Cancer Carepartners: Improving patients' symptom management by engaging informal caregivers

<p>Abstract</p> <p>Background</p> <p>Previous studies have found that cancer patients undergoing chemotherapy can effectively manage their own symptoms when given tailored advice. This approach, however, may challenge patients with poor performance status and/or emotional distress. Our goal is to test an automated intervention that engages a friend or family member to support a patient through chemotherapy.</p> <p>Methods/Design</p> <p>We describe the design and rationale of a randomized, controlled trial to assess the efficacy of 10 weeks of web-based caregiver alerts and tailored advice for helping a patient manage symptoms related to chemotherapy. The study aims to test the primary hypothesis that patients whose caregivers receive alerts and tailored advice will report less frequent and less severe symptoms at 10 and 14 weeks when compared to patients in the control arm; similarly, they will report better physical function, fewer outpatient visits and hospitalizations related to symptoms, and greater adherence to chemotherapy. 300 patients with solid tumors undergoing chemotherapy at two Veteran Administration oncology clinics reporting any symptom at a severity of ≥4 and a willing informal caregiver will be assigned to either 10 weeks of automated telephonic symptom assessment (ATSA) alone, or 10 weeks of ATSA plus web-based notification of symptom severity and problem solving advice to their chosen caregiver. Patients and caregivers will be surveyed at intake, 10 weeks and 14 weeks. Both groups will receive standard oncology, hospice, and palliative care.</p> <p>Discussion</p> <p>Patients undergoing chemotherapy experience many symptoms that they may be able to manage with the support of an activated caregiver. This intervention uses readily available technology to improve patient caregiver communication about symptoms and caregiver knowledge of symptom management. If successful, it could substantially improve the quality of life of veterans and their families during the stresses of chemotherapy without substantially increasing the cost of care.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00983892">NCT00983892</a></p

The National Institute for Health Research Hyperacute Stroke Research Centres and the ENCHANTED trial: the impact of enhanced research infrastructure on trial metrics and patient outcomes

Background The English National Institute for Health Research Clinical Research Network first established Hyperacute Stroke Research Centres (HSRCs) in 2010 to support multicentre hyperacute (< 9 h) and complex stroke research. We assessed the impact of this investment on research performance and patient outcomes in a post-hoc analysis of country-specific data from a large multicentre clinical trial. Methods Comparisons of baseline, outcome and trial metric data were made for participants recruited to the alteplase-dose arm of the international Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) at National Institute for Health Research Clinical Research Network HSRCs and non-HSRCs between June 2012 and October 2015. Results Among 774 ENCHANTED United Kingdom participants (41% female; mean age 72 years), 502 (64.9%) were recruited from nine HSRCs and 272 (35.1%) from 24 non-HSRCs. HSRCs had higher monthly recruitment rates (median 1.5, interquartile interval 1.4–2.2 vs. 0.7, 0.5–1.3; p = 0.01) and shorter randomisation-to-treatment times (2.6 vs. 3.1 min; p = 0.01) compared to non-HSRCs. HSRC participants were younger and had milder stroke severity, but clinically important between-group differences in 90-day death or disability outcomes remained after adjustment for minimisation criteria and important baseline variables at randomisation, whether defined by ordinal modified Rankin scale score shift (adjusted OR 0.82, 95% CI 0.62–1.08; p = 0.15), scores 2 to 6 (adjusted OR 0.71, 95% CI 0.50–1.01; p = 0.05), or scores 3 to 6 (adjusted OR 0.82, 95% CI 0.57–1.17; p = 0.27). There was no significant difference in symptomatic intracerebral haemorrhage, nor heterogeneity in the comparative treatment effects between low- and standard-dose alteplase by HSRCs or non-HSRCs. Conclusions Infrastructure investment in HSRCs was associated with improved research performance metrics, particularly recruitment and time to treatment with clinically important, though not statistically significant, improvements in patient outcomes

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

The LOLIPOP study is supported by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council (G0601966,G0700931), the Wellcome Trust (084723/Z/08/Z), and the NIHR (RP-PG-0407-10371). The work was carried out in part at the NIHR/Wellcome Trust Imperial Clinical Research Facility. The Sikh Diabetes Study is supported by National Institute of Health grants KO1TW006087, funded by the Fogarty International Center, R01DK082766, funded by National Institute of Diabetes and Digestive and Kidney Diseases, and a seed grant from University of Oklahoma Health Sciences Center, Oklahoma City, USA. The Mauritius Family Study is supported by the Mauritius Ministry of Health and Quality of Life, Australian Government National Health and Medical Research Council NHMRC project grant numbers 1020285 and 1037916, the Victorian Government’s OIS Program, and partly funded by US National Institutes of Health Grant DK-25446. We thank the participants and research staff who made the study possible.South Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10−6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans.Yeshttp://www.plosone.org/static/editorial#pee

Changes in leukocyte subsets of pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus and relationships with viral load and fetal outcome

International audienceIn spite of more than two decades of extensive research, the understanding of porcine reproductive and respiratory syndrome virus (PRRSv) immunity is still incomplete. A PRRSv infection of the late term pregnant female can result in abortions, early farrowings, fetal death, and the birth of weak, congenitally infected piglets. The objectives of the present study were to investigate changes in peripheral blood mononuclear cell populations in third trimester pregnant females infected with type 2 PRRSv (NVSL 97–7895) and to analyze potential relationships with viral load and fetal mortality rate. PRRSv infection caused a massive, acute drop in total leukocyte counts affecting all PBMC populations by two days post infection. Except for B cells, cell counts started to rebound by day six post infection. Our data also show a greater decrease of naïve B cells, T-helper cells and cytolytic T cells than their respective effector or memory counterparts. Absolute numbers of T cells and γδ T cells were negatively associated with PRRSv RNA concentration in gilt serum over time. Additionally, absolute numbers of T helper cells may be predictive of fetal mortality rate. The preceding three leukocyte populations may therefore be predictive of PRRSv-related pathological outcomes in pregnant gilts. Although many questions regarding the immune responses remain unanswered, these findings provide insight and clues that may help reduce the impact of PRRSv in pregnant gilts

Plasma membrane nanoswitches generate high-fidelity Ras signal transduction

Ras proteins occupy dynamic plasma membrane nanodomains called nanoclusters. The significance of this spatial organization is unknown. Here we show, using in silico and in vivo analyses of mitogen-activated protein (MAP) kinase signalling, that Ras nanoclusters operate as sensitive switches, converting graded ligand inputs into fixed outputs of activated extracellular signal-regulated kinase (ERK). By generating Ras nanoclusters in direct proportion to ligand input, cells build an analogue–digital–analogue circuit relay that transmits a signal across the plasma membrane with high fidelity. Signal transmission is completely dependent on Ras spatial organization and fails if nanoclustering is abrogated. A requirement for high-fidelity signalling may explain the non-random distribution of other plasma membrane signalling complexes