bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Serum Vancomycin Concentration with Renal Dysfunction
Authors: Westrum Paula J , Koo Ji M , Carson Paul J 
Published: July 2017

Objective: To evaluate the association of vancomycin-related renal dysfunction with age; serum vancomycin trough concentration; baseline serum creatinine concentration; duration of vancomycin treatment; comorbid medical conditions of congestive heart failure, chronic renal failure, diabetes mellitus, and hepatic cirrhosis; and the concurrent use of drugs that can cause impairment of renal function. Design: A retrospective analysis of medical records of hospitalized patients who received intravenous vancomycin was conducted. Setting: This study was conducted in a 125-bed, tertiary care, government teaching hospital. Methods: Data were collected on 122 men, ranging in age from 41 to 95 years, who received vancomycin during a five-year period starting in 1991. Vancomycin-related renal dysfunction, defined as an increase of ≥0.5 mg/dL in serum creatinine concentration from the baseline value, was examined for an association with age; baseline serum creatinine concentration; duration of vancomycin treatment; serum vancomycin trough concentrations >15 μg/mL; and comorbid conditions of congestive heart failure, chronic renal failure, diabetes mellitus, and hepatic cirrhosis. The concurrent use of aminoglycosides, amphotericin B, diuretics, angiotensin-converting enzyme (ACE) inhibitors, Cimetidine, and intravenously administered contrast medium was also analyzed. Results: Stepwise logistic regression and odds ratio analyses failed to identify an association between vancomycin-related renal dysfunction and any factor examined except concurrent use of diuretics and ACE inhibitors. Conclusions: Patients receiving intravenous vancomycin concurrently with diuretics or ACE inhibitors have a higher risk of renal impairment. No incident of renal dysfunction was attributed to vancomycin alone.
The Risk of Hypersensitivity Reactions to Trimethoprim/Sulfamethoxazole as a Function of the CD4+ Count in HIV-Infected Patients
Authors: Morikawa Susan J , Cortese Linda M , Walker Janet S , Oster Charles N , Stoute José A 
Published: July 2017

Background: Trimethoprim/sulfamethoxazole (TMP/SMX) is an important antibiotic for the treatment and prevention of opportunistic infections in patients infected with HIV. However, the high rate of hypersensitivity reactions in this population of patients significantly limits the use of this drug. Objective: To determine whether early initiation of Pneumocystis carinii pneumonia prophylaxis with TMP/SMX in patients with HIV whose CD4+ lymphocyte count is >200 cells/mm3 results in a decrease in the number of hypersensitivity reactions. Methods: Retrospective cohort study. The main outcomes measured were the number of and the time to hypersensitivity reactions. Results: There were 134 patients who met the eligibility criteria (62 with a CD4+ cell count ≤200 cells/mm3 and 72 with a CD4+ cell count >200 cells/mm3). Overall, 47 (35.1%) patients had adverse reactions including 29 (21.6%) episodes of hypersensitivity. The mean time to a hypersensitivity reaction for the group with a CD4+ cell count ≤200 cells/mm3 was 155 days and for the group with a CD4+ cell count >200 cells/mm3 it was 261 days (mean difference = 106; p = 0.07; 95% CI 66 to 146 days). The number of episodes of hypersensitivity reactions was similar among the two groups: 15 (24.2%) and 14 (19.4%), respectively (p = 0.5; relative risk for CD4+ cell count ≤200 cells/mm3 = 1.14; 95% CI 0.7 to 1.7). Log-rank test did not reveal a significant difference in reaction-free survival among the groups (p = 0.3). Conclusions: Our data suggest that initiation of P. carinii pneumonia prophylaxis with TMP/SMX at a CD4+ cell count >200 cells/mm3 would lead to prolongation of the mean time to a hypersensitivity reaction, but would not significantly decrease the risk of a reaction over time.
Training Pharmacy Technicians in Support of Rural Health Initiatives: A South Carolina Experience
Authors: Ballington Don A , Hammett Sharon D 
Published: July 2017

