bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of a multimarker strategy for prediction of mortality in older heart failure patients: a cohort study
Authors: Bjurman Christian , Jensen Juliana , Petzold Max , Hammarsten Ola , Fu Michael L X 
Published: March 2013

ObjectivePrimarily to develop a multimarker score for prediction of 3-year mortality in older patients with decompensated heart failure (HF).DesignProspective cohort study.SettingSecondary care. Single centre.Patients and biomarkers131 patients, aged ≥65 years, with decompensated HF were included. Assessment of biomarkers was performed at discharge.Primary outcome measure3-year mortality.ResultsMean age was 73±11 years; mean left ventricular ejection fraction , 43±14%; 53% were male. The 3-year mortality was 53.4%. The following N-terminal brain natriuretic peptide (NTproBNP) levels could optimally stratify mortality: <2000 ng/l (n=39), 30.8% mortality; 2000–8000 ng/l (n=58), 51.7% mortality; and >8000 ng/l (n=34), 82.4% mortality. However, in the 2000–8000 ng/l range, NTproBNP levels had low-prognostic capacity, based on the area under the receiver operating characteristic curve (AUC=0.53; 95% CI 0.40 to 0.67). In this group, multivariate analysis identified age, cystatin C (CysC), and troponin T (TnT) levels as independent risk factors. A risk score based on these three risk factors separated a high-risk and low-risk groups within the NTproBNP range of 2000–8000 ng/l. The score exhibited a significantly higher AUC (0.75; 95% CI 0.62 to 0.86) than NTproBNP alone (p=0.03) in this NTproBNP group and had similar prognostic capacity as NTproBNP in patients below or above this NTproBNP range (p=0.57). Net reclassification improvement and integrated discriminatory improvement in the group with NTproBNP levels between 2000 and 8000 ng/l was 54% and 23%, respectively, and in the whole cohort 22% and 11%, respectively.ConclusionsOur results suggested that, to assess risk in HF, older patients required significantly higher levels of NTproBNP than younger patients. Furthermore, a risk score that included TnT and CysC at discharge, and age could improve risk stratification for mortality in older patients with HF in particular when NTproBNP was moderately elevated.
The role of organisational and cultural factors in the implementation of system-wide interventions in acute hospitals to improve patient outcomes: protocol for a systematic literature review
Authors: Nosrati Hadis , Clay-Williams Robyn , Cunningham Frances , Hillman Ken , Braithwaite Jeffrey 
Published: March 2013

IntroductionLittle is known about the role of the organisational culture in the success and sustainability of the hospital-wide interventions, and how local culture affects patient outcomes in acute hospitals.Methods and analysisA systematic literature review will be conducted to identify organisational factors influencing hospital-wide interventions and patient outcomes. A search of English language articles will be performed in MEDLINE, CINAHL, EMBASE, Web of Science, PsychInfo and Global Health databases using Medical Subject Headings and keywords. Randomised controlled trials, quasi-randomised trials, controlled before and after design studies and interrupted time-series analysis studies will be included. ‘Grey literature’ will be excluded, however peer-reviewed journals that are likely to publish relevant studies (JAMA,BMJ,BMJ Quality and Safety,LancetandNew England Journal of Medicine and Implementation Science) will be hand searched for the last 5 years. Two reviewers will independently undertake a title and abstract review using inclusion and exclusion criteria. Studies will be excluded only after discussion between at least two reviewers, who will assess and agree on the inclusion, risk of bias and quality rating of the studies. One author will extract summary descriptive data from these studies; the other author will review this documentation for accuracy and completeness.ResultsIt is likely that the studies will be heterogeneous in nature, therefore a narrative synthesis of the findings will be conducted.ConclusionsWe will discuss characteristics of the studies and stratify the results according to the type of hospital-wide interventions, organisational factors associated with them and outcomes measured.
Cognitive ability and educational level in relation to concussion: a population study of young men
Authors: Teasdale Thomas William , Frøsig Anna Julie 
Published: March 2013

ObjectivesTo investigate the association of concussion with cognitive ability (CA) and educational level (EL).DesignEpidemiological—cross-linkage of national computer registers.SettingDenmark.Participants130 420 young men appearing before the Danish draft board during the period 2006–2010.Primary and secondary outcome measuresCA test scores, EL and occurrence of concussion during the period 2004–2009, treated either in an A&E unit or upon admission to a hospital ward.ResultsThe 3067 men who had suffered a concussion had lower CAs (mean=96.5, SD=15, 95% CI 95.0 to 97.0) than the total cohort and they were lower for 1452 who were admitted to a hospital ward (mean CA=95.8, SD=15, 95% CI 95.1 to 96.6) than for 1615 who were treated only at an A&E unit (mean CA=97.1, SD=15, 95% CI 96.3 to 98.0). Multiple logistic regressions revealed that the effects for EL were stronger than those for CA. Among 127 353 men not sustaining a concussion, 48% attended a ‘gymnasium’ (sixth-form college), among men treated for a concussion at an A&E unit, this falls to 36% and among men hospitalised for a concussion to 30%. Transfer to a gymnasium, if it happens, almost invariably does so before the 18th birthday. Among 701 men suffering a concussion and admitted to a hospital department after this date, only 26% (n=182) were previously transferred to a gymnasium. Among the 804 men treated at an A&E unit after their 18th birthday, 33% (n=265) had done so. These two percentages are significantly below the corresponding non-concussed population (48%).ConclusionsTaken together, the results suggest that lower CA and, in particular, lower EL are risk factors for sustaining a concussion, the risk increasing with the severity of the injury.
Statin use and clinical outcomes in older men: a prospective population-based study
Authors: Gnjidic Danijela , Le Couteur David G , Blyth Fiona M , Travison Tom , Rogers Kris , Naganathan Vasi , Cumming Robert G , Waite Louise , Seibel Markus J , Handelsman David J , McLachlan Andrew J , Hilmer Sarah N 
Published: March 2013

ObjectiveThe aim of this analysis was to investigate the relationship of statins with institutionalisation and death in older men living in the community, accounting for frailty.DesignProspective cohort study.SettingCommunity-dwelling men participating in the Concord Health and Ageing in Men Project, Sydney, Australia.ParticipantsMen aged ≥70 years (n=1665).MeasurementsData collected during baseline assessments and follow-up (maximum of 6.79 years) were obtained. Information regarding statin use was captured at baseline, between 2005 and 2007. Proportional hazards regression analysis was conducted to estimate the risk of institutionalisation and death according to statin use (exposure, duration and dose) and frailty status, with adjustment for sociodemographics, medical diagnosis and other clinically relevant factors. A secondary analysis used propensity score matching to replicate covariate adjustment in regression models.ResultsAt baseline, 43% of participants reported taking statins. Over 6.79 years of follow-up, 132 (7.9%) participants were institutionalised and 358 (21.5%) participants had died. In the adjusted models, baseline statin use was not statistically associated with increased risk of institutionalisation (HR=1.60; 95% CI 0.98 to 2.63) or death (HR=0.88; 95% CI 0.66 to 1.18). There was no significant association between duration and dose of statins used with either outcome. Propensity scoring yielded similar findings. Compared with non-frail participants not prescribed statins, the adjusted HR for institutionalisation for non-frail participants prescribed statins was 1.43 (95% CI 0.81 to 2.51); for frail participants not prescribed statins, it was 2.07 (95% CI 1.11 to 3.86) and for frail participants prescribed statins, it was 4.34 (95% CI 2.02 to 9.33).ConclusionsThese data suggest a lack of significant association between statin use and institutionalisation or death in older men. These findings call for real-world trials specifically designed for frail older people to examine the impact of statins on clinical outcomes.
A prospective cohort study of the changing mental health needs of adolescents in custody
Authors: Lennox Charlotte , Bell Vicky , O'Malley Kate , Shaw Jenny , Dolan Mairead 
Published: March 2013

