tbuckley/cabot-search huggingface dataset:
Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes
Authors: Michael Mauer, Bernard Zinman, Robert Gardiner, Samy Suissa, Alan Sinaiko, Trudy Strand, Keith Drummond, Sandra Donnelly, Paul Goodyer, Marie Claire Gubler, Ronald Klein
Journal: New England Journal of Medicine (2009)

Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether their progression is slowed by early administration of drugs that block the renin-angiotensin system.We conducted a multicenter, controlled trial involving 285 normotensive patients with type 1 diabetes and normoalbuminuria and who were randomly assigned to receive losartan (100 mg daily), enalapril (20 mg daily), or placebo and followed for 5 years. The primary end point was a change in the fraction of glomerular volume occupied by mesangium in kidney-biopsy specimens. The retinopathy end point was a progression on a retinopathy severity scale of two steps or more. Intention-to-treat analysis was performed with the use of linear regression and logistic-regression models.A total of 90% and 82% of patients had complete renal-biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over the 5-year period did not differ significantly between the placebo group (0.016 units) and the enalapril group (0.005, P=0.38) or the losartan group (0.026, P=0.26), nor were there significant treatment benefits for other biopsy-assessed renal structural variables. The 5-year cumulative incidence of microalbuminuria was 6% in the placebo group; the incidence was higher with losartan (17%, P=0.01 by the log-rank test) but not with enalapril (4%, P=0.96 by the log-rank test). As compared with placebo, the odds of retinopathy progression by two steps or more was reduced by 65% with enalapril (odds ratio, 0.35; 95% confidence interval [CI], 0.14 to 0.85) and by 70% with losartan (odds ratio, 0.30; 95% CI, 0.12 to 0.73), independently of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 patients receiving enalapril, 6 receiving losartan, and 4 receiving placebo.Early blockade of the renin-angiotensin system in patients with type 1 diabetes did not slow nephropathy progression but slowed the progression of retinopathy. (ClinicalTrials.gov number, NCT00143949.)
Cost-Effectiveness of the Diabetes Care Protocol, a Multifaceted Computerized Decision Support Diabetes Management Intervention That Reduces Cardiovascular Risk
Authors: Frits G.W. Cleveringa, Paco M.J. Welsing, Maureen van den Donk, Kees J. Gorter, Louis W. Niessen, Guy E.H.M. Rutten, William K. Redekop
Journal: Diabetes Care (2009)

OBJECTIVE The Diabetes Care Protocol (DCP), a multifaceted computerized decision support diabetes management intervention, reduces cardiovascular risk of type 2 diabetic patients. We performed a cost-effectiveness analysis of DCP from a Dutch health care perspective. RESEARCH DESIGN AND METHODS A cluster randomized trial provided data of DCP versus usual care. The 1-year follow-up patient data were extrapolated using a modified Dutch microsimulation diabetes model, computing individual lifetime health-related costs, and health effects. Incremental costs and effectiveness (quality-adjusted life-years [QALYs]) were estimated using multivariate generalized estimating equations to correct for practice-level clustering and confounding. Incremental cost-effectiveness ratios (ICERs) were calculated and cost-effectiveness acceptability curves were created. Stroke costs were calculated separately. Subgroup analyses examined patients with and without cardiovascular disease (CVD+ or CVD− patients, respectively). RESULTS Excluding stroke, DCP patients lived longer (0.14 life-years, P = NS), experienced more QALYs (0.037, P = NS), and incurred higher total costs (€1,415, P = NS), resulting in an ICER of €38,243 per QALY gained. The likelihood of cost-effectiveness given a willingness-to-pay threshold of €20,000 per QALY gained is 30%. DCP had a more favorable effect on CVD+ patients (ICER = €14,814) than for CVD− patients (ICER = €121,285). Coronary heart disease costs were reduced (€−587, P &amp;lt; 0.05). CONCLUSIONS DCP reduces cardiovascular risk, resulting in only a slight improvement in QALYs, lower CVD costs, but higher total costs, with a high cost-effectiveness ratio. Cost-effective care can be achieved by focusing on cardiovascular risk factors in type 2 diabetic patients with a history of CVD.
Proton-Pump Inhibitors Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use
Authors: Mette Charlot
Journal: Annals of Internal Medicine (2010)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Background: Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. Objective: To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. Design: A nationwide cohort study based on linked administrative registry data. Setting: All hospitals in Denmark. Patients: All patients discharged after first-time myocardial infarction from 2000 to 2006. Measurements: The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. Results: Of 56 406 included patients, 9137 (16.2%) were re-hospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). Limitations: Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. Conclusion: Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone. Primary Funding Source: The Danish Medical Research Council and the Danish Heart Foundation.
Wyeth responds to news story on oral contraceptives and DVT
Authors: P Brock
Journal: BMJ (2001)

