tbuckley/cabot-search huggingface dataset:
Patients' Perceptions of Quality of Care for Colorectal Cancer by Race, Ethnicity, and Language
Authors: John Z. Ayanian, Alan M. Zaslavsky, Edward Guadagnoli, Charles S. Fuchs, Kathleen J. Yost, Cynthia M. Creech, Rosemary D. Cress, Lilia C. O'Connor, Dee W. West, William E. Wright
Journal: Journal of Clinical Oncology (2005)

To identify opportunities for improving care, we evaluated patients' perceptions of the quality of their cancer care by race, ethnicity, and language.We surveyed a population-based cohort of 1,067 patients with colorectal cancer in northern California approximately 9 months after diagnosis. Adjusting for clinical and demographic factors, mean problem scores were analyzed on a 100-point scale for six domains of care.Mean problem scores were highest for health information (47.8), followed by treatment information (32.3), psychosocial care (31.7), coordination of care (21.3), confidence in providers (13.1), and access to cancer care (12.7). In adjusted comparisons with white patients, African American patients reported more problems with coordination of care (difference, 9.8; P < .001), psychosocial care (difference, 7.2; P = .03), access to care (difference, 6.6; P = .03), and health information (difference, 12.5; P < .001). Asian/Pacific Islander patients reported more problems than did white patients with coordination of care (difference, 13.2; P < .001), access to care (difference, 15.5; P < .001), and health information (difference, 12.6; P = .004). Hispanic patients tended to report more problems with coordination of care (difference, 4.4; P = .06), access to care (difference, 5.8; P = .08), and treatment information (difference, 7.0; P = .06). Non-English-speaking white patients reported more problems than other white patients with coordination of care (difference, 21.9; P < .001), psychosocial care (difference, 16.1; P = .009), access to care (difference, 19.8; P = .003), and treatment information (difference, 17.8; P = .002). Non-English-speaking Hispanic patients reported more problems than other Hispanic patients with confidence in providers (difference, 16.9; P = .01).Efforts to improve patients' experiences with cancer care should address disparities by race, ethnicity, and language, particularly in coordination of care, access to care, and the provision of relevant information.
Risk of vascular disease with gout: overadjustment of the statistical analyses?
Authors: Caroline M van Durme, Bart Spaetgens, Annelies Boonen, Frank de Vries
Journal: Annals of the Rheumatic Diseases (2014)

Risk of vascular disease with gout: overadjustment of the statistical analyses?An increase of 6% in the risk of vascular disease among men with gout (adj.HR 1.06 95% CI 1.01 to 1.12) and of 25% among women with gout (adj.HR 1.25 95%CI 1.15 to 1.35) was reported when analysing data of the world's largest primary care database, the UK Clinical Practice Research Datalink. 1 However, the statistical analyses are likely to suffer from overadjustment, which probably have resulted in an imprecise relative risk with reduced statistical significance which often biases towards the null-hypothesis. 2Cox regression analyses adjusted for both comorbidity using the Charlson Comorbidity Index (CCI) and specific potential confounders, such as hypertension, hyperlipidaemia and chronic kidney disease.The CCI classifies various comorbid conditions which might alter the risk of mortality. 3As moderate and severe renal diseases are already taken into account in the CCI, they should not be used as a separate covariate (chronic kidney disease).Overadjustment bias can be easily dealt with: the variables that are overadjusted for should be removed from the multivariate analyses.We would therefore be interested in the results from a multivariate analysis that is unlikely to suffer from overadjustment.Dealing correctly with comorbidities is especially important when assessing the cardiovascular risk in patients with gout, as comorbidities such as chronic kidney disease are known to be more prevalent in individuals with gout compared with healthy individuals.
Triple Combination of Oncolytic Herpes Simplex Virus-1 Vectors Armed with Interleukin-12, Interleukin-18, or Soluble B7-1 Results in Enhanced Antitumor Efficacy
Authors: Yasushi Ino, Yoshinaga Saeki, Hiroshi Fukuhara, Tomoki Todo
Journal: Clinical Cancer Research (2006)

