bluuebunny/crossref_metadata_2025 huggingface dataset:
Herbal Remedies
Authors: Tyler Varro E
Published: July 2017

Objective:

To provide an overview of basic information required by pharmacists to advise patients on the proper use of selected herbs and phytomedicines (“dietary supplements”) as therapeutic agents.

Data Sources:

The vast literature on this topic in the English, German, and French languages has been researched by the author over a period of many years. Databases that were used include NAPRALERT and MEDLINE.

Study Selection:

Articles and books dealing with the current popularity of botanical medicine and with laws and regulations covering so-called dietary supplements, as well as information on selected toxic herbs and a few of the most popular beneficial herbs used for treating common ailments and syndromes.

Data Synthesis:

Studies suggest that many herbal products currently available are both safe and effective drugs. A few products on the US market are definitely unsafe for human consumption and use.

Conclusions:

The increasing popularity of botanicals, coupled with regulations that prohibit definitive labeling, requires pharmacists to acquire accurate information based on scientifically and clinically acceptable data to advise patients on their use. Useful remedies for several common ailments and information concerning their safety and usefulness provide a starting point for an understanding of this complex field.
Ketoconazole in the Prevention of Acute Respiratory Distress Syndrome
Authors: Earl-Salotti Grace L , Ratzell Michelle D , Maldonado Ivan L
Published: July 2017

Objective:

To describe the pharmacology of ketoconazole and examine the use of ketoconazole in critically ill surgical patients to prevent the development of acute respiratory distress syndrome (ARDS).

Data Source:

An English-language literature search from 1985 to 1994 using MEDLINE-identified relevant articles. Search terms were adult, acute respiratory distress syndrome, ketoconazole, thromboxane, and leukotrienes.

Study Selection:

Two randomized, controlled, double-blind studies were identified that examined the use of ketoconazole in critically ill surgical patients. In vitro and animal studies were included to describe the mechanism of ketoconazole on inhibition of leukotriene and thromboxane synthesis.

Data Extraction:

Studies were evaluated for study design, efficacy, and toxicity.

Data Synthesis:

Two randomized, placebo-controlled clinical trials have been conducted in critically ill surgical patients. One study demonstrated a 6% incidence of ARDS in patients receiving ketoconazole 200 mg/d (n = 35) versus 31% on placebo (n = 36) (p < 0.01). Another study demonstrated a 15% incidence of ARDS in patients receiving ketoconazole 400 mg/d (n = 26) versus 64% on placebo (n = 28) (p < 0.002), and showed a statistically significant decrease in mortality in the ketoconazole group (15%) versus placebo (39%) (p < 0.05). There were no reports of serious adverse events, and patients in both treatment and placebo groups were discontinued for increased liver enzyme concentrations.

Conclusions:

Two studies conducted at single sites using prophylactic ketoconazole therapy in dosages of 200–400 mg/d in a small population of critically ill surgical patients at risk for ARDS have demonstrated a significant decrease in the incidence of ARDS. There are no ongoing multicenter trials that would provide the power to measure the true difference between the groups and minimize the selection bias inherent in these studies.
Women's Health Issues and Counseling Behaviors: A Pilot Survey of West Virginia Pharmacists
Authors: Ponte Charles D
Published: July 2017

Objective:

To assess the counseling behaviors of pharmacists concerning women's health issues.

Design:

A 14-item survey was mailed to 1,050 pharmacists. Data were analyzed using descriptive statistics (frequency and cross-tabulation). An IBM-compatible microcomputer program, Epi Info Version 5, was used for data analysis. Stratified analysis of the data was conducted using chi-square testing. Correlation between selected variables was determined using statistical analysis software.

Setting:

West Virginia.

Participants:

Two hundred seven practicing West Virginia pharmacists who completed or partially completed the questionnaire.

Outcome Measures:

The degree and nature of counseling by West Virginia pharmacists pertaining to women's health issues.

Results:

Almost 77% of the pharmacists were engaged in community practice. Seventy-four percent (151/203) of pharmacists counsel women about healthcare issues at least sometimes during a typical week. Women most often initiate the interaction. Sixty-nine percent were somewhat comfortable counseling women. The most common topics discussed were vaginal infections and estrogen replacement therapy. The most common barriers to effective counseling were time constraints and lack of patient requests. Almost 33% of the pharmacists (n = 68) agreed that academic curricula inadequately prepared them to counsel women. If reimbursement mechanisms were available, 36% of pharmacists (n = 70) would charge up to $5 per session. Sixteen percent (n = 32) would charge no fee.

Conclusions:

The small sample size and design of the survey could affect interpretation of the study results. Future research should address the specific types of counseling performed and the methods used, the practice setting and its influence on counseling, curricular influences on counseling, and pharmacist reimbursement philosophy.
Can Valproate Prevent Migraine Headaches?
Authors: Tran Binh N , Vivian Virginia S , Burch Kelly J
Published: July 2017

Objective:

To investigate the effectiveness of valproate in the prevention of migraine headaches. The drug has been approved by the FDA for migraine prophylaxis in addition to its primary use in seizure control.

Data Sources:

A MEDLINE search (1988–1995) of the English-language literature pertaining to the use of valproate for prophylaxis of migraine headaches was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search.

Study Selection and Data Extraction:

All articles were considered for possible inclusion in the review. Pertinent information was selected for discussion.

