tbuckley/cabot-search huggingface dataset:
Do Findings on Routine Examination Identify Patients at Risk for Primary Open-Angle Glaucoma?
Authors: Hussein Hollands, Davin Johnson, Simon Hollands, David L Simel, Delan Jinapriya, Sanjay Sharma
Journal: JAMA (2013)

Glaucoma is the second leading cause of blindness worldwide, and its insidious onset is often associated with diagnostic delay. Since glaucoma progression can often be effectively diminished when treated, identifying individuals at risk for glaucoma could potentially lead to earlier detection and prevent associated vision loss.To quantify the diagnostic accuracy of examination findings and relevant risk factors in identifying individuals with primary open-angle glaucoma (POAG), the most common form of glaucoma in North America.Structured Medline (January 1950-January 2013) search and a hand search of references and citations of retrieved articles yielding 57 articles from 41 studies.Population-based studies of high-level methods relating relevant examination findings of cup-to-disc ratio (CDR), CDR asymmetry, intraocular pressure (IOP), and demographic risk factors to the presence of POAG.The summary prevalence of glaucoma in the highest-quality studies was 2.6% (95% CI, 2.1%-3.1%). Among risk factors evaluated, high myopia (≥6 diopters; odds ratio [OR], 5.7; 95% CI, 3.1-11) and family history (OR, 3.3; 95% CI, 2.0-5.6) had the strongest association with glaucoma. Black race (OR, 2.9; 95% CI, 1.4-5.9) and increasing age (especially age >80 years; OR, 2.9; 95% CI, 1.9-4.3) were also associated with an increased risk. As CDR increased, the likelihood for POAG increased with a likelihood ratio (LR) of 14 (95% CI, 5.3-39) for CDR of 0.7 or greater. Increasing CDR asymmetry was also associated with an increased likelihood for POAG (CDR asymmetry ≥0.3; LR, 7.3; 95% CI, 3.3-16). No single threshold for CDR or asymmetry ruled out glaucoma. The presence of a disc hemorrhage (LR, 12; 95% CI, 2.9-48) was highly suggestive of glaucoma, but the absence of a hemorrhage was nondiagnostic (LR, 0.94; 95% CI, 0.83-0.98). At the commonly used cutoff for high IOP (≥22), the LR was 13 (95% CI, 8.2-17), while lower IOP made glaucoma less likely (LR, 0.65; 95% CI, 0.55-0.76). We found no studies of screening examinations performed by generalist physicians in a routine setting.Individual findings of increased CDR, CDR asymmetry, disc hemorrhage, and elevated IOP, as well as demographic risk factors of family history, black race, and advanced age are associated with increased risk for POAG, but their absence does not effectively rule out POAG. The best available data support examination by an ophthalmologist as the most accurate way to detect glaucoma.
Ankle injuries in basketball: injury rate and risk factors
Authors: G D McKay
Journal: British Journal of Sports Medicine (2001)

<i>Objectives</i>—To determine the rate of ankle injury and examine risk factors of ankle injuries in mainly recreational basketball players. <i>Methods</i>—Injury observers sat courtside to determine the occurrence of ankle injuries in basketball. Ankle injured players and a group of non-injured basketball players completed a questionnaire. <i>Results</i>—A total of 10 393 basketball participations were observed and 40 ankle injuries documented. A group of non-injured players formed the control group (n = 360). The rate of ankle injury was 3.85 per 1000 participations, with almost half (45.9%) missing one week or more of competition and the most common mechanism being landing (45%). Over half (56.8%) of the ankle injured basketball players did not seek professional treatment. Three risk factors for ankle injury were identified: (1) players with a history of ankle injury were almost five times more likely to sustain an ankle injury (odds ratio (OR) 4.94, 95% confidence interval (CI) 1.95 to 12.48); (2) players wearing shoes with air cells in the heel were 4.3 times more likely to injure an ankle than those wearing shoes without air cells (OR 4.34, 95% CI 1.51 to 12.40); (3) players who did not stretch before the game were 2.6 times more likely to injure an ankle than players who did (OR 2.62, 95% CI 1.01 to 6.34). There was also a trend toward ankle tape decreasing the risk of ankle injury in players with a history of ankle injury (p = 0.06). <i>Conclusions</i>—Ankle injuries occurred at a rate of 3.85 per 1000 participations. The three identified risk factors, and landing, should all be considered when preventive strategies for ankle injuries in basketball are being formulated.
S167 Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic obstructive pulmonary disease
Authors: M. Rashid, J. Brown, H. Z. Ling, M. Mendonca, S. Kang, R. Sofat, M. Okorie, M. Thomas, S. Woldman, H. Booth, D. okonko
Journal: Thorax (2010)

