during their treatment. We found that age is correlated with drug switches and that adverse events are correlated with drug switches and discontinuation. We also found that patients who switched to an alternative endocrine therapy during treatment were more likely to complete 5 years of treatment. Conclusion This study describes long-term adjuvant endocrine treatment in real-world settings and demonstrates the ability to leverage longitudinal EHR data to characterize oral medication treatment patterns in patients with cancer.
Breast Cancer Chemoprevention in an Integrated Health Care Setting
Authors: Nichols Hazel B. , Stürmer Til , Lee Valerie S. , Anderson Chelsea , Lee Jean S. , Roh Janise M. , Visvanathan Kala , Muss Hyman , Kushi Lawrence H. 
Published: July 2017

PurposeNational guidelines encourage counseling high-risk women about pharmacologic breast cancer risk reduction. We evaluated the use of integrated health care data to identify and characterize breast cancer chemoprevention use. Chemoprevention included US Food and Drug Administration–approved use of tamoxifen and raloxifene and off-label use of aromatase inhibitors (AIs).Patients and MethodsUsing electronic medical and pharmacy records (EMRs) in the Kaiser Permanente Northern California health care system, we sampled cancer-free women age 35 to 69 years who used tamoxifen, raloxifene, exemestane, anastrozole, or letrozole from 2005 to 2013. Risk-benefit profiles were calculated for tamoxifen and raloxifene using published indices. The proportion of days covered was calculated from pharmacy records to assess adherence.ResultsAmong 90 chemoprevention users (confirmed with EMR review from a sample of 371 women), 74% used tamoxifen, 11% used raloxifene, and 13% used an AI. For tamoxifen and raloxifene users, the risk-benefit index indicated 23% of women had insufficient evidence that benefits would outweigh risks. For all agents, adherence decreased from an average proportion of days covered of 75% at 1 year to 67% at 5 years. Automated EMR searches identified breast cancer chemoprevention users with 60% positive predictive value overall and 75% for tamoxifen after post hoc modifications.ConclusionOur study contributes to an emerging picture of breast cancer chemoprevention use in real-world settings, where evidence of net benefit is not uniform and nonadherence is common. Among breast cancer chemoprevention agents, our automated selection best performed for tamoxifen use. We also identified off-label use of AIs for chemoprevention, suggesting that expansion of risk-benefit indices to include AIs is warranted.
Tabular Versus Synoptic Reporting of Prostate Core Needle Biopsies
Authors: Renshaw Andrew A. , Mena-Allauca Mercy , Gould Edwin W. 
Published: July 2017

Purpose To compare synoptic versus tabular formats for reporting prostate core needle biopsy results. The format of a report can significantly affect the accuracy, speed, and preference with which a reader can retrieve information. Methods We compared the performance of 20 nonpathologists in the identification of specific information in synoptic and tabular reports using a computerized quiz that measured both accuracy and speed. Results Tabular formatting was significantly more accurate (97% v 93%; P = .001) and faster (mean normalized time, 0.74 + 0.40 v 0.99 + 0.52; P < .001) than synoptic formatting. The improvement in accuracy was a result of questions that involved combining results from two different biopsies (96% v 92%; P = .03). The improvement in speed was observed for both single-value questions (0.77 + 0.41 v 0.87 + 0.39; P = .03) and combination questions (0.73 + 0.40 v 1.05 + 0.56; P < .001). Data extraction from a tabular format into a structured data file using free text extraction on the basis of punctuation was 100% successful. Conclusion Tabular reporting of prostate needle biopsies allows significantly faster and more accurate identification of data by the user, especially when the data involve combining data from several biopsies. The tabular format does not impact the ability to create structured data files.
Randomized Electronic Promotion of Lung Cancer Screening: A Pilot
Authors: Begnaud Abbie L. , Joseph Anne M. , Lindgren Bruce R. 
Published: July 2017