Abstract Conditionally replicating herpes simplex virus-1 (HSV-1) vectors are promising therapeutic agents for cancer. Insertion of therapeutic transgenes into the viral genome should confer desired anticancer functions in addition to oncolytic activities. Herein, using bacterial artificial chromosome and two recombinase-mediated recombinations, we simultaneously created four “armed” oncolytic HSV-1, designated vHsv-B7.1-Ig, vHsv-interleukin (IL)-12, vHsv-IL-18, and vHsv-null, which express murine soluble B7.1 (B7.1-Ig), murine IL-12, murine IL-18, and no transgene, respectively. These vHsv vectors possess deletions in the γ34.5 genes and contain the green fluorescent protein gene as a histochemical marker and the immunostimulatory transgene inserted in the deleted ICP6 locus. The vHsv showed similar replicative capabilities in vitro. The in vivo efficacy was tested in A/J mice harboring s.c. tumors of syngeneic and poorly immunogenic Neuro2a neuroblastoma. The triple combination of vHsv-B7.1-Ig, vHsv-IL-12, and vHsv-IL-18 exhibited the highest efficacy among all single vHsv or combinations of two viruses. Combining 1 × 105 plaque-forming units each of the three armed viruses showed stronger antitumor activities than any single armed virus at 3 × 105 plaque-forming units in inoculated tumors as well as in noninoculated remote tumors. Studies using athymic mice indicated that this enhancement of antitumor efficacy was likely mediated by T-cell immune responses. The combined use of multiple oncolytic HSV-1 armed with different immunostimulatory genes may be a useful strategy for cancer therapy.
Targeted Inhibition of β-Catenin/CBP Signaling Ameliorates Renal Interstitial Fibrosis
Authors: Sha Hao, Weichun He, Yingjian Li, Hong Ding, Yayi Hou, Jing Nie, Fan Fan Hou, Michael Kahn, Youhua Liu
Journal: Journal of the American Society of Nephrology (2011)

Because fibrotic kidneys exhibit aberrant activation of β-catenin signaling, this pathway may be a potential target for antifibrotic therapy. In this study, we examined the effects of β-catenin activation on tubular epithelial-mesenchymal transition (EMT) in vitro and evaluated the therapeutic efficacy of the peptidomimetic small molecule ICG-001, which specifically disrupts β-catenin-mediated gene transcription, in obstructive nephropathy. In vitro, ectopic expression of stabilized β-catenin in tubular epithelial (HKC-8) cells suppressed E-cadherin and induced Snail1, fibronectin, and plasminogen activator inhibitor-1 (PAI-1) expression. ICG-001 suppressed β-catenin-driven gene transcription in a dose-dependent manner and abolished TGF-β1-induced expression of Snail1, PAI-1, collagen I, fibronectin, and α-smooth muscle actin (α-SMA). This antifibrotic effect of ICG-001 did not involve disruption of Smad signaling. In the unilateral ureteral obstruction model, ICG-001 ameliorated renal interstitial fibrosis and suppressed renal expression of fibronectin, collagen I, collagen III, α-SMA, PAI-1, fibroblast-specific protein-1, Snail1, and Snail2. Late administration of ICG-001 also effectively attenuated fibrotic lesions in obstructive nephropathy. In conclusion, inhibiting β-catenin signaling may be an effective approach to the treatment of fibrotic kidney diseases.
Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection
Authors: Yao-Chun Hsu, Hsiu J Ho, Yen-Tsung Huang, Hsi-Hao Wang, Ming-Shiang Wu, Jaw-Town Lin, Chun-Ying Wu
Journal: Gut (2014)

