bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating biomarkers for prognostic enrichment of clinical trials
Authors: Kerr Kathleen F , Roth Jeremy , Zhu Kehao , Thiessen-Philbrook Heather , Meisner Allison , Wilson Francis Perry , Coca Steven , Parikh Chirag R 
Published: December 2017

Background/Aims: A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. Methods: We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)–(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. Results: We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. Conclusion: In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.
Power estimation in biomarker studies where events are already observed
Authors: Polley Mei-Yin C 
Published: December 2017

Background The clinical utility of a new biomarker should ideally be established in a prospective randomized clinical trial. However, such trials are not always practical. As such, it is common for investigators to identify promising biomarkers using archived specimens and clinical data collected from previously completed therapeutic trials. Simon et al. defined such biomarker studies as prospective–retrospective studies and proposed specific conditions to satisfy for such evaluations to be more than hypothesis generating. One condition they proposed is that archived tissues must be available on a sufficiently large number of patients from the pivotal trials to ensure adequately powered analyses. Purpose The purpose of this article is to provide a new perspective on how to estimate power for assessing the prognostic and predictive values of a single binary biomarker in prospective–retrospective biomarker studies. Computer programs are provided to facilitate the use of these methods in practice. Methods The proposed methods utilize additional information that becomes available during the course of the treatment trial including sample size, accrual time, additional follow-up time, and the observed number of events at time of biomarker analysis. These methods involve solving for the exponential hazard rates that give rise to the event numbers that are consistent with those observed while satisfying other design parameter constraints. Conclusion Simon et al. proposed a new paradigm for biomarker design, conduct, analysis, and evaluation in prospective–retrospective studies that offers a more efficient alternative than fully prospective biomarker studies. As a general rule, they suggest that samples from at least two-thirds of the patients be available for analysis. In this article, I expand on this issue and provide a methodological tool useful for estimating study power in prospective–retrospective biomarker studies. It is my hope that these incremental efforts to improve the quality and statistical rigor in biomarker studies will hasten the introduction of useful tumor biomarkers into clinical practice.
The optimal design of stepped wedge trials with equal allocation to sequences and a comparison to other trial designs
Authors: Thompson Jennifer A , Fielding Katherine , Hargreaves James , Copas Andrew 
Published: December 2017

Background/Aims We sought to optimise the design of stepped wedge trials with an equal allocation of clusters to sequences and explored sample size comparisons with alternative trial designs. Methods We developed a new expression for the design effect for a stepped wedge trial, assuming that observations are equally correlated within clusters and an equal number of observations in each period between sequences switching to the intervention. We minimised the design effect with respect to (1) the fraction of observations before the first and after the final sequence switches (the periods with all clusters in the control or intervention condition, respectively) and (2) the number of sequences. We compared the design effect of this optimised stepped wedge trial to the design effects of a parallel cluster-randomised trial, a cluster-randomised trial with baseline observations, and a hybrid trial design (a mixture of cluster-randomised trial and stepped wedge trial) with the same total cluster size for all designs. Results We found that a stepped wedge trial with an equal allocation to sequences is optimised by obtaining all observations after the first sequence switches and before the final sequence switches to the intervention; this means that the first sequence remains in the control condition and the last sequence remains in the intervention condition for the duration of the trial. With this design, the optimal number of sequences is [Formula: see text], where [Formula: see text] is the cluster-mean correlation, [Formula: see text] is the intracluster correlation coefficient, and m is the total cluster size. The optimal number of sequences is small when the intracluster correlation coefficient and cluster size are small and large when the intracluster correlation coefficient or cluster size is large. A cluster-randomised trial remains more efficient than the optimised stepped wedge trial when the intracluster correlation coefficient or cluster size is small. A cluster-randomised trial with baseline observations always requires a larger sample size than the optimised stepped wedge trial. The hybrid design can always give an equally or more efficient design, but will be at most 5% more efficient. We provide a strategy for selecting a design if the optimal number of sequences is unfeasible. For a non-optimal number of sequences, the sample size may be reduced by allowing a proportion of observations before the first or after the final sequence has switched. Conclusion The standard stepped wedge trial is inefficient. To reduce sample sizes when a hybrid design is unfeasible, stepped wedge trial designs should have no observations before the first sequence switches or after the final sequence switches.
Wrist inflammation: a retrospective comparison between septic and non-septic arthritis
Authors: Kang Gavrielle , Leow Mabel Q. H. , Tay Shian-Chao 
Published: December 2017