Purpose Screening for lung cancer with low-dose computed tomography is endorsed by the US Preventive Services Task Force, but many eligible patients have yet to be offered screening. Major barriers to the implementation of screening are physician and system related—the requirement for a detailed smoking history, including pack-years, to determine eligibility. We conducted this pilot to determine the feasibility of lung cancer screening (LCS) promotion that would offer screening to eligible persons and patient completion of smoking history to estimate the size of the population of former smokers who may be eligible for LCS in a single health care system. Patients and Methods Two hundred participants were randomly selected from former smokers who were seen at the University of Minnesota Health in the past 2 years and assigned to control (usual care) and electronic promotion, stratified by age. Electronic messages to promote LCS were sent to an intervention group, including a link to complete a detailed smoking history in the electronic health record. Results Of 99 participants, 66 (67%) in the intervention group read the message, 24 (36%) of 66 responded, and 19 (79%) of 24 respondents completed the smoking history. Ten intervention participants and 13 usual care participants were eligible for screening on the basis of pack-year history. Four eligible participants underwent screening in the intervention group compared with one participant in the usual care group. Conclusion Electronic promotion may help identify patients who are eligible for LCS but will not reliably reach all patients because of low response rates. In this sample of former smokers, the majority are ineligible for LCS on the basis of pack-year history. Electronic methods can improve documentation of smoking history.
Window-of-Opportunity Study of Valproic Acid in Breast Cancer Testing a Gene Expression Biomarker
Authors: Cohen Adam L. , Neumayer Leigh , Boucher Ken , Factor Rachel E. , Shrestha Gajendra , Wade Mark , Lamb John G. , Arbogast Kylee , Piccolo Stephen R. , Riegert Joanna , Schabel Matthias , Bild Andrea H. , Werner Theresa L. 
Published: July 2017

PurposeThe anticancer activity of valproic acid (VPA) is attributed to the inhibition of histone deacetylase. We previously published the genomically derived sensitivity signature for VPA (GDSS-VPA), a gene expression biomarker that predicts breast cancer sensitivity to VPA in vitro and in vivo. We conducted a window-of-opportunity study that examined the tolerability of VPA and the ability of the GDSS-VPA to predict biologic changes in breast tumors after treatment with VPA.Patients and MethodsEligible women had untreated breast cancer with breast tumors larger than 1.5 cm. After a biopsy, women were given VPA for 7 to 12 days, increasing from 30 mg/kg/d orally divided into two doses per day to a maximum of 50 mg/kg/d. After VPA treatment, serum VPA level was measured and then breast surgery or biopsy was performed. Tumor proliferation was assessed by using Ki-67 immunohistochemistry. Histone acetylation of peripheral blood mononuclear cells was assessed by Western blot. Dynamic contrast-enhanced magnetic resonance imaging scans were performed before and after VPA treatment.ResultsThirty women were evaluable. The median age was 54 years (range, 31-73 years). Fifty-two percent of women tolerated VPA at 50 mg/kg/d, but 10% missed more than two doses as a result of adverse events. Grade 3 adverse events included vomiting and diarrhea (one patient) and fatigue (one patient). The end serum VPA level correlated with a change in histone acetylation of peripheral blood mononuclear cells (ρ = 0.451; P = .024). Fifty percent of women (three of six) with triple-negative breast cancer had a Ki-67 reduction of at least 10% compared with 17% of other women. Women whose tumors had higher GDSS-VPA were more likely to have a Ki-67 decrease of at least 10% (area under the curve, 0.66).ConclusionVPA was well tolerated and there was a significant correlation between serum VPA levels and histone acetylation. VPA treatment caused a decrease in proliferation of breast tumors. The genomic biomarker correlated with decreased proliferation. Inhibition of histone deacetylase is a valid strategy for drug development in triple-negative breast cancer using gene expression biomarkers.
Prospective Feasibility Study for Using Cell-Free Circulating Tumor DNA–Guided Therapy in Refractory Metastatic Solid Cancers: An Interim Analysis
Authors: Kim Seung Tae , Banks Kimberly C. , Lee Se-Hoon , Kim Kyung , Park Joon Oh , Park Se Hoon , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Lanman Richard B. , Talasaz AmirAli , Park Keunchil , Lee Jeeyun 
Published: July 2017

