Abstract Purpose Adolescent drivers are at elevated crash risk due to distracted driving behavior (DDB). Understanding parental and peer influences on adolescent DDB may aid future efforts to ...decrease crash risk. We examined the influence of risk perception, sensation seeking, as well as descriptive and injunctive social norms on adolescent DDB using the theory of normative social behavior. Methods 403 adolescents (aged 16–18 years) and their parents were surveyed by telephone. Survey instruments measured self-reported sociodemographics, DDB, sensation seeking, risk perception, descriptive norms (perceived parent DDB, parent self-reported DDB, and perceived peer DDB), and injunctive norms (parent approval of DDB and peer approval of DDB). Hierarchical multiple linear regression was used to predict the influence of descriptive and injunctive social norms, risk perception, and sensation seeking on adolescent DDB. Results 92% of adolescents reported regularly engaging in DDB. Adolescents perceived that their parents and peers participated in DDB more frequently than themselves. Adolescent risk perception, parent DDB, perceived parent DDB, and perceived peer DDB were predictive of adolescent DDB in the regression model, but parent approval and peer approval of DDB were not predictive. Risk perception and parental DDB were stronger predictors among males, whereas perceived parental DDB was stronger for female adolescents. Conclusions Adolescent risk perception and descriptive norms are important predictors of adolescent distracted driving. More study is needed to understand the role of injunctive normative influences on adolescent DDB. Effective public health interventions should address parental role modeling, parental monitoring of adolescent driving, and social marketing techniques that correct misconceptions of norms related to around driver distraction and crash risk.
Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal ...levels of hematologic measures but does not treat the underlying systemic disease.
We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2).
A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period.
Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome. (Funded by Alexion Pharmaceuticals; C08-002 ClinicalTrials.gov numbers, NCT00844545 adults and NCT00844844 adolescents; C08-003 ClinicalTrials.gov numbers, NCT00838513 adults and NCT00844428 adolescents).
To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve ...patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.
DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints.
Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): -1.00 vs -0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY).
CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.
NCT01519791.
Shares the findings of a study aimed at determining the level and timing of lamb loss that occurs during the first year of life on a typical hill country sheep and beef farm in central North Island, ...New Zealand, and whether some loss can be prevented through vaccination against the five main clostridial diseases using a commercially available multivalent clostridial vaccine. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Objective
Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimum clinically important differences (MCID) for some measures, such as the Clinical ...Disease Activity Index (CDAI), have not been well‐defined in real‐world clinic settings, especially for early RA patients with low/moderate disease activity.
Methods
Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cut points were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self‐reported improvement or worsening. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated against patient self‐reported improvement (gold standard) and for change in pain, Health Assessment Questionnaire (HAQ), and Disease Activity Score in 28 joints (DAS28) improvement. Discrimination was examined using the area under receiver operator curves. Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity.
Results
A total of 578 patients (mean ± SD age 54.1 ± 15.3 years, 75% women, median interquartile range disease duration 5.3 3.3, 8.0 months) contributed 1,169 visit pairs to the improvement analysis. The MCID cut points for improvement were 12 (patients starting in high disease activity: CDAI >22), 6 (moderate: CDAI 10–22), and 1 (low disease activity: CDAI <10). Performance characteristics were acceptable using these cut points for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units.
Conclusion
These minimum important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice.
Purpose Fatigue is frequent and often severe and disabling in RA, and there is no consensus on how to measure it. We used online surveys and in-person interviews to evaluate PROMIS Fatigue 7a and 8a ...short forms (SFs) in people with RA. Methods We recruited people with RA from an online patient community (n=200) and three academic medical centers (n=84) in the US. Participants completed both SFs then rated the comprehensiveness and comprehensibility of the items to their fatigue experience. Cognitive debriefing of items was conducted in a subset of 32 clinic patients. Descriptive statistics were calculated, and associations were evaluated using Pearson and Spearman correlation coefficients. Results Mean SF scores were similar (p≥.61) among clinic patients reflecting mild fatigue (i.e., 54.5–55.9), but were significantly higher (p<.001) in online participants. SF Fatigue scores correlated highly (r≥0.82; p<.000) and moderately with patient assessments of disease activity (r≥0.62; p=.000). Most (70–92%) reported that the items "completely" or "mostly" reflected their experience. Almost all (≥94%) could distinguish general fatigue from RA fatigue. Most (≥85%) rated individual items questions as "somewhat" or "very relevant" to their fatigue experience, averaged their fatigue over the past 7 days (58%), and rated fatigue impact versus severity (72 vs. 19%). 99% rated fatigue as an important symptom they considered when deciding how well their current treatment was controlling their RA. Conclusions Results suggest that items in the single-score PROMIS Fatigue SFs demonstrate content validity and can adequately capture the wide range of fatigue experiences of people with RA.
