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John W Day Richard S Finkel Claudia A Chiriboga Anne M Connolly Thomas O Crawford Basil T Darras Susan T Iannaccone Nancy L Kuntz Loren D M Peña Perry B Shieh Edward C Smith Jennifer M Kwon Craig M Zaidman Meredith Schultz Douglas E Feltner Sitra Tauscher-Wisniewski Haojun Ouyang Deepa H Chand Jerry R Mendell 《Lancet neurology》2021,20(4):284-293
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Grant R. Williams Kathryn E. Weaver Glenn J. Lesser Emily Dressler Karen M. Winkfield Heather B. Neuman Anne E. Kazak Ruth Carlos Lucy J. Gansauer Charles S. Kamen Joseph M. Unger Supriya G. Mohile Heidi D. Klepin 《The oncologist》2020,25(12):1032-1038
BackgroundAmerican Society of Clinical Oncology guidelines recommend that patients ≥65 years of age starting chemotherapy undergo a geriatric assessment (GA) to inform and guide management; however, little is known about resources available in community oncology practices to implement these guidelines and to facilitate geriatric oncology research.Materials and MethodsOncology practices within the National Cancer Institute Community Oncology Research Program (NCORP) were electronically surveyed in 2017 regarding the availability of specialty providers, supportive services, and practice characteristics, as part of a larger survey of cancer care delivery research capacity.ResultsOf the 943 NCORP practices, 504 (54%) responded to the survey, representing 210 practice groups. The median new cancer cases per year ≥65 years of age was 457 (interquartile range 227–939). Of respondents, only 2.0% of practices had a fellowship‐trained geriatric oncologist on staff. Geriatricians were available for consultation or comanagement at 37% of sites, and of those, only 13% had availability within the oncology clinic (5% of overall). Practice size of ≥1,000 new adult cancer cases (ages ≥18) per year was associated with higher odds (1.81, confidence interval 1.02–3.23) of geriatrician availability. Other multidisciplinary care professionals that could support GA were variably available onsite: social worker (84%), nurse navigator (81%), pharmacist (77%), dietician (71%), rehabilitative medicine (57%), psychologist (42%), and psychiatrist (37%).ConclusionOnly a third of community oncology practices have access to a geriatrician within their group and only 5% of community sites have access within the oncology clinic. Use of primarily self‐administered GA tools that direct referrals to available services may be an effective implementation strategy for guideline‐based care.Implications for PracticeOnly a minority of community oncology practices in the U.S. have access to geriatric specialty care. Developing models of care that use patient‐reported measures and/or other geriatric screening tools to assess and guide interventions in older adults, rather than geriatric consultations, are likely the most practical methods to improve the care of this vulnerable population. 相似文献
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Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for BrafV600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (TyrCreERT2/+; BrafLSL‐V600E/+; Ptenflox/flox) to Sirt5?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor. 相似文献
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Jerry R. Paugh Alba Alfonso-Garcia Andrew Loc Nguyen Jeffrey L. Suhalim Marjan Farid Sumit Garg Jeremiah Tao Donald J. Brown Eric O. Potma James V. Jester 《The ocular surface》2019,17(1):151-159
Purpose
This study examined whether hyperspectral stimulated Raman scattering (hsSRS) microscopy can detect differences in meibum lipid to protein composition of normal and evaporative dry eye subjects with meibomian gland dysfunction.Methods
Subjects were evaluated for tear breakup time (TBUT), staining, meibum expression and gland dropout. Expressed meibum was analyzed using SRS vibrational signatures in the CH stretching region (2800–3050?cm?1). Vertex component analysis and K-means clustering were used to group the spectral signatures into four fractions containing high lipid (G1) to high protein (G4).Results
Thirty-three subjects could be statistically analyzed using pooled meibum (13 with stable tear films (TBUTs?>?10?s) and 20 with unstable tear films (TBUTs?≤?10?s). Significant differences in meibum from subjects with unstable vs. stable TBUTs were found for the G1 fraction (medians 0.164 and 0.020, respectively; p?=?0.012) and the G2 fraction (medians 0.244 and 0.272, respectively; p?=?0.045). No differences were observed for the G3 and G4 fractions. Single orifice samples were not significantly different vs. pooled samples from the fellow eye, and eyelid sector samples (nasal, central and temporal) G2:G3 fractional components were not significantly different (p?=?0.449). Spearman analysis suggested a significant inverse correlation between G1 fraction and TBUT (R?=??0.351; p?=?0.045).Conclusions
hsSRS microscopy allows compositional analysis of expressed meibum from humans which correlated to changes in TBUT. These findings support the hypothesis that hsSRS may be useful in classifying meibum quality and evaluating the effects of therapy. 相似文献8.
