Improving the external validity of clinical trials: the case of multiple chronic conditions

The U.S. Department of Health and Human Services vision and strategic framework on multiple chronic conditions (MCCs) incorporates recommendations designed to facilitate research that will improve our knowledge about interventions and systems that will benefit individuals with MCCs (or multimorbidity). The evidence base supporting the management of patients with MCCs will be built both through intervention trials specifically designed to address multimorbidity and identification of MCCs in participants across the clinical trial range. This article specifically focuses on issues relating to external validity with specific reference to trials involving patients with MCCs. The exclusion of such patients from clinical trials has been well documented. Randomized control trials (RCTs) are considered the “gold standard” of evidence, but may have drawbacks in relation to external validity, particularly in relation to multimorbidity. It may, therefore, be necessary to consider a broader range of research methods that can provide converging evidence on intervention effects to address MCCs. Approaches can also be taken to increase the usefulness of RCTs in general for providing evidence to inform multimorbidity management. Additional improvements to RCTs would include better reporting of inclusion and exclusion criteria and participant characteristics in relation to MCCs. New trials should be considered in terms of how they will add to the existing evidence base and should inform how interventions may work in different settings and patient groups. Research on treatments and interventions for patients with MCCs is badly needed. It is important that this research includes patient-centered measures and that generalizability issues be explicitly addressed.Journal of Comorbidity 2013;3(2)30–3

Research on patients with multiple health conditions: different constructs, different views, one voice

Technological advances, improvements in medical care and public health policies have resulted in a growing proportion of patients with multiple health conditions. The prevalence of multiple health conditions among individuals increases with age, is substantial among older adults, and will increase dramatically in coming years. This phenomenon has received growing interest in the most recent literature and has led to several – and often differing – conceptualizations.<p></p> The term “comorbidity” was originally defined by Feinstein as “any distinct additional clinical entity that has existed or may occur during the clinical course of a patient who has the index disease under study”. This definition places one disease in a central position and all other condition(s) as secondary, in that they may or may not affect the course and treatment of the index disease. Feinstein’s principle has been applied all too readily as if the effect of comorbidity was secondary or indeed negligible. In clinical research, individuals with a narrowly defined index condition and no major comorbidities are usually enrolled, leaving the majority of the patients seen in a typical family practice out in the cold. In clinical practice, management of the index condition invariably takes priority, with disjointed – if any – treatment plans developed for each of the comorbidities. This model of care is typical of delivery systems constructed around specialized care, where areas of expertise are defined around specific conditions and bodily systems [11]. Not surprisingly, clinical practice guidelines arising from that model of care lack pertinence for patients with multiple health conditions

Occupational Gender Composition and Wages in Canada: 1987-1988

The relationship between occupational gender composition and wages is the basis of pay equity/comparable worth legislation. A number of previous studies have examined this relationship in US data, identifying some of the determinants of low wages in ``female jobs'' well as important limitations of public policy in this area. There is little evidence, however, from other jurisdictions. This omission is particularly disturbing in the case of Canada, which now has some of the most extensive pay equity legislation in the world. In this paper we provide a comprehensive picture, circa the late 1980's, of the occupational gender segregation in Canada and its consequences for wages. The sample period precedes many provincial pay equity initiatives and thus the results should provide a baseline for the evaluation of this legislation. We find that the estimated wage penalties in female jobs in Canada are generally much smaller than the estimates for the United States. Although there is some heterogeneity across worker groups on average, the link between female wages and gender composition is small and not statistically significant.

Occupational Gender Segregation and Women's Wages in Canada: An Historical Perspective

We document the evolution of occupational gender segregation and its implications for women's labour market outcomes over the twentieth century. The first half of the century saw a considerable decline in vertical segregation as women moved out of domestic and manufacturing work into clerical work. This created a substantial amount of horizontal segregation that persists to this day. To study the effects of occupational segregation on the gender gap, we introduce a decomposition technique that divides the gap into between-occupation and within-occupation components. Since the 1990s the component attributable to within-occupation wage differentials has become predominant. Nous traçons un portrait de l'évolution de la ségrégation professionnelle selon le sexe au 20ième siècle, et de ses conséquences sur la condition féminine dans le marché du travail. Dans la première partie du 20ième siècle, la ségrégation professionnelle hiérarchique ou verticale a considérablement déclinée alors que les travailleuses quittaient les emplois de domestique et du secteur manufacturier en faveur des emplois de bureau. Ceci créa néanmoins une importante ségrégation professionnelle horizontale qui persiste jusqu'à aujourd'hui. Pour étudier les effets de la ségrégation professionnelle sur l'écart salarial selon le sexe, nous présentons une technique de décomposition qui divise l'écart salarial en deux composantes: l'une due aux différences intra-occupations et l'autre due aux différences inter-occupations. Depuis le début des années 90, la composante intra-occupation est prédominante.Occupational segregation, gender wage gap, pay equity, economic history, Ségrégation professionnelle, équité salariale, écart salarial selon le sexe, histoire économique