EDITOR—In a News article, van Heteren reports on a Dutch radio broadcast about the issue of deep venous thrombosis and third generation oral contraceptives.1

There is no truth in the allegation made in the broadcast that Wyeth suppressed the results of a research study. The study report was provided to the European Agency for the Evaluation of Medicinal Products in April 2000, and to other regulatory authorities. To repeat this allegation, and particularly …
Single Intragastric Peanut Feeding Leads To Anaphylactic Shock In C3H/HeJ But Not In BALB/c Or C57BL/6 Mice
Authors: B. Proust, C.M.N. Astier, S. Jacquenet, V. Ogier, E. Magueur, B. Thouvenot, M. Morisset, D.A. Moneret-Vautrin, H.A. Sampson, A.W. Burks, B.E. Bihain, G. Kanny
Journal: Journal of Allergy and Clinical Immunology (2007)
Duration of Hospitalization as a Measure of Cost on Children’s Cancer Group Acute Lymphoblastic Leukemia Studies
Authors: Paul S. Gaynon, Bruce C. Bostrom, Raymond J. Hutchinson, Beverly J. Lange, James B. Nachman, Peter G. Steinherz, Martha G. Sensel, Mei K. Lee, Daniel O. Stram, Harland N. Sather
Journal: Journal of Clinical Oncology (2001)

PURPOSE: We used duration of hospitalization as a surrogate for cost and event-free survival as a measure of effectiveness to estimate the cost-effectiveness ratios of various treatment regimens on Children’s Cancer Group trials for acute lymphoblastic leukemia. PATIENTS AND METHODS: The analyses included 4,986 children (2 to 21 years of age) with newly diagnosed acute lymphoblastic leukemia enrolled onto risk-adjusted protocols between 1988 and 1995. Analyses were based on a model of 100 patients. The marginal cost-effectiveness ratio (hospital days per additional patient surviving event-free) was the difference in total duration of hospitalization divided by the difference in number of event-free survivors at 5 years for two regimens. Relapse-adjusted marginal cost of frontline therapy was the difference in total duration of hospitalization for frontline therapy plus relapse therapy divided by the difference in number of event-free survivors at 5 years on the frontline therapy for two regimens. RESULTS: One or two delayed intensification (DI) phases, augmented therapy, and dexamethasone all improved outcome. Marginal cost-effectiveness of these regimens compared with the control regimens was 133 days per patient for DI, 117 days per patient for double DI, and 41 days per patient for augmented therapy. Dexamethasone resulted in 17 fewer days per patient. Relapse-adjusted marginal costs were 68 days per patient for DI and 52 days for double DI. Augmented therapy and dexamethasone-based therapy resulted in 16 and 82 fewer hospital days, respectively. The estimated cost-effectiveness for treating any first relapse was 250 days per patient. CONCLUSION: DI, double DI, augmented therapy, and dexamethasone-based therapy are cost-effective strategies compared with current treatment of first relapse.
High-Virulence Marek's Disease Virus Infection in Chickens Previously Infected With Low-Virulence Virus23
Authors: M. W. Smith, B. W. Calnek
Journal: JNCI Journal of the National Cancer Institute (1974)

