Why do patients with multimorbidity in England report worse experiences in primary care? Evidence from the General Practice Patient Survey.

OBJECTIVES: To describe and explain the primary care experiences of people with multiple long-term conditions in England. DESIGN AND METHODS: Using questionnaire data from 906,578 responders to the English 2012 General Practice Patient Survey, we describe the primary care experiences of patients with long-term conditions, including 583,143 patients who reported one or more long-term conditions. We employed mixed effect logistic regressions to analyse data on six items covering three care domains (access, continuity and communication) and a single item on overall primary care experience. We controlled for sociodemographic characteristics, and for general practice using a random effect, and further, controlled for, and explored the importance of, health-related quality of life measured using the EuroQoL (EQ-5D) scale. RESULTS: Most patients with long-term conditions report a positive experience of care at their general practice (after adjusting for sociodemographic characteristics and general practice, range 74.0-93.1% reporting positive experience of care across seven questions) with only modest variation by type of condition. For all three domains of patient experience, an increasing number of comorbid conditions is associated with a reducing percentage of patients reporting a positive experience of care. For example, compared with respondents with no long-term condition, the OR for reporting a positive experience is 0.83 (95% CI 0.80 to 0.87) for respondents with four or more long-term conditions. However, this relationship is no longer observed after adjusting for health-related quality of life (OR (95% CI) single condition=1.23 (1.21 to 1.26); four or more conditions=1.31 (1.25 to 1.37)), with pain making the greatest difference among five quality of life variables included in the analysis. CONCLUSIONS: Patients with multiple long-term conditions more frequently report worse experiences in primary care. However, patient-centred measures of health-related quality of life, especially pain, are more important than the number of conditions in explaining why patients with multiple long-term conditions report worse experiences of care

Development and validation of the Cambridge Multimorbidity Score

BACKGROUND: Health services have failed to respond to the pressures of multimorbidity. Improved measures of multimorbidity are needed for conducting research, planning services and allocating resources. METHODS: We modelled the association between 37 morbidities and 3 key outcomes (primary care consultations, unplanned hospital admission, death) at 1 and 5 years. We extracted development (n = 300 000) and validation (n = 150 000) samples from the UK Clinical Practice Research Datalink. We constructed a general-outcome multimorbidity score by averaging the standardized weights of the separate outcome scores. We compared performance with the Charlson Comorbidity Index. RESULTS: Models that included all 37 conditions were acceptable predictors of general practitioner consultations (C-index 0.732, 95% confidence interval [CI] 0.731-0.734), unplanned hospital admission (C-index 0.742, 95% CI 0.737-0.747) and death at 1 year (C-index 0.912, 95% CI 0.905-0.918). Models reduced to the 20 conditions with the greatest combined prevalence/weight showed similar predictive ability (C-indices 0.727, 95% CI 0.725-0.728; 0.738, 95% CI 0.732-0.743; and 0.910, 95% CI 0.904-0.917, respectively). They also predicted 5-year outcomes similarly for consultations and death (C-indices 0.735, 95% CI 0.734-0.736, and 0.889, 95% CI 0.885-0.892, respectively) but performed less well for admissions (C-index 0.708, 95% CI 0.705-0.712). The performance of the general-outcome score was similar to that of the outcome-specific models. These models performed significantly better than those based on the Charlson Comorbidity Index for consultations (C-index 0.691, 95% CI 0.690-0.693) and admissions (C-index 0.703, 95% CI 0.697-0.709) and similarly for mortality (C-index 0.907, 95% CI 0.900-0.914). INTERPRETATION: The Cambridge Multimorbidity Score is robust and can be either tailored or not tailored to specific health outcomes. It will be valuable to those planning clinical services, policymakers allocating resources and researchers seeking to account for the effect of multimorbidity

Catastrophizing mediates the relationship between the personal belief in a just world and pain outcomes among chronic pain support group attendees

Health-related research suggests the belief in a just world can act as a personal resource that protects against the adverse effects of pain and illness. However, currently, little is known about how this belief, particularly in relation to one’s own life, might influence pain. Consistent with the suggestions of previous research, the present study undertook a secondary data analysis to investigate pain catastrophizing as a mediator of the relationship between the personal just world belief and chronic pain outcomes in a sample of chronic pain support group attendees. Partially supporting the hypotheses, catastrophizing was negatively correlated with the personal just world belief and mediated the relationship between this belief and pain and disability, but not distress. Suggestions for future research and intervention development are made

GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis under physiological and pathological conditions. Anti-VEGF therapy is a clinically proven strategy for the treatment of a variety of cancers including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the dominant angiogenic signaling receptor, it has become an important target in the development of novel anti-angiogenic therapies. We have reported previously the development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising anti-angiogenic activity <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>In the current study, we utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested alone or in combination with doxorubicin for <it>in vivo </it>efficacy in the MMTV-PyMT transgenic model of breast cancer.</p> <p>Results</p> <p>The derivative GU81 has increased <it>in vitro </it>efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81 alone) had no effect on tumor weight, histology, tumor fat content, or tumor growth index. However, GU81 is able to significantly to reduce total vascular area as a single agent. GU81 used in combination with doxorubicin significantly reduced tumor weight and growth index compared to all other treatment groups. Furthermore, treatment with combination therapy significantly arrested tumor progression at the premalignant stage, resulting in increased tumor fat content. Interestingly, treatment with GU81 alone increased tumor-VEGF levels and macrophage infiltration, an effect that was abrogated when used in combination with doxorubicin.</p> <p>Conclusion</p> <p>This study demonstrates the VEGFR2 antagonist peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous murine MMTV-PyMT breast tumors.</p

Dodecahedral space topology as an explanation for weak wide-angle temperature correlations in the cosmic microwave background

Cosmology's standard model posits an infinite flat universe forever expanding under the pressure of dark energy. First-year data from the Wilkinson Microwave Anisotropy Probe (WMAP) confirm this model to spectacular precision on all but the largest scales (Bennett {\it et al.}, 2003 ; Spergel {\it et al.}, 2003). Temperature correlations across the microwave sky match expectations on scales narrower than $60^{\circ}$, yet vanish on scales wider than $60^{\circ}$. Researchers are now seeking an explanation of the missing wide-angle correlations (Contaldi {\it et al.}, 2003 ; Cline {\it et al.}, 2003). One natural approach questions the underlying geometry of space, namely its curvature (Efstathiou, 2003) and its topology (Tegmark {\it et al.}, 2003). In an infinite flat space, waves from the big bang would fill the universe on all length scales. The observed lack of temperature correlations on scales beyond $60^{\circ}$ means the broadest waves are missing, perhaps because space itself is not big enough to support them. Here we present a simple geometrical model of a finite, positively curved space -- the Poincar\'e dodecahedral space -- which accounts for WMAP's observations with no fine-tuning required. Circle searching (Cornish, Spergel and Starkman, 1998) may confirm the model's topological predictions, while upcoming Planck Surveyor data may confirm its predicted density of $\Omega_0 \simeq 1.013 > 1$. If confirmed, the model will answer the ancient question of whether space is finite or infinite, while retaining the standard Friedmann-Lema\^\i{}tre foundation for local physics.Comment: 10 pages, 4 figures. This is a slightly longer version of the paper published in Nature 425, p. 593, 200

Holocene deglaciation and glacier readvances on the Fildes Peninsula and King George Island (Isla 25 de Mayo), South Shetland Islands, NW Antarctic Peninsula

To provide insights into glacier-climate dynamics of the South Shetland Islands (SSI), NW Antarctic Peninsula, we present a new deglaciation and readvance model for the Bellingshausen Ice Cap (BIC) on Fildes Peninsula and for King George Island/Isla 25 de Mayo (KGI) ~62°S. Deglaciation on KGI began after c. 15 ka cal BP and had progressed to within present-day limits on the Fildes Peninsula, its largest ice-free peninsula, by c. 6.6–5.3 ka cal BP. Probability density phase analysis of chronological data constraining Holocene glacier advances on KGI revealed up to eight 95% probability ‘gaps’ during which readvances could have occurred. These are grouped into four stages – Stage 1: a readvance and marine transgression, well-constrained by field data, between c. 7.4–6.6 ka cal BP; Stage 2: four probability ‘gaps’, less well-constrained by field data, between c. 5.3–2.2 ka cal BP; Stage 3: a well-constrained but restricted ‘readvance’ between c. 1.7–1.5 ka; Stage 4: two further minor ‘readvances’, one less well-constrained by field data between c. 1.3–0.7 ka cal BP (68% probability), and a ‘final’ well-constrained ‘readvance’ after 1950 CE) is associated with recent warming/more positive SAM-like conditions

Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. Methods/design: The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP.Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term. Assessment of outcomes will be blinded and will follow the intention-to-treat principle. Discussion: We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. Trial registration: ISRCTN: ISRCTN5871969

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

Infant Botulism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66984/2/10.1177_000992289303201105.pd

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol