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131.
Defining a new diagnostic assessment parameter for wound care: Elevated protease activity,an indicator of nonhealing,for targeted protease‐modulating treatment
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Thomas E. Serena MD Breda M. Cullen PhD Simon W. Bayliff BSc Molly C. Gibson BSc Marissa J. Carter PhD Lingyun Chen PhD Raphael A. Yaakov MS John Samies MD Matthew Sabo DPM Daniel DeMarco DO Namchi Le MD James Galbraith MD 《Wound repair and regeneration》2016,24(3):589-595
It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil‐derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples (n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2–4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies. 相似文献
132.
Rakesh Awasthi Guohua An Maureen D. Donovan Laura L. Boles Ponto 《Journal of pharmaceutical sciences》2018,107(2):745-755
The medical use of marijuana is increasing, yet little is known about the exposure-response relationship for its psychoactive effects. It is well known that the plasma concentrations of the principal psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), do not directly correlate to the observed psychoactive effects. The purpose of this research was to use an effect-compartment modeling approach to predict and relate the concentrations of the psychoactive components (THC and its active metabolite) in the “hypothetical” effect-site compartment to the observed psychoactive effects. A “hypothetical” effect-compartment model was developed using literature data to characterize the observed delay in peak “highness” ratings compared with plasma concentrations of the psychoactive agents following intravenous administration of THC. A direct relationship was established between the reported psychoactive effects (“highness” or intoxication) and the predicted effect-site concentrations of THC. The differences between estimated equilibration half-lives for THC and THC-OH in the effect-compartment model indicated the differential equilibration of parent drug and the active metabolite between plasma and the effect-site. These models contribute to the understanding of the pharmacokinetic-pharmacodynamic relationships associated with marijuana use and are important steps in the prediction of pharmacodynamic effects related to the psychoactive components in marijuana. 相似文献
133.
Application of a physiologically‐based pharmacokinetic model for the prediction of bumetanide plasma and brain concentrations in the neonate
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Maria D. Donovan Khaled Abduljalil John F. Cryan Geraldine B. Boylan Brendan T. Griffin 《Biopharmaceutics & drug disposition》2018,39(3):125-134
Bumetanide is a loop diuretic that is proposed to possess a beneficial effect on disorders of the central nervous system, including neonatal seizures. Therefore, prediction of unbound bumetanide concentrations in the brain is relevant from a pharmacological prospective. A physiologically‐based pharmacokinetic (PBPK) model was developed for the prediction of bumetanide disposition in plasma and brain in adult and paediatric populations. A compound file was built for bumetanide integrating physicochemical data and in vitro data. Bumetanide concentration profiles were simulated in both plasma and brain using the Simcyp PBPK model. Simulations of plasma bumetanide concentrations were compared against plasma levels published in the literature. The model performance was verified with data from adult studies before predictions in the paediatric population were undertaken. The adult and paediatric intravenous models predicted pharmacokinetic factors, namely area under the concentration–time curve, maximum concentration in plasma and time to maximum plasma concentration, within two‐fold of observed values. However, predictions of plasma concentrations within the neonatal intravenous model did not produce a good fit with the observed values. The PBPK approach used in this study produced reasonable predictions of plasma concentrations of bumetanide, except in the critically ill neonatal population. This PBPK model requires more information regarding metabolic intrinsic clearance and transport parameters prior to further validation of drug disposition predictions in the neonatal population. Given the lack of information surrounding certain parameters in this special population, the model is not appropriately robust to support the recommendation of a suitable dose of bumetanide for use as an adjunct antiepileptic in neonates. 相似文献
134.