The pathogenicity of high-virulence (JM-10 isolate) Marek's disease virus (MDV) was compared in White Leghorn chickens with and without prior infection with a naturally low-virulence MDV isolate (CU-2) or the avirulent FC126 strain of turkey herpesvirus (HVT-4). Infection with CU-2 protected against JM-10 challenge. Route of infection of CU-2 was not a factor in protectivity. CU-2 infection was not protective against simultaneous challenge with JM-10, but only 2 days' prechallenge time with CU-2 infection conferred maximal protection in susceptible birds. One-day-old chickens were no more susceptible than those 4 weeks old to CU-2 infection, but the younger CU-2-infected birds were not protected against JM-10 challenge. Bursectomy at hatching time had 2 effects. It increased the incidence of MD with either CU-2 or JM-10 infection (statistically significant only with the latter). Also, it altered the lesion spectrum in CU-2-infected chickens that developed MD; visceral tumors occurred in bursectomized birds, but only neural lesions were seen in intact birds. There was less viral antigen in lymphoid organs, and degenerative lesions were prevented in JM-10- challenged birds with prior CU-2 or HVT-4 infection. Cell-associated infectivity (both HVT-4 and JM-10) was present in spleen cells of those inoculated with both viruses, and the level of JM-10 infectivity was similar to that of chickens receiving only JM-10.
Chronic T-type Ca2+ channel blockade with mibefradil in hyperinsulinemic, insulin-resistant and hypertensive rats
Authors: S Verma
Journal: Cardiovascular Research (1997)

Objectives: To determine the effects of calcium antagonists on hyperinsulinemia, hypertriglyceridemia and hypertension, we examined the long-term effects of a new calcium channel blocker, mibefradil, on plasma insulin levels, plasma triglyceride levels and systolic blood pressure in insulin-resistant and hyperinsulinemic fructose-hypertensive (FH) rats. To this aim, both prevention and reversal protocols were employed. Methods:Prevention study: Male Sprague-Dawley rats were procured at 6 weeks of age and were divided into: control (C, n=6), control-treated (CT, n=5), fructose (F, n=7) and fructose-treated (FT, n=6). Baseline measurements of plasma glucose, insulin and systolic blood pressure were conducted in all groups. At week 7, chronic mibefradil treatment (30 mg/kg/day, orally for 6 weeks) was initiated in the CT and FT groups. At week 8, the rats in the F and FT groups were started on a 66% fructose diet to induce hyperinsulinemia and hypertension. Weekly measurements of plasma insulin, plasma triglycerides and systolic blood pressure were conducted for the following 4 weeks. Reversal protocol: In a separate study, 8-week-treated FH rats and their age-matched controls were used to examine the effects of mibefradil on reversing fructose-induced hyperinsulinemia and hypertension. Results: The F group exhibited hyperinsulinemia (3.2±0.1 vs. C 2.3±0.07 ng/ml, P<0.05), hypertension (148±3 vs. C 121±1 mmHg, P<0.002) and elevated triglyceride levels (5.4±0.8 vs. C 1.6±0.3 mM, P<0.05). Chronic mibefradil treatment prevented the development of hyperinsulinemia (1.6±0.08 ng/ml, P<0.004 vs. F) and hypertension (123±1 mmHg, P<0.001 vs. F) and attenuated the development of hypertriglyceridemia. In the reversal study, mibefradil treatment reversed the development of hyperinsulinemia, hypertriglyceridemia and elevated BP in FH rats. Treatment did not affect the plasma glucose levels in any group (prevention or reversal). Conclusions: Long-term treatment with the calcium antagonist, mibefradil, both prevents and reverses the development of hyperinsulinemia, hypertriglyceridemia and hypertension in FH rats. These data indicate beneficial effects of mibefradil on carbohydrate and lipid metabolism in hyperinsulinemic and insulin-resistant states.
Mouse Plasmacytoid Cells
Authors: Meredith O'Keeffe, Hubertus Hochrein, David Vremec, Irina Caminschi, Joanna L. Miller, E. Margot Anders, Li Wu, Mireille H. Lahoud, Sandrine Henri, Bernadette Scott, Paul Hertzog, Lilliana Tatarczuch, Ken Shortman
Journal: The Journal of Experimental Medicine (2002)

