2,169 research outputs found

    Values of sleep/wake, activity/rest, circadian rhythms, and fatigue prior to adjuvant breast cancer chemotherapy.

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    Fatigue is the most prevalent and distressing symptom experienced by patients receiving adjuvant chemotherapy for early stage breast cancer. Higher fatigue levels have been related to sleep maintenance problems and low daytime activity in patients who have received chemotherapy, but knowledge describing these relationships prior to chemotherapy is sparse. The Piper Integrated Fatigue Model guided this study, which describes sleep/wake, activity/rest, circadian rhythms, and fatigue and how they interrelate in women with Stage I, II, or IIIA breast cancer during the 48 hours prior to the first adjuvant chemotherapy treatment. The present report describes these variables in 130 females, mean age=51.4 years; the majority were married and employed. Subjective sleep was measured by the Pittsburgh Sleep Quality Index and fatigue was measured by the Piper Fatigue Scale. Wrist actigraphy was used to objectively measure sleep/wake, activity/rest, and circadian rhythms. Mean Pittsburgh Sleep Quality Index score was 6.73+/-3.4, indicating poor sleep. Objective sleep/wake results were within normal limits established for healthy individuals, except for the number and length of night awakenings. Objective activity/rest results were within normal limits except for low mean daytime activity. Circadian rhythm mesor was 132.3 (24.6) and amplitude was 97.2 (22.8). Mean Piper Fatigue Scale score was 2.56+/-2, with 72% reporting mild fatigue. There were significant relationships between subjective and objective sleep, but no consistent patterns. Higher total and subscale fatigue scores were correlated with most components of poorer subjective sleep quality (r=0.25-0.42, P\u3c or =0.005)

    Update on Transanal NOTES for Rectal Cancer: Transitioning to Human Trials

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    The feasibility of natural orifice translumenal endoscopic surgery (NOTES) resection for rectal cancer has been demonstrated in both survival swine and fresh human cadaveric models. In preparation for transitioning to human application, our group has performed transanal NOTES rectal resection in a large series of human cadavers. This experience both solidified the feasibility of resection and allowed optimization of technique prior to clinical application. Improvement in specimen length and operative time was demonstrated with increased experience and newer platforms. This extensive laboratory experience has paved the way for successful clinical translation resulting in an ongoing clinical trial. To date, based on published reports, 4 human subjects have undergone successful hybrid transanal NOTES resection of rectal cancer. While promising, instrument limitations continue to hinder a pure transanal approach. Careful patient selection and continued development of new endoscopic and flexible-tip instruments are imperative prior to pure NOTES clinical application

    Enhanced neuroinflammation and pain hypersensitivity after peripheral nerve injury in rats expressing mutated superoxide dismutase 1

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    <p>Abstract</p> <p>Background</p> <p>Neuroinflammation and nitroxidative stress are implicated in the pathophysiology of neuropathic pain. In view of both processes, microglial and astroglial activation in the spinal dorsal horn play a predominant role. The present study investigated the severity of neuropathic pain and the degree of glial activation in an inflammatory- and nitroxidative-prone animal model.</p> <p>Methods</p> <p>Transgenic rats expressing mutated superoxide dismutase 1 (hSOD1<sup>G93A</sup>) are classically used as a model for amyotrophic lateral sclerosis (ALS). Because of the associated inflammatory- and nitroxidative-prone properties, this model was used to study thermal and mechanical hypersensitivity following partial sciatic nerve ligation (PSNL). Next to pain hypersensitivity assessment, microglial and astroglial activation states were moreover characterized, as well as inflammatory marker gene expression and the glutamate clearance system.</p> <p>Results</p> <p>PSNL induced thermal and mechanical hypersensitivity in both wild-type (WT) and transgenic rats. However, the degree of thermal hypersensitivity was found to be exacerbated in transgenic rats while mechanical hypersensitivity was only slightly and not significantly increased. Microglial Iba1 expression was found to be increased in the ipsilateral dorsal horn of the lumbar spinal cord after PSNL but such Iba1 up-regulation was enhanced in transgenic rats as compared WT rats, both at 3 days and at 21 days after injury. Moreover, mRNA levels of Nox2, a key enzyme in microglial activation, but also of pro-inflammatory markers (IL-1β and TLR4) were not modified in WT ligated rats at 21 days after PSNL as compared to WT sham group while transgenic ligated rats showed up-regulated gene expression of these 3 targets. On the other hand, the PSNL-induced increase in GFAP immunoreactivity spreading that was evidenced in WT rats was unexpectedly found to be attenuated in transgenic ligated rats. Finally, GLT-1 gene expression and uptake activity were shown to be similar between WT sham and WT ligated rats at 21 days after injury, while both parameters were significantly increased in the ipsilateral dorsal region of the lumbar spinal cord of hSOD1<sup>G93A </sup>rats.</p> <p>Conclusions</p> <p>Taken together, our findings show that exacerbated microglial activation and subsequent inflammatory and nitroxidative processes are associated with the severity of neuropathic pain symptoms.</p