Samuel R. Nussbaum Marissa J. Carter Caroline E. Fife Joan DaVanzo Randall Haught Marcia Nusgart Donna Cartwright 《Value in health》2018,21(1):27-32
Objective
The aim of this study was to determine the cost of chronic wound care for Medicare beneficiaries in aggregate, by wound type and by setting.Methods
This retrospective analysis of the Medicare 5% Limited Data Set for calendar year 2014 included beneficiaries who experienced episodes of care for one or more of the following: arterial ulcers, chronic ulcers, diabetic foot ulcers, diabetic infections, pressure ulcers, skin disorders, skin infections, surgical wounds, surgical infections, traumatic wounds, venous ulcers, or venous infections. The main outcomes were the prevalence of each wound type, Medicare expenditure for each wound type and aggregate, and expenditure by type of service.Results
Nearly 15% of Medicare beneficiaries (8.2 million) had at least one type of wound or infection (not pneumonia). Surgical infections were the largest prevalence category (4.0%), followed by diabetic infections (3.4%). Total Medicare spending estimates for all wound types ranged from $28.1 to $96.8 billion. Including infection costs, the most expensive estimates were for surgical wounds ($11.7, $13.1, and $38.3 billion), followed by diabetic foot ulcers ($6.2, $6.9, and $18.7 billion,). The highest cost estimates in regard to site of service were for hospital outpatients ($9.9–$35.8 billion), followed by hospital inpatients ($5.0–$24.3 billion).Conclusions
Medicare expenditures related to wound care are far greater than previously recognized, with care occurring largely in outpatient settings. The data could be used to develop more appropriate quality measures and reimbursement models, which are needed for better health outcomes and smarter spending for this growing population. 相似文献135.
136.
Male breast cancer is a rare condition with scant research into its psychosocial impact. This phenomenologic study sought to elicit its lived experience. Following analysis of interview data, 4 key themes emerged: Living with male breast cancer, concealment as a strategy for managing the diagnosis, a contested masculinity, interacting with health services. Male breast cancer constitutes a unique lived experience for men that is unparalleled in other disease profiles. The idea of living with a feminized illness was very distressing and stigmatizing for some men. Furthermore, treatment resulted in a profound change to the concept of their embodied selves and constituted a significant change to body image and sexuality. This was reinforced in participants who experienced erectile dysfunction related to tamoxifen therapy. Sadly, some health professionals were unable to offer specific psychosocial support, and participants felt marginalized from the potential benefits of the treatment environment. However, participants adapted to the illness by reasserting and renegotiating masculinity and finding ways to accommodate life with a stigmatizing condition and an altered body image. 相似文献
137.
Vickie R. Driver Kara S. Couch Kristen A. Eckert Gary Gibbons Lorena Henderson John Lantis Eric Lullove Paul Michael Richard F. Neville Lee C. Ruotsi Robert J. Snyder Fadi Saab Marissa J. Carter 《Wound repair and regeneration》2022,30(1):7-23
In the wake of the coronavirus pandemic, the critical limb ischemia (CLI) Global Society aims to develop improved clinical guidance that will inform better care standards to reduce tissue loss and amputations during and following the new SARS-CoV-2 era. This will include developing standards of practice, improve gaps in care, and design improved research protocols to study new chronic limb-threatening ischemia treatment and diagnostic options. Following a round table discussion that identified hypotheses and suppositions the wound care community had during the SARS-CoV-2 pandemic, the CLI Global Society undertook a critical review of literature using PubMed to confirm or rebut these hypotheses, identify knowledge gaps, and analyse the findings in terms of what in wound care has changed due to the pandemic and what wound care providers need to do differently as a result of these changes. Evidence was graded using the Oxford Centre for Evidence-Based Medicine scheme. The majority of hypotheses and related suppositions were confirmed, but there is noticeable heterogeneity, so the experiences reported herein are not universal for wound care providers and centres. Moreover, the effects of the dynamic pandemic vary over time in geographic areas. Wound care will unlikely return to prepandemic practices. Importantly, Levels 2–5 evidence reveals a paradigm shift in wound care towards a hybrid telemedicine and home healthcare model to keep patients at home to minimize the number of in-person visits at clinics and hospitalizations, with the exception of severe cases such as chronic limb-threatening ischemia. The use of telemedicine and home care will likely continue and improve in the postpandemic era. 相似文献
138.