This study aims to identify differences in demographics, clinical and laboratory data between wrist septic arthritis and non-septic arthritis in patients admitted for wrist inflammation. A retrospective review of inpatients from May 2012 to April 2015 was conducted. Seventy-seven patients were included. Non-septic arthritis patients were more likely to have chronic kidney disease, pre-existing gout, or both. All septic arthritis patients had normal serum uric acid levels, and two or more raised inflammatory markers (white cell count, C-reactive protein, erythrocyte sedimentation rate). In patients with isolated wrist inflammation, the mean C-reactive protein in the septic arthritis group was significantly higher compared with the non-septic arthritis group (mean difference 132 mg/L, 95% CI 30.9–234). In this study, polyarticular involvement did not exclude a septic cause; nor did it imply a non-septic aetiology. Diabetic or immunosuppressed patients were not more likely to develop septic arthritis. The presence of chondrocalcinosis on wrist radiographs was virtually diagnostic of non-septic arthritis. Level of evidence: IV
A Statistical Study of Metatarsal Anatomy: Toward the Design of Wide-Range Prosthetic Solutions
Authors: Couqueberg Yohann , Augoyard Romain , Augoyard Marc , Berry-Kromer Valérie , Bouby Céline , Girod Loïc 
Published: December 2017

The aim of the study is to provide some characteristic parameters of the anatomy of metatarsals from computed tomography (CT) scans. These data are important for more anatomical metatarsal head resurfacing prosthesis conception. Measures were performed on 20 CT scans from 17 patients with a mean age of 44.35 ± 15.75 years old. The panel was composed of 40% male and 50% left feet. Measurements were divided in 2 distinct categories: linear measurements with length of metatarsal, head radius and head, and diaphysis and base thicknesses, and cross-sectional area measurements, including cortical and cancellous bone area at 10%, 25%, 50%, 60%, 75%, and 90% of the metatarsal’s length. The results included the mean and SD found for each measured value. This study is the first step toward a better understanding of the metatarsal’s anatomy, so as to design a more anatomical range of metatarsal head resurfacing implants. Levels of Evidence: Level IV
A cross-sectional survey of cardiovascular health and lifestyle habits of hospital staff in the UK: Do we look after ourselves?
Authors: Mittal Tarun K , Cleghorn Christine L , Cade Janet E , Barr Suzanne , Grove Tim , Bassett Paul , Wood David A , Kotseva Kornelia 
Published: December 2017

Background A high prevalence of stress-related disorders is well known among healthcare professionals. We set out to assess the prevalence of cardiovascular risk factors and compliance with national dietary and physical activity recommendations in NHS staff in the UK with comparison between clinical and non-clinical staff, and national surveys. Design A multi-centre cross-sectional study. Methods A web-based questionnaire was developed to include anonymised data on demographics, job role, cardiovascular risk factors and diseases, dietary habits, physical activity and barriers towards healthy lifestyle. This was distributed to staff in four NHS hospitals via emails. Results A total of 1158 staff completed the survey (response rate 13%) with equal distribution between the clinical and non-clinical groups. Most staff were aged 26–60 years and 79% were women. Half of the staff were either overweight or obese (51%) with no difference between the groups ( P = 0.176), but there was a lower prevalence of cardiovascular risk factors compared to the general population. The survey revealed a low compliance (17%) with the recommended intake of five-a-day portions of fruit and vegetables, and that of moderate or vigorous physical activity (56%), with no difference between the clinical and non-clinical staff ( P = 0.6). However, more clinical staff were exceeding the alcohol recommendations ( P = 0.02). Lack of fitness facilities and managerial support, coupled with long working hours, were the main reported barriers to a healthy lifestyle. Conclusions In this survey of UK NHS staff, half were found to be overweight or obese with a lower prevalence of cardiovascular risk factors compared to the general population. There was a low compliance with the five-a-day fruit and vegetables recommendation and physical activity guidelines, with no difference between the clinical and non-clinical staff.
Cultural shift in mental illness: a comparison of stress responses in World War I and the Vietnam War
Authors: Skinner Rasjid , Kaplick Paul M 
Published: December 2017

Objectives Post-traumatic stress disorder is an established diagnostic category. In particular, over the past 20 years, there has been an interest in culture as a fundamental factor in post-traumatic stress disorder symptom manifestation. However, only a very limited portion of this literature studies the historical variability of post-traumatic stress within a particular culture. Design Therefore, this study examines whether stress responses to violence associated with armed conflicts have been a culturally stable reaction in Western troops. Setting We have compared historical records from World War I to those of the Vietnam War. Reference is also made to observations of combat trauma reactions in pre-World War I conflicts, World War II, the Korean War, the Falklands War, and the First Gulf War. Participants The data set consisted of literature that was published during and after these armed conflicts. Main outcome measures Accounts of World War I Shell Shock that describe symptom presentation, incidence (both acute and delayed), and prognosis were compared to the observations made of Vietnam War post-traumatic stress disorder victims. Results Results suggest that the conditions observed in Vietnam veterans were not the same as those which were observed in World War I trauma victims. Conclusions The paper argues that the concept of post-traumatic stress disorder cannot be stretched to cover the typical battle trauma reactions of World War I. It is suggested that relatively subtle changes in culture, over little more than a generation, have had a profound effect on how mental illness forms, manifests itself, and is effectively treated. We add new evidence to the argument that post-traumatic stress disorder in its current conceptualisation does not adequately account, not only for ethnocultural variation but also for historical variation in stress responses within the same culture.
Kinematic measures provide useful information after intracranial aneurysm treatment
Authors: Raw Rachael K , Wilkie Richard M , Mon-Williams Mark , Ross Stuart A , Deniz Kenan , Goddard Tony , Patankar Tufail 
Published: December 2017

Introduction Current methods of assessing the outcomes of intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage are relatively insensitive, and thus unlikely to detect subtle deficits. Failures to identify cognitive and motor outcomes of intracranial aneurysm treatment might prevent delivery of optimal post-operative care. There are also concerns over risks associated with using intracranial aneurysm treatment as a preventative measure. Methods We explored whether our kinematic tool would yield useful information regarding motor/cognitive function in patients who underwent intracranial aneurysm treatment for aneurysmal subarachnoid haemorrhage or unruptured aneurysm. Computerised kinematic motor and learning tasks were administered alongside standardised clinical outcome measures of cognition and functional ability, in 10 patients, as a pilot trial. Tests at post-intracranial aneurysm treatment discharge and six-week follow-up were compared to see which measures detected changes. Results Kinematic tests captured significant improvements from discharge to six-week follow-up, indexed by reduced motor errors and improved learning. Increased Addenbrooke’s Cognitive Examination-Revised scores reflected some recovery of memory function for most individuals, but other standardised cognitive measures, functional outcome scores and a psychological questionnaire showed no changes. Conclusions Kinematic measures can identify variation in performance in individuals with only slightly improved abilities post-intracranial aneurysm treatment. These measures may provide a sensitive way to explore post-operative outcomes following intracranial aneurysm treatment, or other similar surgical procedures.
Impact of Preoperative Anemia on Outcomes in Adults Undergoing Elective Posterior Cervical Fusion
Authors: Phan Kevin , Dunn Alexander E. , Kim Jun S. , Capua John Di , Somani Sulaiman , Kothari Parth , Lee Nathan J. , Xu Joshua , Dowdell James E. , Cho Samuel K. 
Published: December 2017