Data Synthesis:

Results of five clinical studies carried out worldwide were reviewed: a historical study of 22 patients from Denmark and studies of 32 patients in Israel, 43 patients in Denmark, 75 patients in California, and 117 patients in the US. Eleven patients (50%) were free of headache in the first study. The number of migraine attacks decreased from 15.5 to 8.8 in the second study, whereas patients treated with valproate reported 3.5 days with migraine versus 6.1 for patients receiving placebo in the third study. Efficacy rates of 85% and 61% were seen for patients with frequent migraine and transformed migraine, respectively, in the fourth study, and 48% of patients treated with divalproex compared with 14% of patients receiving placebo showed at least a 50% reduction in migraine headache frequency in the fifth study.

Conclusions:

Approximately half of the patients were shown to experience roughly a 50% reduction in the number of migraine attacks or days with migraine headaches; thus, valproate appears to provide a therapeutic alternative for patients who do not respond to or cannot tolerate beta-receptor blockers, tricyclic antidepressants, or calcium-channel blockers for prophylaxis of migraine headaches.
Theophylline and Verapamil: Clinically Significant Drug Interaction
Authors: Bangura Luella , Malesker Mark A , Dewan Naresh A
Published: July 2017

Objective:

To report and describe a case of verapamil interacting with theophylline.

Case Summary:

A 33-year-old white man with bronchial asthma was admitted for evaluation of sudden onset of chest pain. During hospitalization, verapamil 120 mg/d was added to the theophylline regimen (600 mg bid). The patient's requirement for theophylline decreased by 50% after the initiation of verapamil.

Discussion:

A review of the literature indicated that concomitant verapamil may reduce theophylline clearance by 12–23%. Other reports suggest that the degree of this interaction is of much smaller magnitude and clinically insignificant.

Conclusions:

Although the most recent FDA labeling guidelines for theophylline mention verapamil as a documented source of drug interaction with theophylline, many clinicians may not realize the potential clinical significance. Therefore, theophylline concentrations should be monitored in patients receiving both theophylline and verapamil, even in the absence of adverse effects.
Reevaluating the Safety of Concurrent Warfarin and Ibuprofen Therapy: A Case Report
Authors: Ernst Michael E , Buys Lucinda M
Published: July 2017

Objective:

To describe a case of subclinical bleeding and elevated international normalized ratio (INR) associated with the concomitant use of ibuprofen and warfarin.

Case Summary:

A 74-year-old white woman receiving warfarin for a history of cerebrovascular accident and deep-vein thrombosis with concomitant chronic obstructive pulmonary disease, hypertension, congestive heart failure, coronary artery disease, osteoarthritis, and erosive esophagitis developed significant elevation of the INR after the addition of ibuprofen to her medication regimen. The patient experienced a decrease in hemoglobin concentration, asymptomatic hypotension, and increased blood urea nitrogen/creatinine ratio. Limited physical examination failed to locate a source of bleeding.

Discussion:

The pharmacokinetic and pharmacodynamic interactions involving nonsteroidal antiinflammatory agents and warfarin are well documented. Limited data from healthy volunteers and patients without complex medical problems suggest that ibuprofen and warfarin may be given concomitantly with relative safety. This report describes an elderly patient with multiple medical problems, treated with numerous medications, including warfarin, who developed signs suggestive of subclinical bleeding and an INR of 14.3 after the addition of low-dose ibuprofen.

Conclusions:

Concomitant use of ibuprofen and warfarin should be avoided in elderly patients with complex medical problems treated with multiple medications.
Use of Erythropoietin in the Severely Anemic Jehovah's Witness Patient: Case Report and Review of the Literature
Authors: Rogers P David , Volles David F
Published: July 2017

Objective:

To describe and discuss the use of erythropoietin as a therapeutic option for treatment of severe anemia in a patient whose religious beliefs preclude the use of blood products.

Case Summary:

A 23-year-old male Jehovah's Witness patient presented to the emergency department with multiple fractures and significant blood loss secondary to trauma experienced in a motor vehicle accident. The patient refused transfusion because of his religious beliefs. He was given oxygen and lactated Ringer's solution, and phlebotomy was kept to a minimum. Erythropoietin was recommended to increase production of red blood cells. Review of the product information revealed that all available erythropoietin products contain human albumin as a stabilizer. After discussion with the clinical pharmacist, the patient and his family agreed to the use of erythropoietin. The patient's hematocrit and hemoglobin improved sufficiently for him to be taken to surgery on hospital day 12, and on hospital day 23 he was discharged.

Discussion:

Because Jehovah's Witnesses refuse to receive blood products, alternative methods for treatment of severe anemia must be used. Although some options are clearly unacceptable, certain volume expanders can be used in conjunction with oxygen and intravenous or oral iron that do not violate the patient's religious convictions. Erythropoietin is acceptable to most Jehovah's Witnesses; however, it contains human album (2.5 mg/mL), which may be of concern to some of these patients.

