Are Patients With Longer Emergency Department Wait Times Less Likely to Consent to Research?

Objectives: There are unique challenges to enrolling patients in emergency department (ED) clinical research studies, including the time-sensitive nature of emergency conditions, the acute care environ- ment, and the lack of an established relationship with patients. Prolonged ED wait times have been asso- ciated with a variety of adverse effects on patient care. The objective of this study was to assess the effect of ED wait times on patient participation in ED clinical research. The hypothesis was that increased ED wait times would be associated with reduced ED clinical research consent rates. Methods: This was a retrospective cohort study of all patients eligible for two diagnostic clinical research studies from January 1, 2008, through December 31, 2008, in an urban academic ED. Sex, age, race, study eligibility, and research consent decisions were recorded by trained study personnel. The wait times to registration and to be seen by a physician were obtained from administrative databases and compared between consenters and nonconsenters. An analysis of association between patient wait times for the outcome of consent to participate was performed using a multivariate logistic regression model. Results: A total of 903 patients were eligible for enrollment and were asked for consent. Overall, 589 eligible patients (65%) gave consent to research participation. The consent rates did not change when patients were stratified by the highest and lowest quartile wait times for both time from arrival to regis- tration (68% vs. 65%, p = 0.35) and time to be seen by a physician (65% vs. 66%, p = 0.58). After adjusting for patient demographics (age, race, and sex) and study, there was still no relationship between wait times and consent (p > 0.4 for both wait times). Furthermore, median time from arrival to registration did not differ between those who consented to participate (15 minutes; interquartile range [IQR] = 9 to 36 minutes) versus those who did not (15.5 minutes; IQR = 10 to 39 minutes; p = 0.80; odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.99 to 1.01). Similarly, there was no difference in the median time to be seen by a physician between those who consented (25 minutes; IQR = 15 to 55 minutes) versus those who did not (25 minutes; IQR = 15 to 56 minutes; p = 0.70; OR = 1.00, 95% CI = 0.99 to 1.01). Conclusions: Regardless of wait times, nearly two-thirds of eligible patients were willing to consent to diagnostic research studies in the ED. These findings suggest that effective enrollment in clinical research is possible in the ED, despite challenges with prolonged wait times

Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.

BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others

Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency

PURPOSE: Primary ovarian insufficiency before the age of 40 years affects 1% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR1 expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for primary ovarian insufficiency, but these are likely to be biased as compared with cases in the general population. The prevalence of FMR1 expansion mutations in early menopause (between the ages of 40 and 45 years) has not been published. METHODS: We studied FMR1 CGG repeat number in more than 2,000 women from the Breakthrough Generations Study who underwent menopause before the age of 46 years. We determined the prevalence of premutation (55–200 CGG repeats) and intermediate (45–54 CGG repeats) alleles in women with primary ovarian insufficiency (n = 254) and early menopause (n = 1,881). RESULTS: The prevalence of the premutation was 2.0% in primary ovarian insufficiency, 0.7% in early menopause, and 0.4% in controls, corresponding to odds ratios of 5.4 (95% confidence interval = 1.7–17.4; P = 0.004) for primary ovarian insufficiency and 2.0 (95% confidence interval = 0.8–5.1; P = 0.12) for early menopause. Combining primary ovarian insufficiency and early menopause gave an odds ratio of 2.4 (95% confidence interval = 1.02–5.8; P = 0.04). Intermediate alleles were not significant risk factors for either early menopause or primary ovarian insufficiency. CONCLUSION: FMR1 premutations are not as prevalent in women with ovarian insufficiency as previous estimates have suggested, but they still represent a substantial cause of primary ovarian insufficiency and early menopause

