bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer
Authors: Lee Jung-Min , Peer Cody J. , Yu Minshu , Amable Lauren , Gordon Nicolas , Annunziata Christina M. , Houston Nicole , Goey Andrew K.L. , Sissung Tristan M. , Parker Bernard , Minasian Lori , Chiou Victoria L. , Murphy Robert F. , Widemann Brigitte C. , Figg William D. , Kohn Elise C. 
Published: September 2016

Abstract
Purpose: Our preclinical studies showed that the PARP inhibitor, olaparib, prior to carboplatin attenuated carboplatin cytotoxicity. We evaluated sequence-specific pharmacokinetic and pharmacodynamic effects, safety, and activity of the combination.
Experimental Design: Eligible patients had metastatic or recurrent women's cancer. Olaparib tablets were introduced (100 or 200 mg twice daily, days 1–7) in a 3 + 3 dose escalation with carboplatin AUC4 or 5 every 21 days, up to eight cycles, followed by olaparib 300 mg twice daily maintenance. Patients were randomly assigned to starting schedule: cohort A (olaparib days 1–7, carboplatin on day 8) or B (carboplatin on day 1, olaparib days 2–8) during cycle 1. Patients received the reversed scheme in cycle 2. Blood was collected for olaparib pharmacokinetics, platinum–DNA adducts, comet assay, and PAR concentrations. The primary objectives were to examine schedule-dependent effects on olaparib pharmacokinetics and platinum–DNA adducts.
Results: A total of 77 (60 ovarian, 14 breast, and 3 uterine cancer) patients were treated. Dose-limiting toxicity was thrombocytopenia and neutropenia, defining olaparib 200 mg twice daily + carboplatin AUC4 as the MTD. Olaparib clearance was increased approximately 50% when carboplatin was given 24 hours before olaparib. In vitro experiments demonstrated carboplatin preexposure increased olaparib clearance due to intracellular olaparib uptake. Quantities of platinum–DNA adducts were not different as a function of the order of drug administration. Responses included 2 CRs and 31 PRs (46%) with a higher RR in BRCA mutation carriers compared with nonmutation carriers (68% vs. 19%).
Conclusions: Tablet olaparib with carboplatin is a safe and active combination. Carboplatin preexposure causes intracellular olaparib accumulation reducing bioavailable olaparib, suggesting carboplatin should be administered prior to olaparib. Clin Cancer Res; 23(6); 1397–406. ©2016 AACR.
Bringing Blood-Based Molecular Testing to the Clinic
Authors: Janku Filip , Kurzrock Razelle 
Published: September 2016

Abstract
In cancer, plasma-derived cell-free DNA can be used for detection of oncogenic aberrations relevant for treatment selection. A cell-free DNA-based test for EGFR mutations has been approved as an alternative to tumor tissue analysis in lung cancer. Testing for other aberrations, including copy number alterations, continues to be investigated. Clin Cancer Res; 22(22); 5400–2. ©2016 AACR.
See related article by Chicard et al., p. 5564
Pharmacokinetically Guided Dosing of Oral Drugs: True Precision Oncology?
Authors: Ornstein Moshe C. , Rini Brian I. 
Published: September 2016

Abstract
Higher plasma concentrations of tyrosine kinase inhibitors (TKI), such as pazopanib, are associated with improved clinical outcomes. However, TKI pharmacokinetics exhibit significant interpatient variability, resulting in inconsistent and unpredictable plasma drug levels. An individualized dosing approach based on patient pharmacokinetics data and toxicity can potentially optimize plasma concentrations of pazopanib. Clin Cancer Res; 22(23); 5626–8. ©2016 AACR.
See related article by Verheijen et al., p. 5738
Implantation of the Medtronic Harmony Transcatheter Pulmonary Valve Improves Right Ventricular Size and Function in an Ovine Model of Postoperative Chronic Pulmonary Insufficiency
Authors: Schoonbeek Rosanne C. , Takebayashi Satoshi , Aoki Chikashi , Shimaoka Toru , Harris Matthew A. , Fu Gregory L. , Kim Timothy S. , Dori Yoav , McGarvey Jeremy , Litt Harold , Bouma Wobbe , Zsido Gerald , Glatz Andrew C. , Rome Jonathan J. , Gorman Robert C. , Gorman Joseph H. , Gillespie Matthew J. 
Published: September 2016

Background—
Pulmonary insufficiency is the nexus of late morbidity and mortality after transannular patch repair of tetralogy of Fallot. This study aimed to establish the feasibility of implantation of the novel Medtronic Harmony transcatheter pulmonary valve (hTPV) and to assess its effect on pulmonary insufficiency and ventricular function in an ovine model of chronic postoperative pulmonary insufficiency.

