bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review finds major deficiencies in sample size methodology and reporting for stepped-wedge cluster randomised trials
Authors: Martin James , Taljaard Monica , Girling Alan , Hemming Karla 
Published: February 2016

BackgroundStepped-wedge cluster randomised trials (SW-CRT) are increasingly being used in health policy and services research, but unless they are conducted and reported to the highest methodological standards, they are unlikely to be useful to decision-makers. Sample size calculations for these designs require allowance for clustering, time effects and repeated measures.MethodsWe carried out a methodological review of SW-CRTs up to October 2014. We assessed adherence to reporting each of the 9 sample size calculation items recommended in the 2012 extension of the CONSORT statement to cluster trials.ResultsWe identified 32 completed trials and 28 independent protocols published between 1987 and 2014. Of these, 45 (75%) reported a sample size calculation, with a median of 5.0 (IQR 2.5–6.0) of the 9 CONSORT items reported. Of those that reported a sample size calculation, the majority, 33 (73%), allowed for clustering, but just 15 (33%) allowed for time effects. There was a small increase in the proportions reporting a sample size calculation (from 64% before to 84% after publication of the CONSORT extension, p=0.07). The type of design (cohort or cross-sectional) was not reported clearly in the majority of studies, but cohort designs seemed to be most prevalent. Sample size calculations in cohort designs were particularly poor with only 3 out of 24 (13%) of these studies allowing for repeated measures.DiscussionThe quality of reporting of sample size items in stepped-wedge trials is suboptimal. There is an urgent need for dissemination of the appropriate guidelines for reporting and methodological development to match the proliferation of the use of this design in practice. Time effects and repeated measures should be considered in all SW-CRT power calculations, and there should be clarity in reporting trials as cohort or cross-sectional designs.
How might health services capture patient-reported safety concerns in a hospital setting? An exploratory pilot study of three mechanisms
Authors: O'Hara Jane Kathryn , Armitage Gerry , Reynolds Caroline , Coulson Claire , Thorp Liz , Din Ikhlaq , Watt Ian , Wright John 
Published: February 2016

IntroductionEmergent evidence suggests that patients can identify and report safety issues while in hospital. However, little is known about the best method for collecting information from patients about safety concerns. This study presents an exploratory pilot of three mechanisms for collecting data on safety concerns from patients during their hospital stay.MethodThree mechanisms for capturing safety concerns were coproduced with healthcare professionals and patients, before being tested in an exploratory trial using cluster randomisation at the ward level. Nine wards participated, with each mechanism being tested over a 3-month study period. Patients were asked to feed back safety concerns via the mechanism on their ward (interviewing at their bedside, paper-based form or patient safety ‘hotline’). Safety concerns were subjected to a two-stage review process to identify those that would meet the definition of a patient safety incident. Differences between mechanisms on a range of outcomes were analysed using inferential statistics. Safety concerns were thematically analysed to develop reporting categories.Results178 patients were recruited. Patients in the face-to-face interviewing condition provided significantly more safety concerns per patient (1.91) compared with the paper-based form (0.92) and the patient safety hotline (0.43). They were also significantly more likely to report one or more concerns, with 64% reporting via the face-to-face mechanism, compared with 41% via the paper-based form and 19% via the patient safety hotline. No mechanism differed significantly in the number of classified patient safety incidents or physician-rated preventability and severity.DiscussionInterviewing at the patient's bedside is likely to be the most effective means of gathering safety concerns from inpatients, potentially providing an opportunity for health services to gather patient feedback about safety from their perspective.
DEPA classification: a proposal for standardising PRP use and a retrospective application of available devices
Authors: Magalon J , Chateau A L , Bertrand B , Louis M L , Silvestre A , Giraudo L , Veran J , Sabatier F 
Published: February 2016