ObjectiveTo investigate changes in mental health and other needs, as well as clinical and diagnostic ‘caseness’, in a sample of adolescents over a 6-month period following entry into a Young Offenders Institution in the UK.DesignProspective cohort study.SettingOne Young Offenders Institution between November 2006 and August 2009.Participants219 male adolescents aged 15–18 years (M=16.56; SD=0.6) were assessed at baseline (median=4; range 0–26 days following reception into custody) on the Salford Needs Assessment Schedule for Adolescents (SNASA) and Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Participants were then reassessed at 3-month and 6-month postbaseline to document any change in mental health.ResultsOf the initial baseline sample, 132 were still in the study at 3-month postbaseline and 63 were still available for assessment at 6 months. There were no differences between those who were not available for assessment at the three key stages in terms of demographic and criminological data. Over time there was a general improvement in mental health. While the proportion of participants with a mental health need (SNASA) did not change over time, symptom severity as measured by the SNASA did reduce significantly. When we assessed diagnostic ‘caseness’ using the K-SADS, three young people showed significant mental health deterioration.ConclusionsIn line with previous studies, we found that symptoms in prison generally improved over time. Prison may provide an opportunity for young people previously leading chaotic lifestyles to settle into a stable routine and engage with services; however, it is unclear if these would be maintained either within the prison or on release into the community.
The impact of a medical undergraduate student-selected module in palliative care
Authors: Sweeney Catherine , Lynch Gerardine , Khashan Ali , Maher Bridget , Murphy Marie , O'Brien Tony 
Published: March 2013

BackgroundThe need for undergraduate medical education in palliative care is widely recognised. An optional student-selected module ‘Fundamentals of Palliative Medicine’ was introduced in 2011 and offered to third-year medical students. The overall objective of the module was to develop students’ knowledge, attitudes and skills in palliative care.AimTo assess impact of the module in terms of qualitative and quantitative measures, and to improve the module design and content for future years.MethodsStudents completed validated tools (Self Efficacy in Palliative Care and Thanatophobia Scale (TS)) premodule and postmodule. A Minute Paper was completed at the penultimate session with students identifying areas they had a good understanding of, and issues they still found unclear.ResultsTwenty-four of 155 eligible students chose the module. Significant differences were seen in premodule and postmodule Self Efficacy in Palliative Care scores (communication p<0.0001, patient management p=0.0002 and teamwork p=0.03). No difference was seen in TS score. Five main themes emerged from the qualitative analysis of the Minute Paper: changes to attitudes and knowledge, psychological effects, teaching methods, careers in palliative care, and further palliative care learning needs. Several students commented that the module should be core curriculum.ConclusionsThe module was a popular choice with students, was well received, and appears to have had a significant educational impact in terms of changing students’ attitudes and perceived knowledge and skills in palliative care.
End-of-life care in a population-based cohort of cancer patients: clinical trial participation versus standard of care
Authors: Thompson Carrie A , Hugo Sarah E , Swetz Keith Mark , Novotny Paul J , Sloan Jeff A , Loprinzi Charles L , Moynihan Timothy J , Shanafelt Tait D 
Published: March 2013

ObjectivesTo evaluate end-of-life care in a cohort of oncology patients in Olmsted County, Minnesota, USA, and compare differences between patients participating in clinical trials and those not in clinical trials.MethodsA population-based cohort of subjects with active oncological disease who died between 2000 and 2002 was constructed retrospectively using institutional databases. Clinical trial participation and care during the last 2 months of life were analysed.ResultsA total of 395 eligible patients were identified. In the 2 months prior to death, 94 (24%) patients received chemotherapy, 232 (59%) were hospitalised, 249 (63%) were in hospice and 315 (80%) had a do not resuscitate (DNR) code status. Only 8 (2%) patients received cardiopulmonary resuscitation (CPR) and 26 (7%) patients participated in a clinical trial. Patients in clinical trials were more likely to receive chemotherapy (69.2% vs 20.6%; p<0.001), undergo intubation/mechanical ventilation (15.4% vs 5.4%; p=0.040) and less likely to have DNR code status (50.0% vs 81.8%; p<0.001) when compared with patients not in clinical trials. However, no differences in hospice enrolment, days in hospice, days in the hospital, CPR or location of death were noted.ConclusionsAlthough opportunities for improvement exist, high quality end-of-life care was found in this study of patients with active malignancy. A majority (over 60%) of patients enrolled in hospice prior to death, 80% had a DNR status and only 2% received CPR. Although clinical trial participants received more aggressive treatments during the last 2 months of life, they did not appear to have lower quality end-of-life care.
Utility of a single early warning score in patients with sepsis in the emergency department
Authors: Corfield Alasdair R , Lees Fiona , Zealley Ian , Houston Gordon , Dickie Sarah , Ward Kirsty , McGuffie Crawford ,   on behalf of the Scottish Trauma Audit Group Sepsis Steering Group
Published: March 2013

