bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variations by state in physician disciplinary actions by US medical licensure boards
Authors: Harris John Alexander , Byhoff Elena 
Published: March 2016

ObjectiveTo investigate the variation in the rate of state medical board physician disciplinary actions between US states.MethodsLongitudinal study of state medical board physician disciplinary action rates using the US National Practitioner Data Bank and American Medical Association estimates of physician demographics across all 50 states and the District of Columbia from 2010 to 2014. Results were reliability adjusted using a multilevel logistic model controlling for year of disciplinary action, physicians per capita in each state and the rate of malpractice claims per physician in each state.ResultsFrom 2010 to 2014, there were a total of 5046 506 physician licensure years present. Medical boards reported a total of 21 647 disciplinary actions, of which 5137 (23.7%) were major disciplinary actions involving revocation, suspension or surrender of licence. The mean, reliability-adjusted rate of all disciplinary actions was 3.76 (95% CI 3.21 to 4.42) with a significant variation between states. State rates ranged from 2.13 (95% CI 1.86 to 2.45) to 7.93 (95% CI 6.33 to 9.93) actions per 1000 physicians. The mean rate of major disciplinary actions was 2.71 (95% CI 1.93 to 3.82), ranging from 0.64 (95% CI 0.53 to 0.76) to 2.71 (95% CI 1.93 to 3.82) actions per 1000 physicians. The correlation between the rate of major disciplinary action and minor disciplinary actions was 0.34.ConclusionsThere is a significant, fourfold variation in the annual rate of medical board physician disciplinary action by state in the USA. When indicated, state medical boards should consider policies aimed at improving standardisation and coordination to provide consistent supervision to physicians and ensure public safety.
Anaemia secondary to erythropoietin resistance: important predictor of adverse outcomes in chronic obstructive pulmonary disease
Authors: Sharma Rahul Kumar , Chakrabarti Shibdas 
Published: March 2016

AbstractPurposeAnaemia is increasingly being linked to chronic obstructive pulmonary disease (COPD) as comorbidity with erythropoietin resistance secondary to chronic inflammation is hypothesised to have some role. This study purported to evaluate the occurrence of anaemia in COPD and its association with inflammatory markers, erythropoietin levels, severity and exacerbations of COPD.MethodsTwo hundred patients with COPD (90% men, mean age 62.4±8.33 years) were enrolled and subjected to detailed clinical and laboratory evaluation, including complete blood count, erythropoietin levels, C-reactive protein (CRP), pulmonary function test, blood gas analysis and chest X-ray. Severity of COPD was defined on the basis of forced expiratory volume in 1 s according to GOLD guidelines.ResultsAnaemia was diagnosed in 14% of patients (n=28, predominantly normocytic normochromic type (92.8%)) and polycythmia in 5% of patients (n=10). The prevalence of anaemia increased with increasing severity of COPD (stage 2: 8%, stage 3: 14.4% and stage 4: 17.2%; p=0.46). Serum erythropoietin was significantly higher in more advanced COPD, with mean levels being 30.2±6.5, 31.78±8.09 and 39.33±7.68 mIU/mL in stage 2, 3 and 4 respectively. Moreover erythropoietin levels inversely correlated with mean haemoglobin levels(r=−0.25), indicating erythropoietin resistance. CRP reactivity increased with increasing stage of disease in patients with anaemia (p=0.026). On follow-up, significant inverse correlation was observed between haemoglobin and COPD exacerbations (p&lt;0.001).ConclusionsAnaemia is a significant comorbidity of COPD with a negative prognostic impact on lung health. It can be ascribed to a state of systemic inflammation resulting in blunting of erythropoietin response with increasing severity of disease, leading to greater morbidity and hospitalisation.
Characteristics of Colorectal Cancer that Produce Positive Immunochemical Occult Blood Test Results on Stool Obtained by Digital Rectal Examination
Authors: Nakama Hidenori , Zhang Bing , Abdul Fattah ASM , Kamijo Noboru , Zhang Xing 
Published: March 2016