Background/aimSignificant biological differences in platelet-rich plasma (PRP) preparations have been highlighted and could explain the large variability in the clinical benefit of PRP reported in the literature. The scientific community now recommends the use of classification for PRP injection; however, these classifications are focused on platelet and leucocyte concentrations. This presents the disadvantages of (1) not taking into account the final volume of the preparation; (2) omitting the presence of red blood cells in PRP and (3) not assessing the efficiency of production.MethodsOn the basis of standards classically used in the Cell Therapy field, we propose the DEPA (Dose of injected platelets, Efficiency of production, Purity of the PRP, Activation of the PRP) classification to extend the characterisation of the injected PRP preparation. We retrospectively applied this classification on 20 PRP preparations for which biological characteristics were available in the literature.ResultsDose of injected platelets varies from 0.21 to 5.43 billion, corresponding to a 25-fold increase. Only a Magellan device was able to obtain an A score for this parameter. Assessments of the efficiency of production reveal that no device is able to recover more than 90% of platelets from the blood. Purity of the preparation reveals that a majority of the preparations are contaminated by red blood cells as only three devices reach an A score for this parameter, corresponding to a percentage of platelets compared with red blood cells and leucocytes over 90%.ConclusionsThese findings should provide significant help to clinicians in selecting a system that meets their specific needs for a given indication.
The death of patients with terminal cancer: the distress experienced by their children and medical professionals who provide the children with support care
Authors: Otani Hiroyuki , Ozawa Miwa , Morita Tatsuya , Kawami Ayako , Sharma Sahana , Shiraishi Keiko , Oshima Akira 
Published: February 2016

BackgroundFew studies have been conducted on the experiences of children of terminally ill patients or hospital-based medical professionals supporting such children.AimThis study explored distress among individuals whose parents died of cancer in childhood and among hospital-based medical professionals supporting such children.DesignA qualitative study.Setting/participantsThe sample was 12 adults whose parents had died of cancer in childhood and 20 hospital-based medical professionals supporting children of patients’ with terminal cancer. In-depth interviews were conducted, focusing on the distress experienced by the participants. The data were analysed thematically.ResultsAmong adults whose parents died of cancer in childhood, we identified themes related to the period before death (eg, concealing the parent's illness), the time of death (eg, alienation due to isolation from the parent), soon after death (eg, fear and shock evoked by the bizarre circumstances, regrets regarding the relationship with the deceased parent before death), several years thereafter (ie, distinctive reflection during adolescence, prompted by the parent's absence) and the present time (ie, unresolved feelings regarding losing the parent). We identified seven themes among the medical professionals (eg, lack of knowledge/experience with children, the family's attempts to shield the child from the reality of death, estrangement from the family once they leave the hospital).ConclusionsAn important finding of the study is that the participants’ grief reaction to their parents’ deaths during childhood was prolonged. Moreover, hospital medical professionals may find it difficult to directly support affected children. Comprehensive support involving organisations (eg, local communities) may be necessary for children who have lost a parent.
Defining and improving the role of emergency medical services in Cape Town, South Africa
Authors: Anest Trisha , Stewart de Ramirez Sarah , Balhara Kamna S , Hodkinson Peter , Wallis Lee , Hansoti Bhakti 
Published: February 2016

IntroductionLow and middle income countries bear a disproportionate burden of paediatric morbidity and mortality. South Africa, a middle income country, has unacceptably high mortality in children less than 5 years of age. Many factors that contribute to the child mortality rate are time sensitive and require efficient access to emergency care. Delays and barriers within the emergency medical services (EMS) system increase paediatric morbidity and mortality from time sensitive illnesses.MethodsThis study is a qualitative evaluation of the prehospital care system for paediatric patients in Cape Town, South Africa. A purposive sample of healthcare personnel within and interacting with the EMS system were interviewed. A structured interview form was used to gather data. All interviews were audio recorded and transcribed; two independent reviewers performed blinded content analysis of the transcribed script.Results33 structured interviews were conducted over a 4 week period. Eight broad themes were identified during coding, including: access, communication, community education, equipment, infrastructure, staffing, training and triage. Subcategories were used to identify areas for targeted intervention. Overall agreement between the two independent coders was 93.36%, with a κ coefficient of 0.69.ConclusionsThe prehospital system is central to delivering time sensitive care for paediatric patients. In a single centre middle income setting, communication barriers between dispatch personnel and medical facilities/EMS personnel were deemed to be a high priority intervention in order to improve care delivery. Other areas for targeted interventions should include broadening the advanced life support provider base and introducing basic medical language in dispatch staff training.
Cerebral vasospasm and delayed cerebral infarctions in 225 patients with non-aneurysmal subarachnoid hemorrhage: the underestimated risk of Fisher 3 blood distribution
Authors: Konczalla Juergen , Kashefiolasl Sepide , Brawanski Nina , Lescher Stephanie , Senft Christian , Platz Johannes , Seifert Volker 
Published: February 2016

