Electron Beam-Treated Enzymatically Mineralized Gelatin Hydrogels for Bone Tissue Engineering

Biological hydrogels are highly promising materials for bone tissue engineering (BTE) due to their high biocompatibility and biomimetic characteristics. However, for advanced and customized BTE, precise tools for material stabilization and tuning material properties are desired while optimal mineralisation must be ensured. Therefore, reagent-free crosslinking techniques such as high energy electron beam treatment promise effective material modifications without formation of cytotoxic by-products. In the case of the hydrogel gelatin, electron beam crosslinking further induces thermal stability enabling biomedical application at physiological temperatures. In the case of enzymatic mineralisation, induced by Alkaline Phosphatase (ALP) and mediated by Calcium Glycerophosphate (CaGP), it is necessary to investigate if electron beam treatment before mineralisation has an influence on the enzymatic activity and thus affects the mineralisation process. The presented study investigates electron beam-treated gelatin hydrogels with previously incorporated ALP and successive mineralisation via incubation in a medium containing CaGP. It could be shown that electron beam treatment optimally maintains enzymatic activity of ALP which allows mineralisation. Furthermore, the precise tuning of material properties such as increasing compressive modulus is possible. This study characterizes the mineralised hydrogels in terms of mineral formation and demonstrates the formation of CaP in dependence of ALP concentration and electron dose. Furthermore, investigations of uniaxial compression stability indicate increased compression moduli for mineralised electron beam-treated gelatin hydrogels. In summary, electron beam-treated mineralized gelatin hydrogels reveal good cytocompatibility for MG-63 osteoblast like cells indicating a high potential for BTE applications

Internet‐Based Pain Self‐Management for Veterans: Feasibility and Preliminary Efficacy of the Pain EASE Program

ObjectiveTo develop and test the feasibility and preliminary efficacy of a cognitive behavioral therapy–based, internet‐delivered self‐management program for chronic low back pain (cLBP) in veterans.MethodsPhase I included program development, involving expert panel and participant feedback. Phase II was a single‐arm feasibility and preliminary efficacy study of the Pain e‐health for Activity, Skills, and Education (Pain EASE) program. Feasibility (ie, website use, treatment credibility, satisfaction) was measured using descriptive methods. Mixed models were used to assess mean within‐subject changes from baseline to 10 weeks post‐baseline in pain interference (primary outcome, West Haven‐Yale Multidimensional Pain Inventory, scale of 0 to 6), pain intensity, mood, fatigue, sleep, and depression.ResultsPhase I participants (n = 15) suggested modifications including style changes, content reduction, additional “Test Your Knowledge” quizzes, and cognitive behavioral therapy skill practice monitoring form revisions for enhanced usability. In Phase II, participants (n = 58) were mostly male (93%) and White (60%), and had an average age of 55 years (standard deviation [SD] = 12) and moderate pain (mean score 5.9/10); 41 (71%) completed the post‐baseline assessment. Participants (N = 58) logged on 6.1 (SD = 8.6) times over 10 weeks, and 85% reported being very or moderately satisfied with Pain EASE. Pain interference improved from a mean of 3.8 at baseline to 3.3 at 10 weeks (difference 0.5 [95% confidence interval 0.1 to 0.9], P = 0.008). Within‐subject improvement also occurred for some secondary outcomes, including mood and depression symptoms.DiscussionVeterans with cLBP may benefit from technology‐delivered interventions, which may also reduce pain interference. Overall, veterans found that Pain EASE, an internet‐based self‐management program, is feasible and satisfactory for cLBP.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154929/1/papr12861.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154929/2/papr12861_am.pd

Development and implementation of a mobile device-based pediatric electronic decision support tool as part of a national practice standardization project

OBJECTIVE: Implementing evidence-based practices requires a multi-faceted approach. Electronic clinical decision support (ECDS) tools may encourage evidence-based practice adoption. However, data regarding the role of mobile ECDS tools in pediatrics is scant. Our objective is to describe the development, distribution, and usage patterns of a smartphone-based ECDS tool within a national practice standardization project. MATERIALS AND METHODS: We developed a smartphone-based ECDS tool for use in the American Academy of Pediatrics, Value in Inpatient Pediatrics Network project entitled Reducing Excessive Variation in the Infant Sepsis Evaluation (REVISE). The mobile application (app), PedsGuide, was developed using evidence-based recommendations created by an interdisciplinary panel. App workflow and content were aligned with clinical benchmarks; app interface was adjusted after usability heuristic review. Usage patterns were measured using Google Analytics. RESULTS: Overall, 3805 users across the United States downloaded PedsGuide from December 1, 2016, to July 31, 2017, leading to 14 256 use sessions (average 3.75 sessions per user). Users engaged in 60 442 screen views, including 37 424 (61.8%) screen views that displayed content related to the REVISE clinical practice benchmarks, including hospital admission appropriateness (26.8%), length of hospitalization (14.6%), and diagnostic testing recommendations (17.0%). Median user touch depth was 5 [IQR 5]. DISCUSSION: We observed rapid dissemination and in-depth engagement with PedsGuide, demonstrating feasibility for using smartphone-based ECDS tools within national practice improvement projects. CONCLUSIONS: ECDS tools may prove valuable in future national practice standardization initiatives. Work should next focus on developing robust analytics to determine ECDS tools\u27 impact on medical decision making, clinical practice, and health outcomes

