tbuckley/cabot-search huggingface dataset:
England’s current GP inspection system misses crucial patient safety warnings, MPs hear
Authors: Adrian O’Dowd
Journal: BMJ (2015)

The current system for checking the quality of care provided by GPs in England is inadequate and fails to measure doctors’ fatigue, which can affect patient safety, leading doctors have told MPs.

Concerns about the system operated by the Care Quality Commission (CQC) were voiced during the latest evidence session of the parliamentary health committee’s inquiry into primary care, held on 15 December.

MPs asked whether the quality of care provided by GP surgeries and their performance was a matter of concern, given that far fewer practices than schools, for example, were rated as outstanding.

Steve Field, chief inspector of general practice at the CQC, giving evidence, said that the standards used for CQC inspections were very different from those used for school inspections. “I think that it is a good picture that 85% of practices are either good …
Biomarkers for bile acid diarrhoea in functional bowel disorder with diarrhoea: a systematic review and meta-analysis
Authors: Nelson Valentin, Michael Camilleri, Osama Altayar, Priya Vijayvargiya, Andres Acosta, Alfred D Nelson, M Hassan Murad
Journal: Gut (2015)

There is no universally available laboratory test to diagnose bile acid diarrhoea (BAD). <h3>Objective</h3> To conduct a systematic review and meta-analysis to identify a biomarker for idiopathic BAD in patients with functional bowel disorder (FBD) with diarrhoea. <h3>Design</h3> We searched multiple databases through 15 May 2015. Data were only available to estimate the diagnostic yield of each test (the prevalence of a positive test). Estimates were pooled across studies using the random effects model. <h3>Results</h3> We included 36 studies, enrolling 5028 patients (24 using <sup>75</sup>selenium homotaurocholic acid test (<sup>75</sup>SeHCAT) retention of &lt;10%, 6 using fasting serum C4, 3 using fasting serum fibroblast growth factor 19 (FGF19) and 2 based on total faecal bile acid (BA) excretion over 48 h). The diagnostic yields (and 95% CI) of abnormal tests were: 0.308 (0.247 to 0.377) for <sup>75</sup>SeHCAT retention (&lt;10%), 0.171 (0.134 to 0.217) for serum C4, 0.248 (0.147 to 0.385) for serum FGF19 and 0.255 (0.071 to 0.606) for total faecal BA excretion over 48 h. The majority of the analyses were associated with substantial heterogeneity. Performance characteristics relative to a gold standard test could not be estimated. <h3>Conclusions</h3> Overall, the test with the highest diagnostic yield conducted in the largest number of studies was <sup>75</sup>SeHCAT retention, which is not widely available in many countries outside Europe and Canada. Using different diagnostic tests, 25% (average) of patients with lower FBD with diarrhoea has evidence of idiopathic BAD. These tests serve to identify idiopathic BAD among patients with FBD with diarrhoea. Further studies are required to appraise the performance characteristics of tests for idiopathic BAD.
Randomised controlled trials: understanding confounding
Authors: Philip Sedgwick
Journal: BMJ (2015)

Researchers assessed the effectiveness of an exercise programme in reducing injurious falls among women at increased risk of falls and injuries. A multicentre parallel group randomised controlled trial study design was used. The intervention consisted of weekly supervised group sessions of progressive balance training offered in community based premises for two years, supplemented by individually prescribed home exercises. The control treatment was standard care. The study took place in 20 study centres throughout France. Participants were aged 75-85 years, living in their own home, and with reduced balance and gait capacities. In total, 706 women were recruited and randomly allocated to the intervention group (exercise programme; n=352) or control group (standard care; n=354). The random allocation of participants was stratified by study centre and body weight (<59 kg v ≥59 kg).1

The primary outcome was the rate of injurious falls (moderate and severe). Secondary outcomes included physical tests and perception of overall physical function. Of those women allocated to the intervention, 306 completed the trial protocol compared with 294 of those women allocated to control treatment. Analysis was by intention to treat. The risk of injurious falls was significantly reduced in the intervention group when compared with the control group (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). At two years, women in the intervention group performed significantly better on all physical tests and had significantly better perception of their overall physical function than women in the control group. It was concluded that the exercise programme was effective …
ASCO Quality Oncology Practice Initiative (QOPI): Lessons in clinical quality improvement (QI) for hematology/oncology fellows
Authors: R. C. Warren, A. J. Tevaarwerk, S. Attia, D. Grade, J. A. Stewart
Journal: Journal of Clinical Oncology (2008)