Objective: To provide an overview of pharmacy technician distance learning based on an established program. Setting: Technical college pharmacy technician training program cooperating with similar institutions located in remote areas of South Carolina. Discussion: Midlands Technical College, Columbia, SC, developed a project to provide pharmacy technician training in underserved rural South Carolina. Didactic instruction is by live television broadcast that is received in the students' local technical college. Laboratory instruction is conducted in two auxiliary laboratories geographically located within reasonable driving distances of the students' local college; instruction is scheduled to require a minimum number of trips. Experiential training is received in the students' home community. Midlands faculty make monthly visits into distance communities to review student progress. Conclusions: The performance of distance-learning students has thus far matched the performance of Columbia-based students. Student performance, both Columbia and distance-learning, was compared using earned grade points. A statistical analysis was not applied to this comparison. Results from the first two years of this project demonstrated a slightly higher grade-point performance for distance-learning students. Success of distance-learning students has shown that pharmacy technician instruction can be delivered successfully into remote sites in South Carolina.
Somnambulism Precipitated by Selective Serotonin-Reuptake Inhibitors
Authors: Alao Adekola O , Yolles Jennifer C , Aumenta Wendy C , Dewan Mantosh J 
Published: July 2017

Objective: To report a case of somnambulism (sleepwalking) potentially precipitated by selective serotonin-reuptake inhibitors (SSRIs) in an HIV-positive woman. Case Summary: A 34-year-old HIV-positive white woman without a prior history of somnambulism began sleepwalking following treatment for depression with two different SSRIs. The sleepwalking episodes disappeared completely with a reduction of the dosages of the SSRIs and began again when the dosages were increased. Discussion: Somnambulism has been associated with psychoactive drugs that affect the physiology of sleep, awareness, arousal, and memory. A biologic plausibility is supported by the fact that SSRIs alter electroencephalogram and sleep patterns and may be prone to precipitating somnambulism in susceptible individuals. Because people who sleepwalk may not be aware of their actions during such episodes, there is a potential for injury if this adverse effect were to occur. Conclusions: Given the widespread use of SSRIs, clinicians should be aware of the possibility that somnambulism may occur with this class of drugs.
Acute Angioedema Associated with Long-Term Benazepril Therapy
Authors: Maliekal James , Rio Gerald Del 
Published: July 2017

Objective: To report a case of acute angioedema associated with long-term use of benazepril in an elderly patient. Case Summary: A 78-year-old white woman with no past history of angioedema presented to the emergency department in respiratory distress. The patient failed to improve after receiving intravenous methylprednisolone, diphenhydramine, and famotidine. Due to pending airway compromise, the patient required emergency tracheostomy. Based on her presentation and medical history, we attributed the angioedema to long-term benazepril use. Discussion: Angiotensin-Converting enzyme (ACE) inhibitors are known to be associated with angioedema. Most cases of angioedema occur within the first week of therapy. The association of acute onset of angioedema early in the course of ACE inhibitor therapy is well described in published reports. However, angioedema associated with long-term ACE inhibitor therapy has rarely been reported. Conclusions: ACE inhibitor-induced angioedema occurring late in therapy is not well understood and has been infrequently reported in published articles. Aggressive intervention is often needed in severe cases of angioedema, which may compromise airway integrity.
Impact of Protease Inhibitors on Drug Use and Cost for Hospital Patients with HIV
Authors: Peyron Florence , Rahmouni Saïd , Flori Angelise , Moreau Jacques , Charbit Jean-Jacques , Buès-Charbit Martine , Balansard Guy 
Published: July 2017

Objective: To evaluate the impact of protease inhibitors on drug cost and frequency of admission-defining events for HIV-infected patients in the infectious diseases unit of F Houphouët Boigny Hospital in Marseilles, France, which provides conventional hospitalization and outpatient care. Methods: Data from a prospective eight-year study conducted from January 1, 1990, to December 31, 1997, were used. Data from nurse records were collected daily by a pharmacy resident. Statistical analyses were performed to compare 1997 data with previous years, since protease inhibitors were not available in France until March 1996. Results: A total of 1,558 inpatients, accounting for 2,717 admissions, participated in the study. From 1995 to 1997, we observed a decrease in the percentage of hospitalized patients compared with the total number of patients (48.8%). We also noticed a reduction in number of stays (52%) and mean duration of stays (from 16.06 ± 1.81 to 11.08 ± 1.80 d). Total drug cost in the inpatient care unit dropped by one-half (based on 100 patients/y). The number of hospital admissions and mean drug cost per stay also decreased for some opportunistic infections described as late complications of AIDS; at the same time, drug costs in the outpatient unit rose sharply. Conclusions: This study confirms recent advances in HIV management. Use of protease inhibitors has reduced the relative risk of opportunistic infections and cost of inpatient treatment. This reduction has been associated with a sharp cost increase for outpatient therapy, resulting from widespread use of protease inhibitors.
Fosinopril Overdose in an Infant
Authors: Stokes Kimberly A , Lanski Steven L , Leikin Jerrold B 
Published: July 2017