OBEJCTIVE: To clarify the clinicopathological features of colorectal cancer that show positive results on an immunochemical fecal occult blood test of stool obtained by digital rectal examination.METHODS: In a cross-sectional study, 9952 subjects received both an immunochemical fecal occult blood test of stool obtained by digital rectal examination and colonoscopy annually over a nine-year period of medical checkups; 64 patients with colorectal cancer were identified. The study subjects comprised 39 patients with colorectal cancer who had positive results (positive group) and 25 patients with colorectal cancer who had negative results (negative group) on an immunochemical fecal occult blood test of stool obtained by digital rectal examination. The positive and negative groups were compared in terms of their individual factors, such as site, size, Dukes classification and histological type of the cancer lesions.RESULTS: The prevalence of rectal cancers was higher in the positive group than in the negative group (P<0.05), but there were no differences between the two groups with respect to any other factors.CONCLUSIONS: These findings indicate that stool obtained during the digital rectal examination is unsuitable for detecting fecal occult blood, especially for the detection of proximal colon neoplasms.
MET Exon 14 Alterations in Lung Cancer: Exon Skipping Extends Half-Life
Authors: Drilon Alexander 
Published: March 2016

Abstract
MET exon 14 alterations are a diverse group of mutations, many of which disrupt splice acceptor or donor sites leading to exon 14 skipping, impaired receptor degradation, and oncogenic transformation. These alterations are clinically targetable with MET-directed therapy. Clin Cancer Res; 22(12); 2832–4. ©2016 AACR.
See related article by Tong et al., p. 3048
Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma
Authors: Lescarbeau Rebecca S. , Lei Liang , Bakken Katrina K. , Sims Peter A. , Sarkaria Jann N. , Canoll Peter , White Forest M. 
Published: March 2016

Abstract
Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332–43. ©2016 AACR.
Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel
Authors: Carreras Edward , Hochholzer Willibald , Frelinger Andrew , Nordio Francesco , O’Donoghue Michelle , Wiviott Stephen , Angiolillo Dominick , Michelson Alan , Sabatine Marc , Mega Jessica 
Published: March 2016

SummaryBoth diabetes mellitus (DM) and carriage of the CYP2C19*2 allele are associated with a reduced response to clopidogrel. The relative contributions of these factors and whether higher clopidogrel doses can overcome both factors remain unknown. The objective of this study was to test the ability of clopidogrel doses up to 300 mg daily to decrease platelet reactivity in patients with DM and/or CYP2C19*2. ELEVATE-TIMI 56 randomised 333 patients with coronary artery disease to different maintenance doses of clopidogrel in four treatment periods, each lasting approximately 14 days. On-treatment platelet reactivity was compared between patients stratified by DM, CYP2C19*2 status and clopidogrel dose. Both DM and CYP2C19*2 were independently associated with elevated on-treatment platelet reactivity with clopidogrel 75 mg daily (p<0.0001 for each). With 75 mg, mean on-treatment PRU was progressively higher (p trend <0.001) when evaluating patients: with neither DM nor CYP2C19*2 (150.7; 95 % CI 140.5–162.6), with only DM (187.2; 95 % CI, 171.3–206.9), with only CYP2C19*2 (227.9; 95 % CI, 205.1–250.8), and with both DM and CYP2C19*2 (239.9; 95 % CI, 209.7–270.1). Notably, with 75 mg, patients with only CYP2C19*2 had higher ontreatment platelet reactivity than those with only DM (p=0.0068). To achieve on-treatment platelet reactivity similar to that seen with clopidogrel 75 mg in patients with neither DM nor CYP2C19*2, the following doses were required: 150 mg with only DM, 225 mg with only CYP2C19*2, and 300 mg with both DM and CYP2C19*2. Patients with both DM and CYP2C19*2 required a four-fold increase in clopidogrel maintenance dose as compared to patients without these factors to achieve a similar antiplatelet response.
Caregiver outcomes and interventions: a systematic scoping review of the traumatic brain injury and spinal cord injury literature
Authors: Baker Anne , Barker Samantha , Sampson Amanda , Martin Clarissa 
Published: March 2016

