tbuckley/cabot-search huggingface dataset:
Development of the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial Protocol
Authors: Karl Y. Bilimoria, Jeanette W. Chung, Larry V. Hedges, Allison R. Dahlke, Remi Love, Mark E. Cohen, John Tarpley, John Mellinger, David M. Mahvi, Rachel R. Kelz, Clifford Y. Ko, David B. Hoyt, Frank H. Lewis
Journal: JAMA Surgery (2015)

Debate continues regarding whether to further restrict resident duty hour policies, but little high-level evidence is available to guide policy changes.To inform decision making regarding duty hour policies, the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) Trial is being conducted to evaluate whether changing resident duty hour policies to permit greater flexibility in work hours affects patient postoperative outcomes, resident education, and resident well-being.Pragmatic noninferiority cluster-randomized trial of general surgery residency programs with 2 study arms. Participating in the study are Accreditation Council for Graduate Medical Education (ACGME)-approved US general surgery residency programs (n = 118), their affiliated hospitals (n = 154), surgical residents and program directors, and general surgery patients from July 1, 2014, to June 30, 2015, with additional patient safety outcomes collected through June 30, 2016. The data collection platform for patient outcomes is the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), thus only hospitals participating in the ACS NSQIP were included.In the usual care arm, programs adhered to current ACGME resident duty hour standards. In the intervention arm, programs were allowed to deviate from current standards regarding maximum shift lengths and minimum time off between shifts through an ACGME waiver.Death or serious morbidity within 30 days of surgery measured through ACS NSQIP, as well as resident satisfaction and well-being measured through a survey delivered at the time of the 2015 American Board of Surgery in Training Examination (ABSITE).A total of 118 general surgery residency programs and 154 hospitals were enrolled in the FIRST Trial and randomized. Fifty-nine programs (73 hospitals) were randomized to the usual care arm and 59 programs (81 hospitals) were randomized to the intervention arm. Intent-to-treat analysis will be used to estimate the effectiveness of assignment to the intervention arm on patient outcomes, resident education, and resident well-being compared with the usual care arm. Several sensitivity analyses will be performed to determine whether there were differential effects when examining only inpatients, high-risk patients, and emergent/urgent cases.To our knowledge, the FIRST Trial is the first national randomized clinical trial of duty hour policies. Results of this study may be informative to policymakers and other stakeholders engaged in restructuring graduate medical training to enhance the quality of patient care and resident education.clinicaltrials.org Identifier: NCT02050789.
Local/regional recurrence following surgery for early-stage lung cancer: A 10-year experience with 975 patients
Authors: C. R. Kelsey, J. A. Boyd, J. L. Hubbs, D. R. Hollis, J. Crawford, N. E. Ready, T. A. D’Amcio, D. H. Harpole, J. Garst, L. B. Marks
Journal: Journal of Clinical Oncology (2008)

7542 Background: Surgery, with or without chemotherapy, is the preferred treatment for early-stage NSCLC. The risk of local/regional recurrence (LRR) after resection is not well defined, but generally considered to be small in comparison to the risk of distant recurrence. We herein evaluate the actuarial risk of LRR after surgery for stage I-II disease and assess surgical and pathologic factors affecting this risk. Methods: The medical records and pertinent radiographs of all patients who underwent surgery for pathological T1- 2N0–1 NSCLC at Duke between 1995–2005 were reviewed. Patients receiving preoperative therapy, or with synchronous/prior lung cancers were excluded. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered a LRR. Nodal failures were defined as a new or enlarging LN≥1 cm on short axis on CT or hypermetabolic on PET. The actuarial rates of LRR and distant recurrence (assessed independently) were estimated using the Kaplan-Meier method. A univariate and multivariate regression analysis assessed factors associated with LRR. Results: Of 975 patients, 45% were stage IA, 40% IB, and 15% stage II; 79% underwent ≥ lobectomy; 85% had sampling/dissection of mediastinal LNs; 4% had positive margins; 7% received adjuvant chemotherapy; 3% received adjuvant radiation therapy. The 5-year actuarial rate of LRR was 22% and distant recurrence was 31%. LRR was higher for stage IB, IIA, and IIB compared with IA (hazard ratio- 2, 2.6, and 1.9). Sublobar resections were associated with a higher risk of LRR on univariate, but not multivariate, analysis. On multivariate analysis, increasing size, squamous or large cell histology, visceral pleural invasion, stage IIA disease, and lack of nodal sampling were independently associated with a higher rate of LRR. Conclusions: The risk of LRR after surgery for stage I-II NSCLC is ≈22%, and is similar to the risk of distant recurrence. Thus, local control remains an important issue justifying continued clinical research in this area. Postoperative RT, utilizing modest doses and small conformal fields directed to sites most at risk, should be reevaluated. As systemic therapy improves, the relative importance of achieving local control will also increase. No significant financial relationships to disclose.
A phase II, non-randomized study of abraxane plus carboplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancer: Evaluation of side effects and tolerability
Authors: A. Al Housseini, P. Daugherty, M. Sofidiya, M. Burrell, J. Boverie, B. Benigno
Journal: Journal of Clinical Oncology (2008)

