tbuckley/cabot-search huggingface dataset:
Sequential vision loss in a patient with headache
Authors: Siegfried Wagner, Saurabh Jain
Journal: BMJ (2016)

A 74 year old woman with a history of bowel cancer and hypertension was admitted under the general medical team from the emergency department because of a constant frontal headache for several weeks and poor oral intake secondary to jaw pain, which was exacerbated by chewing. She described intermittent blurring of vision in her left eye, which had culminated in complete loss of vision three days before presentation. She felt generally unwell with increasing lethargy and generalised myalgia.

On clinical examination she had bilateral tender and pulseless temporal arteries. Fundoscopy of the left eye showed features consistent with central retinal artery occlusion.

Initial blood tests showed raised inflammatory markers (C reactive protein (CRP) 2438 nmol/L, erythrocyte sedimentation rate (ESR) 116 mm in the first hour), and thrombocytosis (platelets 588×109/L). Despite symptomatic and biochemical improvement after prompt institution of appropriate treatment, her right eye deteriorated three days later exhibiting the features seen in the retinal photograph (fig 1⇓). The optic nerve had a swollen pale “chalky white” appearance suggestive of an anterior ischaemic optic neuropathy.



Fig 1  Retinal photograph



1.  What is the diagnosis?

2.  How would you confirm or investigate this diagnosis?

3.  What red flag symptoms should general practitioners be aware of?

4.  How would you treat this condition?

### 1. What is the diagnosis?

#### Short answer

Giant cell arteritis.

#### Discussion

The combination of the patient’s symptoms; the presence of thrombocytosis, raised CRP, and raised ESR; and the fundoscopic appearances is highly suggestive of giant cell arteritis (GCA). Patients with GCA are on average 70 years of age, with a female sex bias, and many have pre-existing polymyalgia rheumatica.1 Symptoms include headache, which can be generalised or localised to the temple, frontal, or occipital region; jaw claudication; and scalp tenderness. Vague constitutional symptoms of malaise, fever, and weight loss may …
Hangover effects on aircraft pilots 14 hours after alcohol ingestion: a preliminary report
Authors: J A Yesavage, V O Leirer
Journal: American Journal of Psychiatry (1986)

Using a repeated measures counterbalanced design, the authors had 10 Navy P3-C Orion pilots fly two carefully designed simulated flights under control (no hangover) and hangover conditions. For the control condition, pilots drank no alcohol within 48 hours before the simulated flight. For the hangover condition, they flew 14 hours after drinking enough ethanol mixed with diet soft drinks to attain a blood alcohol concentration of 100 mg/dl. Pilot performance was worse in the hangover condition on virtually all measures but significantly worse on three of six variance measures and one of six performance measures. The results indicate that caution should be exercised when piloting an aircraft 14 hours or less after ingesting similar quantities of alcohol.
A prospective study on the evolution of the T-cell repertoire in patients with Sézary syndrome treated by extracorporeal photopheresis
Authors: Saskia Ingen-Housz-Oro, Annette Bussel, Béatrice Flageul, Laurence Michel, Louis Dubertret, Philippe Kourilsky, Gabriel Gachelin, Hervé Bachelez, Philippe Musette
Journal: Blood (2002)
The Polynuclear Aromatic Hydrocarbons in Cigarette-Smoke Condensate. II&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: B L VAN DUUREN
Journal: JNCI Journal of the National Cancer Institute (1958)