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) is a multi-system disorder driven partly by diffuse inflammation, malnutrition and haematological aberrations. Because the red blood cell distribution width (RDW) is a surrogate of these anomalies, we hypothesised that it might be of prognostic importance in COPD patients. Additionally, we tested the supposition that iron deficiency (ID) per se could be a prevalent and ominous co-morbidity in these individuals. <h3>Methods</h3> We analysed the relation of red cell indices on admission and over time with mortality in 655 consecutively eligible COPD patients (mean±SD age 77±12 y, FEV1 0.85±0.34 l, FVC 1.44±0.60 l, 54% male). Concomitant heart failure, ischaemic heart disease, and neoplasia were exclusion criteria. The combination of a high RDW and low mean cell haemoglobin (MCH) was utilised to identify ID. <h3>Results</h3> On admission, an RDW&gt;15%, Hb&lt;12.5 g/dl, MCH&lt;27, and ID were evident in 33%, 31%, 12% and 10% of patients. Compared to those with an RDW≤15%, patients with levels &gt;15% had lower Hbs, lower FEV1s, and longer median (±IQR) hospital stays (9±11 vs 8±8 days, P&lt;0.001). Over a mean period of 40±29 months, 227 (35%) patients died. On Cox proportional hazards analyses, a higher RDW predicted increased mortality (adjusted χ<sup>2</sup> 16, P&lt;0.0001) independently of age (χ<sup>2</sup> 11, P&lt;0.001), FEV1 (χ<sup>2</sup> 5, P&lt;0.03), Hb and creatinine (latter two not retained in model) and provided graded prognostic information (abstract S167 figure 1A) incremental to that of FEV1 (P&lt;0.05 for change in χ<sup>2</sup>). Over time, 63%, 72%, 65%, and 46% of patients had a rise in RDW, a fall in Hb, a fall in MCH, and evolving ID (rising RDW and falling MCH), respectively. A rising RDW predicted death (adjusted χ<sup>2</sup> 32, P&lt;0.0001) independently of baseline RDWs and changes in Hb, with an increase greater than 0.03% per month associated with a twofold escalated risk of mortality (Abstract S167 Figure 1B). Evolving ID was also associated with poorer survival (Abstract S167 Figure 1C). <h3>Conclusions</h3> An elevated RDW alone and iron deficiency predict an amplified risk of death in COPD and could be utilised for risk stratification or therapeutically targeted to improve outcomes.
Second-line chemotherapy with pegylated liposomal doxorubicin and carboplatin is highly effective in patients with advanced ovarian cancer in late relapse: a GINECO phase II trial
Authors: J.-M. Ferrero, B. Weber, J.-F. Geay, D. Lepille, H. Orfeuvre, M. Combe, F. Mayer, B. Leduc, H. Bourgeois, D. Paraiso, E. Pujade-Lauraine
Journal: Annals of Oncology (2006)
CpG Island Methylator Phenotype Redefines the Prognostic Effect of t(12;21) in Childhood Acute Lymphoblastic Leukemia
Authors: Jose Roman-Gomez, Antonio Jimenez-Velasco, Xabier Agirre, Juan A. Castillejo, German Navarro, Maria J. Calasanz, Leire Garate, Edurne San Jose-Eneriz, Lucia Cordeu, Felipe Prosper, Anabel Heiniger, Antonio Torres
Journal: Clinical Cancer Research (2006)