16556 Background: Paclitaxel and carboplatin are currently used as a standard therapy for recurrent platinum-sensitive ovarian cancer. However Paclitaxel is solubilized in cremophor which is responsible for some paclitaxel associated hypersensitivity. Abraxane is a Cremophor EL-free, albumin-bound nanoparticle paclitaxel developed to reduce the toxicities associated with Cremophor. This study was designed to evaluate the efficacy and safety of Abraxane for the treatment of recurrent ovarian cancer. Methods: Patients with recurrent platinum-sensitive ovarian or primary peritoneal carcinoma with Measurable Disease to receive Abraxane: 100 mg/m2: day 1, 8, 15, and Carboplatin AUC 5 day 1 every 28 days intravenously for 6 cycles. Response rate and safety will be assessed. 22 patients enrolled. Results: 19 patients completed 6 cycles of chemotherapy with partial or complete response. No hypersensitivity reaction was reported. 4 cases of more than Grade 3 neutropenia were found and 2 cases of more than grade 3 thrombocytopenia and 4 cases needed blood transfusion. 3 patients did not complete the 6 six cycles because of Carboplatin toxicity, severe thrombocytopenia, and progression of the disease respectively. Conclusions: Abraxane could be used to prevent paclitaxel hypersesitivity reaction HSR. No significant financial relationships to disclose.
Induction of potent systemic anti-melanoma immunity through intratumoral CD40 activation and checkpoint blockade
Authors: Manisha Singh, Zhimin Dai, Hiep Khong, Christina Vianden, Mark Cantwell, Willem Overwijk
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Agonistic CD40 antibodies generate strong tumor specific CD8 T cell response and anti-tumor activity; however systemic anti-CD40 therapy has been associated with cytokine release syndrome and liver toxicity. We studied the anti-melanoma activity and mechanism of action of a
THE SECRET NOSTRUM EVIL.
Authors: FRANK BILLINGS
Journal: JAMA (1905)

I shall make no apology for bringing this subject before this Section. Its importance to the profession of medicine and to the public justifies an exposition of the evil now. In no other country has this menace to the welfare of the people and to the best interests of scientific medicine developed as it has with us. Probably the reason is that other countries, with one or two exceptions, protect the people against frauds in foods, medicines, etc. Some day it is to be hoped that the Congress of the United States will enact a national pure food law which shall include the regulation of the copyrighting and exploitation of proprietary and other medicines. Just here it will be well to say that the term "proprietary medicine" does not necessarily stamp a preparation or remedy as a nostrum. Webster says that a nostrum is "a medicine, the ingredients of which
BrainSeq: Neurogenomics to Drive Novel Target Discovery for Neuropsychiatric Disorders
Authors: Christian R. Schubert, Patricio O’Donnell, Jie Quan, Jens R. Wendland, Hualin S. Xi, Ashley R. Winslow, Enrico Domenici, Laurent Essioux, Tony Kam-Thong, David C. Airey, John N. Calley, David A. Collier, Hong Wang, Brian Eastwood, Philip Ebert, Yushi Liu, Laura Nisenbaum, Cara Ruble, James E. Scherschel, Ryan Matthew Smith, Hui-Rong Qian, Kalpana Merchant, Michael Didriksen, Mitsuyuki Matsumoto, Takeshi Saito, Nicholas J. Brandon, Alan J. Cross, Qi Wang, Husseini Manji, Hartmuth Kolb, Maura Furey, Wayne C. Drevets, Joo Heon Shin, Andrew E. Jaffe, Yankai Jia, Richard E. Straub, Amy Deep-Soboslay, Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger
Journal: Neuron (2015)
Future of Kerala depends on its willingness to learn from past [letter]
Authors: Nair Vm
Journal: BMJ (2004)

The Kerala model in health cited by Bhutta et al in the theme issue on health in South Asia as replicable for South Asian countries is facing serious threats. The state has a triple burden of communicable non-communicable and traumatic diseases. Stupendous growth of the private sector has resulted in skyrocketing healthcare costs. Lured by the hi tech sophistication of the private sector people are abandoning basic principles of primary health care. Even poor people prefer private hospitals and a major reason for sustaining poverty is healthcare cost. The government is reducing its investments in health and education due to fiscal crises and pressure from funding and lending agencies. The opening up of the medical education sector to private entrepreneurs lack of guidelines for the private practice of government doctors and shortage of doctors for rural areas are all disturbing developments. Transfer of healthcare institutions under local self-governments is yet to show the desired benefits.  (excerpt)
Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver.
Authors: H R Alexander, D L Bartlett, S K Libutti, D L Fraker, T Moser, S A Rosenberg
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the efficacy and systemic and regional toxicities of hyperthermic isolated hepatic perfusion (IHP) using tumor necrosis factor (TNF) and melphalan for the treatment of unresectable primary or metastatic cancers confined to the liver. PATIENTS AND METHODS Thirty-four patients (18 men and 16 women; mean age, 49 years) underwent a 60-minute hyperthermic (39.5 degrees to 40.0 degrees C) IHP performed by laparotomy that used TNF 1.0 mg and melphalan 1.5 mg/kg. Perfusion inflow was through the gastroduodenal artery and outflow was from a cannula positioned in an isolated segment of retrohepatic inferior vena cava (IVC). Infrahepatic IVC and portal venous blood flow were shunted to the axillary vein using an external venoveno bypass circuit. Complete vascular isolation of the liver was confirmed by an I-131-labelled human serum albumin monitoring technique. RESULTS There was no operative mortality. Seventy-five percent of patients had reversible grade III or IV (National Cancer Institute Common Toxicity Criteria) hepatic toxicity with one treatment-related mortality (3%) because of hepatic venoocclusive disease. In 33 assessable patients, the overall response rate was 75% (complete response, one patient [3%]; partial response, 26 patients [72%]). With a median potential follow-up of 15 months, the mean duration of response was 9 months (range, 2 to 30 months). CONCLUSION IHP with TNF and melphalan results in significant regression of bulky hepatic cancers confined to the liver in the majority of patients. Based on these initial results, further refinement of this treatment technique is warranted; perhaps by the combination of IHP with other regional treatment strategies to provide long-term control of unresectable cancers confined to liver.
A PET imaging study of the vascular disruptive agent OXi4503 to confirm in vivo mechanism of action in a phase I trial
Authors: P. M. Price, M. Asselin, B. Koetz, C. Dickinson, N. Charnley, P. Lorigan, J. Valle, M. Stratford, G. Rustin, A. Saleem
Journal: Journal of Clinical Oncology (2009)

