bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher fasting plasma glucose is associated with striatal and hippocampal shape differences: the 2sweet project
Authors: Zhang Tianqi , Shaw Marnie , Humphries Jacob , Sachdev Perminder , Anstey Kaarin J , Cherbuin Nicolas 
Published: June 2016

ObjectivePrevious studies have demonstrated associations between higher normal fasting plasma glucose levels (NFG) (<6.1 mmol/L), type 2 diabetes (T2D) and hippocampal atrophy and other cerebral abnormalities. Little is known about the association between plasma glucose and the striatum despite sensorimotor deficits being implicated in T2D. This study aimed to investigate the relationship between plasma glucose levels and striatal and hippocampal morphology using vertex-based shape analysis.DesignA population-based, cross-sectional study.SettingCanberra and Queanbeyan, Australia.Participants287 cognitively healthy individuals (mean age 63 years, 132 female, 273 Caucasian) with (n=261) or without T2D (n=26), selected from 2551 participants taking part in the Personality & Total Health (PATH) Through Life study by availability of glucose data, MRI scan, and absence of gross brain abnormalities and cognitive impairment.Outcome measuresFasting plasma glucose was measured at first assessment, and MRI images were collected 8 years later. Shape differences indicating outward and inward deformation at the hippocampus and the striatum were examined with FMRIB Software Library-Integrated Registration and Segmentation Toolbox (FSL-FIRST) after controlling for sociodemographic and health variables.ResultsHigher plasma glucose was associated with shape differences indicating inward deformation, particularly at the caudate and putamen, among participants with NFG after controlling for age, sex, body mass index (BMI), hypertension, smoking and depressive symptoms. Those with T2D showed shape differences indicating inward deformation at the right hippocampus and bilateral striatum, but outward deformation at the left hippocampus, compared with participants with NFG.ConclusionsThese findings further emphasize the importance of early monitoring and management of plasma glucose levels, even within the normal range, as a risk factor for cerebral atrophy.
Research priorities relating to the debate on assisted dying: what do we still need to know? Results of a modified Delphi technique
Authors: Rodgers Mark , Booth Alison , Norman Gill , Sowden Amanda 
Published: June 2016

ObjectiveTo identify the main areas of uncertainty and subsequent research priorities to inform the ongoing debate around assisted dying.DesignTwo-round electronic modified Delphi consultation with experts and interested bodies.Setting and participants110 groups and individuals interested in the subject of end-of-life care and/or assisted dying were approached to participate. Respondents included health and social care professionals, researchers, campaigners, patients and carers predominantly based in the UK. In the first round, the respondents were asked to propose high-priority research questions related to the topic of assisted dying. The collected research questions were then deduplicated and presented to all respondents in a second round in which they could rate each question in terms of importance.Results24% and 26% of participants responded to the first and second rounds, respectively. Respondents suggested 85 unique research questions in the first round. These were grouped by theme and rated in terms of importance in the second round. Emergent themes were as follows: palliative care/symptom control; patient characteristics, experiences and decisions; families and carers; society and the general public; arguments for and against assisted dying; international experiences/analysis of existing national data; suicide; mental health, psychological and psychosocial considerations; comorbidities; the role of clinicians; environment and external influences; broader topics incorporating assisted dying; and moral, ethical and legal issues. 10 of the 85 proposed questions were rated as being important (≥7/10) by at least 50% of respondents.ConclusionsResearch questions with the highest levels of consensus were predominantly concerned with understanding how and why people make end-of-life decisions, and which factors influence those decisions. Dissemination of these findings alongside a focused examination of the existing literature may be the most effective way to add evidence to the ongoing debate around assisted dying.
Using a simple handover to improve the timing of gentamicin levels
Authors: Williamson Andrew , Bradley Alison , Khan Khurram 
Published: June 2016

AbstractThe aminoglycoside gentamicin is commonly used in many NHS trusts to cover gram negative organisms in intra-abdominal sepsis and sepsis of unknown origin. As a result it often forms an important part of thew "Sepsis 6" protocol on surgical wards. Despite it's effectiveness, the antibiotic is well known to have nephrotoxic and ototoxic side effects, making monitoring of serum levels vital. In Hairmyres Hospital, a busy district general hospital in Lanarkshire, levels are typically taken at six to 14 hour post-dose intervals, with the result guiding further gentamicin dosing.A baseline measurement was performed highlighting that 42.2% of these levels were taken after the 14 hour limit. This was thought to have serious implications for patient's, as levels designed to protect them from side effects whilst maintain g an effective antimicrobial action were not being performed properly. As a result, a "gentamicin handover" was introduced to the wards in order to ease the workload on junior staff and improve handover between teams.During our short project the number of late levels initially dropped to 33.3% after one week, falling further to 28.6% following the second week of intervention. From our results it is clear that while more intervention is required gentamicin prescription, this project highlights how a simple intervention to improve ward handover can create a very noticeable improvement in the quality of patient care within a small time period.
Introduction of point of care analysis for prescribing warfarin at a Swedish primary care centre
Authors: Fernholm Rita , Hermansson Jonas 
Published: June 2016