Conclusions:

Effective communication with the patient and the patient's family regarding all treatment options is required for treatment of severe anemia in the Jehovah's Witness patient. Erythropoietin, in conjunction with iron, adequate oxygenation, and good nutritional support, sometimes is an acceptable alternative in Jehovah's Witnesses.
Evaluation of ACE Inhibitor Therapy for Congestive Heart Failure in an Outpatient Setting
Authors: Bleske Barry E , Cornish Laura A , Erickson Steven R , Nicklas John M
Published: July 2017

Objective:

Angiotensin-converting enzyme (ACE) inhibitor therapy is considered the standard of care for the treatment of congestive heart failure. Despite this, clinical experience suggests that not all patients may be receiving ACE inhibitor therapy or may be receiving low dosages. This study was performed to better understand the use of ACE inhibitor therapy in clinical practice.

Design and Participants:

We reviewed the medical therapy of 110 patients with a history of congestive heart failure referred to an outpatient heart failure clinic at a university teaching hospital.

Outcome Measures:

This observational study evaluated the use of ACE inhibitors, including dosage, as well as other drugs to treat congestive heart failure.

Results:

Approximately 85% (93/110) of patients were receiving an ACE inhibitor. Twenty percent (22/110) were receiving enalapril 20 mg/d or more, captopril 150 mg/d or more, lisinopril 20 mg/d or more, or quinapril 40 mg/d or more. The remaining patients (n = 71) were receiving these drugs at lower dosages. However, 21 of the remaining patients (19% of all patients) were receiving lower dosages based on patient-specific parameters; 47 of the remaining patients (43% of all patients) were eligible to have their dosage increased. Ten eligible patients were not receiving an ACE inhibitor. The majority of patients were also receiving digoxin (70%) and loop diuretic (80%) therapy.

Conclusions:

Approximately 85% of patients were receiving ACE inhibitor therapy, with 9% of eligible patients not receiving an ACE inhibitor. In the patients receiving ACE inhibitor therapy, approximately 50% (47/93) were receiving dosages below those suggested in the guidelines. Overall, the use of ACE inhibitor therapy is varied and intervention appears required to ensure that all patients receive appropriate therapy for the treatment of congestive heart failure.
Once-Daily Aminoglycosides: A Meta-Analysis of Nonneutropenic and Neutropenic Adults
Authors: Kale-Pradhan Pramodini B , Habowski Suzette R , Chase Heather C , Castronova Frank C
Published: July 2017

Objective:

To compare the efficacy, nephrotoxicity, and ototoxicity of once-daily dosing of aminoglycosides versus conventional dosing.

Design:

Meta-analysis of 14 randomized trials identified through a MEDLINE search (January 1965-May 1996).

Patients:

Neutropenic and nonneutropenic adults.

Interventions:

Patients were randomly selected to receive an aminoglycoside once daily or in multiple daily doses.

Measurements and Main Outcomes:

The outcomes considered were clinical cure, bacteriologic cure, nephrotoxicity, auditory toxicity, and vestibular toxicity. The data were analyzed in the following subgroups: (1) all trials, (2) nonneutropenic patients, (3) neutropenic patients, and (4) patients with undefined neutrophil status. For all trials the pooled risk ratio was 1.268 (95% CI 0.828 to 1.939) for clinical cure, and was 1.390 (95% CI 1.350 to 1.392) for bacteriologic cure. Nephrotoxicity had a pooled risk ratio of 0.765 (95% CI 0.468 to 1.252), that for auditory toxicity was 1.117 (95% CI 0.151 to 5.636), and that for vestibular toxicity was 1.155 (95% CI 0.221 to 6.039). Analysis of the subgroups, including a separate analysis of neutropenic patients, demonstrated similar results.

Conclusions:

When all trials were considered, once-daily administration of aminoglycosides had similar efficacy and no increase in nephrotoxicity or ototoxicity compared with conventional aminoglycoside dosing.
Impact of Targeted Antibiotic Restriction on Usage and Cost in a Community Hospital
Authors: Mercer Kenneth A , Chintalapudi Srinivasa R , Visconti Ernest B
Published: July 2017

Objective:

To determine whether antibiotic restriction can produce savings.

Design:

Cost comparative analysis before and after antibiotic control.

Methods:

Cost control policy included removal of nonessential antibiotics from the emergency department and the operating room, the use of a clinical pathway protocol for pneumonia, and approval from the infectious disease consultant for certain high-cost antibiotics.

Setting:

Lutheran Medical Center, a community hospital in Brooklyn, New York.

Results:

Between the two 12-month periods analyzed (March 1995-February 1996 vs. March 1996-February 1997), we found a cost reduction of approximately 26% among intravenous antibiotics with a concomitant 10% cost reduction in oral antibiotics. Intravenous antibiotic use decreased by more than 22%, especially with regard to higher priced agents. Furthermore, we documented a 24% reduction in cost per patient. Hospital admission rates declined only 2.5% during the second 12-month period.

Conclusions:

Appropriate restriction of antibiotics can be done effectively and simply in a local hospital with no additional funding and achieve considerable cost savings.
Simvastatin and Rhabdomyolysis — A Case Report and Brief Review
Authors: Pershad Ashish , Cardello Frank P
Published: July 2017

Objective:

To report an unusual case of simvastatin-induced rhabdomyolysis and to discuss the occurrence of this potentially fatal adverse effect.