ObjectiveRecent data have shown increasing numbers of non-aneurysmal subarachnoid hemorrhage (NASAH). However, data are limited and often only small series have been published. Our objective was to analyze the rate of cerebral vasospasm (CVS), delayed cerebral infarction (DCI), and their influence on the clinical outcome, especially in patients with diffuse Fisher 3 bleeding pattern NASAH (Fi3).MethodsBetween 1999 and 2014, 225 patients had NASAH. CVS, DCI, and outcome (according to the modified Rankin Scale at 6 months) were analyzed retrospectively. Patients were stratified according to the bleeding type. After univariate analysis a multivariate analysis was performed and NASAH Fi3 was also compared with aneurysmal SAH Fi3.ResultsPatient characteristics and the outcome of perimesencephalic (PM) and non-PM (NPM) SAH were similar. Excluding Fi3, PM and NPM without Fi3 had similar patient characteristics, clinical course, and outcome. In particular, the Fi3 subgroup had a significantly increased risk of CVS, DCI, unfavorable outcome, hydrocephalus, and death. Early hydrocephalus was associated with Fi3 and intraventricular hemorrhage. The multivariate regression model showed the variables elderly patients, Fi3, and early hydrocephalus as independent and significant predictors for an unfavorable outcome. A further comparison of NASAH Fi3 with aneurysmal SAH Fi3 showed similar characteristics, CVS rate, and mortality.ConclusionsPatients with NASAH without a Fi3 bleeding pattern had a similar excellent outcome to patients with PM-SAH. Patients with Fi3 had a high risk for early hydrocephalus, CVS, DCI, and an unfavorable outcome, similar to patients with aneurysmal SAH. After multivariate analysis, early hydrocephalus, elderly patients, and Fi3 were identified as negative prognostic factors. Therefore, patients with Fi3 are at risk and need careful clinical observation.
Survey of ankle–brachial pressure index use and its perceived barriers by general practitioners in the UK
Authors: Yap Kannan R , Dattani N , Sayers R D , Bown M J 
Published: February 2016

AbstractBackgroundPeripheral arterial disease (PAD) is often undetected until complications arise, despite it being a major healthcare burden and an independent risk factor for cardiovascular death and systemic atherosclerosis. Appropriate diagnostic tools are as important as clinical knowledge and skill to investigate patients for PAD. Currently, the ankle–brachial pressure index (ABPI) is the recommended diagnostic tool for PAD.PurposeWe explore current opinions on ABPI by general practitioners (GPs) and the limitations to its implementation in primary care practice.MethodsGPs attending a regional 1-day study event, were surveyed in October 2014. Survey questionnaires were placed at the top of each conference pack for each attendee. The survey questionnaire was modelled from the ankle–brachial index (ABI) usage survey questionnaire used in the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) preceptorship study.ResultsAll respondents were GPs, with a survey response rate of 77.1%. All respondents regarded ABPI as an important test, that is primarily performed by nursing staff (79.5%) in their respective GP surgeries. 70% and 97% of GPs found ABPI useful for the diagnosis of asymptomatic and symptomatic PAD, respectively. 69% of GPs regarded ABPI as a feasible test in primary care practice. Time constraints (84%), staff availability (89%) and staff training (72%) were cited as the main limitations to its use.ConclusionsTargeted training of nursing staff may improve ABPI usage, although a less time-consuming test for PAD may be another option.
Effective Concentration of a Multikinase Inhibitor within Bone Marrow Correlates with In Vitro Cell Killing in Therapy-Resistant Chronic Myeloid Leukemia
Authors: Mu Chaofeng , Wu Xiaoyan , Ma Helen , Tao Wenjing , Zhang Guodong , Xia Xiaojun , Shen Jianliang , Mai Junhua , Sun Tong , Sun Xiaoping , Arlinghaus Ralph B. , Shen Haifa 
Published: February 2016

