Management of multimorbidity using a patient-centred care model:a pragmatic cluster-randomised trial of the 3D approach

Background: The management of people with multiple chronic conditions challenges health-care systems designed around single conditions. There is international consensus that care for multimorbidity should be patient-centred, focus on quality of life, and promote self-management towards agreed goals. However, there is little evidence about the effectiveness of this approach. Our hypothesis was that the patient-centred, so-called 3D approach (based on dimensions of health, depression, and drugs) for patients with multimorbidity would improve their health-related quality of life, which is the ultimate aim of the 3D intervention. Methods: We did this pragmatic cluster-randomised trial in general practices in England and Scotland. Practices were randomly allocated to continue usual care (17 practices) or to provide 6-monthly comprehensive 3D reviews, incorporating patient-centred strategies that reflected international consensus on best care (16 practices). Randomisation was computer-generated, stratified by area, and minimised by practice deprivation and list size. Adults with three or more chronic conditions were recruited. The primary outcome was quality of life (assessed with EQ-5D-5L) after 15 months' follow-up. Participants were not masked to group assignment, but analysis of outcomes was blinded. We analysed the primary outcome in the intention-to-treat population, with missing data being multiply imputed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN06180958. Findings: Between May 20, 2015, and Dec 31, 2015, we recruited 1546 patients from 33 practices and randomly assigned them to receive the intervention (n=797) or usual care (n=749). In our intention-to-treat analysis, there was no difference between trial groups in the primary outcome of quality of life (adjusted difference in mean EQ-5D-5L 0·00, 95% CI −0·02 to 0·02; p=0·93). 78 patients died, and the deaths were not considered as related to the intervention. Interpretation: To our knowledge, this trial is the largest investigation of the international consensus about optimal management of multimorbidity. The 3D intervention did not improve patients' quality of life. Funding: National Institute for Health Research

The Empty Promise of Estate Tax Repeal

The terms of the debate over the estate tax have been framed largely by abolitionists who have propounded an antitax message that portrays the estate tax as unambiguously harmful and threatening to ordinary families and small businesses. The attack on the estate tax is linked to a larger agenda of eliminating taxes on capital and capital income and dismantling the progressive elements of the federal tax system. The slogan of estate tax repeal, while effective in mobilizing antitax sentiment, makes no sense as a matter of tax policy because it downplays revenue costs, distributional effects, administrative concerns, and consequences for the rest of the tax system. The 2001 Act illustrates the gap between the abolitionists\u27 simplistic antitax agenda and the complex reality of tradeoffs among competing tax and spending priorities. The estate tax cuts enacted in 2001 imply large revenue losses as well as a shift in tax burdens from the very rich to the middle class and from current taxpayers to future taxpayers. This appears to be a step in precisely the wrong direction, given growing inequalities of income and wealth and a looming fiscal gap

Towards a Holistic Approach to Technology and Climate Change:What Would Form Part of an Answer?

This multi-authored piece conducts an interdisciplinary analysis of the fields and principles which could be relevant to securing access to climate change technologies, while at the same time encouraging the initial development of the technologies. The paper is the first part of a project funded by the British Academy, ‘Obtaining, protecting and using essential environmental technologies: a holistic analysis’

The impact of XENON100 and the LHC on Supersymmetric Dark Matter

The effect of 2010 and 2011 LHC data are discussed in connection to the potential for the direct detection of supersymmetric dark matter. The impact of the recent XENON100 results are contrasted to these predictions.Comment: 14 pages, 23 figures, To be published in the Proceedings of the 7th DSU Conference, Beijing Chin

The Growing Up in Singapore Towards Healthy Outcomes Study

Objective Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD) with gestational diabetes mellitus (GDM) and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Methods Plasma 25OHD concentrations, fasting glucose (FG) and 2-hour postprandial glucose (2HPPG) concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26–28 weeks’ gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section. Results In total, 388 (41.3%) women had 25OHD inadequacy. Of these, 131 (33.8%), 155 (39.9%) and 102 (26.3%) were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI) = 0.01, 0.14), but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR) = 1.39, 95% CI = 0.95, 2.05) was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33), while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43) and Indian women (OR = 2.41, 95% CI = 1.01, 5.73). Conclusions 25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency caesarean section in Chinese and Indian women

When Statutory Regimes Collide:Will Wisconsin Right to Life and Citizens United Invalidate Federal Tax Regulation of Campaign Activity?

In Federal Election Commission v. Wisconsin Right to Life (2007) and Citizens United v. Federal Elections Commission (2010), the United States Supreme Court dramatically reduced the ability of Congress to regulate campaign finance activities of corporations and others active in elections. Many of the same activities are still subject to restrictions by the Internal Revenue Code, which regulates the type and amount of political campaign activities that certain nonprofits exempt under federal tax law can engage in. In the wake of the campaign finance decisions, the constitutionality of the tax law’s restrictions on campaign activity is now being challenged in the lower courts. This Article analyzes the two recent campaign finance decisions and campaign finance precedents more broadly to determine how, if at all, the Roberts’ Court’s campaign finance jurisprudence is likely to alter existing tax law jurisprudence in the area of campaign activity. It finds that, for the most part, tax law constitutional doctrines have developed independently of other areas of First Amendment free speech law. Based upon an analysis of the distinctive tax law doctrines, the Article concludes that the tax law provision prohibiting section 501(c)(3) charities from engaging in campaigns is likely to withstand challenges arguing that the provision prevents these nonprofits from engaging in protected political speech. However, there is some likelihood that the tax law prohibition is vulnerable to constitutional attack under traditional doctrines of vagueness or overbreadth due to the lack of precision of the terms of the political prohibition, as these have been elaborated by the IRS and the courts to date

An Active Learning Approach for Rapid Characterization of Endothelial Cells in Human Tumors

Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers

Educational Attainment of Same-Sex and Opposite-Sex Dizygotic Twins: An Individual-Level Pooled Study of 19 Twin Cohorts

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers