tbuckley/cabot-search huggingface dataset:
Abstract 21278: Time to Diagnosis of Acute Coronary Obstruction Following Surgical Repair of Congenital Heart Disease is Associated With Improved Transplant-Listing Free Survival
Authors: Michael P Goldsmith, Kimberlee Gauvreau, Diego Porras
Journal: Circulation (2017)

Objectives: Acute coronary artery obstruction (CAO) following surgical repair of congenital heart disease (CHD) is rare but carries a high burden of morbidity and mortality. Prior reports describe the complication in individual populations of CHD, though few have looked at factors associated with outcomes. We hypothesize that increased time from a clinically significant post-operative sentinel event suggestive of coronary ischemia to diagnosis of CAO is associated with worse clinical outcomes. Methods: Single center retrospective review of patients diagnosed with acute post-operative CAO by coronary angiography following surgical repair of CHD between January 2000 and June 2016. Sentinel events were identified and timestamped. Characteristics compared by Fisher’s Exact and Wilcoxon Rank-Sum test. Exact logistic regression used for primary analysis. Results: A total of 34 patients were identified with acute post-operative CAO, n=32 (94%) had an identifiable sentinel event: n=15 (47%) cardiac arrest, n=12 (38%) persistent ventricular dysfunction, n=5 (16%) malignant arrhythmia. Longer sentinel event to angiography time was associated with composite outcome of death or heart transplant listing (OR 1.08 for each additional hour (1.02-1.17), p = 0.03). This association remained when adjusting for significant covariates of HLHS diagnosis (OR 1.06 (1.01-1.15) p=0.01) and surgical coronary manipulation (OR 1.07 (1.01-1.16), p=0.003). Ultimately in the series, n=27 (79%) required ECMO, n=14 (41%) died, and n=9 (27%) were listed for heart transplant. Conclusions: In the largest cohort described to date, time from a significant post-operative event to diagnosis of CAO by angiography was associated with death or heart transplant listing. Given the high burden of ECMO and death in this population, clinicians should maintain a high index of suspicion for CAO in patients who do not follow typical post-operative trajectory and consider early advanced diagnostics.
SP0036 MASTERPLANS – TAILORING SLE FOR THERAPY
Authors: Ian N. Bruce
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease which is highly heterogeneous in its clinical manifestations and also in its response to specific therapies. Across a number of trials of novel agents, overall response rates are approximately 40-60% and in the past almost 60 years only one drug (belimumab) has been licensed for use in SLE. Current therapy is therefore based on a 'trial and error" approach frequently involving glucocorticoid co-therapy. Delayed and poor control of inflammation results in organ damage, cardiovascular disease and glucocortocoid toxicity. We established a consortium of academia and industry partners (MAximizing Sle ThERapeutic PotentiaL by Application of Novel and Stratified approaches (MASTERPLANS) with the aim of identifying key endotypes associated with response and low disease activity on particular therapies. <h3>Objectives:</h3> Our consortium is addressing the hypothesis that strata exist within SLE populations that will enable more targeted use of existing and novel therapeutic agents and improve response rates. Specifically, B-cell related biomarkers including dynamics and function predict responses to mycophenolate mofetil (MMF) and B-cell targeted biologics and interferon signature/pathway dynamics identifies patients with poorer responses to these agents. <h3>Methods:</h3> Our approach will firstly be to re-analyse data already available from large studies and trials to identify key predictive factors of response. Also, using data from a large UK cohort, the BILAG-Biologics Register, we will assess clinical factors and biomarkers that predict response and low disease activity. Combining results from these studies with that gained from previous studies will enhance our ability to identify endotypes of response. <h3>Conclusion:</h3> Identifying biomarkers of response will allow better selection of therapy for individual patients. Using the right drug at the right time will improve control of inflammation for patients with SLE and contribute to improving long-term outcomes. <h3>Disclosure of Interests:</h3> Ian N. Bruce Grant/research support from: Genzyme Sanofi, GlaxoSmithKline, Consultant for: AstraZeneca, Eli Lilly, GlaxoSmithKline, ILTOO Pharma, MedImmune, Merck Serono, Speakers bureau: GlaxoSmithKline, UCB Pharma