Abstract
Leukemia cells escape BCR-ABL–targeted therapy by developing mutations, such as T315I, in the p210BCR-ABL fusion protein in Philadelphia chromosome–positive chronic myeloid leukemia (CML). Although most effort has been focused on development of new tyrosine kinase inhibitors, enrichment of these small-molecule inhibitors in the tumor tissue can also have a profound impact on treatment outcomes. Here, we report that a 2-hour exposure of the T315I-mutant CML cells to 10 μmol/L of the multikinase inhibitor TG101209 suppressed BCR-ABL–independent signaling and caused cell-cycle arrest at G2–M. Further increase in drug concentration to 17.5 μmol/L blocked phosphorylation of the mutant BCR-ABL kinase and its downstream JAK2 and STAT5. The effective dosage to overcome therapy resistance identified in an in vitro setting serves as a guidance to develop the proper drug formulation for in vivo efficacy. A targeted formulation was developed to achieve sustained bone marrow TG101209 concentration at or above 17.5 μmol/L for effective killing of CML cells in vivo. Potent inhibition of leukemia cell growth and extended survival were observed in two murine models of CML treated with 40 mg/kg intravenously administered targeted TG101209, but not with the untargeted drug at the same dosage. Our finding provides a unique approach to develop treatments for therapy-resistant CML. Mol Cancer Ther; 15(5); 899–910. ©2016 AACR.
Targeting Interleukin-11 Receptor-α Impairs Human Endometrial Cancer Cell Proliferation and Invasion In Vitro and Reduces Tumor Growth and Metastasis In Vivo
Authors: Winship Amy L. , Van Sinderen Michelle , Donoghue Jacqueline , Rainczuk Kate , Dimitriadis Evdokia 
Published: February 2016

Abstract
Endometrial cancer contributes to significant morbidity and mortality in women with advanced stage or recurrent disease. IL11 is a cytokine that regulates cell cycle, invasion, and migration, all hallmarks of cancer. IL11 is elevated in endometrial tumors and uterine lavage fluid in women with endometrial cancer, and alters endometrial epithelial cancer cell adhesion and migration in vitro, but its role in endometrial tumorigenesis in vivo is unknown. We injected mice subcutaneously with human-derived Ishikawa or HEC1A endometrial epithelial cancer cells (ectopic), or HEC1A cells into the uterus (orthotopic) to develop endometrial cancer mouse models. Administration of anti-human IL11 receptor (R) α blocking antibody dramatically reduced HEC1A-derived tumor growth in both models and reduced peritoneal metastatic lesion spread in the orthotopic model, compared with IgG. Anti-human IL11Rα retained a well-differentiated, endometrial epithelial phenotype in the HEC1A ectopic mice, suggesting it prevented epithelial-to-mesenchymal transition. Blockade of mouse IL11Rα with anti-mouse IL11Rα antibody did not alter tumor growth, suggesting that cancer epithelial cell IL11 signaling is required for tumor progression. In vitro, anti-human IL11Rα antibody significantly reduced Ishikawa and HEC1A cell proliferation and invasion and promoted apoptosis. Anti-human, but not anti-mouse, IL11Rα antibody reduced STAT3, but not ERK, activation in HEC1A cells in vitro and in endometrial tumors in xenograft mice. We demonstrated that targeted blockade of endometrial cancer epithelial cell IL11 signaling reduced primary tumor growth and impaired metastasis in ectopic and orthotopic endometrial cancer models in vivo. Our data suggest that therapeutically targeting IL11Rα could inhibit endometrial cancer growth and dissemination. Mol Cancer Ther; 15(4); 720–30. ©2016 AACR.
DNA-Guided Precision Medicine for Cancer: A Case of Irrational Exuberance?
Authors: Voest Emile E. , Bernards Rene 
Published: February 2016

Abstract
Summary: Precision treatment with targeted cancer drugs requires the selection of patients who are most likely to benefit from a given therapy. We argue here that the use of a combination of both DNA and transcriptome analyses will significantly improve drug response prediction. Cancer Discov; 6(2); 130–2. ©2016 AACR.
Pruning Cancer's Evolutionary Tree with Lesion-Directed Therapy
Authors: Hiley Crispin T. , Swanton Charles 
Published: February 2016

Abstract
Summary: Next-generation sequencing of spatially and temporally separated biopsies and circulating tumor DNA directs therapy in response to tumor evolution and acquired resistance in colorectal cancer. Cancer Discov; 6(2); 122–4. ©2016 AACR.
See related article by Russo et al., p. 147.
Probucol-Oxidized Products, Spiroquinone and Diphenoquinone, Promote Reverse Cholesterol Transport in Mice
Authors: Yakushiji Emi , Ayaori Makoto , Nishida Takafumi , Shiotani Kazusa , Takiguchi Shunichi , Nakaya Kazuhiro , Uto-Kondo Harumi , Ogura Masatsune , Sasaki Makoto , Yogo Makiko , Komatsu Tomohiro , Lu Rui , Yokoyama Shinji , Ikewaki Katsunori 
Published: February 2016

Objective—
Oxidized products of probucol, spiroquinone and diphenoquinone, were shown to increase cell cholesterol release and plasma high-density lipoprotein (HDL) by inhibiting degradation of ATP-binding cassette transporter A1. We investigated whether these compounds enhance reverse cholesterol transport in mice.

