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BACKGROUND: Growing interest has motivated recent studies to examine differences in recovery after sport-related concussion (SRC) by sex. However, heterogeneity in study design, participants, and recovery outcomes has led to mixed findings. Further work is needed to evaluate potential differences by sex and to investigate the role of related characteristics, such as sport contact-level, in recovery timelines. This study aimed to investigate whether concussion recovery trajectories differ by sex, considering a priori clinical and demographic covariates, and accounting for the sequence of recovery outcomes. Our secondary question was whether sport contact-level modifies the relationship between sex and time to outcomes. Using data from the Ivy League-Big Ten Epidemiology of Concussion Study, we included SRCs reported across five academic years; 2015-2020 (February 2020). We used Cox proportional hazards regressions to estimate associations between sex and time from injury to three outcomes: (1) symptom resolution, (2) return to academics, (3) return to full play, accounting for measured confounders. RESULTS: Among 1160 SRCs (male, n = 667; female, n = 493) with complete data, median age overall was 20 years (25th-75th percentiles:19-21), and most occurred among athletes playing high-contact sports (78.0%). Males were slightly more likely to complete symptom resolution over time compared to females (HR = 1.18, 95%CI = 1.05-1.33), but results were attenuated in fully adjusted models (HR 1.13, 95%CI = 0.99-1.29). Similarly, the HR of full academic return for males compared to females was 1.22 (95%CI = 1.07-1.38), but was attenuated in fully adjusted models (HR = 1.11, 95%CI = 0.97-1.28). The HR of full return to play for males compared to females was 1.14 (95%CI = 1.02-1.28), and was attenuated after adjustment (HR = 1.06, 95%CI = 0.93-1.20) as well. The interaction between sex and playing a high/low-contact sport was not statistically significant across models, though differences were apparent. CONCLUSIONS: Among a cohort of collegiate athletes with SRC, recovery timelines appeared similar between male and female athletes, adjusting for measured confounders. Differences by sex, considering sport contact-level, were evident and may be important clinically and in future studies. This study used robust methods, accounting for nesting in the sequence of RTP outcomes. Results inform concussion management protocols and planned qualitative work to further elucidate how collegiate athletes experience concussion recovery. KEY POINTS: Heterogeneity in study design, participants, and recovery outcomes has led to mixed findings in determining differences in recovery trajectories after concussion by sex. We found that having longer time to symptom resolution, and also the sequence of having academic return before symptoms resolve and longer time to academic return were confounders in the relationship between sex and RTP timelines. Time to sequential recovery outcomes appeared similar between male and female athletes, adjusting for observable confounders. Further differences by sex were evident when considering contact-level, and may be important to consider clinically and in future research. Results indicate that differences in concussion recovery trajectories by sex may be largely attributed to and driven by differences in sports with a men's or women's team only, such as football, and this should be explored further.
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Importance: Handheld phone use while driving is a major factor in vehicle crashes. Scalable interventions are needed to encourage drivers not to use their phones. Objective: To test whether interventions involving social comparison feedback and/or financial incentives can reduce drivers' handheld phone use. Design, Setting, and Participants: In a randomized clinical trial, interventions were administered nationwide in the US via a mobile application in the context of a usage-based insurance program (Snapshot Mobile application). Customers were eligible to be invited to participate in the study if enrolled in the usage-based insurance program for 30 to 70 days. The study was conducted from May 13 to June 30, 2019. Analysis was completed December 22, 2023. Interventions: Participants were randomly assigned to 1 of 6 trial arms for a 7-week intervention period: (1) control; (2) feedback, with weekly push notification about their handheld phone use compared with that of similar others; (3) standard incentive, with a maximum $50 award at the end of the intervention based on how their handheld phone use compared with similar others; (4) standard incentive plus feedback, combining interventions of arms 2 and 3; (5) reframed incentive plus feedback, with a maximum $7.15 award each week, framed as participant's to lose; and (6) doubled reframed incentive plus feedback, a maximum $14.29 weekly loss-framed award. Main Outcome and Measure: Proportion of drive time engaged in handheld phone use in seconds per hour (s/h) of driving. Analyses were conducted with the intention-to-treat approach. Results: Of 17â¯663 customers invited by email to participate, 2109 opted in and were randomized. A total of 2020 drivers finished the intervention period (68.0% female; median age, 30 [IQR, 25-39] years). Median baseline handheld phone use was 216 (IQR, 72-480) s/h. Relative to control, feedback and standard incentive participants did not reduce their handheld phone use. Standard incentive plus feedback participants reduced their use by -38 (95% CI, -69 to -8) s/h (P = .045); reframed incentive plus feedback participants reduced their use by -56 (95% CI, -87 to -26) s/h (P < .001); and doubled reframed incentive plus feedback participants reduced their use by -42 s/h (95% CI, -72 to -13 s/h; P = .007). The 5 active treatment arms did not differ significantly from each other. Conclusions and Relevance: In this randomized clinical trial, providing social comparison feedback plus incentives reduced handheld phone use while individuals were driving. Trial Registration: ClinicalTrials.gov Identifier: NCT03833219.
