bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Contraindicated Antiplatelet Medications in the Setting of Percutaneous Coronary Intervention
Authors: Barnes Geoffrey D. , Stanislawski Maggie A. , Liu Wenhui , Barón Anna E. , Armstrong Ehrin J. , Ho P. Michael , Klein Andrew , Maddox Thomas M. , Nallamothu Brahmajee K. , Rumsfeld John S. , Tsai Thomas T. , Bradley Steven M. 
Published: June 2016

Background—
Several antiplatelet medications used during and after percutaneous coronary intervention (PCI) are contraindicated for specific patient groups. A broad assessment of contraindicated medication use and associated clinical outcomes is not well described.

Methods and Results—
Using national Veterans Affairs Clinical Assessment, Reporting, and Tracking Program data for all PCI between 2007 and 2013, we evaluated patients with contraindications to commonly used antiplatelet medications during and after PCI, defined in accordance with package inserts. Adjusted association between contraindicated medication use and outcomes of periprocedural bleeding and 30-day mortality were assessed using Cox proportional hazards with inverse probability weighting. Among 64 294 patients undergoing PCI, 11 315(17.6%) had a contraindication to a common antiplatelet medication and 737 (6.5%) of these patients received a contraindicated medication. In unadjusted analyses, any contraindicated medication use was associated with both increased bleeding and 30-day mortality. In adjusted models, contraindicated abciximab use in patients with thrombocytopenia (hazard ratio, 2.23; 95% confidence interval, 1.58–3.16) and in patients with a previous stroke (hazard ratio, 1.93; 95% confidence interval, 1.37–2.71) remained significantly associated with increased bleeding. Contraindicated abciximab use was not significantly associated with 30-day mortality in adjusted models. Use of eptifibatide in dialysis patients was not significantly associated with an increased risk of bleeding or mortality.

Conclusions—
In this national cohort, ≈18% of patients undergoing PCI had contraindications to common antiplatelet medications. Approximately 6% of those patients received a contraindicated medication with attendant bleeding risk, although this did not translate into significantly higher risk of 30-day mortality. Continued efforts to reduce contraindicated medication use may help avoid periprocedural complications.
Novel Biomarkers to Improve the Prediction of Cardiovascular Event Risk in Type 2 Diabetes Mellitus
Authors: van der Leeuw Joep , Beulens Joline W. J. , van Dieren Susan , Schalkwijk Casper G. , Glatz Jan F. C. , Hofker Marten H. , Verschuren W. M. Monique , Boer Jolanda M. A. , van der Graaf Yolanda , Visseren Frank L. J. , Peelen Linda M. , van der Schouw Yvonne T. 
Published: June 2016

Background

We evaluated the ability of 23 novel biomarkers representing several pathophysiological pathways to improve the prediction of cardiovascular event (
CVE
) risk in patients with type 2 diabetes mellitus beyond traditional risk factors.

