Pilot Study For Using Fitbit Activity Trackers To Monitor And Predict Onset Of CAR-T Cell Immunotherapy Related Adverse Events Including Cytokine Release Syndrome

Introduction: Immunotherapy using T Cells with engineered chimeric antigen receptors (CAR) is a revolutionary modality for treating cancer, especially B cell malignancies. It also has specific toxicities. The most common toxicities observed are cytokine-release syndrome (CRS) and neurotoxicity. These therapy-related adverse events can range from mild to fatal. If appropriately and timely treated, they have a good prognosis. Thus, further insight into predictive biomarkers can help clinical management of patients and reduce morbidity and mortality. Objective: One of the constitutional symptoms associated with CRS is fatigue. With the advent of activity tracking digital technology, I propose a pilot study exploring the use of fitness trackers to quantify activity level as a potential predictive biomarker of CRS due to CAR T-Cell immunotherapy. Methods: The proposed study would be a single-arm trial. Patients who are receiving CAR-T Cell immunotherapy will be given a Fitbit Flex 2™ tracker. One week of activity data (measured as steps per day) prior to CAR-T Cell infusion will establish patient baseline activity. From the date of infusion, activity levels will continue to be tracked and analyzed through CRS onset. The patient data will be gathered from Fitbit’s server via a customized app built using Fitbit’s Web Application Programming Interface (API). Results: This is a proposed study. No results have been gathered. Discussion: If a correlation is established between activity levels and onset of CRS, it would enhance the current predictive algorithm, allow easier outpatient management and remote monitoring, decrease costs, and reduce morbidity and mortality

The effect of organic retarders on grout thickening and setting during deep borehole disposal of high-level radioactive waste

Deep borehole disposal (DBD) is being increasingly seen as a viable and potentially superior alternative to comparatively shallow mined repository concepts for disposal of some high-level radioactive wastes. We report here details of proof-of-concept investigations into the use of cementitious grouts as sealing/ support matrices for use in low temperature DBD scenarios. Using the cementitious grout to fill annular space within the disposal zone will not only support waste packages during placement, but will also provide a low permeability layer around them which will ultimately enhance the safety case for DBD. Grouts based on Class G oil well cement are being developed. The use of retarders to delay the accelerated onset of thickening and setting (caused by the high temperature and pressure in the borehole) is being investigated experimentally. Sodium gluconate and a polycarboxylate additive each provide suf- ficient retardation over the range 90e140 °C in order to be considered for this application. Phosphonate and sulphonate additives provide desirable retardation at 90 °C. The additives did not affect grout composition at 14 days curing and the phases formed are durable at elevated temperature and pressure

Effects of HER2 overexpression on cell signaling networks governing proliferation and migration

Although human epidermal growth factor receptor 2 (HER2) overexpression is implicated in tumor progression for a variety of cancer types, how it dysregulates signaling networks governing cell behavioral functions is poorly understood. To address this problem, we use quantitative mass spectrometry to analyze dynamic effects of HER2 overexpression on phosphotyrosine signaling in human mammary epithelial cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). Data generated from this analysis reveal that EGF stimulation of HER2-overexpressing cells activates multiple signaling pathways to stimulate migration, whereas HRG stimulation of these cells results in amplification of a specific subset of the migration signaling network. Self-organizing map analysis of the phosphoproteomic data set permitted elucidation of network modules differentially regulated in HER2-overexpressing cells in comparison with parental cells for EGF and HRG treatment. Partial least-squares regression analysis of the same data set identified quantitative combinations of signals within the networks that strongly correlate with cell proliferation and migration measured under the same battery of conditions. Combining these modeling approaches enabled association of epidermal growth factor receptor family dimerization to activation of specific phosphorylation sites, which appear to most critically regulate proliferation and/or migration

Experimental study of the morphine de-addiction properties of Delphinium denudatum Wall.

BACKGROUND: Our aim was to explore the de-addiction properties of Delphinium denudatum Wall. in morphine dependent rats. METHODS: Charles Foster male albino rats were made morphine dependent by injecting morphine sulphate in increasing doses twice a day for 7 days. The spontaneous withdrawal signs observed 12 h after the last dose were quantified by the 'counted' and 'checked' signs. The drug (alcoholic extract of Delphinium denudatum) was administered p.o. in different regimen: a) single dose (700 mg/kg) 10 h before the first dose of morphine, b) single dose (700 mg/kg) 10 h after the last dose of morphine, c) multiple doses (350 mg/kg) along with morphine twice a day for 7 days. RESULT: Administration of Delphinium denudatum extract caused significant reduction in the frequency of counted signs as well as the presence of checked signs of morphine withdrawal. The maximum reduction was observed in regimen 'b' followed by regimen 'c' and 'a'. CONCLUSION: Delphinium denudatum Wall. significantly reduces the aggregate scores for all parameters in morphine withdrawal syndrome by central action and thus may prove to be an alternative remedy in morphine de-addiction

Remote physiological monitoring: Clinical, financial, and behavioral outcomes in a heart failure population