BackgroundAn important element in improving the care of patients with sepsis is early identification and early intervention. Early warning score (EWS) systems allow earlier identification of physiological deterioration. A standardised national EWS (NEWS) has been proposed for use across the National Health Service in the UK.AimTo determine whether a single NEWS on emergency department (ED) arrival is a predictor of outcome, either in-hospital death within 30 days or intensive care unit (ICU) admission within 2 days, in patients with sepsis.MethodsData were collected over a 3-month period as part of a national audit in 20 EDs in Scotland. All adult patients who were admitted for at least 2 days or who died within 2 days were screened for sepsis criteria. Patients with systemic inflammatory response syndrome criteria were included. An EWS was calculated based on initial physiological observations made in the ED using the NEWS.ResultsComplete data were available for 2003 patients. Each rise in NEWS category was associated with an increased risk of mortality when compared to the lowest category (5–6: OR 1.95, 95% CI 1.21 to 3.14), (7–8: OR 2.26, 95% CI 1.42 to 3.61), (9–20: OR 5.64, 95% CI 3.70 to 8.60). This was also the case for the combined outcome (ICU and/or mortality).ConclusionsAn increased NEWS on arrival at ED is associated with higher odds of adverse outcome among patients with sepsis. The use of NEWS could facilitate patient pathways to ensure triage to a high acuity area of the ED and senior clinician involvement at an early stage.
Immunohistochemistry of deparaffinised sections using antigen retrieval with microwave combined pressure cooking versus immunofluorescence in the assessment of human renal biopsies
Authors: Shi Suozhu , Zhang Ping , Cheng Qingli , Wu Jie , Cui Jing , Zheng Ying , Bai Xue-Yuan , Chen Xiangmei 
Published: March 2013

BackgroundImmunofluorescence of frozen tissue sections (IF-F) is a traditional technique used in renal biopsy. However, IF-F has certain disadvantages, such as a few or even no glomeruli in the section, and limited long-term preservation of the fluorescently labelled samples.MethodsWe compared two-step immunohistochemistry (IHC) staining of deparaffinised sections for antigen retrieval with microwave combined high-pressure cooking to IF-F used to detect antigens of IgG, IgA, IgM, C3, C1q, κ and λ in patient renal biopsy samples. The number of glomeruli detected, sensitivity and specificity of positive staining, tissue structure, and location staining of the antigens were determined using the two methods in 285 patients diagnosed with different renal diseases.ResultsConcordant observations between IF-F and IHC were 99% for all antigen staining (1969 of 1995 observations) and 100% for IgG, IgA and IgM (all 285 observations). The number of glomeruli in IHC sections was significantly greater compared with IF-F sections (p<0.001). IHC provided clearer images of tissue structure, more precise localisation of positive-staining antigens, and IHC staining allowed simultaneous evaluation of tissue by light microscopy. Correlation between tissue structure and immune deposits are not readily attained by IF-F.ConclusionsIHC is superior to IF-F for immunopathological diagnosis of renal biopsy tissue and is a reliable replacement for the more traditional IF-F method.
Abstract A25: Uncommon mutation types of Epidermal Growth Factor Receptor (EGFR) and tyrosine kinase inhibitor response in non-small cell lung carcinoma
Authors: Wong Maria P. , Lee Victor H.F. , Yeung Rebecca M.W. , Tin Vicky P.C. , Choy Kit Chi , Liu Jing 
Published: March 2013