P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. © 2014 Cotoia et al

Modulating Temporal and Spatial Oxygenation over Adherent Cellular Cultures

Oxygen is a key modulator of many cellular pathways, but current devices permitting in vitro oxygen modulation fail to meet the needs of biomedical research. A microfabricated insert for multiwell plates has been developed to more effectively control the temporal and spatial oxygen concentration to better model physiological phenomena found in vivo. The platform consists of a polydimethylsiloxane insert that nests into a standard multiwell plate and serves as a passive microfluidic gas network with a gas-permeable membrane aimed to modulate oxygen delivery to adherent cells. Equilibration time is on the order of minutes and a wide variety of oxygen profiles can be attained based on the device design, such as the cyclic profile achieved in this study, and even oxygen gradients to mimic those found in vivo. The proper biological consequences of the device's oxygen delivery were confirmed in cellular models via a proliferation assay and western analysis of the upregulation of hypoxia inducible transcription factor-1α. These experiments serve as a demonstration for the platform as a viable tool to increase experimental throughput and permit novel experimental possibilities in any biomedical research lab

Is post-trabeculectomy hypotony a risk factor for subsequent failure? A case control study

BACKGROUND: Ocular hypotony results in an increased break down of the blood-aqueous barrier and an increase in inflammatory mediator release. We postulate that this release may lead to an increased risk of trabeculectomy failure through increased bleb scarring. This study was designed to try to address the question if hypotony within one month of trabeculectomy for Primary Open Angle Glaucoma (POAG), is a risk factor for future failure of the filter. METHODS: We performed a retrospective, case notes review, of patients who underwent trabeculectomy for POAG between Jan 1995 and Jan 1996 at our hospital. We identified those with postoperative hypotony within 1 month of surgery. Hypotony was defined as an intraocular pressure (IOP) < 8 mmHg or an IOP of less than 10 mmHg with choroidal detachment or a shallow anterior chamber. We compared the survival times of the surgery in this group with a control group (who did not suffer hypotony as described above), over a 5 year period. Failure of trabeculectomy was defined as IOP > 21 mmHg, or commencement of topical antihypertensives or repeat surgery. RESULTS: 97 cases matched our inclusion criteria, of these 38 (39%) experienced hypotony within 1 month of surgery. We compared the survival times in those patients who developed hypotony with those who did not using the log-rank test. This data provided evidence of a difference (P = 0.0492) with patients in the hypotony group failing more rapidly than the control group. CONCLUSION: Early post-trabeculectomy hypotony (within 1 month) is associated with reduced survival time of blebs

Reported frequency of physical activity in a large epidemiological study: relationship to specific activities and repeatability over time

<p>Abstract</p> <p>Background</p> <p>How overall physical activity relates to specific activities and how reported activity changes over time may influence interpretation of observed associations between physical activity and health. We examine the relationships between various physical activities self-reported at different times in a large cohort study of middle-aged UK women.</p> <p>Methods</p> <p>At recruitment, Million Women Study participants completed a baseline questionnaire including questions on frequency of strenuous and of any physical activity. About 3 years later 589,896 women also completed a follow-up questionnaire reporting the hours they spent on a range of specific activities. Time spent on each activity was used to estimate the associated excess metabolic equivalent hours (MET-hours) and this value was compared across categories of physical activity reported at recruitment. Additionally, 18,655 women completed the baseline questionnaire twice, at intervals of up to 4 years; repeatability over time was assessed using the weighted kappa coefficient (κ_weighted) and absolute percentage agreement.</p> <p>Results</p> <p>The average number of hours per week women reported doing specific activities was 14.0 for housework, 4.5 for walking, 3.0 for gardening, 0.2 for cycling, and 1.4 for all strenuous activity. Time spent and the estimated excess MET-hours associated with each activity increased with increasing frequency of any or strenuous physical activity reported at baseline (tests for trend, P < 0.003), although the associations for housework were by far the weakest (Spearman correlations, 0.01 and -0.03 respectively for housework, and 0.11-0.37 for all other activities). Repeatability of responses to physical activity questions on the baseline questionnaire declined significantly over time. For strenuous activity, absolute agreement was 64% (κ_weighted= 0.71) for questionnaires administered less than 6 months apart, and 52% (κ_weighted= 0.51) for questionnaires more than 2 years apart. Corresponding values for any physical activity were 57% (κ_weighted= 0.67) and 47% (κ_weighted= 0.58).</p> <p>Conclusions</p> <p>In this cohort, responses to simple questions on the frequency of any physical activity and of strenuous activity asked at baseline were associated with hours spent on specific activities and the associated estimated excess MET-hours expended, reported 3 years later. The weakest associations were with housework. Agreement for identical questions asked on two occasions about the frequency of physical activity decreased over time.</p

