bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous Chondrocyte Implantation and Tibial Tubercle Osteotomy for Patellofemoral Chondral Defects: Improved Pain Relief and Occupational Outcomes Among US Army Servicemembers
Authors: Zarkadis Nicholas J. , Belmont Philip J. , Zachilli Michael A. , Holland Courtney A. , Kinsler Allison R. , Todd Michael S. , Pallis Mark P. , Waterman Brian R. 
Published: October 2018

Background: The occupational and functional results of patellofemoral autologous chondrocyte implantation (ACI) are underreported. This investigation sought to establish clinical outcomes and rates for return to work in a predominantly high-demand military cohort undergoing this procedure. Purpose: To determine the return-to-work, pain relief, and perioperative complication rates in a high-demand athletic cohort undergoing patellofemoral ACI. Study Design: Case series; Level of evidence, 4. Methods: All military servicemembers from 2 military medical centers undergoing ACI for high-grade patellofemoral chondral defects between 2006 and 2014 were identified, and data were abstracted from their medical records and clinical databases. Demographic and surgical variables were obtained for patients with at least 2 years of postoperative follow-up, and perioperative complications, rates of return to work, and survivorship from revision were quantified. Results: Seventy-two patients (72%) had >2-year follow-up and had patellofemoral ACI for high-grade chondral defects, with 66 knees (91%) undergoing a concomitant offloading tibial tubercle osteotomy. Mean follow-up was 4.3 years (range, 2.0-9.9 years). The mean ± SD age was 34.4 ± 6.1 years; 86% were male; and 57% were involved in military occupational specialties of heavy or very heavy demand. Second-generation patellofemoral ACI with a type I/III collagen membrane was used for 85% of knees. Most defects were isolated to the patella (n = 40, 55%). The mean total defect surface area was 4.5 ± 2.9 cm2 (range, 2.7-13.5 cm2). Fifty-six servicemembers (78%) returned to their occupational specialties. Three patients (4.1%) were classified as having surgical failures, requiring subsequent knee arthroplasty (n = 2) or a revision chondral procedure (n = 1). Mean visual analog scores improved significantly from 6.5 ± 1.5 to 3.2 ± 2.1 ( P < .0001). Multivariate analysis identified use of a periosteal patch as the only significant independent predictor for surgical ( P = .013) and overall ( P = .033) failures. Age <30 years ( P = .019), female sex ( P = .019), and regular tobacco use ( P = .011) were independent predictors of overall failure. Conclusion: For patellofemoral chondral defects without a failed primary procedure, second-generation ACI successfully returned to work 78% of patients of moderate to very heavy occupational demand with significantly decreased patient-reported knee pain. Risk factors after ACI for patellofemoral articular lesions for overall failure were age <30 years, female sex, and tobacco use, while surgical and overall failures were associated with periosteal patch use.
Development and Preliminary Evaluation of a Pain Management Manual for Hospice Providers to Support and Educate Family Caregivers
Authors: Chi Nai-Ching , Han Soojeong , Barani Emelia , Parker Oliver Debra , Washington Karla T. , Lewis Frances Marcus , Walker Amy , Demiris George 
Published: October 2018

Background: Family caregivers encounter many barriers to managing patients’ pain in the home hospice setting. However, there are limited clinically applicable resources for hospice providers to help family caregivers identify and address these barriers. Aim: To develop a pain management manual for hospice providers to support family caregivers and conduct a preliminary providers’ evaluation of the manual. Design and Participants: A pain management manual was developed and structured into 3 parts: (1) 5 common pain management case scenarios based on a secondary data analysis of a hospice clinical trial; (2) a list of suggested assessment questions and strategies for each case scenario was developed based on a caregiver framework; and (3) pain educational material was included from established clinical guidelines. The manual was vetted by 5 experts and then was evaluated by interviewing 25 hospice providers. Interview data were analyzed using thematic analysis. Results: The hospice providers found that the manual could potentially serve as a reference in their practice and be a source for their continuing education. They suggested enhancing the clarity of the case scenarios and adding additional strategies to the manual. Moreover, they suggested expanding the paper-based version and developing a web-based platform to deliver the content would maximize its utility. Conclusions: The manual has the potential to be integrated into routine hospice care to improve the quality of pain management.
Opioid prescribing and dispensing: Experiences and perspectives from a survey of community pharmacists practising in the province of Quebec
Authors: Dubé Pierre-André , Vachon Julien , Sirois Caroline , Roy Élise 
Published: October 2018