The motor-vehicle crash risk of novice teen drivers is unacceptably high. This article examines the historical trends in fatal crash rates for male and female teen drivers as compared to adult ...drivers by both population and person-miles driven. The effect of motor-vehicle policies on teen driver crashes, characteristics of teen driver crashes, and combinations of these crash characteristics are also examined. A framework of seven categories of influences on teen driving behavior is presented, including the following elements: driving ability, developmental factors, behavioral factors, personality factors, demographics, the perceived environment, and the driving environment. Because a complex set of different factors influence teen drivers' behavior, comprehensive, multilevel interventions are needed to reduce teen drivers' exposure to high-risk driving conditions and to address factors identified in the framework.
•Mechanisms for the crash reductions associated with Graduated Driver Licensing (GDL) are not well understood.•Two components of GDL were examined: the minimum learner license duration, and the ...required minimum hours of supervised driving.•Learner license duration of six months was associated with significant declines in 16–17-year-old drivers’ fatal crash rates.•Meta-analysis found the learner license duration is associated with a significant decline in teen drivers’ fatal crash rates.•Required hours of supervised practice driving were not associated with a decline in teen drivers’ fatal crash rates.
Most studies evaluating the effectiveness of Graduated Driver Licensing (GDL) have focused on the overall system. Studies examining individual components have rarely accounted for the confounding of multiple, simultaneously implemented components. The purpose of this paper is to quantify the effects of a required learner license duration and required hours of supervised driving on teen driver fatal crashes.
States that introduced a single GDL component independent of any other during the period 1990–2009 were identified. Monthly and quarterly fatal crash rates per 100,000 population of 16- and 17-year-old drivers were analyzed using single-state time series analysis, adjusting for adult crash rates and gasoline prices. Using the parameter estimates from each state's time series model, the pooled effect of each GDL component on 16- and 17-year-old drivers’ fatal crashes was estimated using a random effects meta-analytic model to combine findings across states.
In three states, a six-month minimum learner license duration was associated with a significant decline in combined 16- and 17-year-old drivers’ fatal crash rates. The pooled effect of the minimum learner license duration across all states in the sample was associated with a significant change in combined 16- and 17-year-old driver fatal crash rates of −.07 (95% Confidence Interval CI −.11, −.03). Following the introduction of 30h of required supervised driving in one state, novice drivers’ fatal crash rates increased 35%. The pooled effect across all states in the study sample of having a supervised driving hour requirement was not significantly different from zero (.04, 95% CI −.15, .22).
These findings suggest that a learner license duration of at least six-months may be necessary to achieve a significant decline in teen drivers’ fatal crash rates. Evidence of the effect of required hours of supervised driving on teen drivers’ fatal crash rates was mixed.
This paper describes the application of state-estimation techniques for the real-time prediction of the state-of-charge (SoC) and state-of-health (SoH) of lead-acid cells. Specifically, approaches ...based on the well-known Kalman Filter (KF) and Extended Kalman Filter (EKF), are presented, using a generic cell model, to provide correction for offset, drift, and long-term state divergence-an unfortunate feature of more traditional coulomb-counting techniques. The underlying dynamic behavior of each cell is modeled using two capacitors (bulk and surface) and three resistors (terminal, surface, and end), from which the SoC is determined from the voltage present on the bulk capacitor. Although the structure of the model has been previously reported for describing the characteristics of lithium-ion cells, here it is shown to also provide an alternative to commonly employed models of lead-acid cells when used in conjunction with a KF to estimate SoC and an EKF to predict state-of-health (SoH). Measurements using real-time road data are used to compare the performance of conventional integration-based methods for estimating SoC with those predicted from the presented state estimation schemes. Results show that the proposed methodologies are superior to more traditional techniques, with accuracy in determining the SoC within 2% being demonstrated. Moreover, by accounting for the nonlinearities present within the dynamic cell model, the application of an EKF is shown to provide verifiable indications of SoH of the cell pack.
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