Cumulative Burden of Morbidity Among Testicular Cancer Survivors After Standard Cisplatin-Based Chemotherapy: A Multi-Institutional Study

Purpose In this multicenter study, we evaluated the cumulative burden of morbidity (CBM) among > 1,200 testicular cancer survivors and applied factor analysis to determine the co-occurrence of adverse health outcomes (AHOs). Patients and Methods Participants were ≤ 55 years of age at diagnosis, finished first-line chemotherapy ≥ 1 year previously, completed a comprehensive questionnaire, and underwent physical examination. Treatment data were abstracted from medical records. A CBM score encompassed the number and severity of AHOs, with ordinal logistic regression used to assess associations with exposures. Nonlinear factor analysis and the nonparametric dimensionality evaluation to enumerate contributing traits procedure determined which AHOs co-occurred. Results Among 1,214 participants, approximately 20% had a high (15%) or very high/severe (4.1%) CBM score, whereas approximately 80% scored medium (30%) or low/very low (47%). Increased risks of higher scores were associated with four cycles of either ifosfamide, etoposide, and cisplatin (odds ratio [OR], 1.96; 95% CI, 1.04 to 3.71) or bleomycin, etoposide, and cisplatin (OR, 1.44; 95% CI, 1.04 to 1.98), older attained age (OR, 1.18; 95% CI, 1.10 to 1.26), current disability leave (OR, 3.53; 95% CI, 1.57 to 7.95), less than a college education (OR, 1.44; 95% CI, 1.11 to 1.87), and current or former smoking (OR, 1.28; 95% CI, 1.02 to 1.63). CBM score did not differ after either chemotherapy regimen ( P = .36). Asian race (OR, 0.41; 95% CI, 0.23 to 0.72) and vigorous exercise (OR, 0.68; 95% CI, 0.52 to 0.89) were protective. Variable clustering analyses identified six significant AHO clusters (χ2 P < .001): hearing loss/damage, tinnitus (OR, 16.3); hyperlipidemia, hypertension, diabetes (OR, 9.8); neuropathy, pain, Raynaud phenomenon (OR, 5.5); cardiovascular and related conditions (OR, 5.0); thyroid disease, erectile dysfunction (OR, 4.2); and depression/anxiety, hypogonadism (OR, 2.8). Conclusion Factors associated with higher CBM may identify testicular cancer survivors in need of closer monitoring. If confirmed, identified AHO clusters could guide the development of survivorship care strategies

Taking ACTION to reduce pain: ACTION study rationale, design and protocol of a randomized trial of a proactive telephone-based coaching intervention for chronic musculoskeletal pain among African Americans

Abstract Background Rates of chronic pain are rising sharply in the United States and worldwide. Presently, there is evidence of racial disparities in pain treatment and treatment outcomes in the United States but few interventions designed to address these disparities. There is growing consensus that chronic musculoskeletal pain is best addressed by a biopsychosocial approach that acknowledges the role of psychological and environmental factors, some of which differ by race. Methods/Design The primary aim of this randomized controlled trial is to test the effectiveness of a non-pharmacological, self-regulatory intervention, administered proactively by telephone, at improving pain outcomes and increasing walking among African American patients with hip, back and knee pain. Participants assigned to the intervention will receive a telephone counselor delivered pedometer-mediated walking intervention that incorporates action planning and motivational interviewing. The intervention will consist of 6 telephone counseling sessions over an 8–10 week period. Participants randomly assigned to Usual Care will receive an informational brochure and a pedometer. The primary outcome is chronic pain-related physical functioning, assessed at 6 months, by the revised Roland and Morris Disability Questionnaire, a measure recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). We will also examine whether the intervention improves other IMMPACT-recommended domains (pain intensity, emotional functioning, and ratings of overall improvement). Secondary objectives include examining whether the intervention reduces health care service utilization and use of opioid analgesics and whether key contributors to racial/ethnic disparities targeted by the intervention mediate improvement in chronic pain outcomes Measures will be assessed by mail and phone surveys at baseline, three months, and six months. Data analysis of primary aims will follow intent-to-treat methodology. Discussion We will tailor our intervention to address key contributors to racial pain disparities and examine the effects of the intervention on important pain treatment outcomes for African Americans with chronic musculoskeletal pain. Trial registration ClinicalTrials.gov: NCT01983228. Registered 6 November 2013

Taking ACTION to reduce pain: ACTION study rationale, design and protocol of a randomized trial of a proactive telephone-based coaching intervention for chronic musculoskeletal pain among African Americans