Aim: To identify factors reported with negative and positive outcomes for caregivers of the traumatic brain injury and spinal cord injury cohorts, to investigate what interventions have been studied to support carers and to report what effectiveness has been found. Methods: Scoping systematic review. Electronic databases and websites were searched from 1990 to December 2015. Studies were agreed for inclusion using pre-defined criteria. Relevant information from included studies was extracted and quality assessment was completed. Data were synthesised using qualitative methods. Results: A total of 62 studies reported caregiver outcomes for the traumatic brain injury cohort; 51 reported negative outcomes and 11 reported positive outcomes. For the spinal cord injury cohort, 18 studies reported caregiver outcomes; 15 reported negative outcomes and three reported positive outcomes. Burden of care was over-represented in the literature for both cohorts, with few studies looking at factors associated with positive outcomes. Good family functioning, coping skills and social support were reported to mediate caregiver burden and promote positive outcomes. A total of 21 studies further described interventions to support traumatic brain injury caregivers and four described interventions to support spinal cord injury caregivers, with emerging evidence for the effectiveness of problem-solving training. Further research is required to explore the effects of injury severity of the care recipient, as well as caregiver age, on the outcome of the interventions. Conclusion: Most studies reported negative outcomes, suggesting that barriers to caregiving have been established, but not facilitators. The interventions described to support carers are limited and require further testing to confirm their effectiveness.
The effect of desvenlafaxine on cognitive functioning in employed outpatients with major depressive disorder: a substudy of a randomized, double-blind, placebo-controlled trial
Authors: Reddy Sujana , Fayyad Rana , Edgar Chris J , Guico-Pabia Christine J , Wesnes Keith 
Published: March 2016

The objective of this substudy was to examine the effect of desvenlafaxine 50 mg/day compared with placebo on cognitive function in employed outpatients with major depressive disorder. A total of 11/55 (20%) study sites in a 12-week, randomized, double-blind, placebo-controlled trial administered cognitive assessments in memory, attention, and executive functioning domains using the cognitive drug research system. Changes from baseline were subjected to analysis of covariance with baseline levels as covariates, using last observation carried forward data. A significant improvement with desvenlafaxine 50 mg/day ( n=52) compared with placebo ( n=29) was observed on the quality of working memory composite measure (0.081 units (0.005, 0.156); P=0.0365) at last observation carried forward. Improvement from baseline on the speed of working memory composite was significant for desvenlafaxine (−226.6 msec (−316.7, −136.4); P<0.0001) and for placebo (−133.3 msec (−257.2, −9.4); P=0.0354); however, the treatment effect was not significant. No significant differences between groups were observed on composite measures for attention. Treatment of depression with desvenlafaxine 50 mg/day may improve aspects of cognitive functioning, including working memory. Clinical Trial Registry No.: Clinicaltrials.gov identifier: NCT00824291
Predictive modeling and in vivo assessment of cerebral blood flow in the management of complex cerebral aneurysms
Authors: Walcott Brian P , Reinshagen Clemens , Stapleton Christopher J , Choudhri Omar , Rayz Vitaliy , Saloner David , Lawton Michael T 
Published: March 2016

Cerebral aneurysms are weakened blood vessel dilatations that can result in spontaneous, devastating hemorrhage events. Aneurysm treatment aims to reduce hemorrhage events, and strategies for complex aneurysms often require surgical bypass or endovascular stenting for blood flow diversion. Interventions that divert blood flow from their normal circulation patterns have the potential to result in unintentional ischemia. Recent developments in computational modeling and in vivo assessment of hemodynamics for cerebral aneurysm treatment have entered into clinical practice. Herein, we review how these techniques are currently utilized to improve risk stratification and treatment planning.
Increased 8-hydroxy-2’-deoxyguanosine in leukocyte DNA from patients with type 2 diabetes and microangiopathy
Authors: Ye Xiaozhen , Jiang Rong , Zhang Qianqian , Wang Ruifeng , Yang Cuihua , Ma Jian , Du Hong 
Published: March 2016