The social dynamics of lung cancer talk on Twitter, Facebook and Macmillan.org.uk
Authors: Joanna Taylor, Claudia Pagliari
Journal: npj Digital Medicine (2019)

People with lung cancer and others affected by the condition are using social media to share information and support, but little is known about how these behaviours vary between different platforms. To investigate this, we extracted posts from Twitter (using relevant hashtags), the Lung Cancer Support Group on Facebook and the Macmillan.org.uk lung cancer discussion forum for a single month. Interaction Process Analysis revealed that all three platforms were used more for giving than seeking information, opinion or suggestions. However, interaction types (including sentiment) varied between platforms, reflecting their digital architectures, user-base and inclusion of a moderator. For example, a higher percentage of information-seeking and sentiment marked the Macmillan.org.uk, compared with Twitter and the Facebook Group. Further analysis of the messages using a four-dimensional typology of social support revealed that emotional and informational support types were most prevalent on the Macmillan.org.uk forum, closely followed by the Facebook Group. Contrary to expectations, Twitter posts showed the most companionship support, reflecting the use of hashtags as user-generated signals of community belonging and interests. Qualitative analysis revealed an unanticipated sub-category of spiritual support, which featured uniquely in the Lung Cancer Support Group on Facebook. There was little evidence of trolling or stigma, although some users remarked that lung cancer was unfairly resourced compared with other cancers. These findings provide new insights about how people affected by lung cancer use social media and begin to elucidate the value of different platforms as channels for patient engagement and support, or as potential research data sources.
PF743 PENICILLIN PROPHYLAXIS AND PNEUMOCOCCAL VACCINE USE IN ADULT SICKLE CELL PATIENTS: A RETROSPECTIVE ANALYSIS OF CLINICAL PRACTICE AND OUTCOMES IN OXFORD, UK
Authors: A. Ejaz, S. Hayes, M. Akanni, N. Roy
Journal: HemaSphere (2019)

Background: Pneumococcal disease prophylaxis with antibiotics and vaccination has a clear mortality benefit in children with sickle cell disease (SCD), with the greatest benefit in children under 5 years [1]. The benefit in adults, who also have functional hyposplenia, is less clear with no trial evidence to support or refute prophylaxis in this group. Current guidelines [2] recommend that adults with SCD have pneumococcal vaccination every 5 years and take antibiotic prophylaxis only if they are compliant, so reducing the theoretical risks of antimicrobial resistance in those who are partially compliant. Aims: Our aim was to establish the current uptake of pneumococcal vaccination and antibiotic prophylaxis in our adult patients with SCD. We wished to ascertain whether a difference exists in episodes of infection for patients who are fully compliant with pneumococcal prophylaxis and those who are not. MiniTab 18 was used for data analysis. Methods: Adult patients with SCD known to the Oxford Red Cell tertiary centre were identified from annual review assessments and a descriptive analysis was undertaken on patient demographics, co‐morbidities, prophylaxis compliance and pneumococcal vaccination status, and episodes of infection occurring from 2015‐2019. Results: 133 patients with SCD were identified. 53% were female and the median age was 34 years (range 16–75 years) (see Table 1). 67% of patients were prescribed antimicrobial pneumococcal prophylaxis. Of these, 21% were known to be non‐compliant. 