Case Summary:

A 61-year-old white man was admitted to the hospital with angina and myalgia. Laboratory data obtained on admission confirmed the clinical diagnosis of simvastatin-induced rhabdomyolysis. The medication was discontinued, and the patient's rhabdomyolysis resolved. Three months later, a rechallenge with simvastatin resulted in the recurrence of myalgia and elevation of the creatine kinase concentration. Discontinuation of the medication resulted in improvement of symptoms and return of the creatine kinase concentration to within normal limits.

Discussion:

Although simvastatin-induced rhabdomyolysis is a well-described entity, the occurrence of rhabdomyolysis at the lowest prescribed dose in the absence of concomitant interacting drugs is rare. The mechanism of this adverse effect is postulated to be related to mitochondrial dysfunction due to a relative deficiency of skeletal muscle Co Q10 induced by the drug.

Conclusions:

Simvastatin, even at the lowest prescribed dose and in the absence of drugs known to interact adversely with it, can cause potentially life-threatening rhabdomyolysis. This case report shows that cautioning all patients about this rare yet serious adverse effect is critical.
Data-Derived Treatment Duration Goal for Cervical Cancer: Should 8 Weeks Remain the Target in the Era of Concurrent Chemoradiation?
Authors: Hong Julian C. , Foote Jonathan , Broadwater Gloria , Sosa Julie A. , Gaillard Stephanie , Havrilesky Laura J. , Chino Junzo P.
Published: July 2017

Purpose

Prior studies have demonstrated the importance of treatment duration (TD) in radiation therapy (RT) for cervical cancer, with an 8-week goal based primarily on RT alone. This study uses a contemporary cohort to estimate the time point by which completion of chemoradiation therapy is most critical.

Patients and Methods

The National Cancer Database was queried for women with nonmetastatic cervical cancer diagnosed from 2004 to 2012 who underwent chemotherapy, external beam RT, and brachytherapy. Data-derived TD cut points for overall survival (OS) were computed by using recursive partitioning analysis with bootstrapped aggregation (bagging) and 10-fold cross-validation. Models were independently trained with 70% of the population and validated on 30% of the population by log-rank test with and without propensity matching. Multivariable Cox proportional hazards regression was performed for the entire cohort.

Results

In all, 7,355 women were identified with a median TD of 57 days. Bagged recursive partitioning analysis converged to a mean cut point of 66.6 days (median, 64.5 days; interquartile range, 63.5 to 68.5 days). Cross-validation yielded a cut point of 63.3 days. Both cut points differentiated OS in validation. Younger age, recent diagnosis, geographic region, nongovernment insurance, shorter distance to treatment facility, metropolitan location, lower comorbidity, squamous cell carcinoma, lower stage, negative lymph nodes, and shorter TD were independently associated with longer OS. With adjustment, TD within the mean cut point (64.9 days; hazard ratio, 0.79; 95% CI, 0.73 to 0.87) and 56 days (hazard ratio, 0.87; 95% CI, 0.80 to 0.95) were associated with longer OS. Exploratory stratification suggested increasing OS detriment beyond 64 days.

Conclusion

Shorter chemoradiation TD in cervical cancer is associated with longer survival, and TD should be minimized as much as possible. The data-derived cut point was distributed around 64 days, with a continuous relationship between shorter TD and longer OS.
Implementation and Clinical Utility of an Integrated Academic-Community Regional Molecular Tumor Board
Authors: Burkard Mark E. , Deming Dustin A. , Parsons Benjamin M. , Kenny Paraic A. , Schuh Marissa R. , Leal Ticiana , Uboha Nataliya , Lang Joshua M. , Thompson Michael A. , Warren Ruth , Bauman Jordan , Mably Mary S. , Laffin Jennifer , Paschal Catherine R. , Lager Angela M. , Lee Kristy , Matkowskyj Kristina A. , Buehler Darya G. , Rehrauer William M. , Kolesar Jill
Published: July 2017

Purpose

Precision oncology develops and implements evidence-based personalized therapies that are based on specific genetic targets within each tumor. However, a major challenge that remains is the provision of a standardized, up-to-date, and evidenced-based precision medicine initiative across a geographic region.

Materials and Methods

We developed a statewide molecular tumor board that integrates academic and community oncology practices. The Precision Medicine Molecular Tumor Board (PMMTB) has three components: a biweekly Web-based teleconference tumor board meeting provided as a free clinical service, an observational research registry, and a monthly journal club to establish and revise evidence-based guidelines for off-label therapies. The PMMTB allows for flexible and rapid implementation of treatment, uniformity in practice, and the ability to track outcomes.

Results

We describe the implementation of the PMMTB and its first year of activity. Seventy-seven patient cases were presented, 48 were enrolled in a registry, and 38 had recommendations and clinical follow-up. The 38 subjects had diverse solid tumors (lung, 45%; GI, 21%; breast, 13%; other, 21%). Of these subjects, targeted therapy was recommended for 32 (84%). Clinical trials were identified for 24 subjects (63%), and nontrial targeted medicines for 16 (42%). Nine subjects (28%) received recommended therapy with a response rate of 17% (one of six) and a clinical benefit rate (partial response + stable disease) of 38% (three of eight). Although clinical trials often were identified, patients rarely enrolled.