Background: Canada leads in opioid prescription and consumption rates, and this has resulted in high levels of opioid-related morbidity and mortality. Pharmacists’ input could contribute significantly to understanding the disadvantages of opioid prescribing and dispensing and improving the service. This study aimed to examine the experiences of community pharmacists in relation to opioid prescribing and dispensing, with a focus on optimizing collaboration and communication. Methods: An online survey was performed among pharmacists from the province of Quebec, Canada, in 2016. Pharmacists were eligible if registered and working in community pharmacies. Results: In all, 542 questionnaires were analyzed (participation rate of 8.1%). Pharmacotherapy-related problems were reported in at least 50% of opioid prescriptions: additional drug(s) required (reported by 30% of pharmacists), interaction(s) between opioid(s) and other drug(s) (16%), physician did not meet the general issuing standards for opioid prescriptions (26%) and patient had mild to moderate pain that was easily managed by a nonopioid analgesic (20%). Half of the patients were reported as requesting anticipated refills, possibly indicating abuse or poor pain control. Most pharmacists (89.6%) reported needing to contact physicians in 1 to 3 out of 10 opioid prescriptions, but many pharmacists (71.8%, often or very often) reported difficulties communicating with physicians. Conclusions: Pharmacists’ observations of pharmacotherapy-related problems and patients’ unusual behaviours reveal a significant number of issues related to opioid prescribing and dispensing in an outpatient setting. Improved collaboration between physicians and pharmacists appears mandatory to address the issues reported in this study.
Novel Bluetooth-Enabled Tubeless Insulin Pump: A User Experience Design Approach for a Connected Digital Diabetes Management Platform
Authors: Pillalamarri Sandhya S. , Huyett Lauren M. , Abdel-Malek Aiman 
Published: October 2018

Background: Medical device technology is evolving at a rapid pace, with increasing patient expectations to use modern technologies for diabetes management. With the significant expansion of the use of wireless technology and complex, securely connected digital platforms in medical devices, end user needs and behaviors have become essential areas of focus. Methods: This article provides a detailed description of the user-centered design approach implemented in developing the Omnipod DASH™ Insulin Management System (Insulet Corp., Billerica, MA) Bluetooth®-enabled locked-down Android device handheld controller (Personal Diabetes Manager, PDM). Key methodologies used in the PDM design are described, including how the science of user experience (UX) was integrated into new agile product development. UX methods employed included heuristic evaluations of insulin pumps, iterative formative usability testing, information architecture studies, in-home ethnographic visits, participatory design activities, and interviews. Results: Over 343 users participated in UX research and testing. Key design choices informed by UX research included updating the layout of critical data on the PDM home page, providing access to requested contextual information while a bolus is in progress, and creating an easy-to-understand visual of a 24-hour basal program. Task completion rates for comprehending information on the PDM home page were 87% or greater. The System Usability Scale result for the design prior to limited market release was 84.4 ± 13.4 (out of 100; n = 37). Conclusions: The UX process described in this article can serve as a blueprint for medical device manufacturers seeking to enhance product development. Adopting UX research methodologies will help ensure that new diabetes devices are safe, easy-to-use, and meet the needs of users.
Chronic immune response dysregulation in MDS pathogenesis
Authors: Barreyro Laura , Chlon Timothy M. , Starczynowski Daniel T. 
Published: October 2018

Abstract
Chronic innate immune signaling in hematopoietic cells is widely described in myelodysplastic syndromes (MDS), and innate immune pathway activation, predominantly via pattern recognition receptors, increases the risk of developing MDS. An inflammatory component to MDS has been reported for many years, but only recently has evidence supported a more direct role of chronic innate immune signaling and associated inflammatory pathways in the pathogenesis of MDS. Here we review recent findings and discuss relevant questions related to chronic immune response dysregulation in MDS.
Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway
Authors: Khandelwal Sanjay , Ravi Joann , Rauova Lubica , Johnson Alexandra , Lee Grace M. , Gilner Jennifer B. , Gunti Sreenivasulu , Notkins Abner L. , Kuchibhatla Maragatha , Frank Michael , Poncz Mortimer , Cines Douglas B. , Arepally Gowthami M. 
Published: October 2018