6609 Background: Practice-based learning and quality improvement is a core competency in fellowship training. QOPI is a clinical practice assessment program using chart review derived from national cancer care guidelines. ASCO invited several oncology fellowships to pilot QOPI. We describe the experience of the University of Wisconsin (UW) Hematology/Oncology fellows with the QOPI process. Methods: Clinic charts were randomly chosen and screened based on criteria of diagnosis within two years and clinic visit with a fellow within six months. Fellows did not review their own patient charts. Fellows answered questions in three modules: colorectal cancer (CRC), end of life care and Non-Hodgkin's lymphoma (NHL). QOPI scored, tabulated the results and created a UW fellowship practice panel (FPP). Our FPP was then compared to a 136 group practice panel (GPP). Fellows reviewed their results and developed QI projects. Results: Eight fellows reviewed an average of four charts per module (73 total utilizable charts). The GPP reviewed 13,450 charts. Our FPP performed well, but in some areas results were less than expected: CEA measurement in CRC patients following resection or at end of adjuvant chemotherapy (84.6% UW vs. 84.7% overall), guideline-based G-CSF use in NHL (35.3% UW vs. 56.9% overall) and pain assessment at next to last visit (50% UW vs. 77.7% overall). Teams of fellows discussed reasons for scores and methods for improvement. QI plans were formally presented to the faculty, and are being implemented. Reevaluation will be performed in six months. Total time commitment for each fellow was approximately10 hours, and for the fellowship coordinator, 30 hours, for data collection, results review and presentation. Conclusions: QOPI offers a framework for effective fellow-directed practice quality review. With this process, fellows learned to identify strengths and weaknesses in documentation practices and patient care leading to formal plans for improvement. QOPI inspired interaction with the tumor registry, faculty and nursing leading to practice change. While time consuming, fellows perceive QOPI as an enlightening tool for practice-based learning that can be repeated and refined on a regular basis. No significant financial relationships to disclose.
Rituximab or Azathioprine Maintenance in ANCA-Associated Vasculitis
Authors: Christian Pagnoux, Loïc Guillevin
Journal: New England Journal of Medicine (2015)

