tbuckley/cabot-search huggingface dataset:
Abstract P4-11-03: Single nucleotide polymorphism testing for breast cancer risk assessment: patient trust and willingness to pay
Authors: R Howe, Z Omer, Y Hanoch, T Miron-Shatz, C Thorsen, EM Ozanne
Journal: Cancer Research (2012)

Abstract Background: The field of breast cancer risk assessment is advancing rapidly with recent discoveries about risk conferring single nucleotide polymorphisms (SNPs). While these discoveries can promote personalized medicine, they are often brought to the market with direct to consumer (DTC) testing before data can support their widespread use and before reliable options for dealing with testing outcomes can be offered. In this context, and knowing that patients often misunderstand risk information, it is unclear how patients will respond to these options. Methods: We surveyed high risk women's interest in SNP testing. Participants were recruited from the Cancer Genetics Network (CGN), a national network of cancer centers that maintains a database of individuals with a family history of cancer. Participants were asked to answer questions regarding their interest in SNP testing including: whether they trust it, how much they would be willing to pay for testing, how they prefer to be tested, and how they would proceed with information identifying them as below or above average risk. Results: 189 women without a history of breast cancer or SNP testing completed the questionnaire. The average age of the participants was 49, ranging from 30 to 65. All participants had at least one relative with breast or ovarian cancer. 13% had previously tested positive for a BRCA mutation, and 33% had received BRCA testing. Most women (90%) did not know what SNP testing was prior to the survey. Once SNP testing was described, 68% of women were interested in DTC SNP testing; at the same time, only 38% of the participants reported that they trusted DTC SNP testing. Conclusion: While our results show that women are interested in DTC SNP testing, their willingness to pay is lower than the DTC cost (∼$300). Involvement of genetic counselors and providers in SNP testing discussions may be needed to overcome the current lack of trust of DTC testing among patients. Many women showed interest in lifestyle interventions, suggesting that these interventions should be incorporated as part of standard follow-up recommendations. When identified by SNP testing as “below average” risk, women do not seem to trust the results enough to forego regular mammograms. As DTC testing becomes more common, and as more SNP tests become available, it will be necessary for the medical community to address patients' interest in these tests and to assist in interpreting results. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-11-03.
THU0504 The Relationship Between Weight Loss and Reduced Cartilage Loss in the Medial Knee Joint is Non-Linear in Obese People
Authors: A. Wluka, A. Teichtahl, S. Tanamas, Y. Wang, B. Strauss, J. Proietto, J. Dixon, G. Jones, A. Forbes, F. Cicuttini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Obesity is the strongest modifiable risk factor for development and progression of knee osteoarthritis (OA). There is emerging evidence for a beneficial effect of weight loss on knee structure. The amount of weight loss necessary for any knee structural benefits is not known. <h3>Objectives</h3> The aim of this longitudinal study was to examine the effect of weight loss on change in knee cartilage volume in an obese cohort. <h3>Methods</h3> 250 subjects were recruited from various community sources targeting weight loss. Of these subjects, 67 obese subjects (BMI ≥ 30 kg m<sup>-2</sup>) achieved weight loss (&gt; 0kg) over the study period. Anthropometric (weight and height) and knee cartilage volume (determined by magnetic resonance imaging) measures were assessed at baseline and an average of 2.4 years (range 1.7 – 3.9 years) later. <h3>Results</h3> Weight loss was associated with a non-linear reduction in the rate of medial knee cartilage loss. For weight loss between 0 to 7.5% of initial body weight, there was a progressive reduction in cartilage loss (β = 0.64% (95% CI -1.2 - -0.08%; p = 0.03). However, when greater weight loss (&gt; 7.5%) was achieved, there was no additional beneficial effect on cartilage change (β = -0.03% (95% CI -0.17 - 0.20%; p = 0.79). There were no significant relationships between weight loss and change in cartilage volumes at either the lateral tibia or patella. <h3>Conclusions</h3> The relationship between weight loss and medial knee cartilage volume loss is non-linear with even as little as 1% weight loss slowing the progression toward clinical knee OA. Weight loss of up to 7.5% of body weight virtually stops cartilage loss over a period of just over 2 years. Whether the rate of loss of articular cartilage remains static over a longer time-frame in a population who on average, still remains obese, requires further investigation. Nonetheless these results infer that modest weight loss may help to prevent or at least retard the progression of obesity related knee OA. <h3>Disclosure of Interest</h3> None Declared
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER, CROSS-OVER STUDY OF ROSUVASTATIN IN CHILDREN AND ADOLESCENTS (AGED 6 TO &lt;18 YEARS) WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HOFH)
Authors: Evan A. Stein, Eldad J. Dann, Albert Wiegman, Flemming Skovby, Daniel Gaudet, Etienne Sokal, Min-Ji Charng, Mafauzy Mohamed, Stefan Carlsson, Joel Raichlen, John Kastelein
Journal: Journal of the American College of Cardiology (2016)
PTH-127 Appropriateness of use of MRCP (Magnetic Resonance Cholangio-Pancreaticgraphy) in Patients with Suspected CBD Stones – a District General Hospital Experience
Authors: A Uppal, S Latif, G Sheiybani, S Shetty
Journal: Gut (2013)