With the use of methods previously described, the following polynuclear aromatic hydrocarbons, in addition to the 7 previously reported, were detected in cigarette-smoke condensate: chrysene, perylene, benzo[mno]-fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene, 1,2-benz-fluorene, dibenz[a,b]anthracene, a methylbenzo[a]pyrene, benzo[c]-phenanthrene, an alkylfluoranthene, and an alkylchrysene. In addition, one heterocyclic compound, 1,8,9-perinaphthoxanthene, was identified. The concentrations of some of these compounds in cigarette-smoke condensate were determined.
OP0027 Identification of Molecular Disease Drivers Using eQTLS Derived from a Cohort of Rheumatoid Arthritis Patients
Authors: A. Walsh, J.W. Whitaker, C.C. Huang, Y. Cherkas, S. Lamberth, C. Brodmerkel, M. Curran, R. Dobrin
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Genome wide association studies (GWAS) have yielded over 100 genetic loci associated with rheumatoid arthritis (RA). However, the utility of GWAS studies for drug discovery is limited because most GWAS hits do not reside in coding regions and have no known function. Elucidating potential transcriptional regulatory roles of GWAS hits will allow functional annotation of disease-related GWAS loci and lead to better understanding of RA etiology. <h3>Objectives</h3> To identify potential molecular drivers of RA by mapping expression quantitative trait loci (eQTLs) from gene expression and genotype data from a cohort of RA patients. <h3>Methods</h3> eQTLs were mapped using whole blood transcriptome data (Affymetrix microarray) from 377 RA patients with inadequate response to methotrexate enrolled in a clinical trial at baseline. Genotypes were generated from whole genome sequencing of DNA from the same subjects. eQTL mapping was performed by linear regression on adjusted data and FDR was estimated with a permutation method separately for local and distant associations. <h3>Results</h3> We report over 6,000 unique genes with significant eQTLs that represent potential molecular drivers. These eQTLs are enriched for genetic variants associated with RA. Additionally, the genes associated with these RA GWAS loci represent several disease-relevant biological pathways, including antigen presentation and B cell signaling. While there are multiple published eQTL datasets from non-RA cohorts, our analysis suggests that there is utility in detecting eQTLs from disease-relevant cohorts. Indeed, we identified several eQTLs overlapping with RA GWAS loci that have not been reported previously. We also demonstrate that integration with publicly available epigenomics datasets enables elucidation of cell-type-specific relationships. In particular, genes with expression driven by active enhancers in specific immune cell types (e.g., B cells and T helper cells) were identified, generating hypotheses that can be validated experimentally. <h3>Conclusions</h3> As one of the first studies to detect eQTLs from RA patients, this work provides a valuable resource to better understand the genetic basis for RA and aid in translating genetics research into therapeutic interventions. Overall, this analysis highlights the value of studying peripheral blood given the challenge of obtaining large numbers of synovial tissue biopsies from RA patients. <h3>Disclosure of Interest</h3> A. Walsh Employee of: Johnson &amp; Johnson, J. Whitaker Employee of: Johnson &amp; Johnson, C. Huang Employee of: Johnson &amp; Johnson, Y. Cherkas Employee of: Johnson &amp; Johnson, S. Lamberth Employee of: Johnson &amp; Johnson, C. Brodmerkel Employee of: Johnson &amp; Johnson, M. Curran Employee of: Johnson &amp; Johnson, R. Dobrin Shareholder of: Johnson &amp; Johnson, Employee of: Johnson &amp; Johnson
SAT0067 Active Synovitis in Rheumatoid Arthritis Patients while Being on Sdai Remission:
Authors: D. Opris, A. Borangiu, T. Gudu, I. Saulescu, L. Groseanu, D. Predeteanu, A. Balanescu, R. Ionescu
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Active synovitis may persist even with apparent succesfull biologic treatment. <h3>Objectives</h3> To correlate clinical evaluation with disease activity (SDAI) and ultrasound parameters in remission rheumatoid arthritis patients on stable biologic treatment. <h3>Methods</h3> This was a prospective study evaluating rheumatoid arthritis (RA) patients on biologic treatment for at least 6 months. Clinical and US (ultrasound) evaluation were performed by two independent assessors, the same day as all laboratory tests. The scanning technique and the settings of the machine (ESAOTE MY LAB70, 15 MHz linear probe) were the same for all the patients. Examinations were perform by a trained ultrasonografer who was blinded to all clinical evaluations. US of both hands (dorsal wrist, 2nd to 5th volar metacarpophalangeal and 2nd to 4th volar proximal interphalangeal) was done. Synovial hypertrophy and power Doppler (PD) signal were scored (grade 0–3). Synovial hypertrophy &gt;2 plus power Doppler signal was classified as active synovitis. Patients classified as being in SDAI remission were subclassified according to active US synovitis. Statistical analysis was performed using IBM SPSS v20.0. <h3>Results</h3> Initially 106 consecutive RA patients were evaluated, 84% were females, mean age 58.72 (11.49) years, mean disease duration 13.48 (7.4) years. 49.1% (52) patients were treated with rituximab, 27.35% (29) with etanercept, 19.9% (19) with adalimumab, 9.33% (9) with infliximab; 87.7% had a DMARD associated to the biologic. 27.4% (29) subjects were found in SDAI remission, but when US evaluation was performed 51.72% had active synovitis. Significant statistical difference was found between SDAI remission patients with and without active synovitis regarding quantitative CRP, patient9s VAS and SDAI value but not regarding ESR, rheumatoid factor/ACPA or physician global assessment (see table). No significant statistical difference was found between clinical, paraclinical and US parameters when patients were assessed comparing the biologic agent used. <h3>Conclusions</h3> CRP value arround upper normal value, patient9s perception of disease activity and SDAI between 2-3.3 might be useful predictive factors for residual joint inflammation in patients with remission based on composite scores. <h3>Acknowledgements</h3> This paper is partially supported by the Sectoral Operational Program Human Resources Development, financed from the European Social Found POSDRU/159/1.5/S/137390. <h3>Disclosure of Interest</h3> None declared
Healthcare Resource Utilization and Costs Among Patients with Myelodysplastic Syndrome Who Failed 1st-Line Therapy
Authors: Christopher R. Cogle, Sudipto Mukherjee, Tanya GK Bentley, Michael S Broder, Eunice Chang, Moira E. Lawrence, Thomas J. McKearn, Scott Megaffin, Rita Percy, Michael E. Petrone, Gordon H Sun
Journal: Blood (2014)
Alprazolam-induced manic episode in two patients with panic disorder
Authors: J C Pecknold, D Fleury
Journal: American Journal of Psychiatry (1986)

