Estimation of Recurrence of Colorectal Adenomas with Dependent Censoring Using Weighted Logistic Regression

In colorectal polyp prevention trials, estimation of the rate of recurrence of adenomas at the end of the trial may be complicated by dependent censoring, that is, time to follow-up colonoscopy and dropout may be dependent on time to recurrence. Assuming that the auxiliary variables capture the dependence between recurrence and censoring times, we propose to fit two working models with the auxiliary variables as covariates to define risk groups and then extend an existing weighted logistic regression method for independent censoring to each risk group to accommodate potential dependent censoring. In a simulation study, we show that the proposed method results in both a gain in efficiency and reduction in bias for estimating the recurrence rate. We illustrate the methodology by analyzing a recurrent adenoma dataset from a colorectal polyp prevention trial

National Survey of Patients’ Bill of Rights Statutes

BACKGROUND Despite vigorous national debate between 1999–2001 the federal patients' bill of rights (PBOR) was not enacted. However, states have enacted legislation and the Joint Commission defined an accreditation standard to present patients with their rights. Because such initiatives can be undermined by overly complex language, we surveyed the readability of hospital PBOR documents as well as texts mandated by state law. METHODS State Web sites and codes were searched to identify PBOR statutes for general patient populations. The rights addressed were compared with the 12 themes presented in the American Hospital Association's (AHA) PBOR text of 2002. In addition, we obtained PBOR texts from a sample of hospitals in each state. Readability was evaluated using Prose, a software program which reports an average of eight readability formulas RESULTS Of 23 states with a PBOR statute for the general public, all establish a grievance policy, four protect a private right of action, and one stipulates fines for violations. These laws address an average of 7.4 of the 12 AHA themes. Nine states' statutes specify PBOR text for distribution to patients. These documents have an average readability of 15th grade (range, 11.6, New York, to 17.0, Minnesota). PBOR documents from 240 US hospitals have an average readability of 14th grade (range, 8.2 to 17.0) CONCLUSIONS While the average U.S. adult reads at an 8th grade reading level, an advanced college reading level is routinely required to read PBOR documents. Patients are not likely to learn about their rights from documents they cannot read.Pfizer Clear Health Communication Initiativ

Exploring Action Dynamics as an Index of Paired-Associate Learning

Much evidence exists supporting a richer interaction between cognition and action than commonly assumed. Such findings demonstrate that short-timescale processes, such as motor execution, may relate in systematic ways to longer-timescale cognitive processes, such as learning. We further substantiate one direction of this interaction: the flow of cognition into action systems. Two experiments explored match-to-sample paired-associate learning, in which participants learned randomized pairs of unfamiliar symbols. During the experiments, their hand movements were continuously tracked using the Nintendo Wiimote. Across learning, participant arm movements are initiated and completed more quickly, exhibit lower fluctuation, and exert more perturbation on the Wiimote during the button press. A second experiment demonstrated that action dynamics index novel learning scenarios, and not simply acclimatization to the Wiimote interface. Results support a graded and systematic covariation between cognition and action, and recommend ways in which this theoretical perspective may contribute to applied learning contexts

Defining freshwater as a natural resource: a framework linking water use to the area of protection natural resources

