tbuckley/cabot-search huggingface dataset:
P225 Identifying asthma patients in Wales using latent class analysis of routine data
Authors: M Al Sallakh, SE Rodgers, RA Lyons, A Sheikh, GA Davies
Journal: Thorax (2015)

<h3>Background</h3> The Wales Asthma Observatory aims to produce current estimates of asthma prevalence and disease burden using routine data. In the absence of a feasible gold standard to validate case definitions, latent class analysis (LCA) can be employed. <h3>Objectives</h3> To estimate the prevalence of treated asthma in Wales using LCA of routine health data. <h3>Methods</h3> We performed LCA using observed variables of asthma-related healthcare diagnostics and utilisation in the fiscal year 2011–2012 for a random sample of 98,042 individuals in the Secure Anonymised Information Linkage (SAIL) databank. The observed variables were chosen if they exhibited expected distributions. Diagnostic performance of each of the observed variables was calculated. The model was tested for stability over multiple time windows and small area configurations. Since COPD can be misdiagnosed as asthma, a separate LCA was performed to identify COPD patients and cross-validate the asthma model. <h3>Results</h3> Our LCA model estimated the prevalence of treated asthma in Wales in 2011–2012 as 8.9% (95% CI: 8.7%–9.1%), which was higher than estimates from the Quality and Outcome Framework (6.9%), but lower than both the prevalence of self-reported treated asthma estimated by the Welsh Health Surveys in 2011 (11.0%) and 2012 (10.0%) and the prevalence of ‘GP reported and treated asthma’ from the ‘True Costs of Asthma in the UK’ project (13.0%). In our model, prescription of any asthma medication had the highest accuracy among other observed variables (sens. = 99%; spec. = PPV = NPV = 100%), while asthma diagnosis variable had a lower accuracy (sens. = 66%; spec. = 94%; PPV = 51%; NPV = 97%). In the same sample, COPD prevalence was 2.0% (95% CI: 1.9%–2.1%) with only 2.8% of those classified as asthmatics were also classified as having COPD. <h3>Conclusion</h3> Our LCA model provides a reasonable, data-driven, reference identification of people with treated asthma in Wales. Further work is needed to explore potential reasons for the observed differences in the estimates from other sources.
Case 23-2001
Authors: Christopher P. Duggan, Joseph Misdraji
Journal: New England Journal of Medicine (2001)

Presentation of CaseAn 18-month-old girl was admitted to the hospital because of diarrhea with intermittent constipation and vomiting.The child had been born by cesarean section, performed because of a breech presentation, at 41 weeks' gestation; it was the mother's first pregnancy. The child's immunizations were up to date. She had had otitis media at 13 months of age. She was fed cow's milk–protein formula and grew normally, without diarrhea. At 15 months, her weight was 9.8 kg (30th percentile). Her only medication was a fluoride supplement.Six weeks before admission, the child became irritable, and diarrhea developed, with . . .
Massive Bowel Infarction
Authors: Donald J. Glotzer, Robert S. Shaw
Journal: New England Journal of Medicine (1959)

RECENT experience at this hospital and elsewhere suggests that certain cases of massive bowel infarction from arterial insufficiency can be satisfactorily handled by a direct approach to the occluded artery, by either embolectomy1 2 3 or thromboendarterectomy,4 thus expanding therapeutic possibilities in patients in whom resection would be impossible or crippling. Cases have been encountered, however, in which this approach has not been rewarding — for example, where no obstructions are found in the mesenteric vessels despite bowel infarction or where ischemia persists after early and complete embolectomy. In both situations bowel ischemia has been apparently due to a factor other than . . .
430P Direct comparison of diagnostic accuracy between autofluorescence bronchoscopy (AFB) and AFB combined with white light bronchoscopy (AFB + WLB) for lung cancer and precancerous lesions: a systematic review and meta-analysis
Authors: J. Zhang, J. Wu, Y. Yang, H. Liao, Z. Xu, Z. Liang, J. Huang, L. Jiang, X. Zou, Y. Chen, W. Liang, J. He
Journal: Annals of Oncology (2015)
Bortezomib(Velcade) induces p27kip1 associated cell cycle arrest and apoptosis through down-regulation of SKP2 ubiquitin ligase pathway in colorectal carcinoma
Authors: Shahab Uddin, Maqbool Ahmed, Prashant Bavi, Nasser Al-Sanea, Alaa AbdulJabbar, Luai Ashari, Samar Alhomoud, Fouad Al-Dayel, Azhar Hussain, Khawla Al-Kuraya
Journal: Cancer Research (2008)