Objective: To report an accidental fosinopril overdose in an infant. Case Summary: A 20-month-old African-American girl ingested approximately 16 mg/kg of fosinopril. Following aggressive gastric decontamination, the patient experienced an uneventful hospital course. Discussion: This appears to be the first report of accidental fosinopril ingestion in an infant. Virtually no adverse effects were noted after an ingestion that was approximately 10 times a therapeutic adult dose. It seems that fosinopril toxicity was minimal in the accidental overdose following early gastric decontamination (within 1 h of ingestion). Conclusions: Observation of vital signs with no invasive procedures appears to be the primary treatment method following early gastric decontamination for an accidental fosinopril overdose in an infant.
Functional and prognostic effects when emphysema complicates idiopathic pulmonary fibrosis
Authors: Jacob Joseph , Bartholmai Brian J. , Rajagopalan Srinivasan , Kokosi Maria , Maher Toby M. , Nair Arjun , Karwoski Ronald , Renzoni Elisabetta , Walsh Simon L.F. , Hansell David M. , Wells Athol U. 
Published: July 2017

This study aimed to investigate whether the combination of fibrosis and emphysema has a greater effect than the sum of its parts on functional indices and outcome in idiopathic pulmonary fibrosis (IPF), using visual and computer-based (CALIPER) computed tomography (CT) analysis.Consecutive patients (n=272) with a multidisciplinary IPF diagnosis had the extent of interstitial lung disease (ILD) scored visually and by CALIPER. Visually scored emphysema was subcategorised as isolated or mixed with fibrotic lung. The CT scores were evaluated against functional indices forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide (DLCO), transfer coefficient of the lung for carbon monoxide (KCO), composite physiologic index (CPI)) and mortality.The presence and extent of emphysema had no impact on survival. Results were maintained following correction for age, gender, smoking status and baseline severity usingDLCO, and combined visual emphysema and ILD extent. Visual emphysema quantitation indicated that relative preservation of lung volumes (FVC) resulted from tractionally dilated airways within fibrotic lung, ventilating areas of admixed emphysema (p<0.0001), with no independent effect on FVC from isolated emphysema. Conversely, only isolated emphysema (p<0.0001) reduced gas transfer (DLCO).There is no prognostic impact of emphysema in IPF, beyond that explained by the additive extents of both fibrosis and emphysema. With respect to the location of pulmonary fibrosis, emphysema distribution determines the functional effects of emphysema.
Discontinuing noninvasive ventilation in severe chronic obstructive pulmonary disease exacerbations: a randomised controlled trial
Authors: Sellares Jacobo , Ferrer Miquel , Anton Antonio , Loureiro Hugo , Bencosme Carolina , Alonso Rodrigo , Martinez-Olondris Pilar , Sayas Javier , Peñacoba Patricia , Torres Antoni 
Published: July 2017