Conclusion

The PMMTB provides a model for a regional molecular tumor board with clinical utility. This work highlights the need for outcome registries and improved access to clinical trials to pragmatically implement precision oncology.
Plasma DNA-Based Molecular Diagnosis, Prognostication, and Monitoring of Patients With EWSR1 Fusion-Positive Sarcomas
Authors: Shukla Neerav N. , Patel Juber A. , Magnan Heather , Zehir Ahmet , You Daoqi , Tang Jiabin , Meng Fanli , Samoila Aliaksandra , Slotkin Emily K. , Ambati Srikanth R. , Chou Alexander J. , Wexler Leonard H. , Meyers Paul A. , Peerschke Ellinor I. , Viale Agnes , Berger Michael F. , Ladanyi Marc
Published: July 2017

Purpose

Ewing sarcoma (ES) and desmoplastic small round cell tumors (DSRCTs) are aggressive sarcomas molecularly characterized by EWSR1 gene fusions. As pathognomonic genomic events in these respective tumor types, EWSR1 fusions represent robust potential biomarkers for disease monitoring.

Methods

To investigate the feasibility of identifying EWSR1 fusions in plasma-derived cell-free DNA (cfDNA) from patients with ES and DSRCT, we evaluated two complementary approaches in samples from 17 patients with radiographic evidence of disease. The first approach involved identification of patient-specific genomic EWSR1 fusion breakpoints in formalin-fixed, paraffin-embedded tumor DNA using a broad, hybridization capture-based next-generation sequencing (NGS) panel, followed by design of patient-specific droplet digital polymerase chain reaction (ddPCR) assays for plasma cfDNA interrogation. The second approach used a disease-tailored targeted hybridization capture-based NGS panel applied directly to cfDNA, which included EWSR1 as well as several other genes with potential prognostic use.

Results

EWSR1 fusions were identified in 11 of 11 (100%) ES and five of six (83%) DSRCT cfDNA samples by ddPCR, whereas 10 of 11 (91%) and four of six (67%) were identified by NGS. The ddPCR approach had higher sensitivity, ranging between 0.009% and 0.018%. However, the hybrid capture–based NGS assay identified the precise fusion breakpoints in the majority of cfDNA samples, as well as mutations in TP53 and STAG2, two other recurrent, clinically significant alterations in ES, all without prior knowledge of the tumor genotype.

Conclusion

These results provide a compelling rationale for an integrated approach using both NGS and ddPCR for plasma cfDNA-based biomarker evaluations in prospective cooperative group studies.
Programmed Cell Death 1 (PD-1) Ligand (PD-L1) Expression in Solid Tumors As a Predictive Biomarker of Benefit From PD-1/PD-L1 Axis Inhibitors: A Systematic Review and Meta-Analysis
Authors: Khunger Monica , Hernandez Adrian V. , Pasupuleti Vinay , Rakshit Sagar , Pennell Nathan A. , Stevenson James , Mukhopadhyay Sanjay , Schalper Kurt , Velcheti Vamsidhar
Published: July 2017

Purpose

Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway show significant clinical activity across several tumor types. However, a majority of patients do not respond to these agents. Use of biomarker assays to predict response to these agents is an active area of research; however, the predictive value of PD-L1 immunohistochemistry (IHC) assays is largely inconsistent across clinical trials. In this meta-analysis of clinical trials of PD-1/PD-L1–targeted agents, we evaluate the predictive value of a tumor and tumor-infiltrating immune cell PD-L1 IHC assay as a biomarker for objective response to PD-1/PD-L1 inhibitors.

Methods

We searched databases (PubMed, Medline, ASCO abstracts, European Society for Medical Oncology abstracts, and Scopus) up until December 2016 for clinical trials using PD-1/PD-L1 inhibitors with reported PD-L1 biomarker data. Objective response rates (primary end point) from all phase I to III trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab in advanced solid tumors were collected. Odds ratios (ORs) for response in PD-L1–positive patients compared with PD-L1–negative patients were calculated using the DerSimonian-Laird random effects model to combine trials. We performed meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results

Forty-one distinct trials with 6,664 patients were identified. PD-L1 expression was predictive of favorable response across all tumor types (OR, 2.26; 95% CI, 1.85 to 2.75; P < .001), with the significantly largest effect observed in non–small-cell lung cancer (OR, 2.51; 95% CI, 1.99 to 3.17; P < .001). A subgroup analysis across all non–small-cell lung cancer trials using nivolumab and Dako clone 28-8 (Dako, Carpinteria, CA) IHC antibody assay yielded a significantly higher objective response rate in patients with tumor PD-L1 expression even at the minimum cutoff value of 1% (OR, 2.17; 95% CI, 1.03 to 4.57).

Conclusion

Our meta-analysis shows that tumor and tumor-infiltrating immune cell PD-L1 overexpression based on IHC is associated with significantly higher response rates to PD-1/PD-L1 axis inhibitors across a range of malignant solid tumors.
OncoKB: A Precision Oncology Knowledge Base
Authors: Chakravarty Debyani , Gao Jianjiong , Phillips Sarah , Kundra Ritika , Zhang Hongxin , Wang Jiaojiao , Rudolph Julia E. , Yaeger Rona , Soumerai Tara , Nissan Moriah H. , Chang Matthew T. , Chandarlapaty Sarat , Traina Tiffany A. , Paik Paul K. , Ho Alan L. , Hantash Feras M. , Grupe Andrew , Baxi Shrujal S. , Callahan Margaret K. , Snyder Alexandra , Chi Ping , Danila Daniel C. , Gounder Mrinal , Harding James J. , Hellmann Matthew D. , Iyer Gopa , Janjigian Yelena Y. , Kaley Thomas , Levine Douglas A. , Lowery Maeve , Omuro Antonio , Postow Michael A. , Rathkopf Dana , Shoushtari Alexander N. , Shukla Neerav , Voss Martin H. , Paraiso Ederlinda , Zehir Ahmet , Berger Michael F. , Taylor Barry S. , Saltz Leonard B. , Riely Gregory J. , Ladanyi Marc , Hyman David M. , Baselga José , Sabbatini Paul , Solit David B. , Schultz Nikolaus
Published: July 2017