3265   SKP2, an F-box protein targets cell cycle regulators including cycle-dependent kinase inhibitor p27Kip1 via ubiquitin-mediated degradation. SKP2 is frequently overexpressed in variety of cancers. We investigated the role of SKP2 and its ubiquitin-proteasome pathway in colorectal carcinoma using a panel of cell lines, clinical samples and NUDE mouse model. Using immunohistochemical analysis on a large tissue microarray of 448 samples, an inverse association of SKP2 expression with p27Kip1 protein levels was seen. CRC subset with high level of SKP2 and low level of p27Kip1 showed a decreased overall survival (p=0.0057). Treatment of CRC cell lines with Bortezomib or expression of siRNA of SKP2 causes downregulation of SKP2 and accumulation of p27Kip1. Furthermore treatment of CRC cells with Bortezomib causes apoptosis via involving mitochondrial pathway and activation of caspases. In addition, treatment of CRC cells with Bortezomib downregulated the expression of XIAP, cIAP1 and survivin. Finally, treatment of CRC cell line xenografts with Bortezomib resulted in growth inhibition of tumors in NUDE mice via downregulation of SKP2 and accumulation of p27Kip1. Altogether, our results suggest that SKP2 and ubiquitin-proteasome pathway may be a potential target for therapeutic intervention for treatment of CRC.
Association of the hemochromatosis (HFE) gene with pazopanib-induced transaminase elevations in renal cell carcinoma.
Authors: C. Xu, B. H. Reck, V. L. Goodman, Z. Xue, L. Huang, C. F. Spraggs, V. E. Mooser, L. R. Cardon, L. Pandite
Journal: Journal of Clinical Oncology (2010)

3019 Background: Pazopanib (Votrient) has demonstrated clinical activity against multiple tumour types and is generally well tolerated. However, isolated elevations in transaminases have been observed. This study sought to identify genetic determinants of alanine aminotransferase (ALT) elevations in pazopanib-treated renal cell carcinoma (RCC) patients (pts). Methods: A two-stage strategy was adopted in a candidate gene analysis of 7358 markers in 282 genes. All markers were analysed using an exploratory dataset of 116 Caucasians from a phase II study. Association was examined both as continuous variables in a quantitative trait analysis and as discrete values in a case control analysis, with cases defined as pts with maximum on-treatment ALT ≥3 × upper limit of normal (ULN). Markers with p value < 0.01 for association were analysed in an independent dataset of 130 Caucasians from a phase III study. Results: 92 polymorphisms in 40 genes were associated with ALT elevation (p < 0.01) in the exploratory dataset. Only two markers (rs2858996 and rs707889) showed evidence for replication (p < 0.01), both of which are in the HFE gene and are in strong linkage disequilibrium (r2∼1). In the combined dataset, the median (25th- 75th percentile) maximum ALT values were 1.2 (0.7-1.9), 1.1 (0.8-2.5), and 5.4 (1.9-7.6) ×ULN for the rs2858996 GG (n=148), GT (n=82), and TT (n=12) genotypes, respectively. All 12 TT pts had maximum ALT ≥1 xULN, and eight (67%) had ALT ≥3 xULN. Among pts with ALT ≥3×ULN, 17% (8/48) carried the risk TT genotype. Reversibility was documented in 7/8 TT pts; the last pt had withdrawn prior to complete reversal. None of the TT pts developed liver failure. The odds ratio (95% CI) for ALT ≥3×ULN for TT genotype was 39.7 (2.2-703.7) compared to other genotypes. As a predictor of ALT ≥3× ULN, the TT genotype had a negative predictive value of 0.83 and positive predictive value of 0.67. Similar findings were observed for rs707889. Conclusions: Germline genetic variants in the HFE gene were associated with ALT elevation in pazopanib-treated RCC pts. This genetic polymorphism was present in 17% of the pts with ALT elevations and the clinical outcomes appear similar to other pts with ALT elevation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Physical activity guidelines for weight loss: global and national perspectives
Authors: Leon Mabire
Journal: British Journal of Sports Medicine (2016)

Obesity, an excess accumulation of fat mass, poses a significant health risk. A recent review of 1.8 million participants, using body mass index (BMI) as the main measure of adiposity, identified high BMI as the leading risk factor for non-communicable diseases (NCDs), with each gain of one point in BMI, above a BMI of 25 kg/m2, equating to a 5% increase in the risk of NCDs.1 Physical activity is an integral component of a package of lifestyle change used to reduce obesity, but there are no global recommendations on the dose of physical activity required for weight loss for overweight and obese adults.