Methods and Results—

Thirteen sheep underwent baseline cardiac magnetic resonance imaging, surgical pulmonary valvectomy, and transannular patch repair. One month after transannular patch repair, the hTPV was implanted, followed by serial magnetic resonance imaging and computed tomography imaging at 1, 5, and 8 month(s). hTPV implantation was successful in 11 animals (85%). There were 2 procedural deaths related to ventricular fibrillation. Seven animals survived the entire follow-up protocol, 5 with functioning hTPV devices. Two animals had occlusion of hTPV with aneurysm of main pulmonary artery. A strong decline in pulmonary regurgitant fraction was observed after hTPV implantation (40.5% versus 8.3%;
P
=0.011). Right ventricular end diastolic volume increased by 49.4% after transannular patch repair (62.3–93.1 mL/m
2
;
P
=0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m
2
at 8 months,
P
=0.045). Both right ventricular ejection fraction and left ventricular ejection fraction were preserved after hTPV implantation.

Conclusions—
hTPV implantation is feasible, significantly reduces pulmonary regurgitant fraction, facilitates right ventricular volume improvements, and preserves biventricular function in an ovine model of chronic pulmonary insufficiency. This percutaneous strategy could potentially offer an alternative for standard surgical pulmonary valve replacement in dilated right ventricular outflow tracts, permitting lower risk, nonsurgical pulmonary valve replacement in previously prohibitive anatomies.
Factors Associated With Initial Prasugrel Versus Clopidogrel Selection for Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Insights From the Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE‐ACS) Study
Authors: Vora Amit N. , Peterson Eric D. , McCoy Lisa A. , Effron Mark B. , Anstrom Kevin J. , Faries Douglas E. , Zettler Marjorie E. , Fonarow Gregg C. , Baker Brian A. , Stone Gregg W. , Wang Tracy Y. 
Published: September 2016

Background
Few studies have examined how antiplatelet therapies are selected during the routine care of acute myocardial infarction patients, particularly relative to the patient's estimated mortality and bleeding risks.

Methods and Results

We examined patients presenting with acute myocardial infarction treated with percutaneous coronary intervention at 233
US
hospitals in the
TRANSLATE
‐
ACS
observational study from April 2010 to October 2012. We developed a multivariable logistic regression model to identify factors associated with prasugrel selection. Prasugrel use rates and associated 1‐year risk‐adjusted major adverse cardiovascular events and Global Utilization of Streptokinase and t‐PA for Occluded Coronary Arteries (
GUSTO
) moderate/severe bleeding outcomes were also examined in relation to predicted mortality and bleeding using the validated Acute Coronary Treatment and Intervention Outcomes (
ACTION
) risk prediction scores. Among 11 969 patients, 3123 (26%) received prasugrel at the time of percutaneous coronary intervention. The strongest factors associated with prasugrel use included cardiogenic shock (odds ratio [
OR
] 1.68, 95%
CI
1.25–2.26), drug‐eluting stent use (
OR
1.45, 95%
CI
1.31–1.62), and ST‐segment elevation myocardial infarction presentation (
OR
1.23, 95%
CI
1.12–1.35). Older age (
OR
0.57, 95%
CI
0.0.53–0.61), dialysis (
OR
0.56, 95%
CI
0.32–0.96), prior history of stroke/transient ischemic attack (
OR
0.52, 95%
CI
0.38–0.73), and interhospital transfer (
OR
0.50, 95%
CI
0.46–0.55) were associated with lowest prasugrel selection. Prasugrel was used less often than clopidogrel in patients at higher predicted bleeding risk (21.9% versus 29.7%,
P
<0.001). Yet paradoxically, prasugrel was also less likely than clopidogrel to be used in patients with higher predicted mortality risk (21.1% versus 30.2%,
P
<0.001). Adjusted bleeding and outcomes events were similar among those receiving prasugrel and clopidogrel in the 4 subgroups of patients based on bleeding risk and ischemic benefits.