Methods and Results

We used data from 1002 patients with type 2 diabetes mellitus from the Second Manifestations of
ART
ertial disease (
SMART
) study and 288 patients from the European Prospective Investigation into Cancer and Nutrition‐
NL
(
EPIC
‐
NL
). The associations of 23 biomarkers (adiponectin, C‐reactive protein, epidermal‐type fatty acid binding protein, heart‐type fatty acid binding protein, basic fibroblast growth factor, soluble FMS‐like tyrosine kinase‐1, soluble intercellular adhesion molecule‐1 and ‐3, matrix metalloproteinase [MMP]‐1,
MMP
‐3,
MMP
‐9, N‐terminal prohormone of B‐type natriuretic peptide, osteopontin, osteonectin, osteocalcin, placental growth factor, serum amyloid A, E‐selectin, P‐selectin, tissue inhibitor of MMP‐1, thrombomodulin, soluble vascular cell adhesion molecule‐1, and vascular endothelial growth factor) with
CVE
risk were evaluated by using Cox proportional hazards analysis adjusting for traditional risk factors. The incremental predictive performance was assessed with use of the c‐statistic and net reclassification index (
NRI
; continuous and based on 10‐year risk strata 0–10%, 10–20%, 20–30%, >30%). A multimarker model was constructed comprising those biomarkers that improved predictive performance in both cohorts. N‐terminal prohormone of B‐type natriuretic peptide, osteopontin, and
MMP
‐3 were the only biomarkers significantly associated with an increased risk of
CVE
and improved predictive performance in both cohorts. In
SMART
, the combination of these biomarkers increased the c‐statistic with 0.03 (95%
CI
0.01–0.05), and the continuous
NRI
was 0.37 (95%
CI
0.21–0.52). In
EPIC
‐
NL
, the multimarker model increased the c‐statistic with 0.03 (95%
CI
0.00–0.03), and the continuous
NRI
was 0.44 (95%
CI
0.23–0.66). Based on risk strata, the
NRI
was 0.12 (95%
CI
0.03–0.21) in
SMART
and 0.07 (95%
CI
−0.04–0.17) in EPIC‐NL.

Conclusions

Of the 23 evaluated biomarkers from different pathophysiological pathways, N‐terminal prohormone of B‐type natriuretic peptide, osteopontin,
MMP
‐3, and their combination improved
CVE
risk prediction in 2 separate cohorts of patients with type 2 diabetes mellitus beyond traditional risk factors. However, the number of patients reclassified to a different risk stratum was limited.
Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension
Authors: Eirin Alfonso , Ebrahimi Behzad , Kwon Soon Hyo , Fiala Justin A. , Williams Barbara J. , Woollard John R. , He Quan , Gupta Ramech C. , Sabbah Hani N. , Prakash Y.S. , Textor Stephen C. , Lerman Amir , Lerman Lilach O. 
Published: June 2016

Background

Renovascular hypertension (
RVH
) impairs cardiac structure and left ventricular (
LV
) function, but whether mitochondrial injury is implicated in
RVH
‐induced myocardial damage and dysfunction has not been defined. We hypothesized that cardiac remodeling in swine
RVH
is partly attributable to cardiac mitochondrial injury.

Methods and Results

After 12 weeks of hypercholesterolemic (
HC
)‐
RVH
or control (n=14 each), pigs were treated for another 4 weeks with vehicle or with the mitochondrial‐targeted peptide (
MTP
), Bendavia (0.1 mg/kg subcutaneously, 5 days/week), which stabilizes mitochondrial inner‐membrane cardiolipin (n=7 each). Cardiac function was subsequently assessed by multidetector‐computed tomography and oxygenation by blood‐oxygen‐level–dependent magnetic resonance imaging. Cardiolipin content, mitochondrial biogenesis, as well as sarcoplasmic‐reticulum calcium cycling, myocardial tissue injury, and coronary endothelial function were assessed ex vivo. Additionally, mitochondrial cardiolipin content, oxidative stress, and bioenergetics were assessed in rat cardiomyocytes incubated with tert‐butyl hydroperoxide (
tBHP
) untreated or treated with
MTP
. Chronic mitoprotection in vivo restored cardiolipin content and mitochondrial biogenesis. Thapsigargin‐sensitive sarcoplasmic reticulum Ca
2+
‐
ATP
ase activity that declined in
HC
‐
RVH
normalized in
MTP
‐treated pigs. Mitoprotection also improved
LV
relaxation (E/A ratio) and ameliorated cardiac hypertrophy, without affecting blood pressure or systolic function. Myocardial remodeling and coronary endothelial function improved only in
MTP
‐treated pigs. In
tBHP
‐treated cardiomyocytes, mitochondrial targeting attenuated a fall in cardiolipin content and bioenergetics.