Contributions of phonological and verbal working memory to language development in adolescents with fragile X syndrome

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Although language delays are frequently observed in FXS, neither the longitudinal course of language development nor its cognitive predictors are well understood. The present study investigated whether phonological and working memory skills are predictive of growth in vocabulary and syntax in individuals with FXS during adolescence. Forty-four individuals with FXS (mean age = 12.61 years) completed assessments of phonological memory (nonword repetition and forward digit recall), verbal working memory (backward digit recall), vocabulary, syntax, and nonverbal cognition. Vocabulary and syntax skills were reassessed at a 2-year follow-up. In a series of analyses that controlled for nonverbal cognitive ability and severity of autism symptoms, the relative contributions of phonological and working memory to language change over time were investigated. These relationships were examined separately for boys and girls. In boys with FXS, phonological memory significantly predicted gains in vocabulary and syntax skills. Further, verbal working memory was uniquely associated with vocabulary gains among boys. In girls with FXS, phonological and working memory skills showed no relationship with language change across the 2-year time period. Our findings indicate that, for adolescent boys with FXS, acquisition of vocabulary and syntax may be constrained by the ability to maintain and manipulate phonological representations online. Implications for the identification and treatment of language disorders in this population are discussed. The present study is the first to identify specific cognitive mechanisms contributing to language growth over time in individuals with FXS

Checkpoints in a Yeast Differentiation Pathway Coordinate Signaling during Hyperosmotic Stress

All eukaryotes have the ability to detect and respond to environmental and hormonal signals. In many cases these signals evoke cellular changes that are incompatible and must therefore be orchestrated by the responding cell. In the yeast Saccharomyces cerevisiae, hyperosmotic stress and mating pheromones initiate signaling cascades that each terminate with a MAP kinase, Hog1 and Fus3, respectively. Despite sharing components, these pathways are initiated by distinct inputs and produce distinct cellular behaviors. To understand how these responses are coordinated, we monitored the pheromone response during hyperosmotic conditions. We show that hyperosmotic stress limits pheromone signaling in at least three ways. First, stress delays the expression of pheromone-induced genes. Second, stress promotes the phosphorylation of a protein kinase, Rck2, and thereby inhibits pheromone-induced protein translation. Third, stress promotes the phosphorylation of a shared pathway component, Ste50, and thereby dampens pheromone-induced MAPK activation. Whereas all three mechanisms are dependent on an increase in osmolarity, only the phosphorylation events require Hog1. These findings reveal how an environmental stress signal is able to postpone responsiveness to a competing differentiation signal, by acting on multiple pathway components, in a coordinated manner

Fear of predation drives stable and differentiated social relationships in guppies

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.Social relationships can have important consequences for fitness in animals. Whilst numerous studies have shown that individuals often join larger groups in response to perceived predation risk (i.e. fear of predation), the importance of predation risk in driving the formation and stability of social relationships within groups has been relatively ignored. We experimentally tested how predation threat influenced fine-scale social network structure using Trinidadian guppies (Poecilia reticulata). When perceived predation risk was high, individuals developed stable and more differentiated social ties compared to when perceived risk was low. Intriguingly, social differentiation coincided with shoals being somewhat smaller under high-perceived risk, suggesting a possible conflict between forming stable social relationships and larger social groups. Individuals most at risk of predation (large and bold individuals) showed the most exaggerated responses in several social measures. Taken together, we provide the first experimental evidence that proximate risk of predation can increase the intensity of social relationships and fine-scale social structure in animal populations.DPC acknowledges funding from the National Environmental Research Council (NE/E001181/1) and Leverhulme Trust (RPG-175) and SKD and DPC acknowledge funding from The Danish Council for Independent Research (DFF – 1323-00105)