bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterium tuberculosis Pyrazinamide Resistance Determinants: a Multicenter Study
Authors: Miotto Paolo , Cabibbe Andrea M. , Feuerriegel Silke , Casali Nicola , Drobniewski Francis , Rodionova Yulia , Bakonyte Daiva , Stakenas Petras , Pimkina Edita , Augustynowicz-Kopeć Ewa , Degano Massimo , Ambrosi Alessandro , Hoffner Sven , Mansjö Mikael , Werngren Jim , Rüsch-Gerdes Sabine , Niemann Stefan , Cirillo Daniela M. 
Published: October 2014

ABSTRACT

Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the
pncA
gene in
Mycobacterium tuberculosis
. Molecular identification of mutations in
pncA
offers the potential for rapid detection of pyrazinamide resistance (PZA
r
). However, the genetic variants are highly variable and scattered over the full length of
pncA
, complicating the development of a molecular test. We performed a large multicenter study assessing
pncA
sequence variations in 1,950 clinical isolates, including 1,142 multidrug-resistant (MDR) strains and 483 fully susceptible strains. The results of
pncA
sequencing were correlated with phenotype, enzymatic activity, and structural and phylogenetic data. We identified 280 genetic variants which were divided into four classes: (i) very high confidence resistance mutations that were found only in PZA
r
strains (85%), (ii) high-confidence resistance mutations found in more than 70% of PZA
r
strains, (iii) mutations with an unclear role found in less than 70% of PZA
r
strains, and (iv) mutations not associated with phenotypic resistance (10%). Any future molecular diagnostic assay should be able to target and identify at least the very high and high-confidence genetic variant markers of PZA
r
; the diagnostic accuracy of such an assay would be in the range of 89.5 to 98.8%.

IMPORTANCE
Conventional phenotypic testing for pyrazinamide resistance in
Mycobacterium tuberculosis
is technically challenging and often unreliable. The development of a molecular assay for detecting pyrazinamide resistance would be a breakthrough, directly overcoming both the limitations of conventional testing and its related biosafety issues. Although the main mechanism of pyrazinamide resistance involves mutations inactivating the
pncA
enzyme, the highly diverse genetic variants scattered over the full length of the
pncA
gene and the lack of a reliable phenotypic gold standard hamper the development of molecular diagnostic assays. By analyzing a large number of strains collected worldwide, we have classified the different genetic variants based on their predictive value for resistance which should lead to more rapid diagnostic tests. This would assist clinicians in improving treatment regimens for patients.
Assessing the role of a medication-indication resource in the treatment relation extraction from clinical text
Authors: Bejan Cosmin Adrian , Wei Wei-Qi , Denny Joshua C 
Published: October 2014

Abstract
Objective To evaluate the contribution of the MEDication Indication (MEDI) resource and SemRep for identifying treatment relations in clinical text.
Materials and methods We first processed clinical documents with SemRep to extract the Unified Medical Language System (UMLS) concepts and the treatment relations between them. Then, we incorporated MEDI into a simple algorithm that identifies treatment relations between two concepts if they match a medication-indication pair in this resource. For a better coverage, we expanded MEDI using ontology relationships from RxNorm and UMLS Metathesaurus. We also developed two ensemble methods, which combined the predictions of SemRep and the MEDI algorithm. We evaluated our selected methods on two datasets, a Vanderbilt corpus of 6864 discharge summaries and the 2010 Informatics for Integrating Biology and the Bedside (i2b2)/Veteran's Affairs (VA) challenge dataset.
Results The Vanderbilt dataset included 958 manually annotated treatment relations. A double annotation was performed on 25% of relations with high agreement (Cohen's κ = 0.86). The evaluation consisted of comparing the manual annotated relations with the relations identified by SemRep, the MEDI algorithm, and the two ensemble methods. On the first dataset, the best F1-measure results achieved by the MEDI algorithm and the union of the two resources (78.7 and 80, respectively) were significantly higher than the SemRep results (72.3). On the second dataset, the MEDI algorithm achieved better precision and significantly lower recall values than the best system in the i2b2 challenge. The two systems obtained comparable F1-measure values on the subset of i2b2 relations with both arguments in MEDI.
Conclusions Both SemRep and MEDI can be used to extract treatment relations from clinical text. Knowledge-based extraction with MEDI outperformed use of SemRep alone, but superior performance was achieved by integrating both systems. The integration of knowledge-based resources such as MEDI into information extraction systems such as SemRep and the i2b2 relation extractors may improve treatment relation extraction from clinical text.
Effectiveness of cognitive behavioural therapy augmentation in major depression treatment (ECAM study): study protocol for a randomised clinical trial
Authors: Nakagawa Atsuo , Sado Mitsuhiro , Mitsuda Dai , Fujisawa Daisuke , Kikuchi Toshiaki , Abe Takayuki , Sato Yuji , Iwashita Satoru , Mimura Masaru , Ono Yutaka 
Published: October 2014