We assessed whether prolongation of nocturnal noninvasive ventilation (NIV) after recovery from acute hypercapnic respiratory failure (AHRF) in chronic obstructive pulmonary disease (COPD) patients with NIV could prevent subsequent relapse of AHRF.A randomised controlled trial was performed in 120 COPD patients without previous domiciliary ventilation, admitted for AHRF and treated with NIV. When the episode was resolved and patients tolerated unassisted breathing for 4 h, they were randomly allocated to receive three additional nights of NIV (n=61) or direct NIV discontinuation (n=59). The primary outcome was relapse of AHRF within 8 days after NIV discontinuation.Except for a shorter median (interquartile range) intermediate respiratory care unit (IRCU) stay in the direct discontinuation group (4 (2–6)versus5 (4–7) days, p=0.036), no differences were observed in relapse of AHRF after NIV discontinuation (10 (17%)versus8 (13%) for the direct discontinuation and nocturnal NIV groups, respectively, p=0.56), long-term ventilator dependence, hospital stay, and 6-month hospital readmission or survival.Prolongation of nocturnal NIV after recovery from an AHRF episode does not prevent subsequent relapse of AHRF in COPD patients without previous domiciliary ventilation, and results in longer IRCU stay. Consequently, NIV can be directly discontinued when the episode is resolved and patients tolerate unassisted breathing.
Setting Quality Improvement Priorities for Women Receiving Systemic Therapy for Early-Stage Breast Cancer by Using Population-Level Administrative Data
Authors: Enright Katherine A. , Taback Nathan , Powis Melanie Lynn , Gonzalez Alejandro , Yun Lingsong , Sutradhar Rinku , Trudeau Maureen E. , Booth Christopher M. , Krzyzanowska Monika K. 
Published: July 2017

Purpose Routine evaluation of quality measures (QMs) can drive improvement in cancer systems by highlighting gaps in care. Targeting quality improvement at QMs that demonstrate substantial variation has the potential to make the largest impact at the population level. We developed an approach that uses both variation in performance and number of patients affected by the QM to set priorities for improving the quality of systemic therapy for women with early-stage breast cancer (EBC). Patients and Methods Patients with EBC diagnosed from 2006 to 2010 in Ontario, Canada, were identified in the Ontario Cancer Registry and linked deterministically to multiple health care databases. Individual QMs within a panel of 15 QMs previously developed to assess the quality of systemic therapy across four domains (access, treatment delivery, toxicity, and safety) were ranked on interinstitutional variation in performance (using interquartile range) and the number of patients who were affected; then the two rankings were averaged for a summative priority ranking. Results We identified 28,427 patients with EBC who were treated at 84 institutions. The use of computerized physician electronic order entry for chemotherapy, emergency room visits or hospitalizations during chemotherapy, and timely receipt of chemotherapy were identified as the QMs that had the largest potential to improve quality of care at a system level within this cohort. Conclusion A simple ranking system based on interinstitutional variation in performance and patient volume can be used to identify high-priority areas for quality improvement from a population perspective. This approach is generalizable to other health care systems that use QMs to drive improvement.
BRAF: An emerging target for triple-negative breast cancer.
Authors: Albanell Joan , Elvin Julia Andrea , Ali Siraj Mahamed , Schrock Alexa Betzig , Chung Jon , Vergilio Jo-Anne , Suh James , Ramkissoon Shakti , Severson Eric Allan , Daniel Sugganth , Miller Vincent A. , Stephens Philip J. , Gay Laurie M. , Ross Jeffrey S. 
Published: July 2017