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: While many examples have shown unsustainable use of freshwater resources, existing LCIA methods for water use do not comprehensively address impacts to natural resources for future generations. This framework aims to (1) define freshwater resource as an item to protect within the Area of Protection (AoP) natural resources, (2) identify relevant impact pathways affecting freshwater resources, and (3) outline methodological choices for impact characterization model development. Methods: Considering the current scope of the AoP natural resources, the complex nature of freshwater resources and its important dimensions to safeguard safe future supply, a definition of freshwater resource is proposed, including water quality aspects. In order to clearly define what is to be protected, the freshwater resource is put in perspective through the lens of the three main safeguard subjects defined by Dewulf et al. (2015). In addition, an extensive literature review identifies a wide range of possible impact pathways to freshwater resources, establishing the link between different inventory elementary flows (water consumption, emissions, and land use) and their potential to cause long-term freshwater depletion or degradation. Results and discussion: Freshwater as a resource has a particular status in LCA resource assessment. First, it exists in the form of three types of resources: flow, fund, or stock. Then, in addition to being a resource for human economic activities (e.g., hydropower), it is above all a non-substitutable support for life that can be affected by both consumption (source function) and pollution (sink function). Therefore, both types of elementary flows (water consumption and emissions) should be linked to a damage indicator for freshwater as a resource. Land use is also identified as a potential stressor to freshwater resources by altering runoff, infiltration, and erosion processes as well as evapotranspiration. It is suggested to use the concept of recovery period to operationalize this framework: when the recovery period lasts longer than a given period of time, impacts are considered to be irreversible and fall into the concern of freshwater resources protection (i.e., affecting future generations), while short-term impacts effect the AoP ecosystem quality and human health directly. It is shown that it is relevant to include this concept in the impact assessment stage in order to discriminate the long-term from the short-term impacts, as some dynamic fate models already do. Conclusions: This framework provides a solid basis for the consistent development of future LCIA methods for freshwater resources, thereby capturing the potential long-term impacts that could warn decision makers about potential safe water supply issues in the future

Preventing Bias in Cluster Randomised Trials

Bruno Giraudeau and Philippe Ravaud discuss the difficulties in preventing selection bias and applying intention-to-treat analysis in cluster randomized trials, and propose some solutions

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Mathematical Evaluation of Community Level Impact of Combining Bed Nets and Indoor Residual Spraying upon Malaria Transmission in Areas where the main Vectors are Anopheles Arabiensis Mosquitoes.

Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset, PermaNet 2.0, Icon Life nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset or PermaNet 2.0 nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered as LLINs or IRS. The insecticidal action of LLINs and IRS probably already approaches their absolute limit of potential impact upon this persistent vector so personal protection of nets should be enhanced by improving the physical integrity and durability. Combining LLINs and non-pyrethroid IRS in residual transmission systems may nevertheless be justified as a means to manage insecticide resistance and prevent potential rebound of not only An. arabiensis, but also more potent, vulnerable and historically important species such as Anopheles gambiae and Anopheles funestus

Impact of statins and ACE inhibitors on mortality after COPD exacerbations

<p>Abstract</p> <p>Background</p> <p>The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.</p> <p>Methods</p> <p>We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.</p> <p>Results</p> <p>We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.</p> <p>Conclusion</p> <p>Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.</p

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Daycare attendance and risk of childhood acute lymphoblastic leukaemia

The relationship between daycare/preschool (‘daycare’) attendance and the risk of acute lymphoblastic leukaemia was evaluated in the Northern California Childhood Leukaemia Study. Incident cases (age 1–14 years) were rapidly ascertained during 1995–1999. Population-based controls were randomly selected from the California birth registry, individually matched on date of birth, gender, race, Hispanicity, and residence, resulting in a total of 140 case–controls pairs. Fewer cases (n=92, 66%) attended daycare than controls (n=103, 74%). Children who had more total child–hours had a significantly reduced risk of ALL. The odds ratio associated with each thousand child–hours was 0.991 (95% confidence interval (CI): 0.984–0.999), which means that a child with 50 thousand child–hours (who may have, for example, attended a daycare with 15 other children, 25 h per week, for a total duration of 30.65 months) would have an odds ratio of (0.991)50=0.64 (95% CI: 0.45, 0.95), compared to children who never attended daycare. Besides, controls started daycare at a younger age, attended daycare for longer duration, remained in daycare for more hours, and were exposed to more children at each daycare. These findings support the hypothesis that delayed exposure to common infections plays an important role in the aetiology of childhood acute lymphoblastic leukaemia, and suggest that extensive contact with other children in a daycare setting is associated with a reduced risk of acute lymphoblastic leukaemia