100% of patients were asked to attend their GP for vaccination but only 58% of patients had documentation of pneumococcal vaccination. From 2015 to 2019 there were 41 episodes of infection recorded in 31 patients but only 12 had positive cultures. There was no significant difference in infection rate between patients on prophylaxis and compliant (17/31) and remaining patients (14/31) (p = 0.61). There was one episode of confirmed pneumococcal disease and this was in a patient non‐compliant with prophylaxis and not up‐to‐date with vaccination. Summary/Conclusion: While the majority of our patients were prescribed antibiotic prophylaxis, due to non‐compliance, only half of our cohort were taking antibiotics reliably. There were few culture positive cases of infection, indicating that adults with SCD are at lower risk of infection compared with children, consistent with the literature [3]. In our cohort, over the 3 year period, there was only 1 documented case of pneumococcal disease. The low incidence of infection may have been due to our cohort being of younger age, with few comorbidities and a relatively high proportion of lower risk genotype. This work highlights the need for prospective, randomised evidence in SCD patients to establish whether a benefit exists for pneumococcal prophylaxis in adulthood. image
PF665 SERUM FERRITIN LEVELS ARE INCREASED IN IDIOPATHIC ERYTHROCYTOSIS BUT REDUCED IN POLYCYTHEMIA VERA
Authors: G. Biagetti, I. Bertozzi, E. Cosi, F. Fabris, M.L. Randi
Journal: HemaSphere (2019)

Background: Absolute erythrocytosis is characterized by persistently raised Haemoglobin (Hb) and hematocrit (Ht) levels. The most studied form is Polycythemia Vera (PV), a clonal disease in which the proliferation of red cells is driven by mutations in JAK2. Secondary erythrocytosis are represented by rare congenital diseases, acquired forms, or idiopathic erythrocytosis (IE), a poorer studied disease in which the erythrocytosis has not a definite cause. Over‐production of red blood cells should drive a depletion of iron, and thus low serum ferritin levels. However, we often observe increased levels of ferritin at diagnosis in IE and we recently found that mutations or polymorphisms of HFE gene are commonly found in these patients. Aims: Could serum ferritin be an early help to hypothesize the cause of erythrocytosis in a patient? To answer this question, we retrospectively analysed levels of ferritin at diagnosis in PV and IE patients. Methods: We studied 72 patients with PV and 67 patients with IE, followed in our department. In each patient we recorded ferritin at diagnosis out of phlebotomy treatment. Other causes of hypo‐ and hyper‐ ferritinemia were excluded. Ferritin normal levels were considered 20–300 μg/L in men and 15–200 μg/L in women. All patients with a diagnosis of PV carried JAK2V617F or JAK 2 exon 12 mutation, while none of the patients with IE carried JAK2 or EPOR, VHL, PHD2, HIF‐1 alpha genes mutations. Presence and absence of HFE mutations in IE patients, if known, were registered. Statistical analysis was performed using the Mann‐Whitney test, Fisher's exact test and the t Student test. Results: Results are shown in the Table I. In addition, HFE mutations had been searched in 26 (39%) IE patients, and 13 (50%) of them had at least a mutated allele. Summary/Conclusion: Our results show a dramatic difference between levels of ferritin at diagnosis in PV and IE: in fact, 22% of PV patients had reduced ferritin at diagnosis out of phlebotomies, while on the contrary 28% of IE patients had increased levels of ferritin. Then, serum ferritin at diagnosis could address the physician to the origin of erythrocytosis. In addition, nearly half of IE patients have been already studied for presence of HFE mutations, and half of them carry at least one HFE mutated allele. We believe that a large part of IE patients carries a genetic impairment of the iron metabolism that could drive an enhancement of iron production: this could explain why in the presence of erythrocytosis iron is more consumed in PV patients than in IE ones. Further studies are needed about the presence of iron metabolism impairments in IE patients and, on the other hand, possible overlays of JAK2 and HFE mutations in PV patients. image
One-year survival and physical functioning with surgery compared to no surgery in early-stage lung cancer.