report that rituximab prevented relapse of antineutrophil cytoplasm antibody (ANCA)–associated vasculitis better than azathioprine. However, the study de -sign tilted the playing field in favor of rituximab. Figure 2 of their article indicates that a 500-mg infusion of rituximab was administered every 6 months for 18 months. In addition, an extra dose of rituximab was administered at baseline. In contrast, in the azathioprine cohort, azathio-prine therapy was progressively decreased during follow-up. This design begs two questions.First, what would the study outcome have been if the dose of azathioprine had been kept constant and the dose of rituximab had been tapered?Second, why was it deemed necessary to taper the dose of azathioprine? Decades of experience indicate that azathioprine is a relatively safe long-term therapy. That cannot be said for rituximab.
A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with <i>ROS1</i>-Rearranged Lung Cancer
Authors: Alexander Drilon, Romel Somwar, Jacob P. Wagner, Nadeem A. Vellore, Christopher A. Eide, Matthew S. Zabriskie, Maria E. Arcila, Jaclyn F. Hechtman, Lu Wang, Roger S. Smith, Mark G. Kris, Gregory J. Riely, Brian J. Druker, Thomas O'Hare, Marc Ladanyi, Monika A. Davare
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Rearranged ROS1 is a crizotinib-sensitive oncogenic driver in lung cancer. The development of acquired resistance, however, poses a serious clinical challenge. Consequently, experimental and clinical validation of resistance mechanisms and potential second-line therapies is essential. Experimental Design: We report the discovery of a novel, solvent-front ROS1D2033N mutation in a patient with CD74-ROS1–rearranged lung adenocarcinoma and acquired resistance to crizotinib. Crizotinib resistance of CD74-ROS1D2033N was functionally evaluated using cell-based assays and structural modeling. Results: In biochemical and cell-based assays, the CD74-ROS1D2033N mutant demonstrated significantly decreased sensitivity to crizotinib. Molecular dynamics simulation revealed compromised crizotinib binding due to drastic changes in the electrostatic interaction between the D2033 residue and crizotinib and reorientation of neighboring residues. In contrast, cabozantinib binding was unaffected by the D2033N substitution, and inhibitory potency against the mutant was retained. Notably, cabozantinib treatment resulted in a rapid clinical and near-complete radiographic response in this patient. Conclusions: These results provide the first example of successful therapeutic intervention with targeted therapy to overcome crizotinib resistance in a ROS1-rearranged cancer. Clin Cancer Res; 22(10); 2351–8. ©2015 AACR.
Diversity of mutated antigen recognition by tumor infiltrating lymphocytes from patients with metastatic melanoma
Authors: Jessica S Crystal, Todd D Prickett, Jared J Gartner, Maria R Parkhurst, Yong-Chen Lu, Alena Gros, Yong Li, Kasia Trebska-Mcgowan, Mona El-Gamil, Steven A Rosenberg, Paul F Robbins
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The adoptive cell transfer (ACT) of autologous tumor infiltrating lymphocytes (TIL) can mediate durable, complete tumor regression in approximately 20% of patients with metastatic melanoma. Recent observations suggest that autologous melanoma TIL administered to multiple patients
Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection
Authors: Ren-Huan Xu, Eric B. Wong, Daniel Rubio, Felicia Roscoe, Xueying Ma, Savita Nair, Sanda Remakus, Reto Schwendener, Shinu John, Mark Shlomchik, Luis J. Sigal
Journal: Immunity (2015)
Osteoarthritic bone marrow lesions almost exclusively colocate with denuded cartilage: a 3D study using data from the Osteoarthritis Initiative
Authors: Michael A Bowes, Stewart WD McLure, Christopher BH Wolstenholme, Graham R Vincent, Sophie Williams, Andrew Grainger, Philip G Conaghan
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> The aetiology of bone marrow lesions (BMLs) in knee osteoarthritis (OA) is poorly understood. We employed three-dimensional (3D) active appearance modelling (AAM) to study the spatial distribution of BMLs in an OA cohort and compare this with the distribution of denuded cartilage. <h3>Methods</h3> Participants were selected from the Osteoarthritis Initiative progressor cohort with Kellgren–Lawrence scores ≥2, medial joint space narrowing and osteophytes. OA and ligamentous BMLs and articular cartilage were manually segmented. Bone surfaces were automatically segmented by AAM. Cartilage thickness of &lt;0.5 mm was defined as denuded and ≥0.5–1.5 mm as severely damaged. Non-quantitative assessment and 3D population maps were used for analysing the comparative position of BMLs and damaged cartilage. <h3>Results</h3> 88 participants were included, 45 men, mean age (SD) was 61.3 (9.9) years and mean body mass index was 31.1 (4.6) kg/m<sup>2</sup>. 227 OA and 107 ligamentous BMLs were identified in 86.4% and 73.8% of participants; OA BMLs were larger. Denuded cartilage was predominantly confined to a central region on the medial femur and tibia, and the lateral facet of the trochlear femur. 67% of BMLs were colocated with denuded cartilage and a further 21% with severe cartilage damage. In the remaining 12%, 25/28 were associated with cartilage defects. 74% of all BMLs were directly opposing (kissing) another BML across the joint. <h3>Conclusions</h3> There was an almost exclusive relationship between the location of OA BML and cartilage denudation, which itself had a clear spatial pattern. We propose that OA, ligamentous and traumatic BMLs represent a bone response to abnormal loading.
NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases.
Authors: Paul D. Brown, Anthony L. Asher, Karla V. Ballman, Elana Farace, Jane H Cerhan, S. Keith Anderson, Xiomara W. Carrero, Frederick G. Barker, Richard L. Deming, Stuart Burri, Cynthia Menard, Caroline Chung, Volker W. Stieber, Bruce E. Pollock, Evanthia Galanis, Jan C. Buckner, Kurt A. Jaeckle
Journal: Journal of Clinical Oncology (2015)