BioZorb fiducial marker is an implantable device made of six clips to mark the surgical site of tissue removal in three dimensions. The marker facilitates focused radiation therapy, while allowing for tissue ingrowth during the healing process with resorption by the body overtime. Current literature investigating the use of the BioZorb is limited and focused on its value for radiation treatment. Our objective was to investigate the feasibility and surgical complications associated with the BioZorb in breast‐conserving surgery. From April 2015 to June 2018, 89 patients who underwent 91 partial mastectomies with planned adjuvant radiation therapy and placement of the BioZorb. Demographics, type of BioZorb used, complication rate, and postoperative examinations were analyzed. A total of 89 patients who were a median age of 59 years (range 34‐84) underwent 91 operations with BioZorb placement—86.8% underwent a partial mastectomy (n = 79), and 13.2% underwent a breast wide re‐excision for margins at the time of BioZorb placement (n = 12). Of the 79 partial mastectomies, 21.5% (n = 17) were palpable tumors. Location of the tumor and subsequent BioZorb placement was most often in the upper outer quadrant (40.7%), followed by upper inner (27.5%), lower outer (20.9%), and lower inner quadrants (10.9%). 92.3% (n = 84) had a single BioZorb placed, 5.5% (n = 5) had two BioZorbs placed in a single lumpectomy cavity, and 2.2% (n = 2) had two BioZorbs placed in separate lumpectomy cavities of the same breast. Of the 10 different tissue marker sizes used, a 2 × 3 cm BioZorb was most commonly used (37/98, 37.8%), followed by 3 × 4 cm (25/98, 25.5%) and 1 × 3 × 2 (9/98, 9.2%). A total of five patients underwent immediate bilateral breast reduction following placement of the BioZorb. Of the 91 operations, 22 patients had a subsequent reoperation for positive margins after initial placement of the BioZorb, of which 86.4% retained the BioZorb . During these reoperations, only 1 patient had the BioZorb removed due to discomfort (4.5%) and two had it removed due to subsequent mastectomy (9.1%). At a median time of 1.1 years, the BioZorb continued to be palpable on clinical breast examination in 63.6% of patients. The longest time that the BioZorb continued to be palpable was 2.8 years. Additional imaging was ordered because a clinician palpated a mass, unaware it was the BioZorb 8.8% of the time (n = 8). Thirty‐day complications include 3.3% of patients with an infection requiring antibiotics (n = 3) and 2.2% with an abscess requiring aspiration and antibiotics without removal of the BioZorb. One patient had migration of the BioZorb from the breast to the axilla which resulted in surgical explant at 9 months post‐op. BioZorb is feasible to use in breast‐conserving surgery with few short‐ and long‐term complications, but will result in a palpable mass that may persist for more than 1 year. Explantation is rare. 相似文献
139.
Parinita Bhattacharjee Shajy Isac Helgar Musyoki Faran Emmanuel Kennedy Olango Samuel Kuria Martin K Ongaro Jeffrey Walimbwa Janet Musimbi Mary Mugambi Shem Kaosa Japheth Kioko Margret Njraini Memory Melon Juddie Onyoni Kigen Bartilol Marissa Becker Robert Lorway Michael Pickles Stephen Moses James Blanchard Sharmistha Mishra 《Journal of the International AIDS Society》2020,23(Z2)
140.
Adrian Barbul MD Geoffrey C. Gurtner MD Hanna Gordon PhD Katie Bakewell MS Marissa J. Carter MA PhD 《Wound repair and regeneration》2020,28(1):81-89
This retrospective, matched‐cohort study analyzed 1,556 patients with diabetic ulcers treated at 470 wound centers throughout the United States to determine the effectiveness of a cryopreserved bioactive split‐thickness skin allograft plus standard of care when compared to standard of care alone. There were 778 patients treated with the graft in the treatment cohort, who were paired with 778 patients drawn from a pool of 126,864 candidates treated with standard of care alone (controls), by using propensity matching to create nearly identical cohorts. Both cohorts received standard wound care, including surgical debridement, moist wound care, and offloading. Logistic regression analysis of healing rates according to wound size, wound location, wound duration, volume reduction, exposed deep structures, and Wagner grade was performed. Amputation rates and recidivism at 3 months, 6 months, and 1 year after wound closure were analyzed. Diabetic ulcers were 59% more likely to close in the treatment cohort compared to the control cohort (p = 0.0045). The healing rate with the graft was better than standard of care across multiple subsets, but the most significant improvement was noted in the worst wounds that had a duration of 90‐179 days prior to treatment (p = 0.0073), exposed deep structures (p = 0.036), and/or Wagner Grade 4 ulcers (p = 0.04). Furthermore, the decrease in recidivism was statistically significant at 3 months, 6 months, and 1 year, with and without initially exposed deep structures (p < 0.05). The amputation rate in the treatment cohort was 41.7% less than that of the control cohort at 20 weeks (0.9% vs. 1.5%, respectively). This study demonstrated that diabetic ulcers treated with a cryopreserved bioactive split‐thickness skin allograft were more likely to heal and remain closed compared to ulcers treated with standard of care alone. 相似文献