e14510 Background: OXi4500, the active product of OXi4503, reversibly binds at the colchicine binding site on the ß subunit of tubulin. This study investigated its mechanism of action using PET molecular imaging Methods: OXi4503 was administered by 3 weekly IV infusions in a phase 1 trial (32 pts). Between 1.6 &amp; 15.4 mg/m 2 dose levels, PET imaging was performed with 15 O-labelled water (measuring blood perfusion) pretreatment &amp; at 90min &amp; 24hr after first infusion (8pts) &amp; at 28days (1 pt). [ 18 F]fluorodeoxyglucose (FDG) (measuring proliferative activity) was performed pretreatment &amp; at 28 days (9pts) Results: 9 pts (mean age 48.5yrs) were studied: CRC (2), pancreatic (1), MM (6). 2 pts with MM (3.8 &amp; 6.5 mg/m 2 ) achieved stable disease. Toxicity included pyrexia, lethargy &amp; hypertension. There was a dose-dependent linear increase in peak plasma concentrations &amp; AUC of OXi4503 &amp; OXi4500. Sustained tumour blood perfusion reduction (50% at 90min &amp; 24hr) was seen in all metastases in the CRC pt treated at 15.4 mg/m 2 after just one dose &amp; resulted in FDG reduction (23% in all 5 mets) &amp; tumor marker response. Doses between 1.9 &amp; 11.0 mg/m 2 produced dose independent reductions in tumour perfusion which were more variable &amp; less marked with 3/8 pts showing a reduction in tumour FDG uptake. The 1pt studied at 28 days (8.5 g/m 2 ) showed further sustained reduction in tumour blood flow (40%). Variable dose independent changes in normal tissue perfusion were seen at all dose levels eg in 3/4 pt splenic perfusion showed a dose-independent decrease (20–30%) at 90min with recovery at 24hr Conclusions: OXi4503 shows significant activity at 15.4 mg/m 2 in line with its proposed mechanism of action. Characterisation of the mixed tumour perfusion response at lower doses will aid planning &amp; assessing combination studies. The MTD is now being identified. Sponsored by CRUK. [Table: see text]
Health related quality of life and sense of coherence in adolescents with asthma
Authors: Kerstin Sundell Bergström, Sten-Erik Bergström, Gunilla Hedlin, Alf Tunsäter
Journal: European Respiratory Journal (2011)

Aim: To prospectively study adolescents with asthma in transition from child to adult with respect to Health Related quality of life “HRQOL” and Sense of Coherence “SOC”.

Method: Teenagers with asthma (n=156) were screened employing spirometry, bronchial challenge, skin prick test and exercise test at the time of referral and after five years. They completed the “Living with Asthma Questionnaire” and the Sense of Coherence “SOC” instrument. Patients with mild-to-moderate asthma were assigned randomly to an adult asthma clinic or to primary care.

Results: At both time-points the HRQOL of the men was better than that of the women (p<0.001). HRQOL improved for both men and women. Lung function, atopy, bronchial hyper-responsiveness did not exert any impact on HRQOL or SOC. However poor adherence to the recommended asthma treatment was associated with lower HRQOL (OR= 0.29; 95% CI= 0.11-0.73; P<0.01). Young women who exercised regularly exhibited better HRQOL than those who did not (p<0.001). Only women with severe asthma demonstrated a poorer HRQOL. Over the five year period the men showed a significant stronger SOC compared to the women (p<0.05). Lung function and HRQOL remain stable regardless of the randomization to an asthma clinic or to primary care,

Conclusion: The HRQOL of adolescents with asthma improves with age. Young men with asthma have stronger SOC compared to young women. Adolescents with mild-to-moderate asthma receive appropriate care in the primary care system. The negative impact of poor adherence to asthma treatment on HRQOL emphasizes the importance of healthcare programs including patient education and support for adolescents with asthma and with special attention to young women.
Funding New Cancer Drugs in Ontario: Closing the Loop in the Practice Guidelines Development Cycle
Authors: J. L. Pater, G. P. Browman, M. C. Brouwers, M. F. Nefsky, W. K. Evans, D. H. Cowan
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The previously described practice guidelines development cycle follows an iterative model in which recommendations are reached by a process that incorporates practitioners at all phases. A key feature is the separation of the evidence-based systematic review and the generation of recommendations from policy decisions surrounding implementation. This article describes how this implementation phase has evolved in Ontario and how implementation has affected the guidelines process. METHODS: The development of the New Drug Funding Program in Ontario and the appointment of a policy advisory committee (PAC) to make funding recommendations were reviewed. The decision-making framework of the PAC is described in this article. RESULTS: The PAC has had to address a number of issues in making funding recommendations. These issues have included dealing with evidence arising solely from phase II versus phase III trials, using economic information, and involving community representatives in its deliberations. Its activities have had a substantial impact on the practice guidelines initiative. CONCLUSION: It is possible to integrate an evidence-based, practitioner-driven approach to clinical guideline development with a funding program that takes policy considerations into account. However, even though these two roles are conceptually separate, the needs of the funding program have inevitably had an impact on the guidelines process.
Lower seroreactivity to European than to North American H3N2 swine influenza viruses in humans, Luxembourg, 2010
Authors: Y Qiu, C P Muller, K Van Reeth
Journal: Eurosurveillance (2015)