Purpose Retrospective studies have demonstrated that cell-free circulating tumor DNA (ctDNA) hotspot testing predicts matched therapy response to first- and second-line therapies in patients with advanced non–small-cell lung cancer (NSCLC). However, no prospective outcomes studies have evaluated ctDNA-guided matched therapy decision making on the basis of comprehensive plasma genomic testing including all four major classes of alterations. Here, we report the clinical utility of this approach in advanced solid tumor cancers. Patients and Methods We conducted a multiple parallel cohort, open-label, clinical trial using ctDNA-guided matched therapy when tissue was insufficient or unobtainable for next-generation sequencing. Plasma-based digital sequencing identified point mutations in 70 genes and indels, fusions, and copy number amplifications in selected genes. Patients with prespecified targetable alterations in metastatic NSCLC, gastric cancer (GC), and other cancers were matched to several independent targeted agent trials at a tertiary academic center. Results Somatic alterations were detected in 59 patients with GC (78%), and 25 patients (33%) had targetable alterations ( ERBB2, n = 11; MET, n = 5; FGFR2, n = 3; PIK3CA, n = 6). In NSCLC, 62 patients (85%) had somatic alterations, and 34 (47%) had targetable alterations ( EGFR, n = 29; ALK, n = 2; RET, n = 1; ERBB2, n = 2). After confirmation of ctDNA findings on tissue (to meet trial eligibility criteria), 10 patients with GC and 17 patients with NSCLC received molecularly matched therapy. Response rate and disease control rate were 67% and 100%, respectively, in GC and 87% and 100%, respectively, in NSCLC. Response was independent of targeted alteration variant allele fraction in NSCLC ( P = .63). Conclusion To our knowledge, this is the first prospective feasibility study of comprehensive ctDNA-guided treatment in advanced GC and lung cancers. Response rates in this interim analysis are similar to those in tissue-based targeted therapy studies.
Parental Perspectives on Whole-Exome Sequencing in Pediatric Cancer: A Typology of Perceived Utility
Authors: Malek Janet , Slashinski Melody J. , Robinson Jill O. , Gutierrez Amanda M. , Parsons D. Williams , Plon Sharon E. , McCullough Laurence B. , McGuire Amy L. 
Published: July 2017

Purpose To explore how parents of pediatric patients with cancer perceived the utility of clinical tumor and germline whole-exome sequencing (WES) results. Patients and Methods We conducted longitudinal interviews with parents of a diverse pediatric cancer population before disclosure of WES results (n = 64), then 1 to 8 months (n = 33) after disclosure. Interview transcripts were analyzed using a thematic qualitative approach. Results Parents identified a broad range of types of utility for their child’s WES results. Even when results did not affect their child’s current treatment, they expressed optimism about future clinical utility for their child, themselves, and other family members. Parents also reported experiencing psychological utility including peace of mind, relief of guilt, and satisfaction of curiosity. Pragmatic utility, such as the ability to plan for the future and make better reproductive decisions, was also described. Conclusion Parents of pediatric patients with cancer perceive WES to have broad utility, including psychological and pragmatic utility, even if there is no direct impact on clinical care. Additional research will need to consider how the value of genomic information should be characterized, how risks and benefits should be described, and how these results should inform recommendations and decisions about using WES.
Constructing a Sacred Chronology: How the Nova Scotian Institute of Science Made the Mi’kmaq a People without Prehistory
Authors: Lelièvre Michelle A. 
Published: July 2017

AbstractIn the latter half of the nineteenth century, the Mi’kmaq were the focus of two moments in the development of the public sphere in the British settler colony of Nova Scotia. One moment saw concern for the Mi’kmaq’s welfare increase and the focus of that concern become fixed on “civilizing” through assimilation. Another was a growing scientific curiosity expressed through the founding of intellectual organizations such the Nova Scotian Institute of Science, and often at odds with prevailing religious beliefs, which adhered to the “sacred chronology” of the Bible. These moments converged in the addresses on cultural history made by members of the Nova Scotian Institute of Science between 1864 and 1912. The interpretations offered by the institute’s members demonstrate an increasing separation of the contemporary Mi’kmaq from the precontact past of the province, thus constructing a chronology that—if not biblically sacred—was sacrosanct to the narrative of progress that underlay the settler project in Nova Scotia.