Conclusions

Chronic mitoprotection blunted myocardial hypertrophy, improved
LV
relaxation, and attenuated myocardial cellular and microvascular remodeling, despite sustained
HC
‐
RVH
, suggesting that mitochondrial injury partly contributes to hypertensive cardiomyopathy.
Clinical Pregenetic Screening for Stroke Monogenic Diseases
Authors: Bersano Anna , Markus Hugh Stephen , Quaglini Silvana , Arbustini Eloisa , Lanfranconi Silvia , Micieli Giuseppe , Boncoraglio Giorgio B. , Taroni Franco , Gellera Cinzia , Baratta Silvia , Penco Silvana , Mosca Lorena , Grasso Maurizia , Carrera Paola , Ferrari Maurizio , Cereda Cristina , Grieco Gaetano , Corti Stefania , Ronchi Dario , Bassi Maria Teresa , Obici Laura , Parati Eugenio A. , Pezzini Alessando , De Lodovici Maria Luisa , Verrengia Elena P. , Bono Giorgio , Mazucchelli Francesca , Zarcone Davide , Calloni Maria Vittoria , Perrone Patrizia , Bordo Bianca Maria , Colombo Antonio , Padovani Alessandro , Cavallini Anna , Beretta Simone , Ferrarese Carlo , Motto Cristina , Agostoni Elio , Molini Graziella , Sasanelli Francesco , Corato Manuel , Marcheselli Simona , Sessa Maria , Comi Giancarlo , Checcarelli Nicoletta , Guidotti Mario , Uccellini Davide , Capitani Erminio , Tancredi Lucia , Arnaboldi Marco , Incorvaia Barbara , Tadeo Carlo Sebastiano , Fusi Laura , Grampa Giampiero , Merlini Giampaolo , Trobia Nadia , Comi Giacomo Pietro , Braga Massimiliano , Vitali Paolo , Baron Pierluigi , Grond-Ginsbach Caspar , Candelise Livia 
Published: June 2016

Background and Purpose—
Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease

Methods—
We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis.

Results—
In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease.

Conclusions—
In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.
Thermal ablative therapies for treatment of localised renal cell carcinoma: a systematic review of the literature
Authors: Gkentzis Agapios , Oades Grenville 
Published: June 2016

Background and aims Small renal masses are commonly diagnosed incidentally. The majority are malignant and require intervention. The gold standard treatment is partial nephrectomy unless the patient has significant co-morbidities when surveillance or ablative therapies are utilised. The latter are relatively novel and their long-term efficacy and safety remain generally poorly understood. We performed a literature review to establish the current evidence on the oncological outcome of thermal ablative techniques in small renal masses treatment. Methods and results A systematic literature search was performed using PubMed, supplemented with additional references. Articles were reviewed for data on indications, tumour characteristics, ablative techniques, oncological outcome, impact on renal function and complications. The vast majority of articles identified were observational studies. There has not been any direct comparison against partial nephrectomy. Radiofrequency ablation and cryoablation are the techniques that are more commonly used. They have favourable oncological results on intermediate follow-up and indications that successful outcome is sustained long term. The morbidity and impact on renal function appear to be minimal. Conclusion Thermal ablative therapies are valid alternatives to partial nephrectomy for the treatment of small renal masses in patients unfit for surgery. Prospective long-term data will be needed before the indications for their use expand further.
Office‐Based Ultrasound‐Guided FNA with Molecular Testing for Thyroid Nodules
Authors: Dhingra Jagdish K. 
Published: June 2016