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Conducción de Automóvil , Motivación , Humanos , Femenino , Masculino , Adulto , Conducción de Automóvil/psicología , Conducción de Automóvil/estadística & datos numéricos , Persona de Mediana Edad , Uso del Teléfono Celular/estadística & datos numéricos , Aplicaciones Móviles , Retroalimentación , Estados UnidosRESUMEN
Distracted driving is responsible for nearly 1 million crashes each year in the United States alone, and a major source of driver distraction is handheld phone use. We conducted a randomized, controlled trial to compare the effectiveness of interventions designed to create sustained reductions in handheld use while driving (NCT04587609). Participants were 1,653 consenting Progressive® Snapshot® usage-based auto insurance customers ages 18 to 77 who averaged at least 2 min/h of handheld use while driving in the month prior to study invitation. They were randomly assigned to one of five arms for a 10-wk intervention period. Arm 1 (control) got education about the risks of handheld phone use, as did the other arms. Arm 2 got a free phone mount to facilitate hands-free use. Arm 3 got the mount plus a commitment exercise and tips for hands-free use. Arm 4 got the mount, commitment, and tips plus weekly goal gamification and social competition. Arm 5 was the same as Arm 4, plus offered behaviorally designed financial incentives. Postintervention, participants were monitored until the end of their insurance rating period, 25 to 65 d more. Outcome differences were measured using fractional logistic regression. Arm 4 participants, who received gamification and competition, reduced their handheld use by 20.5% relative to control (P < 0.001); Arm 5 participants, who additionally received financial incentives, reduced their use by 27.6% (P < 0.001). Both groups sustained these reductions through the end of their insurance rating period.
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Conducción Distraída , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Conducción Distraída/prevención & control , Anciano , Adolescente , Conducción de Automóvil , Adulto JovenRESUMEN
BACKGROUND: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. OBJECTIVE: The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. METHODS: The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care.â¯This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. RESULTS: Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively. CONCLUSIONS: In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054675.
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Hospitalización , Medición de Resultados Informados por el Paciente , Humanos , Persona de Mediana Edad , Masculino , Hospitalización/estadística & datos numéricos , Femenino , Anciano , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/mortalidadRESUMEN
In this paper, we present and evaluate a novel Bayesian regime-switching zero-inflated multilevel Poisson (RS-ZIMLP) regression model for forecasting alcohol use dynamics. The model partitions individuals' data into two phases, known as regimes, with: (1) a zero-inflation regime that is used to accommodate high instances of zeros (non-drinking) and (2) a multilevel Poisson regression regime in which variations in individuals' log-transformed average rates of alcohol use are captured by means of an autoregressive process with exogenous predictors and a person-specific intercept. The times at which individuals are in each regime are unknown, but may be estimated from the data. We assume that the regime indicator follows a first-order Markov process as related to exogenous predictors of interest. The forecast performance of the proposed model was evaluated using a Monte Carlo simulation study and further demonstrated using substance use and spatial covariate data from the Colorado Online Twin Study (CoTwins). Results showed that the proposed model yielded better forecast performance compared to a baseline model which predicted all cases as non-drinking and a reduced ZIMLP model without the RS structure, as indicated by higher AUC (the area under the receiver operating characteristic (ROC) curve) scores, and lower mean absolute errors (MAEs) and root-mean-square errors (RMSEs). The improvements in forecast performance were even more pronounced when we limited the comparisons to participants who showed at least one instance of transition to drinking.
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Modelos Estadísticos , Consumo de Alcohol en Menores , Adolescente , Teorema de Bayes , Humanos , Distribución de Poisson , PsicometríaRESUMEN
Gray short-tailed opossums are used in a wide variety of research in the areas of developmental biology, oncology, immunology, and comparative biology. Despite many frequent experimental manipulations of these animals under anesthesia, few studies to date have characterized the effects of anesthesia in this species. Our aim was to identify safe and effective injectable anesthetic combinations using ketamine and xylazine or ketamine and dexmedetomidine at doses of 40 mg/kg to 100 mg/kg for ketamine, 5 mg/kg to 10 mg/kg for xylazine, and 0.05 mg/kg to 0.1 mg/kg for dexmedetomidine. Effects of the proposed regimens ranged from light sedation to surgical anesthesia, but only 100 mg/kg ketamine + 0.1 mg/kg dexmedetomidine induced surgical anesthesia in all opossums, with a mean duration of 25.4 min. The 2 lowest doses of ketamine and xylazine (40 mg/kg ketamine + 5 mg/kg xylazine and 40 mg/kg ketamine + 10 mg/kg xylazine) achieved sedation to light anesthesia in all animals but did not produce a surgical plane of anesthesia in any animal. All regimens that induced a surgical plane of anesthesia caused bradycardia and bradypnea, and 75 mg/kg ketamine + 10 mg/kg xylazine and 100 mg/kg ketamine + 0.1 mg/kg dexmedetomidine caused the greatest decreases in SpO2. Except for one opossum that died of unknown causes, all animals remained healthy and apparently free of anesthetic complications. Among all treatments, isoflurane delivered by a precision vaporizer provided the most consistent and reliable anesthesia; therefore, we recommend inhalant anesthesia over the injectable combinations used in this study.