The challenge faced by policymakers is that physical activity confers a systemic physiological and metabolic response that is proportional to the stimulus, and that response is modified by individual variation in age, sex, ethnicity, weight, height, body composition and functional ability. In the absence of specific global recommendations on physical activity for weight loss …
Case 17-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, John H. Growdon, Jean-Paul Vonsattel
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 53-year-old woman died after several years of a dementing illness with intermittent grand-mal seizures and abnormal movements of the extremities.The patient had been well until the age of 47 years, when she became depressed after her son was killed in a traffic accident by a drunken driver. She was treated with doxepin and counseling and returned to her clerical position one week later. Two years thereafter physical examination and laboratory examinations were reported to be negative. The patient took a leave of absence from her job, tapered the dose of doxepin and discontinued the use . . .
Induction of Minor Histocompatibility Antigen HA-1–Specific Cytotoxic T Cells for the Treatment of Leukemia After Allogeneic Stem Cell Transplantation
Authors: Peter Brossart, Brigitte Spahlinger, Frank Grünebach, Gernot Stuhler, Volker L. Reichardt, Lothar Kanz, Wolfram Brugger
Journal: Blood (1999)
Is grossly oversold
Authors: A. Hopkins, S. Shorvon
Journal: BMJ (1995)

Dying for palliatdve care EDrroR,-It seems appropriate that articles communicating poor recognition of the palliative care philosophy should have space "afforded" to them.'They emphasise the crisis in caring for dying people despite the creation of a specialty and reiterate results of other studies showing that patients are still dying unprepared and suffering.2The reason for this is twofold.Firstly, there is still a reluctance to inform patients with cancer of their diagnosis and, through a process of informed consent, to negotiate the appropriateness of active treatment.'Greater emphasis should be placed on distinguishing between cure and care.Furthermore, cure should not be perceived as the only successful outcome of treatment, with anything less as failure.Secondly, a deficit in training exists, which is exacerbated by an inappropriate reliance on specialists in palliative medicine.Most patients do not die in hospices, and so the philosophy of care is most frequently practised by inadequately prepared generalists in the community and hospitals.Dying remains a taboo subject, and the recent articles and correspondence convey a message: where is palliation, dignity, and death as a normal part of the life cycle?In addition, why do some doctors avoid admitting that a patient is dying and why are they reluctant to provide sufficient symptom control?Training in palliative care, for both undergraduates and postgraduates, must be urgently addressed to prevent continuing suffering of terminally ill patients who are not in hospices.As the head of the Cancer and Palliative Care Unit at the World Health Organisation's headquarters, Dr J Stjemsward, stated, "Nothing would have more immediate effect on quality of life and relief from suffering, not only for cancer patients but also for their families, than implementing the knowledge accumulated in the field ofpalliative care."4
Cushing's Syndrome Due to an ACTH-Secreting Chromophobe Adenoma
Authors: Joseph F. Dingman, Nicholas Y. Lim
Journal: New England Journal of Medicine (1962)

NELSON et al.1 , 2 recently described the occurrence of ACTH-secreting chromophobe adenomas in patients with adrenocortical hyperplasia after bilateral total adrenalectomy. Since then, others3 , 4 have reported similar cases, some of which showed enlargement of the sella turcica before adrenalectomy. In none of these cases, however, was the diagnosis of an ACTH-secreting chromophobe adenoma established at the outset, and the present evidence favoring a pituitary etiology is based on retrospective reasoning and demonstration of abnormally high levels of ACTH in the plasma and pituitary glands of adrenalectomized patients.1 , 2 , 5 To our knowledge the only reported case of pituitary tumor with elevated plasma ACTH . . .
PTH-095 Surreptitious use of non-steroidal anti-inflammatory drugs and aspirin may be responsible for small bowel injury seen by capsule endoscopy
Authors: R Sidhu, S Morley, L Brunt, D S Sanders, M E McAlindon
Journal: Gut (2010)

<h3>Introduction</h3> Non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin can cause small bowel injury and present with anaemia, bleeding or symptoms suggestive of Crohn9s disease, the most common indications for capsule endoscopy (CE). Previous studies have suggested that the surreptitious use of these drugs may be a common cause of unexplained peptic ulcer disease.1 We hypothesised that surreptitious NSAID or aspirin use occurred in patients undergoing CE and that this might be responsible for symptoms or abnormalities being investigated. <h3>Methods</h3> Demographic data, indications for CE and medications were recorded prospectively. A salicylate spot test and gas chromatography mass spectrometry for NSAID metabolites were performed on urine samples of consecutive patients undergoing routine CE. Videos were analysed by an experienced gastroenterologist who was blinded to the urinalysis results. <h3>Results</h3> Seventy-six patients (52 female; mean age 50 years) underwent CE for suspected small bowel pathology. Urinalysis was positive in 13.6% of patients (n=10/76), although only one of these patients declared the relevant drug (aspirin) in their drug history. The indication for CE in the 10 patients included iron deficiency anaemia (n=2), investigation of suspected active Crohn9s disease (n=7) and possible coeliac complications (n=1). The presence of salicylates was detected in 3.9% of patients (n=3) while NSAID metabolites were detected in 9.2% (n=7: 6 patients ibuprofen alone and both ibuprofen and diclofenac in 1 patient). While CE was normal in 2 patients, positive findings were seen in 80% of patients (n=8) which included the presence of erosions± red patches in 5 patients, small bowel ulceration in 2 patients and ulceration with early stricturing in one patient. Follow-up data revealed that the patient with small bowel stricturing was subsequently diagnosed as Crohn9s disease while a patient with small bowel ulceration underwent small bowel resection at a further presentation which confirmed NSAID enteropathy histologically. <h3>Conclusion</h3> 13.6% of patients undergoing capsule endoscopy were taking NSAIDs or aspirin, of which the majority were not declared in the clinical history. In 11.8% of patients, NSAIDs or aspirin could have been contributing to the symptoms or anaemia being investigated. Patients should be carefully questioned about their use of these drugs and over the counter medications which might contain them, prior to CE.
PTU-088 Has the European Working Time Directive affected gastrointestinal trainees?
Authors: J S Leeds, R Sidhu, A J Lawson, A Z Haidery, A J Lobo, D S Sanders
Journal: Gut (2010)