The CD45RA(hi)CD11c(int) plasmacytoid predendritic cells (p-preDCs) of mouse lymphoid organs, when stimulated in culture with CpG or influenza virus, produce large amounts of type I interferons and transform without division into CD8(+)CD205(-) DCs. P-preDCs express CIRE, the murine equivalent of DC-specific intercellular adhesion molecule 3 grabbing nonintegrin (DC-SIGN). P-preDCs are divisible by CD4 expression into two subgroups differing in turnover rate and in response to Staphylococcus aureus. The kinetics of bromodeoxyuridine labeling and the results of transfer to normal recipient mice indicate that CD4(-) p-preDCs are the immediate precursors of CD4(+) p-preDCs. Similar experiments indicate that p-preDCs are normally long lived and are not the precursors of the short-lived steady-state conventional DCs. However, in line with the culture studies on transfer to influenza virus-stimulated mice the p-preDCs transform into CD8(+)CD205(-) DCs, distinct from conventional CD8(+)CD205(+) DCs. Hence as well as activating preexistant DCs, microbial infection induces a wave of production of a new DC subtype. The functional implications of this shift in the DC network remain to be determined.
Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial
Authors: Kim-Thanh Ong, Jérôme Perdu, Julie De Backer, Erwan Bozec, Patrick Collignon, Joseph Emmerich, Anne-Laure Fauret, Jean-Noël Fiessinger, Dominique P Germain, Gabriella Georgesco, Jean-Sebastien Hulot, Anne De Paepe, Henri Plauchu, Xavier Jeunemaitre, Stéphane Laurent, Pierre Boutouyrie
Journal: The Lancet (2010)
Matrix metalloproteinase-12 is a therapeutic target for asthma in children and young adults
Authors: Somnath Mukhopadhyay, Joseph Sypek, Roger Tavendale, Ulrike Gartner, John Winter, Wei Li, Karen Page, Margaret Fleming, Jeff Brady, Margot O'Toole, Donald F. Macgregor, Samuel Goldman, Steve Tam, William Abraham, Cara Williams, Douglas K. Miller, Colin N.A. Palmer
Journal: Journal of Allergy and Clinical Immunology (2010)
Evidence for differential acquired drug resistance to anti-tumour necrosis factor agents in rheumatoid arthritis
Authors: A Finckh
Journal: Annals of the Rheumatic Diseases (2005)

Acquired drug resistance or gradual drug failure has been described with most disease modifying antirheumatic drugs (DMARDs) and is also starting to be recognised with anti-tumour necrosis factor (anti-TNF) agents.To study acquired drug resistance to anti-TNF agents in rheumatoid arthritis (RA).Swiss health authorities requested continuous monitoring of patients receiving biological agents. Intensification of co-therapy with traditional DMARDs, gradual dose escalation, and drug discontinuation rates in all patients receiving infliximab, etanercept, or adalimumab, adjusting for potential confounders, were analysed. Intensification of DMARD co-therapy and time to discontinuation of the three anti-TNF agents were analysed using a proportional hazards models. Dose escalation and evolution of RA disease activity (DAS28) were analysed using a longitudinal regression model.1198 patients contributing 1450 patient-years of anti-TNF treatment met the inclusion criteria. The rate of intensification of traditional DMARD co-therapy over time was significantly higher with infliximab (hazards ratio = 1.73 (99% confidence interval (CI) 1.19 to 2.51)) than with the two other agents. Infliximab also showed significant dose escalation over time, with an average dose increase of +12% (99% CI 8% to 16%) after 1 year, and +18% (99% CI 11% to 25%) after 2 years. No significant differences in discontinuation rates were seen between the three anti-TNF agents (ANOVA, p = 0.67). Evolution of disease activity over time indicated a lower therapeutic response to infliximab (DAS28, p<0.001) compared with etanercept, after 6 months' treatment.In this population, infliximab was associated with a higher risk of requiring intensification of DMARD co-therapy than the other anti-TNF agents and a significant dose escalation over time. Analysis of RA disease activity indicated a reduced therapeutic response to infliximab after the first 6 months of treatment, suggestive of acquired drug resistance.
Surgery for secondary pneumothorax caused by Hermansky–Pudlak syndrome
Authors: Kaoru Kaseda, Taichiro Goto, Katsura Emoto, Yuichiro Hayashi
Journal: European Respiratory Journal (2014)