Abstract
Somatic mutations in the tyrosine kinase domain of EGFR are frequent in non-small cell lung cancer especially adenocarcinomas from nonsmokers. Some of the mutations such as exon 19 hotspot deletions and exon 21 L858R are known to activate EGFR downstream signaling, as well as sensitize the tumors to small-molecule tyrosine kinase inhibitors (TKI) treatment. The effects of other, less common mutations are not always predictable from the sequence alterations. The purpose of this study was to study the EGFR mutation profile and correlation with tumor response to first line TKI treatment. EGFR mutations were examined in 77 NSCLC from 62 (80.5%) female (58 nonsmokers, 4 chronic smokers) and 15 (19.5%) male patients (6 chronic smokers, 9 nonsmokers) with late-stage metastatic lung carcinoma given first line gefitinib treatment. Genomic DNA was extracted from microdissected tumor cells from formalin-fixed, paraffin-embedded sections of previous lobectomy, small biopsies, or cytology cell block specimens, including pleural effusion and fine needle aspirations. EGFR exons 18, 19, 20, and 21 were analyzed by bidirectional automated direct sequencing. The results showed EGFR mutations were present in 61 of 77 (79.2 %) tumors comprising 53 (86.9 %) never smokers and 8 (13.1%) chronic smokers. Fifty-eight of 61 mutant tumors had single mutations and the remaining 3 cases showed double mutations. Exon 21 L858R single amino acid substitution was present in 27 (44.1%) cases and exon 19 deletions were observed in 25 (41.0%) cases. Fifty of 77 patients showed initial response to gefitinib and 27 showed primary resistance. All initial responders acquired secondary resistance after various treatment durations. As expected, wild-type tumors showed primary TKI resistance. TKI response was significantly associated with EGFR mutant tumors (p=0.010). L858R, L861Q, and exon19 in-frame deletions were observed in totally 53/61 tumors. 42/53 of them showed initial response to gefitinib but only 2/8 harboring other types of EGFR mutations responded (p&lt;0.001). The EGFR mutant tumors associated with primary TKI resistance included L861R, R831H, double substitutions G719A/E709A, S768I/V774M, exon 18 deletion, exon 20 insertion, and uncommon exon 19 deletions including L747_K754delinsADKG, and L747_S752delinsQH. One patient with concurrent PIK3CA exon 9 G1633A substitution also experienced primary resistance despite the presence of a known activating L858R mutation. In summary, this study has identified novel EGFR mutations associated with primary TKI resistance. While most of the uncommon mutants do not respond to first-line TKI therapy, exon 19 deletions of uncommon types might also be associated with primary TKI resistance.
Left Ventricular Epicardial Electrograms Show Divergent Changes in Action Potential Duration in Responders and Nonresponders to Cardiac Resynchronization Therapy
Authors: Chen Zhong , Hanson Ben , Sohal Manav , Sammut Eva , Child Nick , Shetty Anoop , Boucher Ryan , Bostock Julian , Gill Jaswinder , Carr-White Gerald , Rinaldi C. Aldo , Taggart Peter 
Published: March 2013

Background—
A consistent feature of electrophysiological remodeling in heart failure is ventricular action potential duration (APD) prolongation. However, the effect of reverse remodeling on APD during cardiac resynchronization therapy (CRT) has not been determined in these patients. We hypothesized (1) that CRT may alter APD and (2) that the effect of CRT on APD may be different in patients who exhibit a good hemodynamic response to CRT compared with those with a poor response.

Methods and Results—

Left ventricular (LV) activation recovery intervals, as a surrogate for APD, were measured from the LV epicardium in 13 patients at day 0, 6 weeks, and 6 months after CRT implant. Responders to CRT were defined as those demonstrating a ≥15% reduction in LV end-systolic volume at 6 months. The responder group had a significant reduction in LV activation recovery interval (mean, −13±12 ms; median, −16 ms; interquartile range, −2 to −19 ms) during right ventricular pacing at 6 months (
P
<0.05). Conversely, the nonresponders showed a significant increase in activation recovery interval (mean, +22 ms±16; median, 17 ms; interquartile range, 8 to 35 ms;
P
<0.05). One patient in each group was on amiodarone.

Conclusions—
In patients with heart failure, LV epicardial APD (activation recovery interval) altered during CRT. The effect on APD was opposite in patients showing a good hemodynamic response compared with nonresponders. The findings may provide an explanation for the persistent high incidence of arrhythmias in some patients with CRT and the additional mortality benefit observed in responders of CRT.