LBA4 Background: WBRT significantly improves tumor control in the brain after SRS, yet the role of adjuvant WBRT remains undefined due to concerns regarding neurocognitive risks. Methods: Patients with 1-3 brain metastases, each &lt; 3 cm by contrast MRI, were randomized to SRS alone or SRS + WBRT and underwent cognitive testing before and after treatment. The primary endpoint was cognitive progression (CP) defined as decline &gt; 1 SD from baseline in any of the 6 cognitive tests at 3 months. Time to CP was estimated using cumulative incidence adjusting for survival as a competing risk. Results: 213 patients were enrolled with 2 ineligible and 3 cancels prior to receiving treatment. Baseline characteristics were well-balanced between study arms. The median age was 60 and lung primary the most common (68%). CP at 3 months was more frequent after WBRT + SRS vs. SRS alone (88.0% vs. 61.9% respectively, p = 0.002). There was more deterioration in the WBRT + SRS arm in immediate recall (31% vs. 8%, p = 0.007), delayed recall (51% vs. 20%, p = 0.002), and verbal fluency (19% vs. 2%, p = 0.02). Intracranial tumor control at 6 and 12 months were 66.1% and 50.5% with SRS alone vs. 88.3% and 84.9% with SRS+WBRT (p &lt; 0.001). Median OS was 10.7 for SRS alone vs. 7.5 months for SRS+WBRT respectively (HR = 1.02, p = 0.93). Conclusions: Decline in cognitive function, specifically immediate recall, memory and verbal fluency, was more frequent with the addition of WBRT to SRS. Adjuvant WBRT did not improve OS despite better brain control. Initial treatment with SRS and close monitoring is recommended to better preserve cognitive function in patients with newly diagnosed brain metastases that are amenable to SRS. Clinical trial information: NCT00377156.
FOXP3 Is a Direct Target Of miR15a/16 in Umbilical Cord Blood Regulatory T Cells
Authors: Liu Xiaoying, Shawndeep Tung, Tetsuro Setoyama, Lucilla D’Abundo, Robinson Simon, Hui Yang, Eric Yvon, Nina Shah, Hong Yang, Guillermo Garcia-Manero, Ian K. McNiece, Katy Rezvani, George Calin, Elizabeth J. Shpall, Simrit Parmar
Journal: Blood (2013)
O074 : A metabolomic study of serum from patients with cirrhosis identifies 2 metabolites that accurately predict the acute HVPG response to β-blocker therapy
Authors: E. Reverter, J.J. Lozano, C. Alonso, A. Berzigotti, S. Seijo, F. Turon, M.L. Martínez-Chantar, J. María Mato, V. Hernández-Gea, J. Bosch, J.C. García-Pagán
Journal: Journal of Hepatology (2015)
Fortnightly Review: Tropical medicine for the 21st century
Authors: K. M De Cock, S. B Lucas, D. Mabey, E. Parry
Journal: BMJ (1995)

The specialty of tropical medicine originated from the needs of the colonial era and is removed from many of the health care requirements of tropical countries today. Tropical medicine concentrates on parasitic diseases of warm climates, although other infections and diseases related to poverty rather than climate dominate medicine in developing countries challenged by population pressure, civil strife, and migration. In the new century, tropical medicine would best be absorbed into the specialty of infectious diseases, which should incorporate parasitic diseases, travel medicine, and sexually transmitted diseases. Pressing questions for health care and research in developing countries concern the provision of appropriate services for problems such as HIV/AIDS, tuberculosis, sexually transmitted diseases, and injuries. The question of how to provide appropriate clinical care in resource poor settings for the major causes of morbidity and premature mortality has been neglected by donors, academic institutions, and traditional tropical medicine.
The Clinicopathological Features of Postoperative Extrahepatic Metastasis of Hcc After Hepatectomy
Authors: Masatsugu Ishii, Osamu Itano, Masahiro Shinoda, Minoru Kitago, Yuta Abe, Taizo Hibi, Hiroshi Yagi, Yuko Kitagawa
Journal: Annals of Oncology (2014)
Safety of bevacizumab plus chemotherapy as first-line treatment of patients with metastatic colorectal cancer: Updated results from a large observational registry in the US (BRiTE)
Authors: E. Hedrick, M. Kozloff, J. Hainsworth, S. Badarinath, A. Cohn, P. Flynn, W. Dong, S. Suzuki, M. Sugrue, A. Grothey
Journal: Journal of Clinical Oncology (2006)