To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV.This nationwide cohort study screened 293,480 Taiwanese residents with HCV infection and excluded those with substantial comorbidity. A total of 12,384 eligible patients who had received pegylated interferon plus ribavirin between 1 October 2003 and 31 December 2010 were enrolled in the treated cohort; they were matched 1 : 2 with 24,768 untreated controls in the propensity score and post-diagnosis treatment-free period. The incidences of end-stage renal disease (ESRD), acute coronary syndrome (ACS), ischaemic stroke and catastrophic autoimmune diseases were calculated after adjustment for competing mortality.The treated and untreated cohorts were followed up for a mean (±SD) duration of 3.3 (±2.5) and 3.2 (±2.4) years, respectively, until 31 December 2011. The calculated 8-year cumulative incidences of ESRD, ACS, ischaemic stroke and autoimmune catastrophes between treated and untreated patients were 0.15% vs. 1.32% (p<0.001), 2.21% vs. 2.96% (p=0.027), 1.31% vs. 1.76% (p=0.001) and 0.57% vs. 0.49% (p=0.816), respectively. Multivariate-adjusted Cox regression revealed that antiviral treatment was associated with lower risks of ESRD (HR 0.15; 95% CI 0.07 to 0.31; p<0.001), ACS (HR 0.77; 95% CI 0.62 to 0.97; p=0.026) and ischaemic stroke (HR 0.62; 95% CI 0.46 to 0.83; p=0.001), but unrelated to autoimmune catastrophes. These favourable associations were invalid in incompletely treated patients with duration <16 weeks.Antiviral treatment for HCV is associated with improved renal and circulatory outcomes, but unrelated to catastrophic autoimmune diseases.
New Serum Markers for the Detection of Severe Acute Pancreatitis in Humans
Authors: JEAN-LOUIS FROSSARD, ANTOINE HADENGUE, CATHERINE M. PASTOR
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Acute pancreatitis is an inflammatory process which occurs in a normal organ and which is diagnosed mainly by acute abdominal pain associated with a concomitant rise of serum amylase and lipase concentrations (1, 2). Gallstone migration into the common bile duct and alcohol abuse account for most of the etiologies of the disease. Usually the injury is mild, but 20% of the patients have a severe injury and, among them, 15 to 25% will die. Because it is important to predict the severity of the illness as early as possible in order to optimize the therapy and to prevent organ dysfunction and local complications, several scores of severity have been proposed. Criteria of severity, such as Ranson (3‐5), Glasgow (6), and Acute Physiology and Chronic Health Evaluation (APACHE) (7) scores have been used for a long time. These scores assess the multiple organ dysfunction induced by the disease and consequently, the greater the number of organs injured, the greater the score. New serum markers have recently emerged and their potential for providing additional information on the severity of the disease is currently being evaluated. However, to become useful such markers must be assessed in a large consecutive series of patients, including a significant proportion of severe cases, and the timing of the assessment must be related to the onset of the disease. Moreover, the usefulness of the new marker must be compared with established ones; the results must be reproducible; and the detection of the new marker must be easy to detect in clinical chemistry laboratories. Interestingly, when seeking medical attention (usually 12 to 24 h after the onset of pain) most patients do not exhibit multiple organ dysfunction, which is likely to emerge by the second or third day and, at admission, numerous mediators can be detected in serum. If the concentration of these biologic factors is correlated to the severity of the disease, and if they are detected before the occurrence of multiple organ dysfunction, it is then conceivable that the therapeutic antagonism of these mediators might prevent or attenuate the severity of the multiple organ dysfunction, and consequently the outcome of the disease. These new factors might be important for the rapid scoring of the disease severity in the acute phase and some of them might be used as potential therapeutic targets.
Plasma homocysteine and folate levels in patients with chronic plaque psoriasis
Authors: M. Malerba, P. Gisondi, A. Radaeli, R. Sala, P.G. Calzavara Pinton, G. Girolomoni
Journal: British Journal of Dermatology (2006)