To examine cancer genes undergoing epigenetic inactivation in a set of ETV6/RUNX1-positive acute lymphoblastic leukemias in order to define the CpG island methylator phenotype (CIMP) in the disease and evaluate its relationship with clinical features and outcome.Methylation-specific PCR was used to analyze the methylation status of 38 genes involved in cell immortalization and transformation in 54 ETV6/RUNX1-positive samples in comparison with 190 ETV6/RUNX1-negative samples.ETV6/RUNX1-positive samples had at least one gene methylated in 89% of the cases. According to the number of methylated genes observed in each individual sample, 20 patients (37%) were included in the CIMP- group (0-2 methylated genes) and 34 (67%) in the CIMP+ group (>2 methylated genes). Remission rate did not differ significantly among either group of patients. Estimated disease-free survival and overall survival at 9 years were 92% and 100% for the CIMP- group and 33% and 73% for the CIMP+ group (P = 0.002 and P = 0.04, respectively). Multivariate analysis showed that methylation profile was an independent prognostic factor in predicting disease-free survival (P = 0.01) and overall survival (P = 0.05). A group of four genes (DKK3, sFRP2, PTEN, and P73) showed specificity for ETV6/RUNX1-positive subset of samples.Our results suggest that methylation profile may be a potential new biomarker of risk prediction in ETV6/RUNX1-positive acute lymphoblastic leukemias.
OC-004 In Vitro Steroid Sensitivity Accurately Predicts 6 Month Mortality in Patients with Severe Alcoholic Hepatitis
Authors: A Dhanda, A Di Mambro, A McCune, F Gordon, J Portal, P Collins
Journal: Gut (2013)

Introduction Severe alcoholic hepatitis (SAH) has a high mortality especially in those who fail to respond to steroid treatment. Early identification of steroid resistant patients may allow rapid implementation of other therapies, which may improve patient outcome. An early change in bilirubin has prognostic value but requires 7 days of steroid treatment first. Our group have previously reported that a simple 48h in vitro method for assessing steroid sensitivity (dexamethasone inhibition of lymphocyte proliferation; DILPA) correlates with 6 month mortality in patients with SAH[1]. We aimed to determine the accuracy of the DILPA in predicting outcome and to compare it to existing models of prognosis in SAH. Methods Peripheral blood was drawn from consecutive patients with a clinical diagnosis of SAH (Maddrey discriminant function [MDF] > 32). All subjects gave informed consent and ethical approval was obtained from the regional ethics committee. The primary outcome measure was 6 month mortality. Leukocytes, isolated by density gradient centrifugation, were cultured for 48h with the mitogen PHA in the presence or absence of dexamethasone. Tritiated thymidine was added for the final 6h of culture before proliferation was measured on a beta counter. Maximum suppression of lymphocyte proliferation by dexamethasone was calculated (Imax). An Imax of < 60% indicates in vitro steroid resistance as previously determined. The accuracy of the DILPA and existing scoring systems (MDF, MELD, Glasgow and Lille scores) was calculated by area under the receiver operating characteristic (AUROC). Logistic regression of baseline and day 7 parameters was performed to determine independent predictors of outcome. Results 43 patients were recruited (21% female, median age 45). Patients who survived 6 months had a significantly higher Imax than those who didn’t (79.2% v 41.7%; p = 0.0003). An Imax of > 60% had a 88% sensitivity and 78% specificity in predicting 6 month survival and an AUROC of 0.83. MDF, MELD, Glasgow and Lille scores all had lower AUROC values for predicting 6 months survival than Imax (0.36, 0.4, 0.49 and 0.61 respectively). A stepwise logistic regression demonstrated that only Imax, Day 0 albumin and change in bilirubin at Day 7 of treatment were independent predictors of 6 month survival. Conclusion The DILPA provides a simple, fast and accurate in vitro method of predicting clinical outcome in patients with SAH. This could be applied in clinical practise to identify patients who will not respond to steroid therapy within 2 days of starting treatment. Disclosure of Interest None Declared Reference 1. Di Mambro et al. Hepatology 2011;53:1316–22.
Spectrum of Vibrio Infections in a Gulf Coast Community
Authors: JAMES R. BONNER
Journal: Annals of Internal Medicine (1983)

Infection with Vibrio species was diagnosed in 23 patients over a 10-year period in a Gulf Coast community. Species isolated were Vibrio vulnificus, V. cholerae, V. parahaemolyticus, and V. alginolyticus. Clinical presentations included diarrhea, wound infection, and bacteremia. Gastrointestinal tract infection was infrequently diagnosed, despite the routine use of stool culture media appropriate for vibrio isolation. Bacteremic infections were severe and occurred only in patients with underlying diseases. Wound infections were complicated by tissue necrosis and required surgical debridement. In patients with underlying diseases, soft tissue infections often progressed to fatal septicemias.
THE CARDIAC ION CHANNELS: Relevance to Management of Arrhythmias
Authors: Dan M. Roden, M.D, Alfred L. George
Journal: Annual Review of Medicine (1996)