Conclusions
In community practice, prasugrel use may be driven more by bleeding risk rather than ischemic benefit. This may result in underutilization of higher potency ADP receptor inhibitor among patients more likely to derive ischemic benefit.
Effectiveness of
N
‐Acetylcysteine for the Prevention of Contrast‐Induced Nephropathy: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Xu Renfan , Tao Anyu , Bai Yang , Deng Youbin , Chen Guangzhi 
Published: September 2016

Background

Conflicting results have been obtained in trials that have evaluated the prophylactic efficacy of
N
‐acetylcysteine (
NAC
) pretreatment in the prevention of contrast‐induced nephropathy (
CIN
). In this meta‐analysis of randomized controlled trials, we aimed to assess the effectiveness of
NAC
treatment for the prevention of
CIN
.

Methods and Results

PubMed,
EMBASE
, and the Cochrane Library were electronically searched from inception to January 2016 for all relevant studies. The weighted relative risk (
RR
) and corresponding 95%
CI
for incident
CIN
were estimated using random effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. The study included 11 480 participants and 1653 cases of
CIN
. The incidence of
CIN
was 12.8% in the
NAC
group versus 16.0% in the control group (
RR
: 0.76, 95%
CI
: 0.66–0.88,
P
=0.0002). In the patients undergoing coronary angiography, the incidence of
CIN
in the
NAC
group versus the control group was 13.7% versus 17.2% (
RR
: 0.74, 95%
CI
: 0.63–0.87,
P
=0.0002); in those undergoing peripheral angiography, the incidence was 6.4% versus 5.8% (
RR
: 1.00, 95%
CI
: 0.42–2.40,
P
=1.00); in those undergoing computed tomography, the incidence was 7.7% versus 14.8% (
RR
: 0.51, 95%
CI
: 0.29–0.89,
P
=0.02).

Conclusions

Our meta‐analysis showed an inverse and significant association between
NAC
supplementation and risk of
CIN
in patients undergoing coronary angiography and computed tomography, while a protective role for
NAC
in patients undergoing peripheral angiography was not obvious.
Role of diffusion-weighted MRI in the differential diagnosis of endometrioid and non-endometrioid cancer of the uterus
Authors: Bakir Vuslat Lale , Bakir Baris , Sanli Sükrü , Yildiz Sevda Ozel , Iyibozkurt Ahmet Cem , Kartal Merve Gülbiz , Yavuz Ekrem 
Published: September 2016

Background Many publications have examined the relationship between apparent diffusion coefficient (ADC) values and tumor grade in endometrial cancer. Nevertheless, none were designed to evaluate according to the histopathological type of endometrioid and non-endometrioid tumors. Purpose To evaluate the role of diffusion-weighted imaging (DWI) in the differential diagnosis of endometrioid and non-endometrioid cancer of the uterus, by comparing them with contrast-enhanced magnetic resonance imaging (MRI) findings. Material and Methods Institutional review board approval and informed consent were obtained. The MRI findings of 63 patients with endometrial cancer were retrospectively evaluated and divided into four groups: Grades I, II, and III endometrioid tumors, and non-endometrioid tumors. ADC values, DWI quotients ( b = 1000 s/mm2), and post-contrast signal intensities between lesions and the myometrium (b1000q-Cq values) were evaluated. The one-way-ANOVA, student’s t-test, Kruskal–Wallis test, and receiver operating characteristic (ROC) analysis were used for statistical evaluation. Results Mean ADC values were 0.86 ± 0.14 in Grade I, 0.80 ± 0.7 in Grade II, 0.71 ± 0.14 in Grade III for endometrioid tumors, and 0.70 ± 0.12 in non-endometrioid tumors. There was a significant difference in ADC values between Grade I and Grade III ( P = 0.006), and non-endometrioid tumors ( P = 0.003). The difference was also significant between Grades I + II and Grade III ( P = 0.009), and non-endometrioid tumors ( P = 0.004). Besides, there was a significant difference between endometrioid and non-endometrioid tumors ( P = 0.022). However, when considering b1000q (F = 0.640, P = 0.593) and Cq (χ2 = 6.233; P = 0.101), no significant difference was detected among the groups. Conclusion The difference in ADC values between the endometrioid and non-endometrioid tumors was statistically significant. However, the difference in DWI and contrast-enhancement findings were not statistically significant. Furthermore, the mean ADC values had an inverse relationship with tumor grade in the endometrioid cancer group.
Relationship between bone mineral density and dietary intake of β-carotene, vitamin C, zinc and vegetables in postmenopausal Korean women: a cross-sectional study
Authors: Kim Da Eun , Cho Soo Hyun , Park Hyoung Moo , Chang Yu Kyung 
Published: September 2016