AbstractBoo Health Centre in Nacka, Sweden, manages approximately 240 patients on warfarin treatment. A risk analysis showed that testing and prescribing of warfarin involved 28 different steps and nine parties, leading to a high risk of errors.The aim of the study was to shorten and simplify the process flow for the testing and prescription of warfarin by introducing point of care analysis (POC). The aim was also to evaluate changes in time expenditure and cost related to the new processes well as the quality in form of time in therapeutic range (TTR) and number of adverse events.A study with POC was performed during six months in 2014. Time expenditure, cost, TTR, and adverse events related to warfarin treatment were recorded. An evaluation was also conducted in the form of surveys to patients and staff regarding satisfaction with the new process.The process was shortened from 28 steps and nine parties involved to nine steps and four parties involved. The patient got their test result and met with the prescribing doctor, all within the same visit, meaning that the feedback time for patients was shortened from one to three days by mail to less than 10 minutes at the medical centre. TTR did not change and the incidence of adverse events was not affected. The surveys showed that the overwhelming proportion of patients, doctors, assistant nurses, and laboratory staff were pleased with the changes and the patients would recommend others to monitor their treatment at Boo Health Centre. There was a reduction in time expenditure for the staff. The costs decreased from approximately 8 000 €/month to about 7 000 €/month.The introduction of the POC method enabled a shorter process flow with reduced time expenditure for both patients and staff and reduced costs. TTR did not change. Patients and staff were satisfied with the changes and the patients could take a more active role in their treatment. It is possible that POC analysis may have implications on improved compliance to warfarin treatment, if so, it will increase patient safety.
Promoting oral health practice among patients with diabetes attending primary health care clinics
Authors: Aljaber Abeer , Al-Surimi Khaled 
Published: June 2016

AbstractThe oral public health program for patients with diabetes was initiated by Saudi Arabia Ministry of Health (MoH) based on international quality standard to control the severity of oral disease in patients with diabetes through improving the accessibility of patients to dental clinics in primary health care centers (PHCC). This program intends to deliver oral health care (OHC) for each patient with diabetes at least one visit every six months. However, we found that more than 90% of patients with diabetes that visited prince Mohammed bin Saud PHCC in Riyadh do not get their regular dental check up every six months. We developed a quality improvement project (QIP) using the quality improvement model to activate MoH oral health program for patients with diabetes visiting prince Mohamed bin Saud PHCC.The aim of our QIP was to increase number of patients with diabetes receiving their regular oral health check up during the PHC visit. The quality team tested two simple improvement ideas. The first idea was having the dentist signature on appointment request. The testing of the first idea led to the second idea, that both physician and dentist should sign the referral form. After running several PDSA cycles to test these interventions ideas, we found the number of patients with diabetes seen in dental clinic had increased dramatically compared with the baseline assessment. We conclude that the idea of signing the referral form by both physician and dentist is a practical and simple strategy to be executed and has a direct impact on the patient clinical flow between clinics.
Malnourishment and length of hospital stay among paediatric cancer patients with febrile neutropaenia: a developing country perspective
Authors: Conner J Michael , Aviles-Robles Martha J , Asdahl Peter H , Zhang Fang Fang , Ojha Rohit P 
Published: June 2016

ObjectivesThe prevalence of malnourishment among paediatric cancer patients undergoing chemotherapy in developing countries is poorly documented despite greater potential for malnourishment in such settings. We aimed to estimate the prevalence of malnourishment among paediatric cancer patients in Mexico City, and assess the association between malnourishment and length of hospital stay.MethodsIndividuals eligible for this study were paediatric cancer patients (aged <18 years) admitted to Hospital Infantil de Mexico Federico Gomez (Mexico City) with febrile neutropaenia. Our exposure of interest, malnourishment, was defined as an age-adjusted and sex-adjusted z-score<−2 (ie, 2 SDs below the expected mean of the WHO reference population). We estimated time ratios (TRs) and 95% confidence limits (CLs) for the association between malnourishment and length of hospital stay.ResultsOur study population comprised 111 paediatric cancer patients with febrile neutropaenia, of whom 71% were aged <10 years and 52% were males. The prevalence of malnourishment was 14%, equal to a 530% (standardised morbidity ratio=6.3; 95% CL 3.7, 10) excess of malnourishment compared with the world reference population. The median length of hospital stay for malnourished patients was 15 days, which corresponded with a 50% (TR=1.5, 95% CL 1.0, 2.3) relative increase in length of stay compared with patients who were not malnourished. Patients with body mass indices equal to the mean of the world reference population had the shortest length of stay.ConclusionsFuture studies should explore potential interventions for malnourishment to reduce the length of hospital stay or other established adverse consequences of malnourishment.
Systematic review and meta-analysis of optimal P2Y12blockade in dual antiplatelet therapy for patients with diabetes with acute coronary syndrome
Authors: Rossington Jennifer A , Brown Oliver I , Hoye Angela 
Published: June 2016