Purpose

With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, an urgent need exists for a clinical support tool that distills the clinical implications associated with specific mutation events into a standardized and easily interpretable format. To this end, we developed OncoKB, an expert-guided precision oncology knowledge base.

Methods

OncoKB annotates the biologic and oncogenic effects and prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response on the basis of US Food and Drug Administration labeling, National Comprehensive Cancer Network guidelines, disease-focused expert group recommendations, and scientific literature.

Results

To date, > 3,000 unique mutations, fusions, and copy number alterations in 418 cancer-associated genes have been annotated. To test the utility of OncoKB, we annotated all genomic events in 5,983 primary tumor samples in 19 cancer types. Forty-one percent of samples harbored at least one potentially actionable alteration, of which 7.5% were predictive of clinical benefit from a standard treatment. OncoKB annotations are available through a public Web resource ( http://oncokb.org ) and are incorporated into the cBioPortal for Cancer Genomics to facilitate the interpretation of genomic alterations by physicians and researchers.

Conclusion

OncoKB, a comprehensive and curated precision oncology knowledge base, offers oncologists detailed, evidence-based information about individual somatic mutations and structural alterations present in patient tumors with the goal of supporting optimal treatment decisions.
Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making
Authors: Abida Wassim , Armenia Joshua , Gopalan Anuradha , Brennan Ryan , Walsh Michael , Barron David , Danila Daniel , Rathkopf Dana , Morris Michael , Slovin Susan , McLaughlin Brigit , Curtis Kristen , Hyman David M. , Durack Jeremy C. , Solomon Stephen B. , Arcila Maria E. , Zehir Ahmet , Syed Aijazuddin , Gao Jianjiong , Chakravarty Debyani , Vargas Hebert Alberto , Robson Mark E. , Vijai Joseph , Offit Kenneth , Donoghue Mark T.A. , Abeshouse Adam A. , Kundra Ritika , Heins Zachary J. , Penson Alexander V. , Harris Christopher , Taylor Barry S. , Ladanyi Marc , Mandelker Diana , Zhang Liying , Reuter Victor E. , Kantoff Philip W. , Solit David B. , Berger Michael F. , Sawyers Charles L. , Schultz Nikolaus , Scher Howard I.
Published: July 2017

Purpose

A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in this disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic noncastrate, and metastatic castration-resistant prostate cancer.

Patients and Methods

Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was used to identify single-nucleotide variations, small insertions and deletions, copy number alterations, and structural rearrangements in more than 300 cancer-related genes in tumors and matched normal blood.

Results

We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase pathways. Twenty-seven percent of patients harbored a germline or a somatic alteration in a DNA damage repair gene that may predict for response to poly (ADP-ribose) polymerase inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, whereas ATM alterations were specifically enriched in castration-resistant prostate cancer.

Conclusion

Through genomic profiling of prostate tumors that represent the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis, and castration resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.
Individual variation in metabolic reaction norms over ambient temperature causes low correlation between basal and standard metabolic rate
Authors: Briga Michael , Verhulst Simon
Published: July 2017

Basal metabolic rate (BMR) is often assumed to be indicative of the energy turnover at ambient temperatures (Ta) below the thermoneutral zone (SMR), but this assumption has remained largely untested. Using a new statistical approach, we quantified the consistency in nocturnal metabolic rate across a temperature range in zebra finches (n=3,213 measurements on 407 individuals) living permanently in eight outdoor aviaries. Foraging conditions were either benign or harsh, and body mass and mass-adjusted BMRm and SMRm were lower in individuals living in a harsh foraging environment. The correlation between SMRm at different Tas was high (r=0.91), independent of foraging environment, showing that individuals are consistently ranked according to their SMRm. However, the correlations between BMRm and SMRm were always lower (average: 0.29; range: 0<r<0.50), in particular in the benign foraging environment. Variation in metabolic response to lower Ta at least in part reflected differential body temperature (Tb) regulation: early morning Tb was lower at low Ta's, and more so in individuals with a weaker metabolic response to lower Ta's. Our findings have implications for the use of BMR in the estimation of time-energy budgets and comparative analyses: we suggest that the use of metabolic rates at ecologically relevant ambient temperatures, such as the easily tractable SMR, will be more informative than the use of BMR as a proxy for energy turnover.
Pharyngeal stimulation with sugar triggers local searching behavior in Drosophila
Authors: Murata Satoshi , Brockmann Axel , Tanimura Teiichi
Published: July 2017