Two patients treated with alprazolam for panic disorder and agoraphobia developed a manic episode. Two biological markers--shortened REM latency and nonsuppression on the dexamethasone suppression test--suggested that both patients may have had an underlying affective disorder.
PWE-334 A proactive approach is required for earlier detection of anastomotic leak: 7-year experience in a dgh
Authors: J Kynaston, J Coles, J Tate
Journal: Gut (2015)

<h3>Introduction</h3> Predictive markers of anastomotic leak have been identified and include the use of post-operative C-reactive protein (CRP). A rising or post-operative day (POD) 3 CRP ≥ 140 is suggestive of anastomotic leak. \We performed a retrospective review of post-operative CRP in anastomotic leak against the timing of clinical or radiologically detected anastomotic leak. <h3>Method</h3> A prospectively collected database was used to identify all colorectal cancer resections over a 7-year period at a District General Hospital. This included both elective and emergency resections. From this data anastomotic leaks were identified. Post-operative CRP at day 1 and 3 and the time of clinical or imaging confirmed leak was retrospectively recorded for these patients. The data was then analysed. Hospital stay and in-hospital mortality was also recorded. <h3>Results</h3> A total of 1311 patients underwent colorectal cancer resections between January 2008 and December 2014. Of these we identified 45 anastomotic leaks (3.4%). These included 31 anterior resections, 8 right hemicolectomy, 4 left hemicolectomy and 2 other. Of the 31 anterior resections 48% (15/31) were de-functioned. 80% (35/44) of anastomotic leaks had a rising CRP and/or CRP ≥ 140 on POD 3. Of these 64% (29/44) had a POD 3 CRP ≥ 140 on its own. 84% (38/45) of patients underwent a diagnostic CT for clinically suspected anastomotic leak. The mean average days to clinical or radiologically detected anastomotic leak was 7 days. The mean average length of stay was 33 days (range 10–88). There was a 4% (2/45) associated in-hospital mortality. <h3>Conclusion</h3> Overall anastomotic leak rate is low. CRP has been shown to be sensitive and clinically relevant in our cohort. A proactive approach responding to CRP could lead to earlier detection of anastomotic leak. We recommend early CT imaging if CRP ≥140 on POD 3. <h3>Disclosure of interest</h3> None Declared.
Progression to COPD in smokers with normal spirometry/low <i>D</i><sub>LCO</sub> using different methods to determine normal levels
Authors: Ben-Gary Harvey, Yael Strulovici-Barel, Robert J. Kaner, Abraham Sanders, Thomas L. Vincent, Jason G. Mezey, Ronald G. Crystal
Journal: European Respiratory Journal (2016)