IntroductionMajor depression is a serious mental disorder that causes substantial distress and impairment in individuals and places an enormous burden on society. Although antidepressant treatment is the most common therapy provided in routine practice, there is little evidence to guide second-line therapy for patients who have failed to respond to antidepressants. The aim of this paper is to describe the study protocol for a randomised controlled trial that measures the clinical effectiveness of cognitive behavioural therapy (CBT) as an augmentation strategy to treat patients with non-psychotic major depression identified as suboptimal responders to usual depression care.Methods and analysisThe current study is a 16-week assessor-blinded randomised, parallel-groups superiority trial with 12-month follow-up at an outpatient clinic as part of usual depression care. Patients aged 20–65 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Major Depressive Disorder who have experienced at least one failed trial of antidepressants as part of usual depression care, will be randomly assigned to receive CBT plus treatment as usual, or treatment as usual alone. The primary outcome is the change in clinician-rated 17-item GRID-Hamilton Depression Rating Scale (GRID-HAMD) score at 16 weeks, and secondary outcomes include severity and change in scores of subjective depression symptoms, proportion of responders and remitters, safety and quality of life. The primary population will be the intention-to-treat patients.Ethics and disseminationAll protocols and the informed consent form comply with the Ethics Guideline for Clinical Research (Japanese Ministry of Health, Labour and Welfare). Ethics review committees at the Keio University School of Medicine and the Sakuragaoka Memorial Hospital approved the study protocol. The results of the study will be disseminated at several research conferences and as published articles in peer-reviewed journals. The study will be implemented and reported in line with the CONSORT statement.Trial registration numberUMIN Clinical Trials Registry: UMIN000001218.
Sequential Use of the Androgen Synthesis Inhibitors Ketoconazole and Abiraterone Acetate in Castration-Resistant Prostate Cancer and the Predictive Value of Circulating Androgens
Authors: Kim Won , Zhang Li , Wilton John H. , Fetterly Gerald , Mohler James L. , Weinberg Vivian , Morse Allison , Szmulewitz Russell Z. , Friedlander Terence W. , Fong Lawrence , Lin Amy M. , Harzstark Andrea L. , Molina Arturo , Small Eric J. , Ryan Charles J. 
Published: October 2014

Abstract
Purpose: Patients previously treated with ketoconazole were excluded from phase III trials of abiraterone acetate due to potential overlapping mechanism of action. The purpose of this study was to determine the clinical utility of abiraterone and its impact on circulating androgens following ketoconazole.
Experimental Design: Chemotherapy-naïve patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and prior ketoconazole therapy ≥28 days received abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. The primary endpoint was the proportion of patients with PSA response, defined as ≥30% PSA decline at 12 weeks. H0 = 0.30 versus H1 = 0.50 (α = 0.05, power = 0.83). Circulating androgen levels were measured using liquid chromatography tandem mass spectrometry.
Results: Thirty-nine patients were included in the final analysis. Twenty (51%; 95% confidence interval, 36%–66%) patients had ≥30% PSA decline; the null hypothesis was rejected. Sixteen (41%) had ≥50% PSA decline. Median PFS (progression-free survival) was 16 weeks; median radiographic PFS (rPFS) was 36 weeks. Samples for measurement of baseline androgens were available in 37 patients. The PSA response proportion was 59% in 29 patients with DHEA ≥ limit of quantitation (LOQ), compared with 13% in 8 patients with DHEA &lt; LOQ (P = 0.042). Median PFS was 6 and 16 weeks in DHEA &lt; LOQ and DHEA ≥ LOQ patients, respectively (P = 0.017); median rPFS was 14 and 36 weeks in DHEA &lt; LOQ and DHEA ≥ LOQ patients, respectively (P &lt; 0.001).
Conclusions: Abiraterone demonstrates modest clinical efficacy in mCRPC patients previously treated with ketoconazole. Patients with DHEA ≥ LOQ were more likely to demonstrate PSA responses and longer PFS. Analysis of circulating androgens merits further investigation as a biomarker for response to androgen synthesis inhibitor therapy. Clin Cancer Res; 20(24); 6269–76. ©2014 AACR.
Costs of Periprocedural Complications in Patients Treated With Transcatheter Aortic Valve Replacement
Authors: Arnold Suzanne V. , Lei Yang , Reynolds Matthew R. , Magnuson Elizabeth A. , Suri Rakesh M. , Tuzcu E. Murat , Petersen John L. , Douglas Pamela S. , Svensson Lars G. , Gada Hemal , Thourani Vinod H. , Kodali Susheel K. , Mack Michael J. , Leon Martin B. , Cohen David J. 
Published: October 2014