Foraging behavior is essential for all organisms to find food containing nutritional chemicals. A hungry fly of Drosophila melanogaster performs local searching behavior after drinking a small amount of sugar solution. Using video tracking we examined how the searching behavior is regulated in D. melanogaster. We found that a small amount of highly concentrated sugar solution induced a long-lasting searching behavior. After the intake of sugar solution, a fly moved around in circles and repeatedly returned to the position where the sugar droplet had been placed. The non-nutritious sugar, D-arabinose, but not the non-sweet nutritious sugar, D-sorbitol, was effective in inducing the behavior, indicating that sweet sensation is essential. Furthermore, pox-neuro mutant flies with no external taste bristles showed local searching behavior, suggesting the involvement of the pharyngeal taste organ. Experimental activation of pharyngeal sugar-sensitive gustatory receptor neurons by capsaicin using the Gal4/UAS system induced local searching behavior. In contrast, inhibition of pharyngeal sugar-responsive gustatory receptor neurons abolished the searching behavior. Together our results indicate that in Drosophila the pharyngeal taste-receptor neurons trigger searching behavior immediately after ingestion.
Cone Beam Computed Tomography Study of Root Canal Morphology of Permanent Mandibular Incisors in Indian Subpopulation
Authors: Verma Gaurav Ravishankar , Bhadage Chetan , Bhoosreddy Ajay R. , Vedpathak Priyanka R. , Mehrotra Gayatri P. , Nerkar Ashwini C. , Bhandari Akanksha , Chaubey Shweta
Published: July 2017

Background: The aim of the study was to determine the root canal morphology of permanent mandibular incisor teeth in the Indian subpopulation with the use of cone beam computed tomography (CBCT).

Material/Methods: CBCT images of 200 patients with 800 permanent mandibular incisors, fulfilling necessary inclusion criteria and aged 18 to 60 years were evaluated. The number of roots, number of root canals and canal configuration were investigated and then classified according to Vertucci’s classification of root canals. The effect of gender on the incidence of root canal morphology was also investigated.

Results: All the permanent mandibular incisors had a single root. The majority of mandibular incisors (66.5%) had a single root with a single canal. The prevalence of second canals was as follows: right central incisor – 33.5%, left central incisor – 30%, right lateral incisors – 33.5% and left lateral incisor – 36.5%. According to gender, 15.2% of men and 20.4% of women had a second root canal. Type 1 Vertucci configuration was most prevalent, followed by type 3, type 2, type 5 and type 4 in that order.

Conclusions: Type 1 Vertucci’s classification (64.5%) was the most prevalent canal configuration in the mandibular anterior teeth in the Indian population. Type 5 Vertucci’s classification was the most frequently observed canal configuration of the two-canalled teeth. CBCT is an excellent imaging modality for detection of different canal configurations of mandibular incisors.
Enterprise Project Management: Systems Approach
Authors: Ильина  , Ilina Olga
Published: July 2017

The articles deals with historical analysis of systems approach usage in project management. Definition of Enterprise Project Management as a system is suggested. The article describes research results about usage of different project management methods and tools at different levels of management in an organization. Thus, top management mostly uses project portfolio management tools, project control and project procurement methods, i.e. project suppliers’ reliability appraisal. Mid level management prefers project planning and control tools as well as project change management tools. Low level management uses project initiation and control tools such as project charter, Gantt charts, project progress reports and strategic milestone plans. The proposed approach can be used in the process of Enterprise Project Management methodology development.
Business-Value Creation Management in Organizational IT-Projects
Authors: Зуйков  , Zuykov Kirill
Published: July 2017

The paper is devoted to the new approach to value creation management in IT-based organizational change projects that utilizes the product service model, management by stages and value control. The approach solves the problem that a business-value created in a project is out of control because it is realized in the post-project stage. The paper studies value control problems that are conditioned by the utilization of the traditional IT-project lifecycle. The method of value metrics definition that is based on the product service model is presented together with the released value method a new method of value control that extends the earned value method with a vector of value creation performance indices. Those are to be considered in conjunction with the schedule performance index. Scope changes are used as an instrument to control the value creation process. The scope creep risk control is performed by calculation of stability margin based on previously done changes data.
The future of artificial wombs
Authors: Winter George F
Published: July 2017

The news that scientists had managed to keep premature lambs alive in artificial wombs has launched a complex debate. George Winter examines the moral and technological issues at stake
What influences women to bottle-feed from birth and to discontinue breastfeeding early?
Authors: Goncalves Andreia VAS
Published: July 2017

Background

Internationally, breast milk is recognised as the best form of infant feeding, yet in the UK, bottle feeding rates are among the highest in the world.

Aims

The aim of this research study was to investigate the relationship between socioeconomic, demographic, family-related, pregnancy and birth factors, and bottle feeding in the UK.

Methods

A secondary analysis of the Infant Feeding Survey 2010 was conducted and two time points differentiated: bottle feeding from birth and early breastfeeding cessation.

Findings

Results demonstrated that bottle feeding from birth was predicted by a range of independent social disadvantage factors, namely being young, single, unemployed, white British and poorly educated. Other influencing factors were the increased number of children, having a caesarean section, no underlying health problems post birth and having friends who bottle-fed. Early breastfeeding cessation was predicted by the same independent determinants except for working in intermediate or routine/manual occupations, having friends that mix-fed, and developing health problems post birth.