Objective To evaluate oxidative damage in leukocytes from patients with type 2 diabetes by examining 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels. Methods Patients with type 2 diabetes and healthy controls were assessed for demographic, clinical and biochemical characteristics. Levels of 8-OHdG in extracted leukocyte DNA were determined by enzyme linked immunosorbent assay. Results Of 108 patients with type 2 diabetes (56 with microangiopathy, 52 without) and 65 healthy controls, leukocyte 8-OHdG levels were higher in patients with type 2 diabetes versus controls (median ± interquartile range [IQR], 3.19 ± 2.17 versus 0.38 ± 1.00 ng/ml), and higher in patients with type 2 diabetes and microangiopathy versus those without microangiopathy (median ± IQR, 3.34 ± 1.87 versus 2.71 ± 2.26 ng/ml). Patients with type 2 diabetes and microangiopathy had higher serum creatinine and urinary albumin levels versus those without microangiopathy. Leukocyte 8-OHdG levels, duration of type 2 diabetes, albuminuria, use of insulin and use of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) were independently associated with microangiopathy in patients with type 2 diabetes after adjustment for smoking. Conclusions Leukocyte oxidative DNA damage was high in patients with type 2 diabetes and microangiopathy. Presence of microangiopathy was associated with leukocyte 8-OHdG levels, duration of type 2 diabetes, albuminuria and use of ACE inhibitors/ARBs or insulin.
Abnormal tyrosine metabolism in chronic cluster headache
Authors: D’Andrea Giovanni , Leone Massimo , Bussone Gennaro , Fiore Paola Di , Bolner Andrea , Aguggia Marco , Saracco Maria Gabriella , Perini Francesco , Giordano Giuseppe , Gucciardi Antonina , Leon Alberta 
Published: March 2016

Objective Episodic cluster headache is characterized by abnormalities in tyrosine metabolism (i.e. elevated levels of dopamine, tyramine, octopamine and synephrine and low levels of noradrenalin in plasma and platelets.) It is unknown, however, if such biochemical anomalies are present and/or constitute a predisposing factor in chronic cluster headache. To test this hypothesis, we measured the levels of dopamine and noradrenaline together with those of elusive amines, such as tyramine, octopamine and synephrine, in plasma of chronic cluster patients and control individuals. Methods Plasma levels of dopamine, noradrenaline and trace amines, including tyramine, octopamine and synephrine, were measured in a group of 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster), and 16 control participants. Results The plasma levels of dopamine, noradrenaline and tyramine were several times higher in chronic cluster headache patients compared with controls. The levels of octopamine and synephrine were significantly lower in plasma of these patients with respect to control individuals. Conclusions These results suggest that anomalies in tyrosine metabolism play a role in the pathogenesis of chronic cluster headache and constitute a predisposing factor for the transformation of the episodic into a chronic form of this primary headache.
Effects of lowered dialysate sodium on left ventricle function and brain natriuretic peptide in maintenance of hemodialysis patients
Authors: Akyol A , Akdag S , Asker M , Gumrukcuoglu HA , Duz R , Demirel KC , Ozturk F , Yaman M , Sahin M , Simsek H , Tuncer M , Begenik H 
Published: March 2016