<h3>Introduction</h3> Patients with CBD (Common Bile Duct) stones require high risk interventions. Around 10–20% patients with symptomatic gallstones have CBD stones. Where the initial clinical, biochemical and ultrasound examinations failed to correctly predict CBD stones in a patient with gall stones, one should resort to either MRCP or EUS (Endoscopic Ultrasound) depending on the local expertise. Without the availability of either national or local proposed strategy for these investigations we feel either test may be inappropriately used. Our aim was to study the clinical details of patients undergoing MRCP for the suspected CBD stones and assess for their appropriateness. <h3>Methods</h3> We randomly selected 45 patients who underwent MRCP for suspected CBD stones in the last one year. We assigned the risk of choledocholithiasis based on ASGE (American Society Gastrointestinal Endoscopy) guidelines and compared with their suggested management strategy. Finally we assessed their appropriateness based on the predictive factors and MRCP findings. <h3>Results</h3> There were 28 females and 17 males. The age range was 21 to 91 years (mean 63.7 yrs). Based on the ASGE guidelines we assigned 24 (53.33%) patients to intermediate, 16 to low (35.55%) %) and 5(11.11%) to high likelihood of choledocholithiais based on clinical predictors. Only 6 patients (13.33%) had choledocholithiasis on MRCP three in high risk (3/5), 3(3/24) in intermediate risks and none (0/16) in low risk group <h3>Conclusion</h3> Our audit suggests inappropriate use of MRCP in patients with low predictable group (35%). We feel those patients with high predictability should be carefully considered directly for ERCP. Currently we are extending this audit and also plan to re-audit after formulating local guidelines for the use of MRCP in suspected bile duct stones. We feel with careful clinical judgement, MRCP can be used selectively in those patients where it is going to be more useful and saving these radiological slots for more needy patients in a busy DGH. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Guidelines on the management of common bile duct stones (CBDS) - BSG Guidelines July 2008 The role of endoscopy in the evaluation of suspected choledocholithiasis- ASGE Guidelines GI Endoscopy Vol 71, No 1 2010
Second Neoplasms after Acute Lymphoblastic Leukemia in Childhood
Authors: Joseph P. Neglia, Anna T. Meadows, Leslie L. Robison, Tae H. Kim, William A. Newton, Frederick B. Ruymann, Harland N. Sather, G. Denman Hammond
Journal: New England Journal of Medicine (1991)

Effective forms of treatment for acute lymphoblastic leukemia (ALL) in childhood now result in survival rates above 70 percent at five years, but the treatments are potentially carcinogenic. To determine the magnitude of this risk and identify possible risk factors for the development of second neoplasms, we studied a large cohort of children treated for ALL.
Case 11-2011
Authors: Christopher Newton-Cheh, Angela E. Lin, Aaron L. Baggish, He Wang
Journal: New England Journal of Medicine (2011)

A 47-year-old man with systemic lupus erythematosus (SLE) was transferred to the hospital after cardiac arrest. Electrocardiography showed ST elevation, a long QT interval, and left ventricular hypertrophy (LVH). Echocardiography showed LVH and mitral-valve regurgitation.
Henry Bower Kedward
Authors: J. Sylph
Journal: BMJ (2012)