BackgroundPatients with diabetes are at increased risk of acute coronary syndromes (ACS) and their mortality and morbidity outcomes are significantly worse following ACS events, independent of other comorbidities. This systematic review sought to establish the optimum management strategy with focus on P2Y12blockade in patients with diabetes with ACS.MethodsMEDLINE (1946 to present) and EMBASE (1974 to present) databases, abstracts from major cardiology conferences and previously published systematic reviews were searched to June 2014. Relevant randomised control trials with clinical outcomes for P2Y12inhibitors in adult patients with diabetes with ACS were scrutinised independently by 2 authors with applicable data was extracted for primary composite end point of cardiovascular death, myocardial infarction (MI) and stroke; enabling calculation of relative risks with 95% CI with subsequent direct and indirect comparison.ResultsFour studies studied clopidogrel in patients with diabetes, with two (3122 patients) having primary outcome data showing superiority of clopidogrel against placebo with RR0.84 (95% CI 0.72–0.99). Irrespective of management strategy, the newer agents prasugrel (2 studies) and ticagrelor (1 study) had a lower primary event rate compared with clopidogrel; RR 0.80 (95% CI 0.66 to 0.97) and RR 0.89 (95% CI 0.77 to 1.02), respectively. When ticagrelor was indirectly compared with prasugrel, there was a trend to an improved primary outcome with prasugrel (RR 1.11 (95% CI 0.94 to 1.31)) particularly in those managed with percutaneous coronary intervention (PCI) (RR 1.23 (95% CI 0.95 to 1.59)). Prasugrel demonstrated a statistical superiority with prevention of further MI with RR 1.48 (95% CI 1.11 to 1.97). This was not at the expense of increased major thrombolysis in MI (TIMI) bleeding rates RR 0.94 (95% CI 0.59 to 1.51).ConclusionsThis meta-analysis shows the addition of a P2Y12inhibitor is superior to placebo, with a trend favouring the use of prasugrel in patients with diabetes with ACS, particularly those undergoing PCI.
A prognostic scoring system for arm exercise stress testing
Authors: Xie Yan , Xian Hong , Chandiramani Pooja , Bainter Emily , Wan Leping , Martin Wade H 
Published: June 2016

ObjectiveArm exercise stress testing may be an equivalent or better predictor of mortality outcome than pharmacological stress imaging for the ≥50% for patients unable to perform leg exercise. Thus, our objective was to develop an arm exercise ECG stress test scoring system, analogous to the Duke Treadmill Score, for predicting outcome in these individuals.MethodsIn this retrospective observational cohort study, arm exercise ECG stress tests were performed in 443 consecutive veterans aged 64.1 (11.1) years. (mean (SD)) between 1997 and 2002. From multivariate Cox models, arm exercise scores were developed for prediction of 5-year and 12-year all-cause and cardiovascular mortality and 5-year cardiovascular mortality or myocardial infarction (MI).ResultsArm exercise capacity in resting metabolic equivalents (METs), 1 min heart rate recovery (HRR) and ST segment depression ≥1 mm were the stress test variables independently associated with all-cause and cardiovascular mortality by step-wise Cox analysis (all p<0.01). A score based on the relation HRR (bpm)+7.3×METs−10.5×ST depression (0=no; 1=yes) prognosticated 5-year cardiovascular mortality with a C-statistic of 0.81 before and 0.88 after adjustment for significant demographic and clinical covariates. Arm exercise scores for the other outcome end points yielded C-statistic values of 0.77–0.79 before and 0.82–0.86 after adjustment for significant covariates versus 0.64–0.72 for best fit pharmacological myocardial perfusion imaging models in a cohort of 1730 veterans who were evaluated over the same time period.ConclusionsArm exercise scores, analogous to the Duke Treadmill Score, have good power for prediction of mortality or MI in patients who cannot perform leg exercise.
Cardiovascular MR T2-STIR imaging does not discriminate between intramyocardial haemorrhage and microvascular obstruction during the subacute phase of a reperfused myocardial infarction
Authors: Hansen Esben Søvsø Szocska , Pedersen Steen Fjord , Pedersen Steen Bønløkke , Kjærgaard Uffe , Schmidt Nikolaj Hjort , Bøtker Hans Erik , Kim Won Yong 
Published: June 2016

ObjectiveMicrovascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are known complications of myocardial ischaemia-reperfusion injury. Whereas MVO is an established marker for a poor clinical outcome, the clinical significance of IMH remains less well defined. Cardiovascular MR (CMR) and T2 weighted short tau inversion recovery (T2-STIR) imaging have been used to detect IMH and to explore its clinical importance. IMH is typically identified within the area-at-risk as a hypointense signal core on T2-STIR images. Because MVO will also appear as a hypointense signal core, T2-STIR imaging may not be an optimal method for assessing IMH. In this study, we sought to investigate the ability of T2-STIR to discriminate between MVO with IMH in a porcine myocardial ischaemia-reperfusion model that expressed MVO with and without IMH.MethodMVO with and without IMH (defined from both macroscopic evaluation and T1 weighted CMR) was produced in 13 pigs by a 65-min balloon occlusion of the mid left anterior descending artery, followed by reperfusion. Eight days after injury, all pigs underwent CMR imaging and subsequently the hearts were assessed by gross pathology.ResultsCMR identified MVO in all hearts. CMR and pathology showed that IMH was present in 6 of 13 (46%) infarcts. The sensitivity and specificity of T2-STIR hypointense signal core for identification of IMH was 100% and 29%, respectively. T2-values between hypointense signal core in the pigs with and without IMH were similar (60.4±3 ms vs 63.0±4 ms).ConclusionsT2-STIR did not allow identification of IMH in areas with MVO in a porcine model of myocardial ischaemic/reperfusion injury in the subacute phase of a reperfused myocardial infarction.
CD44 Expression Level and Isoform Contributes to Pancreatic Cancer Cell Plasticity, Invasiveness, and Response to Therapy
Authors: Zhao Shujie , Chen Chen , Chang Katherine , Karnad Anand , Jagirdar Jaishree , Kumar Addanki P. , Freeman James W. 
Published: June 2016

Abstract
Purpose: A subpopulation of pancreatic ductal adenocarcinoma (PDAC) cells is thought to be inherently resistant to chemotherapy or to give rise to tumor cells that become resistant during treatment. Here we determined the role of CD44 expression and its isoforms as a marker and potential target for tumor cells that give rise to invasive and gemcitabine-resistant tumors.
Experimental Design: RT-PCR, Western blotting, and DNA sequencing was used to determine CD44 isoform and expression levels. Flow cytometry was used to sort cells on the basis of their CD44 expression level. CD44 expression was knocked down using shRNA. Tumorigenic properties were determined by clonogenic and Matrigel assays, IHC, tumor growth in vivo using luciferase imaging and by tumor weight.
Results: We identified an invasive cell population that gives rise to gemcitabine-resistant tumors. These cancer cells express a high level of CD44 standard isoform and have an EMT phenotype (CD44s/EMT). In vivo, CD44s/EMT engraft and expand rapidly and give rise to tumors that express high levels of CD44 isoforms that contain multiple exon variants. CD44low-expressing cells show continued sensitivity to gemcitabine in vivo and knockdown of CD44 in CD44s/EMT cells increases sensitivity to gemcitabine and decreases invasiveness.
Conclusions: PDAC cells expressing high levels of CD44s with a mesenchymal-like phenotype were highly invasive and developed gemcitabine resistance in vivo. Thus, initial targeting CD44 or reversing the CD44high phenotype may improve therapeutic response. Clin Cancer Res; 22(22); 5592–604. ©2016 AACR.
A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia
Authors: Kuriakose Moni Abraham , Ramdas Kunnambath , Dey Bindu , Iyer Subramanya , Rajan Gunaseelan , Elango Kalavathy K. , Suresh Amritha , Ravindran Divya , Kumar Rajneesh R. , R Prathiba , Ramachandran Surya , Kumar Nisha Asok , Thomas Gigi , Somanathan Thara , Ravindran Hiran K. , Ranganathan Kannan , Katakam Sudhakar Babu , Parashuram Shivashankar , Jayaprakash Vijayvel , Pillai M. Radhakrishna 
Published: June 2016

AbstractOral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-κB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n = 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n = 111) or placebo (n = 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4–75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1–64.2) in placebo arm (P = 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2–96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months follow-up. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45–1.71; P = 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27–0.92; P = 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683–91. ©2016 AACR.