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Anestesia/veterinaria , Anestésicos/farmacología , Dexmedetomidina/farmacología , Ketamina/farmacología , Monodelphis , Xilazina/farmacología , Anestésicos/administración & dosificación , Animales , Dexmedetomidina/administración & dosificación , Relación Dosis-Respuesta a Droga , Inyecciones Intravenosas , Ketamina/administración & dosificación , Monodelphis/sangre , Oxígeno/sangre , Xilazina/administración & dosificaciónRESUMEN
BACKGROUND: In occupational settings, boilermakers are exposed to high levels of metallic fine particulate matter (PM2.5) generated during the welding process. The effect of welding PM2.5 on heart rate variability (HRV) has been described, but the relationship between PM2.5, DNA methylation, and HRV is not known. METHODS: In this repeated-measures panel study, we recorded resting HRV and measured DNA methylation levels in transposable elements Alu and long interspersed nuclear element-1 (LINE-1) in peripheral blood leukocytes under ambient conditions (pre-shift) and right after a welding task (post-shift) among 66 welders. We also monitored personal PM2.5 level in the ambient environment and during the welding procedure. RESULTS: The concentration of welding PM2.5 was significantly higher than background levels in the union hall (0.43 mg/m3 vs. 0.11 mg/m3, p < 0.0001). The natural log of transformed power in the high frequency range (ln HF) had a significantly negative association with PM2.5 exposure (ß = -0.76, p = 0.035). pNN10 and pNN20 also had a negative association with PM2.5 exposure (ß = -0.16%, p = 0.006 and ß = -0.13%, p = 0.030, respectively). PM2.5 was positively associated with LINE-1 methylation [ß = 0.79%, 5-methylcytosince (%mC), p = 0.013]; adjusted for covariates. LINE-1 methylation did not show an independent association with HRV. CONCLUSIONS: Acute decline of HRV was observed following exposure to welding PM2.5 and evidence for an epigenetic response of transposable elements to short-term exposure to high-level metal-rich particulates was reported.
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Metilación de ADN/genética , Frecuencia Cardíaca , Leucocitos/metabolismo , Metales , Exposición Profesional/efectos adversos , Material Particulado/efectos adversos , Soldadura , Adulto , Estudios de Cohortes , Elementos Transponibles de ADN/genética , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Exposición Profesional/análisis , Material Particulado/análisisRESUMEN
The higher criticism is effective for testing a joint null hypothesis against a sparse alternative, e.g., for testing the effect of a gene or a genetic pathway that consists of d genetic markers. Accurate p-value calculations for the higher criticism based on the asymptotic distribution require a very large d, which is not the case for the number of genetic variants in a gene or a pathway. In this paper we propose an analytic method that accurately computes the p-value of the higher criticism test for finite d problems. Unlike previous treatments, this method does not rely on asymptotics in d or simulation, and is exact for arbitrary d when the test statistics are normally distributed. The method is particularly computationally advantageous when d is not large. We illustrate the proposed method with a case-control genome-wide association study of lung cancer and compare its power to competing methods through simulations.
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In the increasing number of sequencing studies aimed at identifying rare variants associated with complex traits, the power of the test can be improved by guided sampling procedures. We confirm both analytically and numerically that sampling individuals with extreme phenotypes can enrich the presence of causal rare variants and can therefore lead to an increase in power compared to random sampling. Although application of traditional rare variant association tests to these extreme phenotype samples requires dichotomizing the continuous phenotypes before analysis, the dichotomization procedure can decrease the power by reducing the information in the phenotypes. To avoid this, we propose a novel statistical method based on the optimal Sequence Kernel Association Test that allows us to test for rare variant effects using continuous phenotypes in the analysis of extreme phenotype samples. The increase in power of this method is demonstrated through simulation of a wide range of scenarios as well as in the triglyceride data of the Dallas Heart Study.