Hyperhomocysteinaemia is a well-known risk factor for cardiovascular diseases. Patients with severe chronic plaque psoriasis have a higher risk of death due to arterial and/or venous thrombosis.To investigate the relationship among plasma homocysteine and folate levels and severity of chronic plaque psoriasis in a selected cohort of patients with psoriasis without known risk factors for acquired hyperhomocysteinaemia.We performed a case-control study in 40 patients with chronic plaque psoriasis and 30 age- and sex-matched healthy controls. Cases and controls were selected excluding individuals with conditions or diseases associated with acquired hyperhomocysteinaemia, and were also asked to stop alcohol and coffee consumption for 1 week before blood sampling. The plasma levels of homocysteine and folic acid were measured and were correlated with the severity of psoriasis (Psoriasis Area and Severity Index, PASI).Patients with psoriasis had plasma homocysteine levels higher than controls (mean +/- SD 16.0 +/- 5.6 vs. 10.4 +/- 4.7 micro mol L(-1); P < 0.001). Conversely, folic acid levels were lower in patients with psoriasis compared with controls (mean +/- SD 3.6 +/- 1.7 vs. 6.5 +/- 1.7 nmol L(-1); P < 0.001). Plasma homocysteine levels in patients with psoriasis correlated directly with disease severity (PASI) and inversely with folic acid levels. Plasma folic acid levels were inversely correlated with the PASI. No abnormalities of plasma vitamin B(6) and B(12) were found.Patients with psoriasis may have a tendency to hyperhomocysteinaemia, which may predispose to higher cardiovascular risk. Dietary modification of this risk factor appears relevant to the global management of patients with moderate to severe psoriasis.
An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer
Authors: M. Schmidt, M.E. Scheulen, C. Dittrich, P. Obrist, N. Marschner, L. Dirix, M. Schmidt, D. Rüttinger, M. Schuler, C. Reinhardt, A. Awada
Journal: Annals of Oncology (2009)
HRAS1 Rare Minisatellite Alleles and Breast Cancer in Australian Women Under Age Forty Years
Authors: F A Firgaira, R Seshadri, C R McEvoy, G S Dite, G G Giles, M R McCredie, M C Southey, D J Venter, J L Hopper
Journal: JNCI Journal of the National Cancer Institute (1999)

A recent meta-analysis of 23 studies supported the empirically derived hypothesis that women who lack one of the four common minisatellite alleles at the HRAS1 locus are at increased risk of breast cancer. These studies relied on visual sizing of alleles on electrophoretic gels and may have underreported rare alleles. We determined whether this hypothesis applied to early-onset breast cancer by using a new method to size minisatellite alleles.We conducted a population-based, case-control-family study of 249 Australian women under 40 years old at diagnosis of a first primary breast cancer and 234 randomly selected women, frequency matched for age. We sized HRAS1 minisatellite alleles with an Applied Biosystems model 373 automated DNA sequencer and GENESCAN(TM) software. All P values are two-sided.We found no association of rare alleles with breast cancer, before or after adjustment for risk factors and irrespective of how their effects were modeled (crude odds ratio = 1.04; 95% confidence interval [CI] = 0.071-1.53; P =.8). The rare allele frequency was 0. 173 (95% CI = 0.149-0.197), three times the pooled estimate of 0.058 (95% CI = 0.050-0.066) from previous studies (P<.001), and was similar for case subjects, 0.177 (95% CI = 0.143-0.221), and control subjects, 0.169 (95% CI = 0.135-0.203) (P =.7).There was no support for an association between rare HRAS1 alleles and the risk of early-onset breast cancer, despite 80% power to detect effects of the magnitude of those associations (1.7-fold) previously suggested.The question of whether cancer risk is associated with rare minisatellite HRAS1 alleles needs to be revisited with the use of new methods that have a greater ability to distinguish rare alleles from similarly sized common alleles.
Oncolytic and Immunotherapeutic Vaccinia Induces Antibody-Mediated Complement-Dependent Cancer Cell Lysis in Humans
Authors: Mi Kyung Kim, Caroline J. Breitbach, Anne Moon, Jeong Heo, Yu Kyoung Lee, Mong Cho, Jun Woo Lee, Seong-Geun Kim, Dae Hwan Kang, John C. Bell, Byeong Ho Park, David H. Kirn, Tae-Ho Hwang
Journal: Science Translational Medicine (2013)

The oncolytic and immunotherapeutic vaccinia virus Pexa-Vec (JX-594) induces antibody-mediated complement-dependent cancer cell cytolysis in rabbits and cancer patients, prolonging their survival.
Safety, Pharmacokinetic, and Pharmacodynamic Phase I Dose-Escalation Trial of PF-00562271, an Inhibitor of Focal Adhesion Kinase, in Advanced Solid Tumors
Authors: Jeffrey R. Infante, D. Ross Camidge, Linda R. Mileshkin, Eric X. Chen, Rodney J. Hicks, Danny Rischin, Howard Fingert, Kristen J. Pierce, Huiping Xu, W. Gregory Roberts, S. Martin Shreeve, Howard A. Burris, Lillian L. Siu
Journal: Journal of Clinical Oncology (2012)