Conclusions

The context in which mothers live is a key determinant of how they feed their babies and that, for many women, feeding method is a consequence of their social context and not a choice.
The science of adverse childhood experiences
Authors: Hammond Paula
Published: July 2017

A recently released one-hour documentary follows a group of paediatricians, therapists, educators, and communities, who are devising and using practical techniques to combat what is known as ‘toxic stress’.
Influence of Storage Temperature, Storage Duration and Disbudding on Bulb Production in Asiatic Lilium cv. ‘Royal Trinity’
Authors: M. Malik K. , Q. Shiekh M. , T. Nazki I. , A. Mir S.
Published: July 2017

ABSTRACT: The main focus in lily cultivation has been on flowering attributes and bulb programming has not got a due attention Thus the experiment was carried out to investigate the effects of different storage temperatures and durations along with the two stages of disbudding on bulb development of Asiatic lilium at AICRP floriculture research unit Regional research station Wadura. (SKUAST-K). Freshly harvested bulbs were subjected to four storage temperatures (Ambient, 40C, 00C,-40C) three durations (2, 4 and 6 weeks) and plants were disbudded at first bud appearance and third bud appearance. Results of this Investigation revealed that bulbs stored under ambient conditions sprouted earliest (8.18days) with maximum height (57.60cm) and more leaves plant-1(55.89) whereas earlier flower bud appearance (52.59 days) maximum number of bulbs(3.37), heaviest bulb(97.32g),maximum diameter(4.59cm),increased number of daughter bulbs(3.12) maximum diameter of daughter bulbs (1.36), maximum scale size(1.30cm) and efficient propagation coefficient(3.37) were observed at40C but number of scales per bulb was highest at -40C(14.82). Storage duration on other hand played a pivotal role in bulb production in lilium. Among three storage durations (2, 4 and 6 weeks).Earliest sprouting (8.03days) was observed under six week duration. Maximum plant height (67.84cm) with increased leaf number (72.74) was observed at two week duration. Similarly maximum number of bulbs(4.88),number of daughter bulbs(4.15),number of scales(15.97) and propagation coefficient(4.88) was observed at two week duration and heaviest bulb(102.83g),maximum diameter of bulb (4.89cm) and number of daughter bulb(1.58) along with scale size(1.46cm) were observed for six weeks. On the other hand stage of disbudding had a negative impact on plant height. Plant height was reduced in plants disbudded at first bud appearance (49.65cm) compared to non disbudded plants (62.42cm). Plants disbudded at first bud stage had least number of leaves (44.86) as compared to non disbudded plants (48.68). Plants disbudded after three bud appearance produced increased number of bulbs(3.46) with maximum bulb weight(120.13g) and diameter(5.87cm) as well as increased number of daughter bulbs (3.20 plant-1). Disbudding after three bud appearance also significantly increased diameter of daughter bulbs (1.99cm) Scale size (1.92cm) and propagation coefficient (3.46) were also higher in plants disbudded after three bud appearances. However number of scales per bulb (18.93) was more in non disbudded plants
Antibacterial Activity of Aqueous Extracts of Artemisia species against some Pathogenic Bacteria
Authors: A. Alwathnani Hend
Published: July 2017

ABSTRACT: The present study was lead with a view to evaluate the antibacterial potentials of aqueous extracts of Artemisia species against human pathogenic bacteria: Escherichia coli (E.coli), Pseudomonas aeruginosa (Ps. aeruginosa) , Staphylococcus aureus (Staph. aureus) and Enterococcus faecalis (Entero. faecalis) by two methods, first method was minimum inhibitory concentration (abbreviation: MIC) and sound method was minimum bactericidal concentration (abbreviation: MBC). Three crude plants extracts namely Artemisia monosperma, Artemisia cina and Artemisia argyi were found to show potential antibacterial properties against the isolated human pathogenic bacterial isolates. The results of MIC and MBC values of Artemisia monosperma for Enterococcus faecalis strains were at least concentration almost 2.3 and 4.1 mg/ml respectively, while MIC and MBC of Artemisia cina for Escherichia coli were highest concentration 3.9 and 4.9 mg/ml respectively. Moreover, MIC and MBC values for Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis strains was correspondent with MIC and MBC values of Escherichia coli for aqueous extracts of Artemisia species meanwhile it is Artemisia cina which showed maximum activity against Escherichia coli. Among the Artemisia species tested, Artemisia cina showed the most promising result. Form these results prove the antibacterial potential of the plants and hence provide support for the use of them in traditional medicine.
Genomic DNA Extraction for Molecular Identification of Endophytic Fungi: An Easy and Efficient Protocol
Authors: Gul Farzana , Hussain Anwar , Jan Gul , Hamayun Muhammad
Published: July 2017

ABSTRACT: Presence of tough chitinous cell wall in fungi is a challenge for cell lysis and subsequent DNA isolation which has several downstream applications. We have developed an efficient protocol for extracting genomic DNA from endophytic fungi, which was isolated from different parts of Solanum xanthocarpum L. The procedure used was based on sodium dodecyl sulfate/ phenol/chloroform extraction method to remove polysaccharides and protein. The isolated genomic DNA was used to successfully amplify ITS region. The amplified ITS region was sequenced and homology of its sequence was used for confirming identity of the fungal endophyte. This rapid and inexpensive method can efficiently isolate high quality and quantity of genomic DNA suitable for PCR amplification and sequencing.