▪ Abstract The electrical activity of cardiac tissue is determined by the highly regulated flow of ions across the cell membrane during the cardiac action potential. Ion channels are pore-forming proteins through which these electric currents flow. In this review, the ion currents that underlie the action potential are first described. Then, the way in which expression of individual ion-channel genes results in such ion currents is discussed. Finally, the concept that arrhythmias may be due to abnormalities of structure, function, or number of ion channels, or the way in which they respond to abnormalities in their environment (such as acute ischemia), is reviewed. Further understanding of the molecular mechanisms underlying normal and abnormal cardiac electrophysiologic behavior should allow the development of safer and more effective antiarrhythmic interventions.
Heterogeneity of narrowing in normal and asthmatic airways measured by HRCT
Authors: G.G. King, J.D. Carroll, N.L. Müller, K.P. Whittall, M. Gao, Y. Nakano, P.D. Paré
Journal: European Respiratory Journal (2004)

Asthmatic airway narrowing is heterogeneous and contributes to airway hyperresponsiveness. The present study compared heterogeneity of narrowing during methacholine challenge in asthmatics and normal subjects using high-resolution computed tomography (HRCT). The current authors defined heterogeneity as variability in narrowing greater than the repeatability of measurement. Airways of &lt;2 mm diameter were compared with larger airways from baseline and postmethacholine HRCT of the right lower lung in 13 normals (seven had repeat baseline scans) and seven asthmatics. The coefficient of repeatability was calculated from repeat scans (RepAi) and was compared with heterogeneity of narrowing measured by the variability in narrowing from pre versus postmethacholine scans (VarΔAi). Forced expiratory volume in one second decreased 27±6% and 24±8% in normals and asthmatics, respectively. Airways &gt;2 mm narrowed more heterogeneously in asthmatics (VarΔAi=±0.85 mm) compared with normals (VarΔAi=±0.67 mm), with both being greater than the measure of repeatability (RepAi=±0.16 mm). Small airway narrowing was not heterogeneous in asthmatics (VarΔAi=±0.59 mm) or normals (VarΔ Ai =±0.53 mm) compared with repeatability (RepAi=0.51 mm). It is possible to study heterogeneity of airway narrowing in small and large airways using high resolution computed tomography. Airway narrowing is heterogeneous in the large airways of asthmatics and normals, being greater in asthmatics.
The Relationship of Mucus Concentration (Hydration) to Mucus Osmotic Pressure and Transport in Chronic Bronchitis
Authors: Wayne H. Anderson, Raymond D. Coakley, Brian Button, Ashley G. Henderson, Kirby L. Zeman, Neil E. Alexis, David B. Peden, Eduardo R. Lazarowski, C. William Davis, Summer Bailey, Fred Fuller, Martha Almond, Bahjat Qaqish, Elena Bordonali, Michael Rubinstein, William D. Bennett, Mehmet Kesimer, Richard C. Boucher
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB.Objectives: We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance.Methods: We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB.Measurements and Results: CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV1, and both were significantly correlated.Conclusions: Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis.
Clinical Classification of<i>BRCA1</i>and<i>BRCA2</i>DNA Sequence Variants: The Value of Cytokeratin Profiles and Evolutionary Analysis—A Report From the kConFab Investigators
Authors: Amanda B. Spurdle, Sunil R. Lakhani, Sue Healey, Suzanne Parry, Leonard M. Da Silva, Ross Brinkworth, John L. Hopper, Melissa A. Brown, Davit Babikyan, Georgia Chenevix-Trench, Sean V. Tavtigian, David E. Goldgar
Journal: Journal of Clinical Oncology (2008)