AbstractThe mechanisms by which exposure to heparin initiates antibody responses in many, if not most, recipients are poorly understood. We recently demonstrated that antigenic platelet factor 4 (PF4)/heparin complexes activate complement in plasma and bind to B cells. Here, we describe how this process is initiated. We observed wide stable variation in complement activation when PF4/heparin was added to plasma of healthy donors, indicating a responder “phenotype” (high, intermediate, or low). Proteomic analysis of plasma from these healthy donors showed a strong correlation between complement activation and plasma immunoglobulin M (IgM) levels (r = 0.898; P &lt; .005), but not other Ig isotypes. Complement activation response to PF4/heparin in plasma displaying the low donor phenotype was enhanced by adding pooled IgM from healthy donors, but not monoclonal IgM. Depletion of IgM from plasma abrogated C3c generation by PF4/heparin. The complement-activating features of IgM are likely mediated by nonimmune, or natural, IgM, as cord blood and a monoclonal polyreactive IgM generate C3c in the presence of PF4/heparin. IgM facilitates complement and antigen deposition on B cells in vitro and in patients receiving heparin. Anti-C1q antibody prevents IgM-mediated complement activation by PF4/heparin complexes, indicating classical pathway involvement. These studies demonstrate that variability in plasma IgM levels correlates with functional complement responses to PF4/heparin. Polyreactive IgM binds PF4/heparin, triggers activation of the classical complement pathway, and promotes antigen and complement deposition on B cells. These studies provide new insights into the evolution of the heparin-induced thrombocytopenia immune response and may provide a biomarker of risk.
BH3-mimetic toolkit guides the respective use of BCL2 and MCL1 BH3-mimetics in myeloma treatment
Authors: Gomez-Bougie Patricia , Maiga Sophie , Tessoulin Benoît , Bourcier Jessie , Bonnet Antoine , Rodriguez Manuel S. , Le Gouill Steven , Touzeau Cyrille , Moreau Philippe , Pellat-Deceunynck Catherine , Amiot Martine 
Published: October 2018

Abstract
BH3 mimetics are promising drugs for hematologic malignancies that trigger cell death by promoting the release of proapoptotic BCL2 family members from antiapoptotic proteins. Multiple myeloma is considered to be a disease dependent mainly on MCL1 for survival, based mostly on studies using cell lines. We used a BH3-mimetic toolkit to study the dependency on BCL2, BCLXL, or MCL1 in malignant plasma cells from 60 patients. Dependencies were analyzed using an unbiased BH3 mimetics cell-death clustering by k-means. In the whole cohort of patients, BCL2 dependency was mostly found in the CCND1 subgroup (83%). Of note, MCL1 dependence significantly increased from 33% at diagnosis to 69% at relapse, suggesting a plasticity of the cellular dependency favoring MCL1 dependencies at relapse. In addition, 35% of overall patient samples showed codependencies on either BCL2/MCL1 or BCLXL/MCL1. Finally, we identified a group of patients not targeted by any of the BH3 mimetics, predominantly at diagnosis in patients not presenting the common recurrent translocations. Mechanistically, we demonstrated that BAK is crucial for cell death induced by MCL1 mimetic A1210477, according to the protection from cell death observed by BAK knock-down, as well as the complete and early disruption of MCL1/BAK complexes on A1210477 treatment. Interestingly, this complex was also dissociated in A1210477-resistant cells, but free BAK was simultaneously recaptured by BCLXL, supporting the role of BCLXL in A1210477 resistance. In conclusion, our study opens the way to rationally use venetoclax and/or MCL1 BH3 mimetics for clinical evaluation in myeloma at both diagnosis and relapse.
Next-generation sequencing–based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse
Authors: Kim TaeHyung , Moon Joon Ho , Ahn Jae-Sook , Kim Yeo-Kyeoung , Lee Seung-Shin , Ahn Seo-Yeon , Jung Sung-Hoon , Yang Deok-Hwan , Lee Je-Jung , Choi Seung Hyun , Lee Ja-yeon , Tyndel Marc S. , Shin Myung-Geun , Lee Yoo Jin , Sohn Sang Kyun , Park Seong-Kyu , Zhang Zhaolei , Kim Hyeoung-Joon , Kim Dennis Dong Hwan 
Published: October 2018