This article reports on the outcomes associated with remote physiological monitoring (RPM) conducted as part of a heart failure disease management program. Claims data, medical records, data transmission records, and survey results for 91 individuals ages 50–92 (mean 74 years) successfully completing a heart failure RPM program were analyzed for time periods before, during, and after the monitoring intervention. The program was associated with significant reductions in per member per month costs and emergency room and hospital utilization. More detailed analyses were performed for specific gender and age subgroups. Participant surveys indicated high levels of satisfaction, and improvements in self-perceived health status, self-efficacy, and self-management behaviors. This study is the first to assess the impact of a RPM program following removal of the monitoring equipment. The results indicate that RPM, as a component of a traditional disease management program, has a sustained, beneficial effect on participants’ lifestyles after the monitoring period has ended

IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

Evaluation of selected South African ethnomedicinal plants as mosquito repellents against the Anopheles arabiensis mosquito in a rodent model

<p>Abstract</p> <p>Background</p> <p>This study was initiated to establish whether any South African ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito repellent properties.</p> <p>Methods</p> <p>Extracts of a selection of South African taxa were tested for repellency properties in an applicable mosquito feeding-probing assay using unfed female <it>Anopheles arabiensis</it>.</p> <p>Results</p> <p>Although a water extract of the roots of <it>Chenopodium opulifolium </it>was found to be 97% as effective as DEET after 2 mins, time lag studies revealed a substantial reduction in efficacy (to 30%) within two hours.</p> <p>Conclusions</p> <p>None of the plant extracts investigated exhibited residual repellencies >60% after three hours.</p

Clinical features and predictors of mortality in admitted patients with community- and hospital-acquired legionellosis: A Danish historical cohort study

<p>Abstract</p> <p>Background</p> <p>Legionella is a common cause of bacterial pneumonia. Community-acquired [CAL] and hospital-acquired legionellosis [HAL] may have different presentations and outcome. We aimed to compare clinical characteristics and examine predictors of mortality for CAL and HAL.</p> <p>Methods</p> <p>We identified hospitalized cases of legionellosis in 4 Danish counties from January 1995 to December 2005 using the Danish national surveillance system and databases at departments of clinical microbiology. Clinical and laboratory data were retrieved from medical records; vital status was obtained from the Danish Civil Registration System. We calculated 30- and 90-day case fatality rates and identified independent predictors of mortality using logistic regression analyses.</p> <p>Results</p> <p>We included 272 cases of CAL and 60 cases of HAL. Signs and symptoms of HAL were less pronounced than for CAL and time from in-hospital symptoms to legionellosis diagnosis was shorter for CAL than for HAL (5.5 days vs. 12 days p < 0.001). Thirty-day case fatality was 12.9% for CAL and 33.3% for HAL; similarly 90-day case fatalities in the two groups were 15.8% and 55.0%, respectively. In a logistic regression analysis (excluding symptoms and laboratory tests) age >65 years (OR = 2.6, 95% CI: 1.1-5.9) and Charlson comorbidty index ≥2 (OR = 2.7, 95% CI: 1.1-6.5) were associated with an increased risk of death in CAL. We identified no statistically significant predictors of 30-day mortality in HAL.</p> <p>Conclusions</p> <p>Signs and symptoms were less pronounced in HAL compared to CAL. Conversely, 30-day case fatality was almost 3 times higher. Clinical awareness is important for the timely diagnosis and treatment especially of HAL. There is a need for further studies of prognostic factors in order to improve the therapeutic approach to legionellosis and potentially reduce mortality.</p

Assessing the Validity of Sexual Behaviour Reports in a Whole Population Survey in Rural Malawi

Background: Sexual behaviour surveys are widely used, but under-reporting of particular risk behaviours is common, especially by women. Surveys in whole populations provide an unusual opportunity to understand the extent and nature of such under-reporting.Methods: All consenting individuals aged between 15 and 59 within a demographic surveillance site in northern Malawi were interviewed about their sexual behaviour. Validity of responses was assessed by analysis of probing questions; by comparison of results with in-depth interviews and with Herpes simplex type-2 (HSV-2) seropositivity; by comparing reports to same sex and opposite sex interviewers; and by quantifying the partnerships within the local community reported by men and by women, adjusted for response rates.Results: 6,796 women and 5,253 men (83% and 72% of those eligible) consented and took part in sexual behaviour interviews. Probing questions and HSV-2 antibody tests in those who denied sexual activity identified under-reporting for both men and women. Reports varied little by sex or age of the interviewer. The number of marital partnerships reported was comparable for men and women, but men reported about 4 times as many non-marital partnerships. The discrepancy in reporting of non-marital partnerships was most marked for married women (men reported about 7 times as many non-marital partnerships with married women as were reported by married women themselves), but was only apparent in younger married women.Conclusions: We have shown that the under-reporting of non-marital partnerships by women was strongly age-dependent. The extent of under-reporting of sexual activity by young men was surprisingly high. The results emphasise the importance of triangulation, including biomarkers, and the advantages of considering a whole population