a diagnosis of DVT.Cases were more likely to have been prescribed warfarin (OR 1.52, p,0.001) prior to the index date.After adjusting for matching factors, smoking and warfarin prescription, the rates of pulmonary embolus and DVT were six and two times higher, respectively, in people with IPF compared with controls (table 1).There was no evidence that the proportional hazards assumptions were not met.In this large population based study, we found that people with IPF have higher incidence rates of pulmonary embolus and DVT, and are more likely to be prescribed warfarin, compared with the general population.Possible explanations for our finding include 1) IPF increasing the risk of VTE, and 2) a prothrombotic state leading to the development of IPF and VTE.This study supports the hypothesis that activation of the coagulation cascade may be involved in the pathogenesis of IPF [2,7].People with IPF have higher incidence rates of venous thromboembolism and are more likely to be prescribed warfarin http://ow.ly/B2IP6
Association between foot type and tibial stress injuries: a systematic review
Authors: A Barnes, J Wheat, C Milner
Journal: British Journal of Sports Medicine (2007)

Objectives: To systematically review published articles investigating the association between structural foot characteristics and tibial stress injuries, and to suggest possible future avenues of research in this area. Methods: Literature was identified, selected and appraised in accordance with the methods of a systematic review. Articles potentially relevant to the research question were identified by searching the following electronic databases: Amed, Cinahl, Index to UK theses, Medline, PubMed, Scopus, Sports discus and Web of science. Duplicates were removed and, based on the title and abstract, the full text of relevant studies were retrieved. Two reviewers independently assessed papers; this formed the basis for the inclusion of the most appropriate trials. Results: From the 479 articles originally identified, nine were deemed appropriate for inclusion in the review. In general, specific data relating to this relationship was limited. Outcomes of the nine investigations were difficult to compare due to differing methods used across studies. Results have proved conflicting, with limited evidence found to implicate any specific foot type as a potential risk factor for tibial stress injuries. Conclusions: No definitive conclusions can be drawn relating foot structure or function to an increased risk of tibial stress injuries. Extremes of foot types are likely to pose an increased risk of tibial stress injuries compared to normal arched feet.
Nonatopic asthma is associated with helminth infections and bronchiolitis in poor children
Authors: M. U. Pereira, P. D. Sly, P. M. Pitrez, M. H. Jones, D. Escouto, A. C. O. Dias, S. K. Weiland, R. T. Stein
Journal: European Respiratory Journal (2007)

Asthma is common in urban centres in Latin America, but atopic asthma may not be the main phenotype among children. Helminth infections are highly prevalent in poor populations, and it was hypothesised that they attenuate allergic asthma, whereas other factors are related to the expression of a nonatopic wheeze/asthma phenotype. A total of 1,982 children from Southern Brazil with a mean+/-sd age of 10.1+/-0.76 yrs completed asthma questionnaires, and 1,011 were evaluated for intestinal parasites and atopy using skin-prick tests (SPTs). Wheeze in the previous 12 months was reported by 25.6%, and 9.3% showed current asthma; 13% were SPT-positive and 19.1% were positive for any helminths. Most children with either wheeze or asthma were SPT-negative; however, severe wheeze was more prevalent among the atopic minority. Helminth infections were inversely associated with positive SPT results. Bronchiolitis before the age of 2 yrs was the major independent risk factor for asthma at age 10 yrs; high-load Ascaris infection, a family history of asthma and positive SPT results were also asthma risk factors. Most asthma and wheeze are of the nonatopic phenotype, suggesting that some helminths may exert an attenuating effect on the expression of the atopic portion of the disease, whereas viral bronchiolitis predisposes more specifically to recurrent airway symptoms.