Key Points
Higher allelic burden at day 21 of post-HCT is associated with higher risk of relapse and mortality. Longitudinal tracking of AML patients receiving HCT is feasible and provides clinically relevant information.
Reversing anti–factor Xa agents and the unmet needs in trauma patients
Authors: Hunt Beverley J. , Neal Matthew D. , Stensballe Jakob 
Published: October 2018

AbstractAndexanet alfa, a reversing agent for anticoagulants that inhibit factor Xa, has recently been licensed in the United States. We discuss the impact of this licensure on current practice and review in detail the problems of a neglected and growing clinical area: reversing the anticoagulation effect of factor Xa inhibitors in bleeding trauma patients. We identify areas of practice that need research so that care of bleeding trauma patients receiving direct factor Xa inhibitors can be improved.
Humanized Mcl-1 mice enable accurate preclinical evaluation of MCL-1 inhibitors destined for clinical use
Authors: Brennan Margs S. , Chang Catherine , Tai Lin , Lessene Guillaume , Strasser Andreas , Dewson Grant , Kelly Gemma L. , Herold Marco J. 
Published: October 2018

Key PointsDue to the higher affinity of current MCL-1 inhibitors, huMcl-1 mice have been established. A therapeutic window for S63845 can be established in huMcl-1 mice transplanted with huMcl-1;Eµ-Myc lymphomas.
A multi-hop graph-based approach for an energy-efficient routing protocol in wireless sensor networks
Authors: Rhim Hana , Tamine Karim , Abassi Ryma , Sauveron Damien , Guemara Sihem 
Published: October 2018

Abstract
Emerging technological advances in wireless communication and networking have led to the design of large scale networks and small sensor units with minimal power requirements and multifunctional processing. Though energy harvesting technologies are improving, the energy of sensors remains a scarce resource when designing routing protocols between sensor nodes and base station. This paper proposes a multi-hop graph-based approach for an energy-efficient routing (MH-GEER) protocol in wireless sensor networks which aims to distribute energy consumption between clusters at a balanced rate and thus extend networks’ lifespans. MH-GEER deals with node clustering and inter-cluster multi-hop routing selection. The clustering phase is built upon the centralized formation of clusters and the distributed selection of cluster heads similar to that of low-energy adaptive clustering hierarchy (LEACH). The routing phase builds a dynamic multi-hop path between cluster heads and the base station. Our strategy is about exploring the energy levels in the entire network and using these to select the next hop in a probabilistic, intelligent way. Performance evaluation shows that MH-GEER minimizes energy depletion in distant clusters and ensures load balancing in a network, thus improving the network’s lifetime and stability compared with single-hop conventional LEACH protocol.
Surface area wiped, product type, and target strain impact bactericidal efficacy of ready-to-use disinfectant Towelettes
Authors: West Alyssa M , Nkemngong Carine A , Voorn Maxwell G , Wu Tongyu , Li Xiaobao , Teska Peter J , Oliver Haley F 
Published: October 2018

Abstract
Background
Disinfectant products are often used on environmental surfaces (e.g. countertops, patient beds) and patient care equipment in healthcare facilities to help prevent the transmission of healthcare-associated infections. Ready-to-use (RTU) disinfectants in the form of pre-wetted towelettes are increasingly popular among healthcare facilities. Currently, the EPA does not require disinfectant manufacturers to include a recommended maximum surface area per towelette on their product labels. The objective of this study was to investigate the efficacy of disinfectant towelette products on a hard non-porous surface across different coverage areas using a quantitative EPA method. We hypothesized that there would be significant differences in the efficacy of disinfectant towelette products, and that the greater surface area(s) wiped would result in reduced bactericidal efficacy.

Methods
This study tested ten disinfectant towelette products against Staphylococcus aureus strain ATCC CRM-6538 and Pseudomonas aeruginosa strain ATCC 15442 on Formica surfaces. Defined surface areas were wiped and the towelette weighed before and after wiping to determine the amount of liquid released. Bactericidal efficacy testing was also performed after wiping following standard EPA protocols.

Results
We found that disinfectant product, area of surface wiped, and strain impacted the bactericidal efficacy achieved. Disinfectant product type and area of surface wiped significantly impacted the percent of liquid released per ft2from the towelette.