We thank Drs Quanjer and Miller for their commentaries to our recently published manuscript in the European Respiratory Journal [1]. Our manuscript describes a follow-up study of pulmonary function tests (PFTs) in two groups of healthy smokers with normal post-bronchodilator spirometry and total lung capacity (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and total lung capacity (TLC) ≥80% predicted and FEV1/FVC >0.7, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) initiative) [2–5]. The smokers in one group had normal spirometry and normal diffusion capacity of the lung for CO ( D LCO) defined as ≥ 80% pred (“normal spirometry/normal D LCO”, n=59) and the smokers in the other group had normal spirometry but low D LCO (<80% pred, “normal spirometry/low D LCO”, n=46). The groups were similar in age, sex and ethnicity, with no difference in exposure to risk factors ( i.e. , smoking history, pack-year history, packs per day or age of smoking initiation), cough or sputum scores or emphysema score. At the end of the follow-up period (<4 years, on average, for both groups), 2 (3%) out of 59 of the normal spirometry/normal D LCO smokers developed GOLD-defined COPD (FEV1/FVC <0.7) versus 10 (22%) out of 46 of the normal spirometry/low D LCO smokers (p<0.009). We concluded that despite appearing “normal” by GOLD, smokers with normal spirometry but low D LCO are at significantly higher risk for developing COPD with obstruction to airflow. Smokers with normal spirometry/low D LCO are at higher risk of COPD versus those with normal D LCO <http://ow.ly/4mQBwZ>
Report calls for bold action to prevent early deaths
Authors: Jacqui Wise
Journal: BMJ (2016)

A new report has forecast that 250 000 people in the United Kingdom will die from preventable conditions by 2025 unless major action is taken.1

The report, by a coalition of UK health and social care charities, identifies 12 interventions that could reduce deaths and disability caused by long term illnesses such as coronary heart disease, type 2 diabetes, cancer, chronic lung disease, and dementia. The interventions target smoking, alcohol consumption, poor diet, and physical inactivity.

The World Health Organisation has set a target for a 25% reduction in the numbers of early …
Transfusion Therapy
Authors: Morten Grove-Rasmussen, Mark Falcon Lesses, Harold B. Anstall
Journal: New England Journal of Medicine (1961)

Blood-Group Immunology in Transfusion TherapyOne of the major reasons for the increased safety of blood-transfusion therapy during the last decade is found in the developing knowledge of human blood groups and blood-group immunology during this period.From the basic ABO blood groups discovered by Landsteiner sixty years ago blood grouping has now proceeded to the stage where it is almost certain that Landsteiner's prediction of individuality in bloodgroup pattern as well as fingerprints will hold true. This will mean sthat an absolutely matched blood can only be obtained from the person who is going to receive it or from . . .
Multimedia: Life Without Disease: The Pursuit of Medical Utopia
Authors: Stephen Birch
Journal: BMJ (1999)

William B Schwartz


University of California Press, £17.95, pp 159 




ISBN 0 520 21467 6

———————

Rating: ★★

Schwartz provides a framework for understanding how the increasing potential of a disease-free existence can be reconciled with the pressure for containing costs in a US context. To understand where we are and where we may be headed, the book is divided into separate sections focused on the last half of the 20th century, the next 20 years, and the period leading up to 2050. Each section begins with a discussion of actual or prospective developments in what medicine can do, followed by consideration of the challenges these developments have presented or will present for the organisation of health care in the United States. The underlying theme is that cost control requires rationing in one form or another.

The strength of the book lies in the “potted” descriptions of medical advances past, present, and future. The mind boggles at what we can now do and what we might be able to do. The “boggling” is intensified when one recognises that only a small proportion of the US population has access to many of these advances—a rationing mechanism given little attention within the volume.

Rationing in the United Kingdom, France, Germany, and Canada is described. However, the seven pages devoted to this international perspective fail to do justice to an important and well researched topic. Rationing in the United States in the form of “managed care” is dealt with somewhat superficially in 14 pages, though this is sufficient to illustrate that the “programmes” in question have nothing to do with either patient care or population health and much to do with corporate profits. The author’s own “proposal” is “Oregon-esque” in the underlying principle of seeking the biggest (health) bang for the healthcare buck. However, the Oregon approach is enhanced by recognition that the outcomes of pairings of treatment and disease will vary according to the severity of the condition. Under Schwartz’s approach less severe cases would be less likely to be served (something closely resembling the NHS approach that Schwartz has previously condemned). Emerging evidence shows that healthcare outcomes may be systematically related to other determinants of health, such as the social, cultural, economic, or environmental conditions to which individuals are exposed. The proposed approach would then produce widening disparities in health within societies. Moreover, the approach assumes that the opportunity cost of better health is the same for all—yet the trade-offs underlying “choices for health” may be very different between social groups.