ObjectiveUltrasound‐guided fine‐needle aspiration (FNA) biopsy is the primary method of evaluating thyroid nodules. Up to one‐third of FNA results are reported to be of “indeterminate” cytology, which carries a 25% malignancy risk. Most of these patients are referred for diagnostic surgery, which results in many unnecessary interventions. We implemented an FNA protocol combining expert thyroid cytopathology and molecular testing of indeterminate lesion in our community practice. This study is a report of the outcomes from this protocol as compared with historical data in the same setting over a similar period.Study DesignCase series with planned data collections and retrospective chart reviews.SettingA large community‐based practice with multiple satellite offices.Subjects and MethodsA total of 264 thyroid nodules (196 patients) were evaluated under the new protocol from January to December 2014, and data were collected in a prospective manner. Historical data for a similar period (2012), obtained by chart review, included 164 nodules (134 patients) biopsied in a hospital setting by a number of radiologists, with cytologic interpretations completed by community‐based pathologists. Statistical analyses included χ2 and Fischer’s exact tests.ResultsBased on the new protocol, the rate of indeterminate lesion diagnosis was reduced from 24% to 10% (P =. 006) and the rate of diagnostic surgery from 24% to 6% (P <. 001). Of the patients who underwent diagnostic surgery, 58% had evidence of malignancy, as compared with 12% in our previous experience (P =. 04).ConclusionExpert cytopathologic analysis combined with molecular testing of indeterminate FNA samples significantly reduced unnecessary operations.
To explore the relationship between the use of midazolam and cessation of oral intake in the terminal phase of hospice inpatients: A retrospective case note review: Does midazolam affect oral intake in the dying?
Authors: Giles Alison , Sykes Nigel 
Published: June 2016

Background: Sedative drugs are used to improve comfort in dying patients but have been accused of shortening survival by reducing patients’ ability to maintain nutrition and hydration. However, as part of the dying process, patients in the last days of life often have impaired conscious levels and an inability to maintain oral intake. Aim: To establish whether the decline in oral intake is related to the use of midazolam in the last week of life. Design: This is a retrospective case note review. Setting/participants: The data were obtained from nursing records and medication charts of 125 consecutive hospice inpatients who died at a hospice in South London. Results: A total of 72 patients received midazolam on one or more days within the last 7 days of life (midazolam group) and 49 patients received no midazolam (control group). Conclusion: Mean oral intake was reduced 7 days prior to death and declined sequentially over subsequent days in both patient groups. More patients required midazolam as death approached and most patients received midazolam for less than 3 days. Mean doses of midazolam used were low. Patients in the midazolam group had lower oral intake than those in the control group, but this association does not indicate causation.
Health-related quality-of-life outcome measures in paediatric palliative care: A systematic review of psychometric properties and feasibility of use
Authors: Coombes Lucy H , Wiseman Theresa , Lucas Grace , Sangha Amrit , Murtagh Fliss EM 
Published: June 2016

Background: The number of children worldwide requiring palliative care services is increasing due to advances in medical care and technology. The use of outcome measures is important to improve the quality and effectiveness of care. Aim: To systematically identify health-related quality-of-life outcome measures that could be used in paediatric palliative care and examine their feasibility of use and psychometric properties. Design: A systematic literature review and analysis of psychometric properties. Data sources: PsychInfo, Medline and EMBASE were searched from 1 January 1990 to 10 December 2014. Hand searches of the reference list of included studies and relevant reviews were also performed. Results: From 3460 articles, 125 papers were selected for full-text assessment. A total of 41 articles met the eligibility criteria and examined the psychometric properties of 22 health-related quality-of-life measures. Evidence was limited as at least half of the information on psychometric properties per instrument was missing. Measurement error was not analysed in any of the included articles and responsiveness was only analysed in one study. The methodological quality of included studies varied greatly. Conclusion: There is currently no ‘ideal’ outcome assessment measure for use in paediatric palliative care. The domains of generic health-related quality-of-life measures are not relevant to all children receiving palliative care and some domains within disease-specific measures are only relevant for that specific population. Potential solutions include adapting an existing measure or developing more individualized patient-centred outcome and experience measures. Either way, it is important to continue work on outcome measurement in this field.
Anti-beta-2 glycoprotein I epitope specificity: from experimental models to diagnostic tools
Authors: Meroni P L 
Published: June 2016