On graduating, Henry Bower Kedward won the year surgical prize, which resulted in the offer of a surgical house job in Manchester Royal Infirmary. He chose instead to enter general practice in Farnsfield, Notts., where, over the next eight years, he developed a lifelong interest in the sociology of healthcare and in health research. This led first …
Endoscopic placement of a large-bore covered self-expandable metallic stent for cholangitis caused by mucus from a pancreatic mucinous neoplasm
Authors: Naotaka Hayasaka, Tsuyoshi Hayashi, Michihiro Ono, Hirotoshi Ishiwatari, Naoki Uemura, Toshinori Okuda, Junji Kato
Journal: Endoscopy (2014)

A 76-year-old woman, in whom an intraductal papillary mucinous neoplasm (IPMN) of the pancreas head had been diagnosed 28 months earlier, was admitted for the treatment of cholangitis; however, she refused surgical treatment. Upon progression, she had experienced recurrent cholangitis for 16 months caused by mucus within the bile duct, which was coming from an IPMN-linked fistula ([Fig. 1]). To preserve bile flow, 10-mm-diameter covered self-expandable metallic stents were placed endoscopically. However, the procedure had to be repeated five times in 8 months because the stents migrated distally or were clogged by mucus despite preventative measures, such as placement above the papilla of Vater, simultaneous placement of a covered self-expandable metallic stent and a double pigtail stent to prevent migration, partial stent-in-stent placement to connect the hilar biliary duct and the duodenum, and side-by-side placement of two covered self-expandable metallic stents to occlude the fistula completely.
A3.03 Formation of novel citrullinated peptides by<i>porphyromonasgingivalis</i>pad enzyme: Implications for autoimmunity in rheumatoid arthritis
Authors: AB Montgomery, J Kopec, L Shrestha, A Schewenzer, RE Correia, R Fischer, N Burgess-Brown, WW Yue, PJ Venables
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Peptidylarginine deiminase (PAD) enzymes are thought to be involved in rheumatoid arthritis (RA) due to presence of anti-citrullinated protein antibodies (ACPA). Periodontitis is a risk factor for RA, and periodontal pathogen <i>Porphyromonas gingivalis</i>has been proposed as the link due to expression of the unique prokaryotic PAD enzyme PPAD. PPAD has specificity for C-terminal arginine substrates, resulting in formation of citrullinated epitopes distinct from those formed by mammalian PADs, which could induce a citrulline specific response. By solving the 3D crystal structures of wild-type (wtPPAD) and inactive mutant PPAD (mutPPAD) we aimed to determine mechanisms for the unique activity of PPAD, and compare function to human PAD2 and PAD4 <i>in vitro.</i> <h3>Materials and methods</h3> Recombinant PAD2, PAD4 and wt-/mutPPAD were expressed and purified from <i>E.coli. </i>wt-/mutPPAD was crystallised with bound arginine ligands and the 3D structure solved using molecular replacement.&nbsp;<i>In vitro</i>, PPAD/PAD activity was measured using a colourimetric assay for detection of citrulline from synthetic peptides. &nbsp;PPAD/PAD specificity was then quantified by mass spectrometry of citrullinated peptides formed from fibrinogen, following cleavage by proteinase K or <i>P.gingivalis</i> protease arginine gingipain (RgpB). <h3>Results</h3> Structural information from wtPPAD and mutPPAD identified the key residues (R152, R154) in determining the C-terminal specificity of PPAD. Mutation of these residues significantly reduced enzyme activity. <i>In vitro</i>, PPAD citrullinates C-terminal arginines only, measured by both colourimetriccitrulline detection and mass spectrometry of citrullinated fibrinogen peptides. PAD2 and PAD4 produced 3 and 2.5 times more citrulline respectively from internal compared to C-terminal arginine residues from synthetic peptides. Sequencing of citrullinated fibrinogen peptides formed by PAD2 and PAD4 also showed higher occurrence of internally citrullinated peptides (65% and 25%), than C-terminal (15% and 4%). <h3>Conclusions</h3> PPAD has unique substrate specificity for C-terminal arginine, determined by residues R152 and R154. We have shown the peptides formed by PPAD are not formed readily by human PAD2 or PAD4 and thus would be unlikely to occur <i>in vivo</i>. Following <i>P.gingivalis</i> infection, production of novel citrullinated epitopes could be involved in the breach of tolerance to citrullinated peptides observed in RA.
SP0156 Improving Access to Rheumatologist for Patients with Inflammatory Arthritis: What Role Should the GP Play?
Authors: C.D. Mallen
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Primary care is a key partner in the successful diagnosis and management of patients with inflammatory arthritis. Not only do general practitioners (GPs) have a critical role in the early and accurate diagnosis of patients with suspected inflammatory disease but also have expertise in the managing the physical and psychological comorbidity that is frequently associated with inflammatory arthritis. This lecture will describe core ways in which high-quality primary care can improve access to rheumatologists for patients with inflammatory arthritis, highlighting the need to support diagnostic decision making and the importance of responsive care pathways to support clinicians and patients. Innovative chronic disease clinics will be described emphasising the need to carefully monitor patients in community settings, freeing time for rheumatologists to manage more complex patients. The lecture will conclude with suggestions for how primary and secondary care can better work together to enhance outcomes for patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6116
Phase II study of PX-866 in recurrent glioblastoma
Authors: Marshall W Pitz, Elizabeth A Eisenhauer, Mary V MacNeil, Brian Thiessen, Jacob C Easaw, David R Macdonald, David D Eisenstat, Ankineedu S Kakumanu, Muhammad Salim, Haji Chalchal, Jeremy Squire, Ming Sound Tsao, Suzanne Kamel-Reid, Shantanu Banerji, Dongsheng Tu, Jean Powers, Diana F Hausman, Warren P Mason
Journal: Neuro-Oncology (2015)

Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system in adults. Increased activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway is common. We performed a phase II study using PX-866, an oral PI3K inhibitor, in participants with recurrent GBM. Patients with histologically confirmed GBM at first recurrence were given oral PX-866 at a dose of 8 mg daily. An MRI and clinical exam were done every 8 weeks. Tissue was analyzed for potential predictive markers. Thirty-three participants (12 female) were enrolled. Median age was 56 years (range 35–78y). Eastern Cooperative Oncology Group performance status was 0–1 in 29 participants and 2 in the remainder. Median number of cycles was 1 (range 1–8). All participants have discontinued therapy: 27 for disease progression and 6 for toxicity (5 liver enzymes and 1 allergic reaction). Four participants had treatment-related serious adverse events (1 liver enzyme, 1 diarrhea, 2 venous thromboembolism). Other adverse effects included fatigue, diarrhea, nausea, vomiting, and lymphopenia. Twenty-four participants had a response of progression (73%), 1 had partial response (3%, and 8 (24%) had stable disease (median, 6.3 months; range, 3.1–16.8 months). Median 6-month progression-free survival was 17%. None of the associations between stable disease and PTEN, PIK3CA, PIK3R1, or EGFRvIII status were statistically significant. PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of participants obtained durable stable disease. This study also failed to identify a statistically significant association between clinical outcome and relevant biomarkers in patients with available tissue.
P225 The post pandemic influenza experience in a busy district general hospital
Authors: R. Taylor, A. Graham, N. Martin
Journal: Thorax (2011)

The 2009/2010 swine origin influenza virus (H1N1) pandemic created a national helpline, vaccination program and advertising campaign that cost many millions of pounds. There were a number of deaths in young pregnant people and those with existing respiratory morbidity. In contrast, in the post pandemic we have seen budgetary cuts, no advertising campaign and a reluctance to give vaccination to anyone but clearly defined groups. Our experience during the December 2010 holiday period suggests this was ill advised. We analysed all admissions with H1N1 in December 2010–January 2011. In total we had 63 cases in a take that has a mean of 27 (SEM ±1.97) patients per day. Over 70% of patients presented between 30th December and 2nd January. These patients were young (mean age 47 (SEM 1.81)), had an increased length of stay (mean LOS 6.2 days (SEM 1.54)) and were from low risk populations (35/63 (56%) had no co-morbidities or risk factors). All had a significant fever (&gt;38°C) and most had a successful recovery (95% discharged home). CXR was normal in the majority (78%), mean WCC was normal (8.83 (SEM 0.51)) but most were lymphopaenic (mean lymph 1.01 (SEM 0.09)). Only one had a positive sputum culture, (<i>Haemophilus influenzae</i>) and all blood cultures were negative. Six were admitted to ITU (9.6%, but 100% of ITU beds available) and 3 died (4.8%), all of whom had significant respiratory co-morbidity. Our small DGH experienced a significant number of extra admissions over what is perhaps the busiest and least well staffed period the NHS has to deal with. These included a high number of young, previously well patients who had significant illness and lengths of stay. At one point 100% of critical care and level 2 beds were full of patients with H1N1. Vaccination would have prevented this crisis and at a reasonable cost and is as important in the post pandemic year as during a pandemic. It should be freely available to all on an annual basis.
Improving quality in locum general practice
Authors: S. O'Connell
Journal: BMJ (1998)