Approach and Results—

Spiroquinone and diphenoquinone increased ATP-binding cassette transporter A1 protein (2.8- and 2.6-fold, respectively,
P
<0.01) and apolipoprotein A-I–mediated cholesterol release (1.4- and 1.4-fold,
P
<0.01 and
P
<0.05, respectively) in RAW264.7 cells. However, diphenoquinone, but not spiroquinone, enhanced cholesterol efflux to HDL (+12%,
P
<0.05), whereas both increased ATP-binding cassette transporter G1 protein, by 1.8- and 1.6-fold, respectively. When given orally to mice, both compounds significantly increased plasma HDL-cholesterol, by 19% and 20%, respectively (
P
<0.05), accompanied by an increase in hepatic and macrophage ATP-binding cassette transporter A1 but not ATP-binding cassette transporter G1. We next evaluated in vivo reverse cholesterol transport by injecting RAW264.7 cells labeled with
3
H-cholesterol intraperitoneally into mice. Both spiroquinone and diphenoquinone increased fecal excretion of the macrophage-derived
3
H-tracer, by 25% and 28% (
P
<0.01 and
P
<0.05), respectively. spiroquinone/diphenoquinone did not affect fecal excretion of HDL-derived
3
H-cholesterol, implying that macrophage-to-plasma was the most important step in spiroquinone/diphenoquinone-mediated promotion of in vivo reverse cholesterol transport. Finally, spiroquinone significantly reduced aortic atherosclerosis in apolipoprotein E null mice when compared with the vehicle.

Conclusions—
Spiroquinone and diphenoquinone increase functional ATP-binding cassette transporter A1 in both the macrophages and the liver, elevate plasma HDL-cholesterol, and promote overall reverse cholesterol transport in vivo. These compounds are promising as therapeutic reagents against atherosclerosis.
Modeling Future Cardiovascular Disease Mortality in the United States
Authors: Pearson-Stuttard Jonathan , Guzman-Castillo Maria , Penalvo Jose L. , Rehm Colin D. , Afshin Ashkan , Danaei Goodarz , Kypridemos Chris , Gaziano Tom , Mozaffarian Dariush , Capewell Simon , O’Flaherty Martin 
Published: February 2016

Background—
Accurate forecasting of cardiovascular disease mortality is crucial to guide policy and programming efforts. Prior forecasts often have not incorporated past trends in rates of reduction in cardiovascular disease mortality. This creates uncertainties about future trends in cardiovascular disease mortality and disparities.

Methods and Results—
To forecast US cardiovascular disease mortality and disparities to 2030, we developed a hierarchical bayesian model to determine and incorporate prior age, period, and cohort effects from 1979 to 2012, stratified by age, sex, and race, which we combined with expected demographic shifts to 2030. Data sources included the National Vital Statistics System, Surveillance, Epidemiology, and End Results (SEER) single-year population estimates, and US Bureau of Statistics 2012 national population projections. We projected coronary disease and stroke deaths to 2030, first on the basis of constant age, period, and cohort effects at 2012 values, as is most commonly done (conventional), and then with the use of more rigorous projections incorporating expected trends in age, period, and cohort effects (trend based). We primarily evaluated absolute mortality. The conventional model projected total coronary and stroke deaths by 2030 to increase by ≈18% (67 000 additional coronary deaths per year) and 50% (64 000 additional stroke deaths per year). Conversely, the trend-based model projected that coronary mortality would decrease by 2030 by ≈27% (79 000 fewer deaths per year) and stroke mortality would remain unchanged (200 fewer deaths per year). Health disparities will be improved in stroke deaths but not coronary deaths.

Conclusions—
After prior mortality trends and expected demographic shifts are accounted for, total US coronary deaths are expected to decline, whereas stroke mortality will remain relatively constant. Health disparities in stroke but not coronary deaths will be improved but not eliminated. These age, period, and cohort approaches offer more plausible predictions than conventional estimates.