Steven D. Criss Davis T. Weaver Deirdre F. Sheehan Richard J. Lee Pari V. Pandharipande Chung Yin Kong 《Urologic oncology》2019,37(3):180.e11-180.e18
Purpose
Our purpose was to evaluate the effect of PD-L1 testing on the cost-effectiveness of pembrolizumab for second-line treatment of advanced urothelial carcinoma in the bladder from the U.S. societal perspective.Materials and methods
We developed a microsimulation model to compare 3 treatment strategies: (1) treat all patients with standard-of-care chemotherapy, (2) treat all patients with pembrolizumab, and (3) treat patients with PD-L1-positive tumors at a ≥1% expression threshold with pembrolizumab, and all others with standard-of-care chemotherapy. Additionally, we performed a budget impact analysis based on the projected number of urothelial carcinoma patients eligible for second-line pembrolizumab treatment.Results
Treating all patients with chemotherapy resulted in a mean cost of $17,232 and mean effect of 0.43 quality-adjusted life-years. The PD-L1 test strategy was the most efficient strategy, with an incremental cost-effectiveness ratio of $122,933/quality-adjusted life-year. Treating all patients with pembrolizumab resulted in an incremental cost-effectiveness ratio of $197,383/quality-adjusted life-year compared to the PD-L1 test strategy. The PD-L1 test strategy would produce an incremental budget impact of $14.9 million in the first year of use compared to chemotherapy, increasing to $16.5 million in the fifth year of use. Treating all patients with pembrolizumab would produce an incremental budget impact of $19.6 million compared to the PD-L1 test strategy in its first year of use, increasing to $20.9 million by year 5.Conclusions
Pembrolizumab was not cost-effective in either strategy based on a $100,000/quality-adjusted life-year willingness-to-pay threshold. Using PD-L1 testing to select for patients who may have better associated outcomes may improve the affordability of pembrolizumab. 相似文献9.
Devin R. Halleran Alejandra Vilanova-Sanchez Rebecca M. Rentea Mana H. Vriesman Tassiana Maloof Peter L. Lu Amanda Onwuka Laura Weaver Karla KH Vaz Desale Yacob Carlo Di Lorenzo Marc A. Levitt Richard J. Wood 《Journal of pediatric surgery》2019,54(1):123-128
Background
Appendicostomy and cecostomy are two approaches for antegrade enema access for children with severe constipation or fecal incontinence as adjuncts to a mechanical bowel management program. Each technique is associated with a unique set of complications. The purpose of our study was to report the rates of various complications associated with antegrade enema access techniques to help guide which option a clinician offers to their patients.Methods
We reviewed all patients in our Center who received an appendicostomy or cecostomy from 2014 to 2017 who were participants in our bowel management program.Results
204 patients underwent an antegrade access procedure (150 appendicostomies and 54 cecostomies). Skin-level leakage (3% vs. 22%) and wound infections (7% vs. 28%) occurred less frequently in patients with appendicostomy compared to cecostomy. Nineteen (13%) appendicostomies required revision for stenosis, 4 (3%) for mucosal prolapse, and 1 (1%) for leakage. The rates of stenosis (33 vs. 12%) and wound infection (13 vs. 6%) were higher in patients who received a neoappendicostomy compared to an in situ appendicostomy. Intervention was needed in 19 (35%) cecostomy patients, 15 (28%) for an inability to flush or a dislodged tube, and 5 for major complications including intraperitoneal spillage in 4 (7%) and 1 (2%) for a tube misplaced in the ileum, all occurring in patients with a percutaneously placed cecostomy. One appendicostomy (1%) patient required laparoscopic revision after the appendicostomy detached from the skin.Conclusion
Patients had a lower rate of minor and major complications after appendicostomy compared to cecostomy. The unique complication profile of each technique should be considered for patients needing these procedures as an adjunct to their care for constipation or fecal incontinence.Type of study
Retrospective comparative study.Level of evidence
Level III. 相似文献10.
Farah Ladak Jerry T. Dang Noah J. Switzer Valentin Mocanu Daniel W. Birch Shahzeer Karmali 《Surgery for obesity and related diseases》2019,15(3):431-440
BackgroundComplications arising from laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are not insignificant and can necessitate additional invasive interventions or reoperations.ObjectivesIn this study, we identify early complications that result in nonoperative and operative interventions after LSG and LRYGB, the timeframe within which to expect them, and factors that influence the likelihood of their occurrence.SettingMulti-institutional database from across North America.MethodsData for this study were obtained from Metabolic and Bariatric Accreditation and Quality Improvement Program participant use files for 2015 and 2016. Statistical analysis was performed using STATA 15. Univariate analysis using Χ2 for categoric data and independent t test for continuous data was performed to determine between group differences. Multivariable logistic regression analysis was used to identify predictors of operative and nonoperative reinterventions.ResultsIn 2015 and 2016, 243,747 underwent LRYGB or LSG, of which 3013 (1.24%) required a second operative procedure and 1536 (0.63%) required an invasive but nonoperative intervention. Complications occurred in 5.48% of LRYGB patients and 2.28% of LSG patients, the most common of which was bleeding. LSG was associated with far fewer nonoperative and operative interventions (.85% versus 2.2%, respectively) than LRYGB (.67% versus 2.5%). Renal insufficiency, including dialysis dependency, was an important predictor of reoperations among bariatric surgery patients. This was also true of nonoperative interventions; however, history of pulmonary embolism, and use of therapeutic anticoagulation were marginally stronger predictors.ConclusionsIn a representative, multinational sample, operative and nonoperative interventions were half as likely among LSG patients compared with LRYGB; however, overall rates still remained low. These findings, in conjunction with new efficacy data demonstrating comparable long-term weight loss between LRYGB and LSG, provide further support for the safety, effectiveness, and cost efficiency of LSG. 相似文献