Beta-2 glycoprotein I (β2GPI) is the main antigenic target for anti-phospholipid antibodies (aPL), the serological markers of anti-phospholipid syndrome (APS). Conformational changes of the molecule seem to be essential for exposing the cryptic epitope for aPL binding and to trigger pathogenic pathways. There is increasing evidence that a conformational epitope located in the Domain I (DI) of the molecule is the main epitope targeted by human autoantibodies. The pathogenic role of the DI epitope has been recently supported by in vivo models and by immuno-histopathological findings in APS patients. Antibodies targeting β2GPI-DI are more frequently detected in patients with full-blown APS compared to asymptomatic aPL carriers or patients with infectious diseases who have antibodies directed against the whole molecule. Anti-DI antibodies are positively correlated with medium to high titres of aPL, with the presence of lupus anticoagulant and thrombotic and pregnancy manifestations, enabling identification of patients at higher risk of clinical events. However, some APS patients develop antibodies reacting against β2GPI epitopes other than DI, suggesting that other anti-β2GPI antibody subsets may be clinically relevant. Although preliminary results suggest that anti-DI antibodies can be detected by different assays in a comparable manner, further prospective studies are needed to support their use in the clinical setting and their predictive value.
Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus
Authors: Magro-Checa C , Schaarenburg R A , Beaart H J L , Huizinga T W J , Steup-Beekman G M , Trouw L A 
Published: June 2016

Objective The objective of this paper is to analyse serum levels of anti-C1q, C1q circulating immune complexes (CIC), complement activation and complement components in systemic lupus erythematosus (SLE) patients during the first central nervous system neuropsychiatric (NP) event and to define the possible association between these results and clinical and laboratory characteristics. Methods A total of 280 patients suspected of having NP involvement due to SLE were recruited in the Leiden NPSLE-clinic. All SLE patients were classified according to the ACR 1982 revised criteria for the classification of SLE. The clinical disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and NP diagnoses were classified according to the 1999 ACR case definitions for NPSLE. We measured in serum of all patients anti-C1q and C1q CIC levels, the activation capacity of complement (CH50 and AP50) and different complement components (C1q, C3, C4). Results In 92 patients the symptoms were attributed to SLE. NPSLE patients consisted of 63 patients with focal NPSLE and 34 patients with diffuse NPSLE. Anti-C1q antibodies were significantly higher and CH50, AP50 and C3 were significantly lower in NPSLE patients compared with SLE patients without NPSLE. This association was specially marked for diffuse NPSLE while no differences were found for focal NPSLE. After using potential predictors, decreased C4 remained significantly associated with focal NPSLE, but only when antiphospholipid antibodies (aPL) were included in the model. C3 and AP50 were independently associated with diffuse NPSLE. When SLEDAI-2K was included in the model these two associations were lost. When individual NPSLE syndromes were analysed, psychosis and cognitive dysfunction showed significantly lower values of complement activation capacity and all complement components. No significant associations were seen for other individual NPSLE syndromes. Conclusion The associations between diffuse NPSLE and anti-C1q, C3/AP50 and focal NPSLE and C4 may be explained by disease activity and the presence of aPL, respectively. The role of complement activation and complement components in lupus psychosis and cognitive dysfunction merits further research.
Failure of an International Joint Venture: Implications for the India Enthusiasts
Authors: Agrawal Mohan L , Hollensen Svend 
Published: June 2016

‘Joint Ventures are fanned out of choice a11d not due to regulatory and policy requirements, according to 81% of the respondents to a FICCI study’, Hindustan Times, New Delhi, August 17, 2001 The paper analyses failure of an international joint venture (IJV) in India, which the Indian media highlighted as an icon of the internationalization of Indian industries. IJVs are deemed to be an excellent mode to penetrate overseas market by international aspirants. Although their present failure rate is estimated between 30 to 60% , the enthusiasm for forging IJVs in India is still undiluted. The paper surveys current literature in respect of their importance and of the reasons for which they break-up. Analyzing the break up of an IJV between Timex (USA) and Titan Industries (India) through a conceptual framework, the paper draws implications that might come handy to the IJV enthusiasts in India.