Background—
In patients with severe aortic stenosis, transcatheter aortic valve replacement (TAVR) improves survival when compared with nonsurgical therapy but with higher in-hospital and lifetime costs. Complications associated with TAVR may decrease with greater experience and improved devices, thereby reducing the overall cost of the procedure. Therefore, we sought to estimate the effect of periprocedural complications on in-hospital costs and length of stay of TAVR.

Methods and Results—
Using detailed cost data from 406 TAVR patients enrolled in the Placement of Aortic Transcatheter Valve (PARTNER) I trial, we developed multivariable models to estimate the incremental cost and length of stay associated with specific periprocedural complications. Attributable costs and length of stay for each complication were calculated by multiplying the independent cost of each event by its frequency in the treatment group. Mean cost for the initial hospitalization was $79 619±40 570 ($50 891 excluding the valve); 49% of patients had ≥1 complication. Seven complications were independently associated with increased hospital costs, with major bleeding, arrhythmia, and death accounting for the largest attributable cost per patient. Renal failure and the need for repeat TAVR, although less frequent, were also associated with substantial incremental and attributable costs. Overall, complications accounted for $12 475 per patient in initial hospital costs and 2.4 days of hospitalization.

Conclusions—
In the PARTNER trial, periprocedural complications were frequent, costly, and accounted for ≈25% of non-implant–related hospital costs. Avoidance of complications should improve the cost-effectiveness of TAVR for inoperable and high-risk patients, but reductions in the cost of uncomplicated TAVR will also be necessary for optimal efficiency.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00530894.
Depletion of B‐Cells With Rituximab Improves Endothelial Function and Reduces Inflammation Among Individuals With Rheumatoid Arthritis
Authors: Hsue Priscilla Y. , Scherzer Rebecca , Grunfeld Carl , Imboden John , Wu Yuaner , del Puerto Gus , Nitta Elaine , Shigenaga Judy , Schnell Heringer Amanda , Ganz Peter , Graf Jonathan 
Published: October 2014

Background

Individuals with rheumatoid arthritis (
RA
) are at increased risk for cardiovascular disease, partly due to systemic inflammation and endothelial dysfunction. B‐cells play an important pathogenic role in the inflammatory process that drives
RA
disease activity. Rituximab, a chimeric murine/human monoclonal antibody that depletes B‐cells, is an effective therapy for
RA
. The purpose of this study was to determine whether B‐cell depletion with rituximab reduces systemic inflammation and improves macrovascular (brachial artery flow‐mediated dilation,
FMD
) and microvascular (reactive hyperemia) endothelial function in
RA
patients.

Methods and Results

RA
patients received a single course of rituximab (1000 mg
IV
infusion at baseline and on day 15).
FMD
, reactive hyperemia, inflammatory markers, and clinical assessments were performed at baseline, week 12, and week 24. Twenty patients (95% female, median age 54 years) completed the study. Following treatment,
FMD
improved from a baseline of 4.5±0.4% to 6.4±0.6% at 12 weeks (mean±
SE
;
P
<0.0001), followed by a decline at week 24; a similar pattern was observed for hyperemic velocity. Significant decreases in
RA
disease scores, high‐sensitivity C‐reactive protein, erythrocyte sedimentation rate, and circulating
CD
19+ B‐cells were sustained through week 24. Cholesterol and triglycerides became significantly although modestly elevated during the study.

Conclusions

Depletion of B‐cells with rituximab improved macrovascular and microvascular endothelial function and reduced systemic inflammation, despite modest elevation in lipids. Given these results, rituximab should be evaluated in the future for its possible role in reducing excess cardiovascular risk in
RA
.

Clinical Trial Registration

URL
http://ClinicalTrials.gov
. Unique identifier:
NCT
00844714.
Thienopyridine Use After Coronary Stenting in Low Income Patients Enrolled in Medicare Part D Receiving Maintenance Dialysis
Authors: Chang Tara I. , Montez‐Rath Maria E. , Shen Jenny I. , Solomon Matthew D. , Chertow Glenn M. , Winkelmayer Wolfgang C. 
Published: October 2014

Background

Coronary stenting in patients on dialysis has increased by nearly 50% over the past decade, despite heightened risks of associated stent thrombosis and bleeding relative to the general population. We examined clopidogrel, prasugrel or ticlopidine use after percutaneous coronary intervention (
PCI
) with stenting in patients on dialysis. We conducted 3‐, 6‐, and 12‐month landmark analyses to test the hypothesis that thienopyridine discontinuation prior to those time points would be associated with higher risks of death, myocardial infarction, or repeat revascularization, and a lower risk of major bleeding episodes compared with continued thienopyridine use.

Methods and Results

Using the
US
Renal Data System, we identified 8458 patients on dialysis with Medicare Parts A+B+D undergoing
PCI
with stenting between July 2007 and December 2010. Ninety‐nine percent of all thienopyridine prescriptions were for clopidogrel. At 3 months, 82% of patients who received drug‐eluting stents (
DES
) had evidence of thienopyridine use. These proportions fell to 62% and 40% at 6 and 12 months, respectively. In patients who received a bare‐metal stent (
BMS
), 70%, 34%, and 26% of patients had evidence of thienopyridine use at 3, 6, and 12 months, respectively. In patients who received a
DES
, there was a suggestion of higher risks of death or myocardial infarction associated with thienopyridine discontinuation in the 3‐, 6‐, and 12‐months landmark analyses, but no higher risk of major bleeding episodes. In patients who received a
BMS
, there were no differences in death or cardiovascular events, and possibly lower risk of major bleeding with thienopyridine discontinuation in the 3‐ and 6‐month landmark analyses.

Conclusions

The majority of patients on dialysis who undergo
PCI
discontinue thienopyridines before 1 year regardless of stent type. While not definitive, these data suggest that longer‐term thienopyridine use may be of benefit to patients on dialysis who undergo
PCI
with
DES
.
Blood versus crystalloid cardioplegia for pediatric cardiac surgery: a meta-analysis
Authors: Fang Y , Long C , Lou S , Guan Y , Fu Z 
Published: October 2014

Objective: Blood and crystalloid cardioplegia are the main myocardial protective solutions used in pediatric cardiac surgery. However, the effectiveness of these two solutions on myocardial metabolism, reperfusion injury and clinical outcomes in pediatric patients is still under debate. The purpose of this meta-analysis was to compare the efficacy of these two cardioplegia solutions in pediatric cardiac surgery. Methods: Keyword searches were performed on PUBMED, EMBASE and The Cochrane Library for randomized, controlled, clinical studies which were primarily comparing blood and crystalloid cardioplegia in pediatric cardiac surgery and provided data of postoperative cardiac troponin I (cTnI), lactate, mechanical ventilation time, length of intensive care unit (ICU) stay and inotropic support. Databases were searched from 1966 to June 2013 and were restricted to peer-reviewed English language publications of human subjects. We summarized the combined results of the data as mean difference (MD, when outcome measurements were made on the same scale) or standard mean difference (SMD, when the studies assess the same outcome with different scales), with 95% confidence intervals. Results: Five studies were identified, with a total of 323 patients. Lactate level after cardiopulmonary bypass (CPB) was significantly lower after blood cardioplegia compared with crystalloid cardioplegia (SMD 1.09, 95%CI 0.12 to 2.06, p=0.03); cTnI release postoperatively at 4-6 h (MD 0.92 ng/ml, 95%CI -0.13 to 1.97, p=0.09), 12 h (MD 0.2 ng/ml, 95% CI -0.43 to 0.84, p=0.53) and 24 h (MD 0.98 ng/ml, 95%CI -0.26 to 2.22, p=0.12) was not significantly different between the groups; ventilation duration (MD 5.15 hours, 95%CI -7.51 to 17.81, p=0.42) and length of ICU stay (SMD -0.3, 95%CI -0.80 to 0.21, p=0.25) were not significantly different between the groups either. Conclusion: Myocardial metabolism was better in the blood cardioplegia group compared with the crystalloid cardioplegia group. However, there was no evidence of improvement in myocardial damage or clinical outcome for either cardioplegia solution.
Some ethical conflicts in emergency care
Authors: Jiménez-Herrera Maria F , Axelsson Christer 
Published: October 2014