Introduction: Impaired diastolic flow is characterized by decreased left ventricular (LV) filling diastole, abnormal LV distensibility, or delayed relaxation. B-Type natriuretic peptide (BNP) is an indicator of various cardiovascular diseases and body volume status. The aim of this study was to determine whether the lowering of dialysate sodium (Na) levels is effective on LV systolic and diastolic parameters and BNP in the maintenance of hemodialysis patients. Materials and Methods: The study included 49 chronic hemodialysis patients. Left atrium (LA) diameter and LV ejection fraction, LV systolic and diastolic diameter, deceleration time (DT), pulmonary artery pressure (PAP), inferior vena cava diameter (IVCD), early diastolic transmitral flow ( E) and late diastolic transmitral flow ( A) velocities, E/ A ratio, isovolumic relaxation time, peak early diastolic velocity ( E′), late diastolic velocity ( A′) of tissue Doppler mitral annulus, and flow propagation velocity of mitral inflow ( Vp) were measured before and 6 months after hemodialysis with low Na dialysate. Results: Six months after low Na hemodialysis, a decrease was observed in echocardiographic parameters such as PAP and IVCD ( p < 0.05, p < 0.001, and p < 0.001, respectively). However, a significant difference was not observed in LA diameter. In LV diastolic measurement of E and A waves, E/ A ratio, DT, Vp, septal E′ and A′, and lateral E′ and A′ exhibited significant improvement by low Na HD. BNP level was significantly reduced ( p < 0.001). Conclusions: Lowered dialysate Na concentration improves PAP, IVCD, and LV diastolic properties assessed by mitral inflow filling, tissue Doppler velocity, and mitral inflow velocity propagation.
The effect of tobacco smoke on oxytocin concentrations and selected oxidative stress parameters in plasma during pregnancy and post-partum – an experimental model
Authors: Napierala M , Merritt TA , Mazela J , Jablecka K , Miechowicz I , Marszalek A , Florek E 
Published: March 2016

Background: Tobacco smoking is a serious threat to life and health of society. Among the most vulnerable to the toxic effects of tobacco smoke are foetuses and newborns. The objective of the research was to assess the impact of tobacco smoke exposure on oxytocin levels and biochemical oxidative stress parameters during pregnancy and after birth in an experimental model. Methods: In the experiment, exposure to tobacco smoke of gravid and non-gravid rats was monitored. A reliable biomarker of exposure – cotinine – was used in the process and it was determined by means of high-performance liquid chromatography with diode array detection, which ensured high analytical accuracy and precision. Determination of oxytocin was performed by means of enzyme-linked immunosorbent assay. The levels of selected oxidative stress parameters: total protein concentration, uric acid, trolox equivalent antioxidant capacity, protein S-nitrosylation and lipid peroxidation (thiobarbituric acid reactive substances) were measured by spectrophotometric methods. Results and conclusions: The effect of prenatal and postnatal exposure to tobacco smoke was a lower medium body mass of rat foetuses and pups. Oxidative stress during pregnancy, additionally intensified by tobacco smoke exposure, led to adaptive changes in properties of plasmatic antioxidant barriers. Moreover, the disturbance of oxidoreductive balance by tobacco smoke affects oxytocin fluctuations, what was observed in this study during lactation period. Therefore, women who smoke may breastfeed their children less frequently and for a shorter period.
A grounded theory of humanistic nursing in acute care work environments
Authors: Khademi Mojgan , Mohammadi Eesa , Vanaki Zohreh 
Published: March 2016

Background: Humanistic nursing practice which is dominated by technological advancement, outcome measurement, reduced resources, and staff shortages is challenging in the present work environment. Objective: To examine the main concern in humanistic nursing area and how the way it is solved and resolved by Iranian nurses in acute care setting. Research design: Data were collected from interviews and observations in 2009–2011 and analyzed using classic grounded theory. Memos were written during the analysis, and they were sorted once theoretical saturation occurred. Participants and research context: In total, 22 nurses, 18 patients, and 12 families from two teaching hospitals in Tehran were selected by purposeful and theoretical sampling. Ethical considerations: The research was approved by the Ethics Committee of the university and hospitals. Results: The main concern for the nurses is the violation of their rights. They overcome this concern when there is a synergy of situation–education/learning, that is, a positive interaction between education and learning of values and sensitivity of the situation or existence of care promotion elements. They turn to professional values and seeking and meeting others’ needs, resulting in “success and accomplishment” of nurse/nursing manager and patient/family. Conclusion: This theory shows that professional values, elements of care promotion, and sensitivity of the situation have a key role in activation of humanistic approach in nursing. Violation of the nurses’ professional rights often leads to a decrease in care, but these factors make the nurses practice in an unsparing response approach. It is necessary to focus on development of professional values and provide essential elements of care promotion as changeable factors for realization of humanistic nursing although there is a context in which the nurses’ rights are violated.