Conclusion
Overall, bactericidal efficacy varied by towelette product, surface area wiped, and strain. This study also found that wiping larger surface areas may lead to decreased bactericidal efficacy. Further research is needed to test its implication.
Optimizing Outcome Prediction in Diffuse Large B-Cell Lymphoma by Use of Machine Learning and Nationwide Lymphoma Registries: A Nordic Lymphoma Group Study
Authors: Biccler Jorne L. , Eloranta Sandra , de Nully Brown Peter , Frederiksen Henrik , Jerkeman Mats , Jørgensen Judit , Jakobsen Lasse Hjort , Smedby Karin E. , Bøgsted Martin , El-Galaly Tarec C. 
Published: October 2018

PurposePrognostic models for diffuse large B-cell lymphoma (DLBCL), such as the International Prognostic Index (IPI) are widely used in clinical practice. The models are typically developed with simplicity in mind and thus do not exploit the full potential of detailed clinical data. This study investigated whether nationwide lymphoma registries containing clinical data and machine learning techniques could prove to be useful for building modern prognostic tools.Patients and MethodsThis study was based on nationwide lymphoma registries from Denmark and Sweden, which include large amounts of clinicopathologic data. Using the Danish DLBCL cohort, a stacking approach was used to build a new prognostic model that leverages the strengths of different survival models. To compare the performance of the stacking approach with established prognostic models, cross-validation was used to estimate the concordance index (C-index), time-varying area under the curve, and integrated Brier score. Finally, the generalizability was tested by applying the new model to the Swedish cohort.ResultsIn total, 2,759 and 2,414 patients were included from the Danish and Swedish cohorts, respectively. In the Danish cohort, the stacking approach led to the lowest integrated Brier score, indicating that the survival curves obtained from the stacking model fitted the observed survival the best. The C-index and time-varying area under the curve indicated that the stacked model (C-index: Denmark [DK], 0.756; Sweden [SE], 0.744) had good discriminative capabilities compared with the other considered prognostic models (IPI: DK, 0.662; SE, 0.661; and National Comprehensive Cancer Network–IPI: DK, 0.681; SE, 0.681). Furthermore, these results were reproducible in the independent Swedish cohort.ConclusionA new prognostic model based on machine learning techniques was developed and was shown to significantly outperform established prognostic indices for DLBCL. The model is available at https://lymphomapredictor.org .
Baseline characteristics of infected foot ulcers in patients with diabetes at a tertiary care hospital in Pakistan
Authors: Yasin Muhammad , Zafar Shaista , Rahman Hazir , Khan Taj Ali , Nazir Shabnum , Shah Salman , Dawood Muhammad , Ahmad Shahbaz , Basit Abdul , Khan Shahid Niaz , Saleha Shamim 
Published: October 2018

Objective: Studies on diabetic foot ulcers (DFU) involving a representative sample of patients in Pakistan are scarce. This study aimed to determine baseline characteristics of infected DFUs in patients hospitalised at the Pakistan Institute of Medical Sciences Islamabad. Method: In this cross-sectional study, carried out during May 2015 and June 2016, foot ulcer characteristics of patients with DFUs were investigated and documented. From infected DFUs, aerobic bacterial pathogens were isolated, identified and evaluated for antimicrobial susceptibility. Results: A total of 214 patients were recruited to the study, 62.6% of which were male, 90.2% were aged ≥40 years, 76.2% had type 1 diabetes and 78.5% had poor glycaemic control at time of presentation to hospital. Most patients had grade 3/moderate ulceration (based on the Wagner and International Working Group on the Diabetic Foot/Infectious Diseases Society of America criteria). Over half of the DFUs (57.9%) were of ≤3 months' duration and 70.1% were ≥3 cm2. Of the patients with deep infection grade ulcers, 26.6% underwent amputation, accounting for their prolonged hospital stay (≥20 days). Significant differences were observed between patients with type 1 and type 2 diabetes with DFUs in relation to gender (p≤0.0001), ulcer size (p=0.0421) and duration of hospital stay (p=0.0253). The most significant predictors for lower extremity amputation were osteomyelitis (p=0.0114), retinopathy (p=0.0001) and neuropathy (p=0.0001. Piperacillin/tazobactam was found to be an effective antibiotic against the most commonly isolated Staphylococcus non-aureus (35.48%), Pseudomonas aeruginosa (22.26%), and Staphylococcus aureus (20.96%) species indentified in the DFU infections. Conclusion: The findings of this study may be helpful in the optimal management and appropriate treatment of patients with infected DFUs.