Authors: Paul R. Walker, Sam Cykert, Franklin McGuire, Lloyd Edwards, Peggye Dilworth-Anderson
Journal: Journal of Clinical Oncology (2013)

6584 Background: Medical co-morbidities in patients with lung cancer frequently impact a treatment decision out of fear of doing harm without a benefit. A prospective study looking at racial disparity factors associated with surgery decisions in early lung cancer identified &gt; 2 co-morbidities with an Odds Ratio (OR) of 0.04 of going to surgery for African Americans (AA) patients, yet a 10-fold higher likelihood of Caucasians (C) going to surgery with an OR 0.45. (Cykert et al JAMA 2010: 303: 2368). Methods: 386 out of the original437 patients with early stage lung cancer and no absolute contraindications to surgery were evaluated at multiple institutions for relative co-morbidities and with an initial Short Form 12 (SF-12) to assess physical functional status at enrollment and one year after enrollment. One year mortality and physical functional status was assessed. Results: 66% of C underwent surgery compared to 55% of AA (p = .048). One year mortality was not different between the AA (15%) and C (15.4%) populations (p=0.9); however not powered for a survival difference between surgery and no surgery. One year mortality in the overall surgical group was 10.8% compared to 22.8% in the non-surgical group; OR 0.50 (p&lt;0.001). Patients with &gt; 2 co-morbidities at diagnosis had a 27.5% one year mortality compared to 13.5% with &lt; 2 co-morbidities; OR 1.7 (p=0.01). Combined analysis of co-morbidities and surgery revealed those with &lt; 2 co-morbidities having surgery experienced a 10% one year mortality and those with &gt; 2 co-morbidities 19%; without surgery one year mortality was 20% and 31% respectively. Despite &gt; 2 co-morbidities, there was a 12% absolute mortality reduction with surgery. Regression analysis controlling for age and co-morbidities identified no physical functioning decline with surgery compared to the non-surgical group. Conclusions: One year mortality was doubled in patients with early lung cancer who declined surgery compared to those treated with surgery. There was no increased physical functioning decline in patients treated with surgery compared to no surgery. Treatment decisions in early lung cancer should be based on the survival benefit and not a perceived concern of physical functioning decline.
SP0152 3D PRINTED DRUGS
Authors: Matthew Peak
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> With the advent of personalised medicine, the need for flexible dosing is increasingly important. Conventional pharmaceutical manufacturing processes can be constrained in their ability to offer flexible dosing options to meet patient need. This is particularly important in specific populations, for example children, where available formulations are frequently not age-appropriate and need to be modified to achieve an intended dose. 3D-printing of solid dosage forms offers a disruptive technology which enables solid-dosage forms of medicines to be manufactured at flexible, precise doses meeting the needs of individual patients. This technology has relevance for manufacture of existing active pharmaceutical ingredients for a range of conditions including inflammatory diseases. <h3>Objectives:</h3> To develop 3D-printed oral solid dosage forms of medicines which are age-appropriate for children and young people. To determine the acceptability of 3D-printed medicines to children and young people by conducting interventional studies of tablet administration. <h3>Methods:</h3> Tablets containing a range of active pharmaceutical ingredients (API) were produced using two stages: (i) holt melt extrusion of a filament containing API and excipients; (ii) 3D printing of the filament using fused deposition modelling (FDM) to produce the desired shape in a layer-by-layer pattern. Acceptability of 3D-printed tablets to children and young people (CYP) aged 4-12 years was assessed by the swallowability and mouthfeel following administration of different size 3D-printed placebo tablets. <h3>Results:</h3> Using hydrocortisone as an exemplar API, Tablets were successfully produced by the FDM 3D printing process. Thermal analysis indicated that HC remained stable below 160°C and the tablets had very high mechanical strength with friability of 0%. This illustrates the ability of the printer to produce a ready-to-use-tablet without the need for a drying or finishing step. The disintegration took 9.2–14 min confirming immediate release properties. We administered for the first time globally an ingestible 3D-printed tablet to a child. CYP were able to swallow and ingest 3D-printed bi-convex tablets of either 6mm, 8mm or 10mm diameter. The 3D tablets were reported by CYP to have a slightly more discernible mouthfeel than placebo tablets of the same size manufactured in a GMP facility. <h3>Conclusion:</h3> FDM 3D printing offers a disruptive technology for the manufacture of solid dosage forms of medicines of flexible doses with excellent dose precision and pharmacopeial properties. In circumstances where modification of existing dosage forms is needed, this offers an alternative reliable means of achieving the intended dose. This technology is also suited to the manufacture of solid dosage forms of small molecules which may be particularly important in the treatment of inflammatory disease. <h3>Disclosure of Interests:</h3> None declared
Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study
Authors: Rebecca C Richmond, Emma L Anderson, Hassan S Dashti, Samuel E Jones, Jacqueline M Lane, Linn Beate Strand, Ben Brumpton, Martin K Rutter, Andrew R Wood, Kurt Straif, Caroline L Relton, Marcus Munafò, Timothy M Frayling, Richard M Martin, Richa Saxena, Michael N Weedon, Debbie A Lawlor, George Davey Smith
Journal: BMJ (2019)

To examine whether sleep traits have a causal effect on risk of breast cancer.