<h3>Introduction</h3> The European Working Time Directive (EWTD) came into force in August 2009 and dictates that junior doctors should not work &gt;48 h on an average week. Many trusts have had to alter on call rotas to be compliant with the directive. Many trainees, particularly in procedure based specialities, have been concerned about the reduction in procedural training. Previous studies have mainly looked at number of hours worked and not the impact on number of procedures performed or new patients seen in outpatients. Our aim was to examine the effect of the EWTD on important training areas; number of colonoscopies performed, number of ERCPs performed and new outpatients seen by gastroenterology trainees. <h3>Methods</h3> Working hours changed from 56 h per week to 48 h per week in February 2009. In our unit, this was delivered by increasing numbers of days off during a full rota cycle without changing individual timetables. Personal logs and local IT systems were examined for 6 months prior to and for 6 months following the change to determine number of new patients seen in outpatients and number of colonoscopies/ERCPs performed. Only three of the trainees attended colonoscopy lists as the fourth post is a hepatology fellowship post and only two of the trainees performed ERCP. Both periods included the same amount of annual and study leave. <h3>Results</h3> From August 2008 to February 2009 the four trainees saw 602 new patients and were present at/performed 196 colonoscopies. The two trainees performing ERCP attended/performed 120 procedures during this period. From February 2009 to August 2009 there was a reduction in the number of colonoscopies attended/performed down to 160 (19.4% reduction, p=0.002). There was also a reduction in the number of new patients seen to 456 (24.3% reduction, p=0.01). There was a reduction in the number of ERCPs performed to 104 (13.3% reduction, p=0.1) but this was not statistically significant. Extrapolating these figures to a 5-year training programme, under the 48 h limit trainees would see 730 less new patients, perform 180 less colonoscopies and 80 less ERCPs. Each reductions of these accounts for around a least a year of training. <h3>Conclusion</h3> There has been significant impact of the EWTD on training in gastroenterology particularly in colonoscopy training and new patient assessment. ERCP may be impacted however the current numbers are too small. New models of training will be required to address this problem perhaps focusing on post training fellowships.
SOME FACTORS IN WOUND HEALING
Authors: T A McLennan
Journal: JAMA (1934)

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Spontaneous Rupture of the Normal Esophagus
Authors: Richard E. Alt, Frank E. Bixby, Russell J. Rowell
Journal: New England Journal of Medicine (1953)

WITHIN a month during the past spring we had the unusual experience at the Beverly Hospital of caring for 2 patients with spontaneous rupture of the esophagus. Although this condition is not a medical curiosity, it is infrequent, and as a result, the clinical picture is not widely recognized. If this accident is undiagnosed and untreated, the result is invariably fatal. There are few other surgical emergencies in which early diagnosis and prompt treatment are so necessary to save life. The chief cause of death is delay, and the cause of delay is that esophageal rupture is not suspected. Yet . . .
Clinical Evaluation of Aureomycin and Chloramphenicol in Herpes Zoster
Authors: Edward H. Kass, Robert R. Aycock, Maxwell Finland
Journal: New England Journal of Medicine (1952)

FROM a previous study of 24 consecutive cases of herpes zoster treated with aureomycin1 the impression was gained that this antibiotic favorably influenced the course of the cutaneous lesions. Although postherpetic pain was not prevented in patients whose treatment was begun more than two weeks after the first appearance of the lesions, such pain was infrequent in those whose treatment was begun early and maintained in adequate dosage. Similar favorable results from the use of either aureomycin2 3 4 5 6 7 8 9 10 11 12 13 14 15 or chloramphenicol15 16 17 18 19 20 21 in isolated cases or in small numbers of cases of herpes zoster have now been reported by many observers.One report, . . .