    Recycling Industrial Sites in Erie County: Meeting the Challenge of Brownfield Redevelopment

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    This is an updated version of a report originally released in May, 1994, which was prepared in cooperation with Richard M. Tobe, Erie County Commissioner of Environment and Planning. The authors were members of the Spring, 1994 Environment and Development seminar. This updated version is still in the form of a report. A fuller historical and analytical treatment of many of the issues presented here can be found in the forthcoming article, Comment, Urban Decay and the Role of Superfund: Legal Barriers to Redevelopment and the Prospects for Change, 43 BuFF.L.RBv. _ (1995), written by Julia A. Solo, one of the authors of this report. We want to acknowledge substantial contributions made to this report by earlier drafts of that article. We received many helpful comments on drafts of the original report and particularly wish to thank Barry Boyer, Peter Pitegoff, John Sheffer and Rich Tobe

    Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice

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    Background The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs). A tool to identify high-risk patients is needed to support healthcare providers in handling automatically generated alerts in clinical practice. The main aim of this study was to develop and validate a tool to assess the risk of QT-DDIs in clinical practice. Methods A model was developed based on risk factors associated with QTc-prolongation determined in a prospective study on QT-DDIs in a university medical center inthe Netherlands. The main outcome measure was QTc-prolongation defined as a QTc interval > 450 ms for males and > 470 ms for females. Risk points were assigned to risk factors based on their odds ratios. Additional risk factors were added based on a literature review. The ability of the model to predict QTc-prolongation was validated in an independent dataset obtained from a general teaching hospital against QTc-prolongation as measured by an ECG as the gold standard. Sensitivities, specificities, false omission rates, accuracy and Youden's index were calculated. Results The model included age, gender, cardiac comorbidities, hypertension, diabetes mellitus, renal function, potassium levels, loop diuretics, and QTc-prolonging drugs as risk factors. Application of the model to the independent dataset resulted in an area under the ROC-curve of 0.54 (95% CI 0.51-0.56) when QTc-prolongation was defined as > 450/470 ms, and 0.59 (0.54-0.63) when QTc-prolongation was defined as > 500 ms. A cut-off value of 6 led to a sensitivity of 76.6 and 83.9% and a specificity of 28.5 and 27.5% respectively. Conclusions A clinical decision support tool with fair performance characteristics was developed. Optimization of this tool may aid in assessing the risk associated with QT-DDIs.Clinical Pharmacy and Toxicolog

    MsrR contributes to cell surface characteristics and virulence in Staphylococcus aureus

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    MsrR, a factor contributing to methicillin resistance in Staphylococcus aureus, belongs to the LytR-CpsA-Psr family of cell envelope-associated proteins. Deletion of msrR increased cell size and aggregation, and altered envelope properties, leading to a temporary reduction in cell surface hydrophobicity, diminished colony-spreading ability, and an increased susceptibility to Congo red. The reduced phosphorus content of purified cell walls of the msrR mutant suggested a reduction in wall teichoic acids, which may explain some of the observed phenotypes. Microarray analysis of the msrR deletion mutant revealed only minor changes in the global transcriptome, suggesting that MsrR has structural rather than regulatory functions. Importantly, virulence of the msrR mutant was decreased in a nematode-killing assay as well as in rat experimental endocarditis. MsrR is therefore likely to play a role in cell envelope maintenance, cell separation, and pathogenicity of S. aureu

    Comparison of two algorithms to support medication surveillance for drug-drug interactions between QTc-prolonging drugs

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    Background: QTc-prolongation is an independent risk factor for developing life-threatening arrhythmias. Risk management of drug-induced QTc-prolongation is complex and digital support tools could be of assistance. Bindraban et al. and Berger et al. developed two algorithms to identify patients at risk for QTc-prolongation. Objective: The main aim of this study was to compare the performances of these algorithms for managing QTcprolonging drug-drug interactions (QT-DDIs). Materials and Methods: A retrospective data analysis was performed. A dataset was created from QT-DDI alerts generated for inand outpatients at a general teaching hospital between November 2016 and March 2018. ECGs recorded within 7 days of the QT-DDI alert were collected. Main outcomes were the performance characteristics of both algorithms. QTc-intervals of > 500 ms on the first ECG after the alert were taken as outcome parameter, to which the performances were compared. Secondary outcome was the distribution of risk scores in the study cohort. Results: In total, 10,870 QT-DDI alerts of 4987 patients were included. ECGs were recorded in 26.2 % of the QT-DDI alerts. Application of the algorithms resulted in area under the ROC-curves of 0.81 (95 % CI 0.79-0.84) for Bindraban et al. and 0.73 (0.70-0.75) for Berger et al. Cut-off values of >= 3 and >= 6 led to sensitivities of 85.7 % and 89.1 %, and specificities of 60.8 % and 44.3 % respectively. Conclusions: Both algorithms showed good discriminative abilities to identify patients at risk for QTcprolongation when using >= 2 QTc-prolonging drugs. Implementation of digital algorithms in clinical decision support systems could support the risk management of QT-DDIs