Schwartz considers that “exploding knowledge” begins to make possible the once impossible dream of a disease-free existence and an average life expectancy at birth of 130 years. Whether that knowledge can be turned into wisdom to provide improvements in health expectancy for all our fellow citizens remains to be seen.
Most antidepressants are ineffective in children and teenagers, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Most currently available antidepressants “do not seem to offer a clear advantage” in children and teenagers with major depression, a comprehensive meta-analysis has shown.1

The researchers carried out a systematic review and network meta-analysis of all published and unpublished randomised trials comparing any antidepressant with placebo or with another antidepressant in the acute treatment of major depressive disorder in children and adolescents (mean age 9-18 years). They included 34 trials published from 1986 to 2014 looking at the effects of 14 antidepressants in a total of 5260 participants.

Results showed that only one antidepressant drug, fluoxetine, was significantly more effective …
SAT0179 Ready to Use CE-IVD Smart Elisa Kits from Sanquin for Infliximab and Adalimumab Levels Correlate with the Golden Standard and can be Used for Optimisation of Personalised Treatment in RA Patients
Authors: Y. van Hensbergen, H. te Velthuis
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> An increasing number of studies indicate that the success of treatment with anti-TNF therapy in RA patients depends on circulating levels of these drugs. For (cost-) effective and safe treatment, assays to reliably measure drug levels in patients therefore seem indispensable. <h3>Objectives</h3> To test the performance of the newly developed, ready to use CE-IVD SMART ELISA kits from Sanquin for measuring circulating levels of adalimumab and infliximab. And to verify its role as tool for optimising the treatment of RA patients with these drugs. <h3>Methods</h3> The ready to use, complete SMART ELISA kits for infliximab (Remicade®) and adalimumab (Humira®) were developed to measure levels in serum, Li-heparin and EDTA plasma. The drugs bind to recombinant TNF coated on the plate through anti-TNF antibodies. Subsequently, the drugs are detected with drug specific HRP-conjugated monoclonal antibodies. Controls are developed for the clinical low and normal concentration range. The performance of the new kits was tested and we did a method comparison with the in-house test of Sanquin Diagnostic Services, the current golden standard. <h3>Results</h3> The kit covers the clinically relevant drug concentration range. For samples with concentrations within the clinically relevant area, all recommended dilutions (1:200, 1:1500, 1:2000) give similar results (%CV&lt;10%). In addition, both intra-assay and inter-assay reliability are good (%CV&lt;10%) as well as the precision of the SMART ELISA kits, including for the low (drug ±1 μg/mL) and high control (drug ±5 μg/mL) (%CV&lt;10%). The new CE-IVD kits highly correlated with the well-established tests of Sanquin Diagnostic Services (slope Passing and Bablok 0.9 – 1.1, correlation ≤0.95). Concordance tables for drug concentrations in the low, adequate and high drug concentration range show that more than 95% of the samples were categorized identical. <h3>Conclusions</h3> This study shows that ready to use CE-IVD SMART ELISA kits from Sanquin for adalimumab and infliximab levels are highly reliable, with results that are identical to the results from Sanquin Diagnostic Services. This makes the tests an excellent tool for diagnostic laboratories to monitor drug levels in RA patients in order to achieve (cost-) effective, safe and personalised treatment. <h3>Disclosure of Interest</h3> None declared
Positive and negative symptoms and social competence in adolescents at risk for schizophrenia and affective disorder
Authors: R H Dworkin, S R Green, N E Small, M L Warner, B A Cornblatt, L Erlenmeyer-Kimling
Journal: American Journal of Psychiatry (1990)

The authors compared adolescents at risk for schizophrenia and affective disorder and normal adolescents. The subjects at risk for schizophrenia had significantly poorer social competence, and formal thought disorder was greater in both high-risk groups. There were no group differences in negative symptoms.