Seroreactivity to H3N2 swine influenza viruses (SIVs) was evaluated in serum samples collected from 843 people aged 0 to 100 years in 2010 in Luxembourg. Sera were analysed by haemagglutination inhibition (HI) and virus neutralisation (VN) assays targeting a European H3N2 SIV, a North American H3N2 variant of swine origin (H3N2v) and human seasonal H3N2 viruses isolated in 1975, 1995 and 2005. HI antibodies (titre?≥?10) against European H3N2 SIV were almost exclusively detected in those born before 1990, of whom 70% were seropositive. HI antibodies against H3N2v were predominantly found in those born before 2000, with 86% seropositive. Titres against the North American H3N2v were higher than against the European H3N2 SIV. VN patterns were similar, but with higher rates and titres. We also demonstrated lower seroreactivity to European H3N2 SIV than to North American H3N2v virus. Finally, we found a strong correlation between HI titres against the European H3N2 SIV and H3N2v and their respective human ancestors, A/Victoria/3/75 and A/Nanchang/933/95. This finding and the minimal contacts between humans and pigs in Luxembourg suggest that anti-SIV antibodies in human serum samples reflect serological cross-reactivity with historical human H3N2 viruses. Our findings help assess the pandemic risk of H3N2 SIV.
The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study
Authors: Tjun Y. Tang, Simon P.S. Howarth, Sam R. Miller, Martin J. Graves, Andrew J. Patterson, Jean-Marie U-King-Im, Zhi Y. Li, Stewart R. Walsh, Andrew P. Brown, Peter J. Kirkpatrick, Elizabeth A. Warburton, Paul D. Hayes, Kevin Varty, Jonathan R. Boyle, Michael E. Gaunt, Andrew Zalewski, Jonathan H. Gillard
Journal: Journal of the American College of Cardiology (2009)
High levels of proliferation regulators and an impaired senescence response pathway to identify early-stage breast tumors with a poor prognosis.
Authors: Fiona T. Lanigan, Eiseart J. Dunne, Gerard L. Brien, Fatima Al Oraifi, Yue Fan, Cecily Quinn, Louise Flanagan, Marie Fridberg, Karin Jirstrom, James G. Geraghty, William M. Gallagher, Adrian P. Bracken
Journal: Journal of Clinical Oncology (2013)

43 Background: Predicting the risk of tumour recurrence, and thus the need for chemotherapy, for lymph node-negative breast cancer patients is a significant problem for clinicians and patients. Methods: We have identified a ‘core proliferation signature,’ which is consistently high in proliferating primary cultures, and is downregulated during cellular senescence. Using a reverse engineering approach on a breast cancer-specific regulatory network, and confirmed by ChIP-seq analysis, we have identified a hierarchy of several highly interconnected Master Transcriptional Regulators upstream of these core proliferation genes. Results: Further analysis of the expression of these factors in breast cancer cohorts at the mRNA and protein levels reveals a remarkable ability to reliably predict recurrence risk for early-stage breast cancer. Strikingly, in our analyses, a combination of just two of these factors outperforms the currently used clinical biomarkers for breast cancer recurrence risk, as well as recently developed multi-gene prognostic assays. Moreover, the addition of the senescence regulator p16 INK4A to this panel further increases its prognostic capability. Conclusions: We propose that this novel approach has succeeded in identifying ‘drivers’ of breast cancer proliferation which, when combined with a marker of senescence such as p16 INK4A , successfully identify actively proliferating tumours with an impaired senescence response pathway. Furthermore, we suggest that this gene combination has the potential to become an improved prognostic assay for early-stage breast cancer.
Programming the lymph node microenvironment to enhance anti-tumor T cell immunity in neuroblastoma
Authors: Joshua M Gammon, Christopher M Jewell
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Current cancer therapies rely on nonspecific chemotherapies which cause severe side effects without combating relapse. Therapeutic cancer vaccines aim to harness the adaptive immune response to specifically target and eliminate established tumors, while generating durable tumor-
CD34+ Selected Cells For The Treatment Of Poor Graft Function Following Allogeneic Stem Cell Transplantation
Authors: Alessandra Stasia, Anna Ghiso, Anna Maria Raiola, Federica Galaverna, Riccardo Varaldo, Francesca Gualandi, Alida Dominietto, Sarah Pozzi, Silvia Luchetti, Enrico Maria Pogliani, Andrea Bacigalupo
Journal: Blood (2013)