Background: Decision-making and assessment in emergency situations are complex and result many times in ethical conflicts between different healthcare professionals. Aim: To analyse and describe situations that can generate ethical conflict among nurses working in emergency situations. Methods: Qualitative analysis. A total of 16 emergency nurses took part in interviews and a focus group. Ethical considerations: Organisational approval by the University Hospital, and informed consent and confidentiality were ensured before conducting the research. Result/conclusion: Two categories emerged: one in ‘ethical issues’ and one in ‘emotions and feelings in caring’. The four ethical subcategories are presented: Autonomy, the first sub category: first, the nurse’s ability to practise care on an emergency ward and, second, to support the patient and/or relatives in terms of care and medical treatment. The conflicts arise when the nurse ends up in the middle between the patient and the physician responsible for the diagnosis and treatment from a nature scientific perspective. Reification of injured body: patient was often reified and fragmented, becoming just a leg or arm. Different factors contributed in this perspective. Pain: pain relief was often inadequate but more effectively treated in the emergency medical services than at the emergency department. The nurses highlighted the phenomenon of suffering because they felt that pain was only an object, forgetting the patients’ care need, like separating mind from body. Death: the nurses felt that the emergency services are only prepared to save lives and not to take care of the needs of patients with ‘end-of-life’ care. Another issue was the lack of ethical guidelines during a cardiac arrest. Resuscitation often continues without asking about the patient’s ‘previous wishes’ in terms of resuscitation or not. In these situations, the nurses describe an ethical conflict with the physician in performing their role as the patient’s advocate. The nurses express feelings of distress, suffering, anger and helplessness.
The role of government policy in service development in a New Zealand statutory mental health service: implications for policy planning and development
Authors: Stanley-Clarke Nicky , Sanders Jackie , Munford Robyn 
Published: October 2014

Objective: To explore the relationship between government policy and service development in a New Zealand statutory mental health provider, Living Well. Method: An organisational case study utilising multiple research techniques including qualitative interviews, analysis of business and strategic documents and observation of meetings. Results: Staff understood and acknowledged the importance of government policy, but there were challenges in its implementation. Conclusion: Within New Zealand’s statutory mental health services staff struggled to know how to implement government policy as part of service development; rather, operational concerns, patient need, local context and service demands drove the service development process.
Being a pedestrian with dementia: A qualitative study using photo documentation and focus group interviews
Authors: Brorsson Anna , Öhman Annika , Lundberg Stefan , Nygård Louise 
Published: October 2014

The aim of the study was to identify problematic situations in using zebra crossings. They were identified from photo documentations comprising film sequences and the perspectives of people with dementia. The aim was also to identify how they would understand, interpret and act in these problematic situations based on their previous experiences and linked to the film sequences. A qualitative grounded theory approach was used. Film sequences from five zebra crossings were analysed. The same film sequences were used as triggers in two focus group interviews with persons with dementia. Individual interviews with three informants were also performed. The core category, the hazard of meeting unfolding problematic traffic situations when only one layer at a time can be kept in focus, showed how a problematic situation as a whole consisted of different layers of problematic situations. The first category, adding layers of problematic traffic situations to each other, was characterized by the informants’ creation of a problematic situation as a whole. The different layers were described in the subcategories of layout of streets and zebra crossings, weather conditions, vehicles and crowding of pedestrians. The second category, actions used to meet different layers of problematic traffic situations, was characterized by avoiding problematic situations, using traffic lights as reminders and security precautions, following the flow at the zebra crossing and being cautious pedestrians. In conclusion, as community-dwelling people with dementia commonly are pedestrians, it is important that health care professionals and caregivers take their experiences and management of problematic traffic situations into account when providing support.