AB0626 INCIDENCE OF SERIOUS INFECTIONS AND PATTERNS OF COTRIMOXAZOLE PROPHYLAXIS IN PATIENTSWITH ANCA-ASSOCIATED VASCULITIDES
Authors: Konstantinos Thomas, Aglaia Chalkia, Dimitrios Drekolias, Christina Tsalapaki, Argyro Lazarini, Kalliopi Klavdianou, Katerina Antonatou, Anastasia Makris, Chrisoula Hatzara, Emilia Hadziyannis, Pinelopi Kouki, Dimitrios Petras, Dimitrios Vassilopoulos
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Infections are among the most serious complications in patients with aNCA-associated vasculitides (AAV) and contribute significantly in overall mortality. <h3>Objectives:</h3> To describe the incidence and risk factors for serious infections, as well as the patterns of cotrimoxazole prophylaxis in aAV patients (GPA and MPA). <h3>Methods:</h3> Retrospective, descriptive study of aAV patients followed in a tertiary referral center (Clinical Immunology-Rheumatology Unit and Nephrology department). Patient and disease characteristics treatments and serious infections were recorded. <h3>Results:</h3> 56 aAV patients were included (women: 50%, mean age at diagnosis: 59.8 years, mean disease duration: 5.1 years, GPA: 68%, generalized disease: 82%). Most frequent organ involvement was renal (71%), lung (68%), nervous (20%), skin (18%) and mucous membranes/eyes (14%). 21 serious infections were recorded in 16 patients (incidence: 7.2 per 100 patient-years), with respiratory tract infections (43%) and herpes zoster (19%) being the most frequent. Incidence was 6.2-times higher in patients with severe combined lung-kidney involvement compared to those without (20 vs 3.2 per 100 patient-years, p&lt;0.001). Plasma exchange and/or hemodialysis (44% vs 12%, p=0.01), age &gt;60 years (62% vs 35%) and treatment with cyclophosphamide (CYC)/rituximab (RTX) combination (38% vs 3%, p=0.001) were more common among those who developed a serious infection. Lung-kidney involvement and combined CYC/RTX treatment remained statistically significant in multivariate logistic regression analysis. Cotrimoxazole prophylaxis was given in 70% of patients treated with CYC and/or RTX (n=46). Patients with combined lung-kidney involvement were more likely to receive prophylaxis (82% vs 58%, p=0.08). No case of pneumocystis pneumonia was diagnosed during follow-up. <h3>Conclusion:</h3> In this real-life cohort, more than one out of four aAV patients experienced a serious infection during follow-up, with pneumonia and herpes zoster being the most frequent. Patients with combined lung and kidney involvement had a ∼6 times higher risk for developing a serious infections and were more likely to receive appropriate cotrimoxazole prophylaxis. <h3>Disclosure of interests:</h3> None declared