Neutron stars with hyperon cores: stellar radii and EOS near nuclear density

The existence of 2 Msun pulsars puts very strong constraints on the equation of state (EOS) of neutron stars (NSs) with hyperon cores, which can be satisfied only by special models of hadronic matter. The radius-mass relation for these models is sufficiently specific that it could be subjected to an observational test with future X-ray observatories. We want to study the impact of the presence of hyperon cores on the radius-mass relation for NS. We aim to find out how, and for which particular stellar mass range, a specific relation R(M), where M is the gravitational mass, and R is the circumferential radius, is associated with the presence of a hyperon core. We consider a set of 14 theoretical EOS of dense matter, based on the relativistic mean-field (RMF) approximation, allowing for the presence of hyperons in NSs. We seek correlations between R(M) and the stiffness of the EOS below the hyperon threshold needed to pass the 2 Msun test. For NS masses 1.013km, because of a very stiff pre-hyperon segment of the EOS. At nuclear density, the pressure is significantly higher than a robust upper bound obtained recently using chiral effective field theory. If massive NSs do have a sizable hyperon core, then according to current models the radii for M=1.0-1.6 Msun are necessarily >13km. If, on the contrary, a NS with a radius R<12 km is observed in this mass domain, then sizable hyperon cores in NSs, as we model them now, are ruled out. Future X-ray missions with <5% precision for a simultaneous M and R measurement will have the potential to solve the problem with observations of NSs. Irrespective of this observational test, present EOS allowing for hyperons that fulfill condition M_max>2 Msun yield a pressure at nuclear density that is too high relative to up-to-date microscopic calculations of this quantity.Comment: 10 pages, 10 figures, published in A&

Collider Constraints on Dipole-Interacting Dark Matter

Dark matter which interacts through a magnetic or electric dipole moment is an interesting possibility which may help to resolve the discrepancy between the DAMA annual modulation signal and the null results of other searches. In this article we examine relic density and collider constraints on such dark matter, and find that for couplings needed to explain DAMA, the thermal relic density is generically in the right ballpark to account for cosmological measurements. Collider constraints are relevant for light WIMPs, but less constraining that direct searches for masses above about 10 GeV.Comment: 11 pages, 2 figures, extended discussion, added references, conclusion unchange

Rotating neutron stars with exotic cores: masses, radii, stability

A set of theoretical mass-radius relations for rigidly rotating neutron stars with exotic cores, obtained in various theories of dense matter, is reviewed. Two basic observational constraints are used: the largest measured rotation frequency (716 Hz) and the maximum measured mass ($2\;M_\odot$). Present status of measuring the radii of neutron stars is described. The theory of rigidly rotating stars in general relativity is reviewed and limitations of the slow rotation approximation are pointed out. Mass-radius relations for rotating neutron stars with hyperon and quark cores are illustrated using several models. Problems related to the non-uniqueness of the crust-core matching are mentioned. Limits on rigid rotation resulting from the mass-shedding instability and the instability with respect to the axisymmetric perturbations are summarized. The problem of instabilities and of the back-bending phenomenon are discussed in detail. Metastability and instability of a neutron star core in the case of a first-order phase transition, both between pure phases, and into a mixed-phase state, are reviewed. The case of two disjoint families (branches) of rotating neutron stars is discussed and generic features of neutron-star families and of core-quakes triggered by the instabilities are considered.Comment: Matches published version. Minor modifications and reference adde

VSAERO analysis of tip planforms for the free-tip rotor

The results of a numerical analysis of two interacting lifting surfaces separated in the spanwise direction by a narrow gap are presented. The configuration consists of a semispan wing with the last 32 percent of the span structurally separated from the inboard section. The angle of attack of the outboard section is set independently from that of the inboard section. In the present study, the three-dimensional panel code VSAERO is used to perform the analysis. Computed values of tip surface lift and pitching moment coefficients are correlated with experimental data to determine the proper approach to model the gap region between the surfaces. Pitching moment data for various tip planforms are also presented to show how the variation of tip pitching moment with angle of attack may be increased easily in incompressible flow. Calculated three-dimensional characteristics in compressible flow at Mach numbers of 0.5 and 0.7 are presented for new tip planform designs. An analysis of sectional aerodynamic center shift as a function of Mach number is also included for a representative tip planform. It is also shown that the induced drag of the tip surface is reduced for negative incidence angles relative to the inboard section. The results indicate that this local drag reduction overcomes the associated increase in wing induced drag at high wing lift coefficients