Purpose PF-00562271 is a novel inhibitor of focal adhesion kinase (FAK). The objectives of this study were to identify the recommended phase II dose (RP2D) and assess safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-00562271. Patients and Methods Part 1 was a dose escalation without and with food. Part 2 enrolled specific tumor types in an expansion at the RP2D and also assessed the effect of PF-00562271 on single-dose midazolam PK in a subgroup of patients. Results Ninety-nine patients (median age, 60 years; 98% with Eastern Cooperative Oncology Group performance status of 0 or 1) were treated in 12 fasting and three fed cohorts. The 125-mg twice-per-day fed dose was deemed the maximum-tolerated dose (MTD) and RP2D. Grade 3 dose-limiting toxicities included headache, nausea/vomiting, dehydration, and edema. Nausea was the most frequently observed toxicity (60% of patients, all grades 1 or 2 at RP2D). PF-00562271 exposure increased with increasing dose; serum concentration–time profiles showed characteristic nonlinear disposition. Steady-state exposures were reached within 1 week. On coadministration, geometric mean values of midazolam maximal observed serum concentration and area under the serum concentration–time curve increased by 60% and more than two-fold, respectively. Of 14 patients evaluable by [ 18 F]fluorodeoxyglucose positron emission tomography in the expansion cohorts, seven metabolic responses were observed. With conventional imaging, 31 patients had stable disease at first restaging scans, and 15 of these remained stable for six or more cycles. Conclusion The MTD and RP2D of PF-00562271 is 125 mg twice per day with food. PF-00562271 displayed time- and dose-dependent nonlinear PK and is likely a potent CYP 3A inhibitor. This first-in-class study supports further investigation of FAK as a promising therapeutic target.
The challenge of tuberculosis
Authors: P D O Davies
Journal: Journal of the Royal Society of Medicine (2003)

The most important challenge for tuberculosis (TB) care in the UK today is the re-education of the medical and allied professions in diagnosis and management of the disease. In the first half of 2001 there were an exceptionally large number of outbreaks of TB, one of which with over 70 secondary cases (and still counting) is the largest since the advent of specific chemotherapy. 1 I often see patients with a diagnosis of TB who have at some point been told by a doctor that they do not have TB. One was even told that nobody gets TB these days. A missed diagnosis of lung infection, specifically TB, is the second most common cause of litigation from a respiratory cause after pulmonary embolus (Evans CC, personal communication). TB is usually missed because it is not considered.
Blood, urine, stool, breath, money, and Helicobacter pylori
Authors: D VAIRA
Journal: Gut (2001)

Helicobacter pylori infection can be diagnosed by invasive (that is, endoscopy and biopsy) and non-invasive techniques. The choice of a diagnostic test should depend on the clinical circumstances, the pre-test probability of infection, sensitivity and specificity of the test (or more correctly the likelihood ratio of a positive and negative test), the cost effectiveness of the testing strategy, and the availability of the test. Some clinical circumstances warrant invasive studies: patients who have failed eradication therapy may need culture and antimicrobial sensitivity testing to help determine an appropriate regimen, older patients with new onset dyspepsia, and those with “alarm” symptoms (bleeding, weight loss, etc) that raise the concern of malignancy. Non-invasive studies are preferable in epidemiological studies and in young children. Recent studies have also demonstrated that a strategy to test and treat H pylori in uninvestigated young (<50 years) dyspeptic patients in primary care is safe and reduces the need for endoscopy.1

Until recently, only two non-invasive methods of testing for H pylori have been available: (1) the13C or 14C labelled urea breath test (UBT), which is based on detection of 13C or 14C labelled CO2 in expired air as a result of H pylori urease activity2-4and (2) serology (which is based on detection of a specific anti- H pylori IgG antibody in the patient's serum.5 6 Several new methods of detecting H pylori have recently been described and include detection of antibodies in saliva7 and urine,8 and detection of antigens in stool.

### SEROLOGY

There are a number of different techniques for antibody detection in serum, including enzyme linked immunosorbant assay (ELISA), agglutination tests, and western blotting but ELISA is the most widely used clinically. Antibody levels persist in the blood for long periods of time. Not surprisingly, …