328 research outputs found
Phase 1 dose escalation study of the allosteric AKT inhibitor BAY 1125976 in advanced solid cancer-Lack of association between activating AKT mutation and AKT inhibition-derived efficacy
This open-label, phase I first-in-human study (NCT01915576) of BAY 1125976, a highly specific and potent allosteric inhibitor of AKT1/2, aimed to evaluate the safety, pharmacokinetics, and maximum tolerated dose of BAY 1125976 in patients with advanced solid tumors. Oral dose escalation was investigated with a continuous once daily (QD) treatment (21 days/cycle) and a twice daily (BID) schedule. A dose expansion in 28 patients with hormone receptor-positive metastatic breast cancer, including nine patients harboring th
Estimation of transient increases in bleeding risk associated with physical activity in children with haemophilia
BACKGROUND: Although it is widely appreciated that vigorous physical activity can increase the risk of bleeding episodes in children with haemophilia, the magnitude of the increase in risk is not known. Accurate risk estimates could inform decisions made by children with haemophilia and their parents about participation in physical activity and aid the development of optimal prophylactic schedules. The aim of this study is to provide an accurate estimate of the risks of bleeding associated with vigorous physical activity in children with haemophilia. METHODS/DESIGN: The study will be a case-crossover study nested within a prospective cohort study. Children with moderate or severe haemophilia A or B, recruited from two paediatric haematology departments in Australia, will participate in the study. The child, or the child's parent or guardian, will report bleeding episodes experienced over a 12-month period. Following a bleeding episode, the participant will be interviewed by telephone about exposures to physical activity in the case period (8 hours before the bleed) and 2 control periods (an 8 hour period at the same time on the day preceding the bleed and an 8 hour period two days preceding the bleed). Conditional logistic regression will be used to estimate the risk of participating in vigorous physical activity from measures of exposure to physical activity in the case and control periods. DISCUSSION: This case-control study will provide estimates of the risk of participation in vigorous physical activity in children with haemophilia
Changes in Drug Utilization during a Gap in Insurance Coverage: An Examination of the Medicare Part D Coverage Gap
Jennifer Polinski and colleagues estimated the effect of the "coverage gap" during which US Medicare beneficiaries are fully responsible for drug costs and found that the gap was associated with a doubling in discontinuing essential medications
The impact of standardizing the definition of visits on the consistency of multi-database observational health research
A dynamic network approach for the study of human phenotypes
The use of networks to integrate different genetic, proteomic, and metabolic
datasets has been proposed as a viable path toward elucidating the origins of
specific diseases. Here we introduce a new phenotypic database summarizing
correlations obtained from the disease history of more than 30 million patients
in a Phenotypic Disease Network (PDN). We present evidence that the structure
of the PDN is relevant to the understanding of illness progression by showing
that (1) patients develop diseases close in the network to those they already
have; (2) the progression of disease along the links of the network is
different for patients of different genders and ethnicities; (3) patients
diagnosed with diseases which are more highly connected in the PDN tend to die
sooner than those affected by less connected diseases; and (4) diseases that
tend to be preceded by others in the PDN tend to be more connected than
diseases that precede other illnesses, and are associated with higher degrees
of mortality. Our findings show that disease progression can be represented and
studied using network methods, offering the potential to enhance our
understanding of the origin and evolution of human diseases. The dataset
introduced here, released concurrently with this publication, represents the
largest relational phenotypic resource publicly available to the research
community.Comment: 28 pages (double space), 6 figure
A self-controlled case series to assess the effectiveness of beta blockers for heart failure in reducing hospitalisations in the elderly
Background: To determine the suitability of using the self-controlled case series design to assess improvements in health outcomes using the effectiveness of beta blockers for heart failure in reducing hospitalisations as the example. Methods: The Australian Government Department of Veterans' Affairs administrative claims database was used to undertake a self-controlled case-series in elderly patients aged 65 years or over to compare the risk of a heart failure hospitalisation during periods of being exposed and unexposed to a beta blocker. Two studies, the first using a one year period and the second using a four year period were undertaken to determine if the estimates varied due to changes in severity of heart failure over time. Results: In the one year period, 3,450 patients and in the four year period, 12, 682 patients had at least one hospitalisation for heart failure. The one year period showed a non-significant decrease in hospitalisations for heart failure 4-8 months after starting beta-blockers, (RR, 0.76; 95% CI (0.57-1.02)) and a significant decrease in the 8-12 months post-initiation of a beta blocker for heart failure (RR, 0.62; 95% CI (0.39, 0.99)). For the four year study there was an increased risk of hospitalisation less than eight months post-initiation and significant but smaller decrease in the 8-12 month window (RR, 0.90; 95% CI (0.82, 0.98)). Conclusions: The results of the one year observation period are similar to those observed in randomised clinical trials indicating that the self-controlled case-series method can be successfully applied to assess health outcomes. However, the result appears sensitive to the study periods used and further research to understand the appropriate applications of this method in pharmacoepidemiology is still required. The results also illustrate the benefits of extending beta blocker utilisation to the older age group of heart failure patients in which their use is common but the evidence is sparse.Emmae N Ramsay, Elizabeth E Roughead, Ben Ewald, Nicole L Pratt and Philip Rya
Instrumental variable meta-analysis of individual patient data: application to adjust for treatment non-compliance
<p>Abstract</p> <p>Background</p> <p>Intention-to-treat (ITT) is the standard data analysis method which includes all patients regardless of receiving treatment. Although the aim of ITT analysis is to prevent bias due to prognostic dissimilarity, it is also a counter-intuitive type of analysis as it counts patients who did not receive treatment, and may lead to "bias toward the null." As treated (AT) method analyzes patients according to the treatment actually received rather than intended, but is affected by the selection bias. Both ITT and AT analyses can produce biased estimates of treatment effect, so instrumental variable (IV) analysis has been proposed as a technique to control for bias when using AT data. Our objective is to correct for bias in non-experimental data from previously published individual patient data meta-analysis by applying IV methods</p> <p>Methods</p> <p>Center prescribing preference was used as an IV to assess the effects of methotrexate (MTX) in preventing debilitating complications of chronic graft-versus-host-disease (cGVHD) in patients who received peripheral blood stem cell (PBSCT) or bone marrow transplant (BMT) in nine randomized controlled trials (1107 patients). IV methods are applied using 2-stage logistic, 2-stage probit and generalized method of moments models.</p> <p>Results</p> <p>ITT analysis showed a statistically significant detrimental effect with the use of day 11 MTX, resulting in cGVHD odds ratio (OR) of 1.34 (95% CI 1.02-1.76). AT results showed no difference in the odds of cGVHD with the use of MTX [OR 1.31 (95%CI 0.99-1.73)]. IV analysis further corrected the results toward no difference in the odds of cGVHD between PBSCT vs. BMT, allowing for a possibility of beneficial effects of MTX in preventing cGVHD in PBSCT recipients (OR 1.14; 95%CI 0.83-1.56).</p> <p>Conclusion</p> <p>All instrumental variable models produce similar results. IV estimates correct for bias and do not exclude the possibility that MTX may be beneficial, contradicting the ITT analysis.</p
Identifying patients with asthma-chronic obstructive pulmonary disease overlap syndrome using latent class analysis of electronic health record data: a study protocol
Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid arthritis
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