Abstract Background Rates of chronic pain are rising sharply in the United States and worldwide. Presently, there is evidence of racial disparities in pain treatment and treatment outcomes in the United States but few interventions designed to address these disparities. There is growing consensus that chronic musculoskeletal pain is best addressed by a biopsychosocial approach that acknowledges the role of psychological and environmental factors, some of which differ by race. Methods/Design The primary aim of this randomized controlled trial is to test the effectiveness of a non-pharmacological, self-regulatory intervention, administered proactively by telephone, at improving pain outcomes and increasing walking among African American patients with hip, back and knee pain. Participants assigned to the intervention will receive a telephone counselor delivered pedometer-mediated walking intervention that incorporates action planning and motivational interviewing. The intervention will consist of 6 telephone counseling sessions over an 8–10 week period. Participants randomly assigned to Usual Care will receive an informational brochure and a pedometer. The primary outcome is chronic pain-related physical functioning, assessed at 6 months, by the revised Roland and Morris Disability Questionnaire, a measure recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). We will also examine whether the intervention improves other IMMPACT-recommended domains (pain intensity, emotional functioning, and ratings of overall improvement). Secondary objectives include examining whether the intervention reduces health care service utilization and use of opioid analgesics and whether key contributors to racial/ethnic disparities targeted by the intervention mediate improvement in chronic pain outcomes Measures will be assessed by mail and phone surveys at baseline, three months, and six months. Data analysis of primary aims will follow intent-to-treat methodology. Discussion We will tailor our intervention to address key contributors to racial pain disparities and examine the effects of the intervention on important pain treatment outcomes for African Americans with chronic musculoskeletal pain. Trial registration ClinicalTrials.gov: NCT01983228. Registered 6 November 2013

Testing implementation facilitation of a primary care-based collaborative care clinical program using a hybrid type III interrupted time series design: a study protocol

Abstract Background Dissemination of evidence-based practices that can reduce morbidity and mortality is important to combat the growing opioid overdose crisis in the USA. Research and expert consensus support reducing high-dose opioid therapy, avoiding risky opioid-benzodiazepine combination therapy, and promoting multi-modal, collaborative models of pain care. Collaborative care interventions that support primary care providers have been effective in medication tapering. We developed a patient-centered Primary Care-Integrated Pain Support (PIPS) collaborative care clinical program based on effective components of previous collaborative care interventions. Implementation facilitation, a multi-faceted and dynamic strategy involving the provision of interactive problem-solving and support during implementation of a new program, is used to support key organizational staff throughout PIPS implementation. The primary aim of this study is to evaluate the effectiveness of the implementation facilitation strategy for implementing and sustaining PIPS in the Veterans Health Administration (VHA). The secondary aim is to examine the effect of the program on key patient-level clinical outcomes—transitioning to safer regimens and enhancing access to complementary and integrative health treatments. The tertiary aim is to determine the categorical costs and ultimate budget impact of PIPS implementation. Methods This multi-site study employs an interrupted time series, hybrid type III design to evaluate the effectiveness of implementation facilitation for a collaborative care clinical program—PIPS—in primary care clinics in three geographically diverse VHA health care systems (sites). Participants include pharmacists and allied staff involved in the delivery of clinical pain management services as well as patients. Eligible patients are prescribed either an outpatient opioid prescription greater than or equal to 90 mg morphine equivalent daily dose or a combination opioid-benzodiazepine regimen. They must also have an upcoming appointment in primary care. The Consolidated Framework for Implementation Research will guide the mixed methods work across the formative evaluation phases and informs the selection of activities included in implementation facilitation. The RE-AIM framework will be used to assess Reach, Effectiveness, Adoption, Implementation, and Maintenance of PIPS. Discussion This implementation study will provide important insight into the effectiveness of implementation facilitation to enhance uptake of a collaborative care program in primary care, which targets unsafe opioid prescribing practices.https://deepblue.lib.umich.edu/bitstream/2027.42/146542/1/13012_2018_Article_838.pd

STROGAR – STrengthening the Reporting Of Genetic Association studies in Radiogenomics

AbstractDespite publication of numerous radiogenomics studies to date, positive single nucleotide polymorphism (SNP) associations have rarely been reproduced in independent validation studies. A major reason for these inconsistencies is a high number of false positive findings because no adjustments were made for multiple comparisons. It is also possible that some validation studies were false negatives due to methodological shortcomings or a failure to reproduce relevant details of the original study. Transparent reporting is needed to ensure these flaws do not hamper progress in radiogenomics. In response to the need for improving the quality of research in the area, the Radiogenomics Consortium produced an 18-item checklist for reporting radiogenomics studies. It is recognised that not all studies will have recorded all of the information included in the checklist. However, authors should report on all checklist items and acknowledge any missing information. Use of STROGAR guidelines will advance the field of radiogenomics by increasing the transparency and completeness of reporting