    Diversity among Equals: Educational Opportunity and the State of Affirmative Admissions in New England

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    This report reviews the practice of Affirmative Admissions as a strategy for achieving diversity within New England colleges and universities. It shows how educational leaders perceive Affirmative Admissions, the nature of regional Affirmative Admissions policies, and the numbers of student affected by current enrollment strategies. This report is part of a larger series on educational access and opportunity in New England. Research was organized into five components: (1) analysis of pertinent legal issues related to postsecondary access and equity; (2) interviews with postsecondary campus and state leaders (n=104); (3) interviews with K-12 leaders and educators at state, district, and school levels (n=45); (4) a survey of 221 postsecondary education institutions in New England; and (5) econometric analyses of student data. The focus was on groups of institutions, 18 groups clustered by admissions policies and restrictions. The most compelling conclusion is that there is no significant evidence that colleges have reduced standards to admit greater numbers of minority students. By increasing educational access to a broader segment of the population, the regions higher education institutions have taken crucial steps toward assuring the vitality and vibrancy of New Englands future economy and civic life. The study also indicates that the pool of qualified minority students is much too small, highlighting the need to improve the preparation of minority students. Three appendixes contain details about survey methodology, participating institutions, and regression coefficients. Prepared by the Center for Education Policy (CEP) and Massachusetts Institute for Social and Economic Research (MISER), University of Massachusetts at Amherst. Sponsored by the Nellie Mae Education Foundation

    Initiation of a critical pathway for pancreaticoduodenectomy at an academic institution -- the first step in multi-disciplinary team building

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    Objective: This study was designed to identify quantifiable parameters to track performance improvements brought about by the implementation of a critical pathway for complex alimentary tract surgery. Background: Pancreaticoduodenectomy (PD) is a complex general surgical procedure performed in varying numbers at many academic institutions. Originally associated with significant perioperative morbidity and mortality, multiple studies have now shown that this operation can be performed quite safely at high volume institutions that develop a particular expertise. Critical pathways are one of the key tools used to achieve consistently excellent outcomes as these institutions. It remains to be determined if implementation of a critical pathway at an academic institution with prior moderate experience with PD will result in performance gains and improved outcomes. Methods: Between January 1, 2004 and October 15, 2006 135 patients underwent PD, 44 before the implementation of a critical pathway on October 15, 2005, and 91 after. Perioperative and postoperative parameters were analyzed retrospectively to identify those that could be used to track performance improvement and outcomes. Key aspects of the pathway include spending the night of surgery in the intensive care unit with careful attention to fluid balance, early mobilization on post-operative day one, aggressive early removal of encumbrances such as nasogastric tubes and urinary catheters, early post-operative feeding, and targeting discharge for postoperative day 6 or 7. Results: The pre- and post-pathway implementation groups were not statistically different with regards to age, sex, race, or pathology (malignant versus benign). Perioperative mortality, operative blood loss, and number of transfused units of packed red blood cells were also similar. As compared to the pre-pathway group, the post-pathway group had a significantly shorter postoperative length of stay (13 versus 7 days, P ≤ 0.0001), operative time (435 ± 14 minutes versus 379 ± 12 minutes, P ≤ 0.0001), and in room non-operative time (95 ± 4 minutes versus 76 ± 2 minutes, P ≤ 0.0001). Total hospital charges were significantly reduced from 240,242±240,242 ± 32,490 versus 126,566±126,566 ± 4883 (P ≤ 0.0001) after pathway implementation. Postoperative complication rates remained constant (44% pre-pathway versus 37% after, P = NS). Readmission rates were not negatively affected by the reduction in length of stay, with a 7% readmission rate prior to implementation and a 7.7% rate after implementation. Conclusion: Implementation of a critical pathway for a complex procedure can be demonstrated to improve short-term outcomes at an academic institution. This improvement can be quantified and tracked and has implications for better utilization of resources (greater OR and hospital bed availability) and overall cost containment. With a very conservative estimate of 75 pancreaticoduodenectomies per year by this group, this translates to a savings of 450 hospital days and over $8,550,000 in hospital charges on an annual basis. As we enter the pay for performance era, institutions will be required to generate such data in order to retain patient volumes, attract new patients, and receive incentive payments for high quality services rendered
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