1099 Background: A series of reports demonstrating the successful use of BRAF and MEK inhibitors in clinically advanced non-melanoma cancers has recently emerged. BRAF alterations in metastatic breast cancer (mBC) are rare and BRAF is not currently considered a target for the disease. Methods: DNA was extracted from 40 microns of FFPE sections from a series of 10,428 cases of metastatic breast cancer (mBC). Comprehensive genomic profiling (CGP) was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of > 550X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Results: 135 (1.2%) of the mBC featured alterations in BRAF. The median age of the 135 female patients was 66 years (range 27 to 83 years). The primary tumor was used for CGP in 50 (37%) and from metastatic sites including lymph nodes, liver, bone, lung, brain, adrenal and soft tissue in 85 (67%). Using CDH1 mutation as the definition of lobular mBC, 126 (93%) were ductal and 9 (7%) were lobular histology. Activating BRAF alterations included amplifications (48%), SV mutations (39%) and rearrangements (13%). No (0%) mBC had multiple BRAF GA in the same case. 34% of BRAF SV were V600E and 66% were a wide variety of non-V600E GA. 10 (7.4%) of 135 BRAF mutated mBC featured ERBB2 amplification with 1 (1%) having an ERBB2 SV mutation and 1 (1%) having both ERBB2 amplification and SV GA. Of the 115 BRAF GA cases with known hormone receptor status 71 (62%) were ER negative, 44 (38%) were ER positive and 63 (55%) were triple negative (TNBC). Other targetable genes enriched in mBC with BRAF GA included CDK6 (p = 0.001), HGF (p < 0.001) and MET(p < 0.001). The median TMB was 4.5 with 17 (13%) of cases with TMB > 10 mut/Mb and 7 (5%) of cases with > 20 mut/Mb. Conclusions: BRAF alterations, although uncommon in mBC representing only 1.2% of cases, are enriched in TNBC and feature both targetable base substitutions and rare fusions. BRAF GA may be a rare cause of anti-HER2 therapy resistance in a subset of ERBB2 driven mBC. Targetable genes co-altered with BRAF in mBC include CDK6, HGF and MET. The TMB in BRAF altered mBC is significantly higher than that for mBC in general and indicates potential role for immunotherapy for these patients.
Genomic profiling of squamous malignancies across anatomic sites.
Authors: Chung Christine H. , Frampton Garrett Michael , Chalmers Zachary Rockow , Chung Jon , Khan Saad A. , Schrock Alexa Betzig , Gay Laurie M. , Sharma Neelesh , Elvin Julia Andrea , Fabrizio David , Connelly Caitlin F. , Kang Hyunseok , Stephens Philip J. , Miller Vincent A. , Johnson Jennifer Maria , Ross Jeffrey S. , Ali Siraj Mahamed , Ganesan Shridar 
Published: July 2017

11512 Background: Primary squamous cell carcinomas (SCCs) have diverse etiologies, but can share genomic features. We reviewed the genomic profiles of a series of SCC cases of differing anatomic origin. Methods: Hybrid-capture based genomic profiling of 182 or 236 or 315 genes was performed on 4783 squamous malignancies in the course of clinical care, with baits for HPV6, 11, 16, and 18, and assessment of tumor mutation burden (TMB; mutations/Mb) and microsatellite instability. Results: Sites of origin were head and neck (HNSCC, n = 1300), cervical (cSCC; n = 318), anal (aSCC, n = 248), esophageal (n = 242), lung (lSCC, n = 2386), and cutaneous (sSCC, n = 289) SCC cases. For HNSCC, cSCC, and aSCC (collectively termed HCA SCC), 395 (30%), 215 (68%), and 211 (83%) were HPV positive, respectively. For HCA SCC, the most common GA were in TP53 (45%), CDKN2A (29%), PIK3CA (24%), TERT (21%), and FAT1 (14%). The most frequent GA differentially associated with HPV status were in PIK3CA (34.9% versus 16.0%), CYLD (11.4% versus 1.4%) and PTEN (14.8% versus 6.1%) for HPV+ cases, and TP53 (3.8% versus 76.5%), CDKN2A ()1.4% versus 49.8%), and TERT (4.3% versus 33.0%) for HPV- cases. Mean TMB for HPV+ and HPV- cases were 6.6 (STDEV 7.3) and 13.7 (STDEV 29.7), respectively. TMB of all SCC cases was significantly different (p < 10-12) when stratified by HPV status. For lSCC and eSCC, the most common GA were found in TP53 (86%) CDKN2A (40%), and PIK3CA (26%) and mean TMB was 11.6 with HPV found in 3.1% of cases. In sSCC, the most common GA were in TP53 (85.5%), CDKN2A (54.3%), and TERT(44.0%), and mean TMB was 59.5 with HPV in 3.1% of cases. Subsets of SCC cases had defining and targetable GA including bi-allelic deletion of SMARCB1 ( < 0.3%), amplification of PD-L1 (~2% ), and various kinase fusions. Cases demonstrating radiologic response to immunotherapy and matched targeted therapies, as well as subsequent development of multiple mechanisms of acquired resistance, will be presented. Conclusions: HPV driven SCC have similar genomic profiles regardless of of site origin, and have a significantly lower median TMB than HPV negative SCC. Early consistency of responses of SCC to matched therapies may strengthen the case for site independent genomic predictors of therapy response.