3536 Background: Bevacizumab (BV) prolongs overall survival and progression-free survival when added to standard chemotherapy for patients with metastatic colorectal cancer (mCRC). BRiTE is a large, community-based observational registry of patients with mCRC receiving BV plus first-line chemotherapy. Safety and efficacy information in unselected patients with mCRC are collected. Chemotherapy regimen choice is at the physician’s discretion. Methods: To facilitate and evaluate enrollment of a typical community-based mCRC population, eligibility criteria were minimized. Cohort demographics were consistent with the NCI Surveillance, Epidemiology, and End Results (SEER) database for mCRC. Patients are followed for up to 3 years, and safety data including targeted BV-associated serious adverse events (SAEs) are updated every 3 months (mo). Results are based on descriptive analyses and are not adjusted for propensity of treatment, baseline characteristics, and treatment effects. Results: 1968 patients were enrolled between Feb 2004 and Jun 2005. Median study follow-up was 10 mo by Nov 4, 2005. SAEs were reported in 12.0% of patients including gastrointestinal perforation (GIP) (1.7%), postoperative bleeding/wound healing complications (1.2%), arterial thromboembolic events (ATE) (2.1%), and grade 3–4 bleeding (1.9%). 3.2% of patients discontinued BV due to a BV-related toxicity, most commonly bleeding. For patients with the respective event(s), median time to first event was 2.1 mo for GIP, 3.5 mo for ATE and 4.0 mo for grade 3–4 bleeding. 8.9% of patients with no history of hypertension (HTN) developed HTN requiring medication and 6.2% of patients who had HTN requiring medication at baseline experienced worsening of their HTN while on study treatment. Conclusions: In this unselected population of patients with mCRC, the safety profile of BV plus various chemotherapy regimens appears consistent with that observed in the pivotal BV trial. Overall discontinuation of BV due to a BV-related toxicity was uncommon. In this large community-based observational registry, no new BV associated safety issues have been identified. [Table: see text]
Review: Digoxin does not affect all-cause mortality but reduces hospital admissions
Authors: P. Dileep Kumar
Journal: Annals of Internal Medicine (2015)

ACP Journal Club15 December 2015Review: Digoxin does not affect all-cause mortality but reduces hospital admissionsP. Dileep Kumar, MD, FACPP. Dileep Kumar, MD, FACPMcLaren Port Huron Hospital, Port Huron, Michigan, USA. (P.D.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2015-163-12-011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationZiff OJ, Lane DA, Samra M, et al. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015;351:h4451. https://pubmed.ncbi.nlm.nih.gov/26321114Clinical Impact RatingsGIM/FP/GP: Cardiology: References1. Withering W. An Account of the Foxglove and Some of its Medical Uses: With Practical Remarks on Dropsy and Other Diseases. London: J and J Robinson; 1785. Google Scholar2. Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525-33. [PMID: 9036306] Google Scholar3. Centers for Medicare and Medicaid Services. Readmission reduction program. 2014. www.cms.gov/medicare/medicare-fee-for-service-payment/acuteinpatientpps/readmissions-reduction-program.html (accessed 15 Oct 2015). Google Scholar4. Yancy CW, Jessup M, Bozkurt B, Butler J, et al;American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128:e240-327. [PMID: 23741058] Google Scholar5. Ewy GA, Kapadia GG, Yao L, Lullin M, Marcus FI. Digoxin metabolism in the elderly. Circulation. 1969;39:449-53. [PMID: 5778245] Google Scholar Author, Article, and Disclosure InformationAuthors: P. Dileep Kumar, MD, FACPAffiliations: McLaren Port Huron Hospital, Port Huron, Michigan, USA. (P.D.K.)This article was published at Annals.org on 1 December 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 2015Volume 163, Issue 12Page: JC11KeywordsAtrial fibrillationCongestive heart failureDrugsHeart failureHospitalizationsLongitudinal studiesMortalityRisk ratioSafetySystematic reviews ePublished: 15 December 2015 Issue Published: 15 December 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Biology/Genetics
Authors: Franziska Jundt, Kurt Bommert, Florian Emmerich, Gerd Muller, Hans-Dieter Foss, Hans-Dieter Royer, Harald Stein, Bernd Dorken'-, R Liang, W Au, C Lee, C Chim, A Lie, Y Kwong, L Xerri, E Devilard, R Bouabdallah, A Stoppa, J Hassoun, F Birg, Lymphopma Nagai, T Kinoshita, H Suzuki, T Uchida, T Murate, H Saito, U Hasse, M Tinguely, E Oppliger, J Cajot, A Tobler, B Borisch, Edoardo Pcscannona, Maria Nardocci, Anna Lavinia, Sabina Signoretti, Antonella Stoppacdaro, Cristini Lazzeri, Carlo Croce, Carlo Baroni, G Rnsso, M Dreyling, K Hiibler, S Roth, G Ott, H Muller-Hermelink, W Hiddemann, Brunangelo Falini', Marco Fizzotti, ' Dalla-Favera
Journal: Annals of Oncology (1999)