Objective To examine the relationship between nutritional intake and bone mineral density (BMD) in postmenopausal Korean women. Methods Dietary intake was recorded in postmenopausal Korean women using a semiquantitative questionnaire. The frequency of consumption of various food groups and nutrient intake were calculated. BMD T-scores were measured at the lumbar spine, femoral neck and total hip using dual-energy X-ray absorptiometry. Associations between T-scores and dietary intake were analysed using partial correlation coefficients and multiple linear regression analysis. Results A total of 189 postmenopausal women were included in the study. β-Carotene intake was positively correlated with the lumbar spine T-score. Sodium and vitamin C intake were positively associated and folate intake negatively associated with the femoral neck T-score. Sodium, zinc and vitamin C intake were positively correlated and potassium intake was negatively correlated with the total hip T-score. Vegetable intake showed a positive association with the femoral neck and total hip T-scores. Conclusion In postmenopausal Korean women, β-carotene, vitamin C, zinc and sodium intakes were positively associated with bone mass. Furthermore, frequency of vegetable consumption was positively associated with femoral neck and total hip T-scores.
Cognitive stimulation therapy (CST) for people with dementia in practice: An observational study
Authors: Streater Amy , Spector Aimee , Aguirre Elisa , Orrell Martin 
Published: September 2016

Introduction The delivery of cognitive stimulation as a cognitive based psychosocial intervention for people with mild to moderate dementia is supported in the National Institute for Health and Care Excellence guidelines. There is a strong evidence base for its effectiveness in providing improvements in cognition and quality of life for people with dementia. However, less is known about its delivery and its impact using outcome measures when used in practice. Methods A 1-year observational study was conducted, which measured the cognition and quality of life of 89 people with dementia living in care homes and the community and were in receipt of cognitive stimulation therapy and a maintenance programme as part of their usual care in practice. Results A paired sample T-test demonstrated a significant improvement in cognition. Quality of life remained unchanged for people with mild to moderate dementia. Conclusions This study reports promising findings with demonstrated benefits for people with dementia and strengthens the evidence base supporting its use in routine care. However, attention should be given to the level of cognitive impairment of attendees. This research is relevant to the field of occupational therapy as the profession has knowledge of using psychosocial interventions and a commitment to evidence-based practice.
The influence of muscle pennation angle and cross-sectional area on contact forces in the ankle joint
Authors: Sopher Ran S , Amis Andrew A , Davies D Ceri , Jeffers Jonathan RT 
Published: September 2016

Data about a muscle’s fibre pennation angle and physiological cross-sectional area are used in musculoskeletal modelling to estimate muscle forces, which are used to calculate joint contact forces. For the leg, muscle architecture data are derived from studies that measured pennation angle at the muscle surface, but not deep within it. Musculoskeletal models developed to estimate joint contact loads have usually been based on the mean values of pennation angle and physiological cross-sectional area. Therefore, the first aim of this study was to investigate differences between superficial and deep pennation angles within each muscle acting over the ankle and predict how differences may influence muscle forces calculated in musculoskeletal modelling. The second aim was to investigate how inter-subject variability in physiological cross-sectional area and pennation angle affects calculated ankle contact forces. Eight cadaveric legs were dissected to excise the muscles acting over the ankle. The mean surface and deep pennation angles, fibre length and physiological cross-sectional area were measured. Cluster analysis was applied to group the muscles according to their architectural characteristics. A previously validated OpenSim model was used to estimate ankle muscle forces and contact loads using architecture data from all eight limbs. The mean surface pennation angle for soleus was significantly greater (54%) than the mean deep pennation angle. Cluster analysis revealed three groups of muscles with similar architecture and function: deep plantarflexors and peroneals, superficial plantarflexors and dorsiflexors. Peak ankle contact force was predicted to occur before toe-off, with magnitude greater than five times bodyweight. Inter-specimen variability in contact force was smallest at peak force. These findings will help improve the development of experimental and computational musculoskeletal models by providing data to estimate force based on both surface and deep pennation angles. Inter-subject variability in muscle architecture affected ankle muscle and contact loads only slightly. The link between muscle architecture and function contributes to the understanding of the relationship between muscle structure and function.
Revalidating the Religious/Spiritually Integrated Practice Assessment Scale With Five Helping Professions
Authors: Oxhandler Holly K. 
Published: September 2016