Purpose Rare missense substitutions and in-frame deletions of BRCA1 and BRCA2 genes present a challenge for genetic counseling of individuals carrying such unclassified variants. We assessed the value of tumor immunohistochemical markers in conjunction with genetic and evolutionary approaches for investigating the clinical significance of unclassified variants. Patients and Methods We studied 10 BRCA1 and 12 BRCA2 variants identified in Australian families with breast cancer. Analyses assumed a prior probability based on revised cross-species sequence alignment methods assessing amino acid evolutionary conservation and position, combined with likelihoods from data on co-occurrence with pathogenic mutations in the same gene, segregation analysis, and immunohistochemistry. We specifically explored the value of estrogen receptor, cytokeratin 5/6, and cytokeratin 14 as tumor markers of BRCA1 mutation status. Results Posterior probabilities classified 72% of variants. BRCA1 variants IVS18+1 G&gt;T (del exon 18) and 5632 T &gt;A (V1838E) were classified as pathogenic, with &gt;99% posterior probability of being deleterious, and tumor histopathology was particularly important for their classification. BRCA2 variant classification was improved over previous studies, largely by incorporating the prior probability of pathogenicity based on amino acid cross-species sequence alignments. Conclusion Variant classification was considerably improved by analysis of estrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumor expression, and use of updated methods estimating the clinical relevance of amino acid evolutionary conservation and position. These methodologies may assist genetic counseling of individuals with unclassified sequence variants.
Muscle Dysmorphia in Male Weightlifters: A Case-Control Study
Authors: R Olivardia, H G Pope, J I Hudson
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Muscle dysmorphia is a form of body dysmorphic disorder in which individuals develop a pathological preoccupation with their muscularity. METHOD: The authors interviewed 24 men with muscle dysmorphia and 30 normal comparison weightlifters, recruited from gymnasiums in the Boston area, using a battery of demographic, psychiatric, and physical measures. RESULTS: The men with muscle dysmorphia differed significantly from the normal comparison weightlifters on numerous measures, including body dissatisfaction, eating attitudes, prevalence of anabolic steroid use, and lifetime prevalence of DSM-IV mood, anxiety, and eating disorders. The men with muscle dysmorphia frequently described shame, embarrassment, and impairment of social and occupational functioning in association with their condition. By contrast, normal weightlifters displayed little pathology. Indeed, in an a posteriori analysis, the normal weightlifters proved closely comparable to a group of male college students recruited as a normal comparison group in an earlier study. CONCLUSIONS: Muscle dysmorphia appears to be a valid diagnostic entity, possibly related to a larger group of disorders, and is associated with striking and stereotypical features. Men with muscle dysmorphia differ sharply from normal weightlifters, most of whom display little psychopathology. Further research is necessary to characterize the nosology and potential treatment of this syndrome.
Pilot Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of the Combination of Exemestane and Tamoxifen
Authors: Edgardo Rivera, Vicente Valero, Deborah Francis, Aviva G. Asnis, Larry J. Schaaf, Barbara Duncan, Gabriel N. Hortobagyi
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We conducted a pilot study assessing the effects of the selective estrogen receptor modulator, tamoxifen, on the pharmacokinetics, pharmacodynamics, and safety of the steroidal, irreversible aromatase inhibitor (AI), exemestane, when the two were coadministered in postmenopausal women with metastatic breast cancer. Experimental Design: Patients with documented or unknown hormone receptor sensitivity were eligible. Patients received oral exemestane at 25-mg once daily. Starting day 15, oral tamoxifen at 20-mg once daily, was added. We measured plasma concentrations of exemestane, estrone, estrone sulfate, and estradiol after 14 days of exemestane monotherapy and after ∼4 weeks of combination therapy. The incidence and severity of adverse events were assessed by physical examination and patient reporting. Results: We treated 18 patients. All had received prior chemotherapy and/or hormonal therapy, eight and six, respectively, with single-agent selective estrogen receptor modulators or irreversible aromatase inhibitors; no hormonal therapy was given within 30 days of study entry. Plasma exemestane concentrations and estrone, estrone sulfate, and estradiol suppression were unchanged after ∼4 weeks of tamoxifen coadministration. All drug-related adverse events were grades 1 or 2; none was unexpected. Although not a formal study end point, antitumor activity was noted, with two partial responses and four cases of stable disease among 17 evaluable patients after a 9-month median follow-up (range, 2.5–19 months). Conclusions: This pilot study provides evidence that coadministration of tamoxifen does not affect exemestane pharmacokinetics or pharmacodynamics and that the combination is well-tolerated and active. Further clinical investigation is warranted.