“You can't expect him to know, Mrs Jones. He's just the locum.” The receptionist sighed sympathetically. “Look, I can squeeze you in with Dr Brown next Tuesday … he's going to be very busy when he gets back.” Such scenarios are enacted across the country every day, destroying patients' confidence in general practice and doctors' morale - principals and locums alike. The receptionist's words are probably contrary to the General Medical Council's guidance(1): “You must not make any patient doubt a colleague's knowledge or skills by making unsustainable comments about them.”

Who is to blame if locums really don't know? Amid an explosion of non-principals' self assertion and a recognition of the need for non-principals in general practice, it is essential to look at where we are going wrong. The National Association of Non-Principals has just published its Code of Good Practice.(2) This attempts, for the first time, to establish standards of behaviour for non-principals and practices. In doing so it hopes to reduce the frequency of situations such as that described above.

This is more than just a locums' charter. With the endorsement of the Council of the Royal College of General Practitioners, it aims to improve the quality of the service delivered to patients.

Many factors contribute to patients' needs not being met. Adequate qualifications to do the job should not be a problem. Most non-principals qualified recently,(3) are vocationally trained,(4, 5) and have one or more postgraduate qualifications.(4) However, experience shows that, while bogus locums are fortunately rare, practices' failure to check even GMC registration, let alone qualification to work in general practice, is distressingly common. This is despite it being a specific GMC expectation of general practitioners.(1) The NHS Executive has issued guidance to secondary care trusts, which, though …
Adrenal androgens and cortisol in major depression
Authors: H Osran, C Reist, C C Chen, E T Lifrak, A Chicz-DeMet, L N Parker
Journal: American Journal of Psychiatry (1993)

Nine depressed subjects and nine comparison subjects completed a study of abnormalities in adrenal androgen and cortisol metabolism. Serum levels of cortisol and dehydroepiandrosterone (DHA) at 8:00 a.m. and 4:00 p.m. revealed hypercortisolemia and loss of diurnal DHA variation but not cortisol variation in the depressed group. These findings suggest that in depression, adrenal androgens, in contrast to cortisol, are partially regulated by mechanisms independent of ACTH.
PWE-073 Are We Using Anti-tnf Early Enough In Crohn’s Disease In The Uk?: Abstract PWE-073 Table 1
Authors: H Steed, A Rowlinson, F Leslie
Journal: Gut (2014)

<h3>Introduction</h3> Anti-TNF (a-TNF) prescription is tightly controlled by NICE guidelines and reserved for severe or resistant Crohn’s disease in the UK, with annual review of ongoing prescription required and discontinuation for patients in remission. <h3>Methods</h3> Retrospective review of 135 patients with Crohn’s disease who have received anti-TNF at UHNS. <h3>Results</h3> 135 patients received a-TNF; 51 male, 84 female with a mean age of 29 at diagnosis. 28% of patients smoke. Table 1 shows most advanced stage of disease at diagnosis and when a-TNF started. 58% of patients had already had surgery for CD prior to commencement of a-TNF, 13% had major abdominal surgery after a-TNF. The number of patients with stricturing disease had doubled from diagnosis to the time of a-TNF commencement. 7/23 (30%) required surgery in less than 6 months of commencement of anti-TNF, 10/23 (43%) in under 12 months. <h3>Conclusion</h3> a-TNF is being commenced late in the disease process, with significant accumulated damage and 73% of ongoing surgical requirements occurring in less than 1 year after commencing a-TNF. This may be a reflection of current prescription prohibition. What remains to be demonstrated is whether earlier intervention could have prevented the large amount of intra-abdominal surgery in these high risk cohorts. <h3>Disclosure of Interest</h3> None Declared.