Study Design: Retrospective analysis of prospectively collected data. Objectives: Few studies have investigated the role of preoperative anemia on postoperative outcomes of posterior cervical fusion. This study looked to investigate the potential relationship between preoperative anemia and postoperative outcomes following posterior cervical spine fusion. Methods: Data from patients undergoing elective posterior cervical fusions between 2005 and 2012 was collected from the American College of Surgeons National Surgical Quality Improvement Program database using inclusion/exclusion criteria. Multivariate analyses were used to identify the predictive power of anemia for postoperative outcomes. Results: A total of 473 adult patients undergoing elective posterior cervical fusions were identified with 106 (22.4%) diagnosed with anemia preoperatively. Anemic patients had higher rates of diabetes ( P = .0001), American Society of Anesthesiologists scores ≥3 ( P < .0001), and higher dependent functional status prior to surgery ( P < .0001). Intraoperatively, anemic patients also had higher rates of neuromuscular injuries ( P = .0303), stroke ( P = .013), bleeding disorders ( P = .0056), lower albumin ( P < .0001), lower hematocrit ( P < .0001), and higher international normalized ratio ( P = .002). Postoperatively, anemic patients had higher rates of complications ( P < .0001), death ( P = .008), blood transfusion ( P = .001), reoperation ( P = .012), unplanned readmission ( P = .022), and extended length of stay (>5 days; P < .0001). Conclusions: Preoperative anemia is linked to a number of postoperative complications, which can increase length of hospital stay and increase the likelihood of reoperation. Identifying preoperative anemia may play a role in optimizing and minimizing the complication rates and severity of comorbidities following posterior cervical fusion.
Functional Outcome of Neurologic-Controlled HAL-Exoskeletal Neurorehabilitation in Chronic Spinal Cord Injury: A Pilot With One Year Treatment and Variable Treatment Frequency
Authors: Jansen Oliver , Schildhauer Thomas A. , Meindl Renate C. , Tegenthoff Martin , Schwenkreis Peter , Sczesny-Kaiser Matthias , Grasmücke Dennis , Fisahn Christian , Aach Mirko 
Published: December 2017

Study Design: Longitudinal prospective study. Objectives: Whether 1-year HAL-BWSTT of chronic spinal cord injured patients can improve independent ambulated mobility further as a function of training frequency, after an initial 3-month training period. Methods: Eight patients with chronic SCI were enrolled. They initially received full standard physical therapy and neurorehabilitation in the acute/subacute posttrauma phase. During this trial, all patients first underwent a daily (5 per week) HAL-BWSTT for 12 weeks. Subsequently, these patients performed a 40-week HAL-BWSTT with a training session frequency of either 1 or 3 to 5 sessions per week. The patients’ functional status including HAL-associated treadmill-walking time, -distance, and -speed with additional analysis of gait pattern, and their independent (without wearing the robot suit) functional mobility improvements, were assessed using the 10-Meter-Walk Test (10MWT), Timed-Up-and-Go Test (TUG) and 6-Minute-Walk Test (6MinWT) on admission, at 6 weeks, 12 weeks, and 1 year after enrollment. The data were analyzed separately for the 2 training frequency subgroups after the initial 12-week training period, which was identical in both groups. Results: During the 1-year follow-up, HAL-associated walking parameters and independent functional improvements were maintained in all the patients. This result held irrespective of the training frequency. Conclusions: Long-term 1-year maintenance of HAL-associated treadmill walking parameters and of improved independent walking abilities after initial 12 weeks of daily HAL-BWSTT is possible and depends mainly on the patients’ ambulatory status accomplished after initial training period. Subsequent regular weekly training, but not higher frequency training, seems to be sufficient to preserve the improvements accomplished.
Glyburide/Glipizide Combination Therapy in Type 2 Diabetes
Authors: Jaber Linda A 
Published: December 2017

Objective Research has determined differences in the pharmacokinetics and therapeutic actions of glyburide and glipizide. The goal of this study was to evaluate the hypoglycemic effects of glyburide/glipizide combination therapy in the management of patients with diabetes not adequately controlled on either agent alone. Methods Nine patients (3 men, mean age 50.6 ± 11 y) who were hyperglycemic on either glyburide or glipizide monotherapy continued their previous regimen with doses titrated up to maximum daily doses and dietary therapy for 4 weeks, and then they were placed on morning glipizide/evening glyburide combination therapy for 12 weeks. Results Combination therapy had no significant effect on glycemic control; no differences in glycosylated hemoglobin (HbAIC) were observed (baseline, 15.3% ± 3.6%; monotherapy, 14.8% ± 3.3%; combination, 13.4% ± 3.5%). However, during combined glyburide/glipizide therapy, fasting plasma glucose was significantly reduced by 53.4 ± 20.0 mg/dL in young (age <50 y) and increased by 73.7 ± 26.9 mg/dL in older subjects. HbAIC was reduced by 3.8% ± 4.0% in young and increased by 1.7% ± 1.3% in older subjects. No significant changes in blood pressure, body weight, or lipid parameters occurred. Conclusions Our preliminary data indicate the limited usefulness of combined glyburide/glipizide therapy. The modest reduction in hyperglycemia observed in patients younger than 50 years of age warrant future studying.