Objective: This article describes the validation of the Religious/Spiritually Integrated Process Assessment Scale (RSIPAS) across five helping professions. The RSIPAS was originally developed to measure clinical social workers’ self-efficacy, attitudes, perceived feasibility, behaviors, and overall orientation toward integrating clients’ religion and spirituality in practice. Method: The current study examines the internal consistency and criterion, discriminant, convergent, and factorial validity of this instrument with a sample of clinical social workers, psychologists, nurses, counselors, and marriage and family therapists in Texas ( N = 550). Results: Findings support the reliability (α = .95) and various forms of validity, with an improved fit in the factor structure among this more diverse sample. Conclusions: The RSIPAS may be used among these five helping professions to identify training needs or evaluate training efforts related to the integration of clients’ religious or spiritual beliefs in mental and behavioral health treatment.
Percutaneous Triple and Double Osteotomies for the Treatment of Hallux Valgus
Authors: Díaz Fernández Rodrigo 
Published: September 2016

Background: Percutaneous surgery to correct deformities of the forefoot presents the advantages of using a minimal incision, which involves less soft tissue damage and less risk of wound complications. For severe deformities, percutaneous techniques have not been proven as effective. We propose a technique for the treatment of severe hallux valgus. Methods: In a sample of 52 feet operated on 48 patients, we performed a double percutaneous osteotomy (closure proximal osteotomy and a distal Akin) or triple when a Reverdin-Isham osteotomy was added. We measured preoperatively the American Orthopaedic Foot & Ankle Society (AOFAS) score at the 1-year and 2-year follow-up, as well as the values of hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal articular ankle (DMAA), and shortening and elevation of the first metatarsal. The presence of metatarsalgia was recorded before and after the surgery. Results: HVA, IMA, and DMAA improved from 39.3 ± 7.1, 17.0 ± 2.0, and 16 ± 8.7 to 11.2 ± 6.2, 8.4 ± 3.4, and 8.3 ± 6.2, respectively. In 5 cases (10%), there was an elevation of the distal metatarsal bone, but only in 2 cases did a transfer metatarsalgia develop. There were no significant correlations between the amount of shortening and the presence of postoperative metatarsalgia. Scores on the AOFAS scale improved from 47.6 ± 5.6 to 89.7 ± 10.1 points. Conclusion: The results are comparable to those reported with other more established techniques. Transfer metatarsalgia did not correlate with lifting or shortening of the metatarsal. We indicate the percutaneous technique for IMA above 15 degrees and increased DMAA or congruent joints. Level of Evidence: Level IV, retrospective case series.
Plasma levels of trastuzumab in gastric cancer: Case report
Authors: González-García J , Alonso-Alvarez B , Nazco-Casariego GJ , Batista-López N , Guttiérrez-Nicolás F 
Published: September 2016

Introduction The use of trastuzumab with a fluoropyrimidine and platinum compound is currently the standard first-line treatment of patients with metastatic HER2-positive gastric cancer, but it appears that serum levels of trastuzumab determine the clinical effectiveness of this treatment, affecting progression-free survival and overall survival. Case report We report the case of a patient with metastatic HER2-positivegastric cancer, receiving XELOX (fluoropyrimidine and oxaliplatin) plus trastuzumab at standard doses, who presented sub-therapeutic serum levels during the first two treatment cycles and rapid disease progression (progression-free survival = 5.6 months). Discussion This case reveals a possible cause of poor effectiveness of trastuzumab treatment for metastatic gastric cancer in some patients, namely low circulating levels of the drug. It highlights the importance of monitoring as a possible tool for individual dose adjustment to optimize this therapy.