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BACKGROUND: The majority of opioid analgesics prescribed for pain after ambulatory pediatric surgery remain unused. Most parents do not dispose of these leftover opioids or dispose of them in an unsafe manner. We aimed to evaluate the association of optimal opioid disposal with a multidisciplinary quality improvement (QI) initiative that proactively educated parents about the importance of optimal opioid disposal practices and provided a home opioid disposal kit before discharge after pediatric ambulatory surgery. METHODS: Opioid disposal behaviors were assessed during a brief telephone interview pre- (Phase I) and post-implementation (Phase II) after surgery. For each phase, we aimed to contact the parents of 300 pediatric patients ages 0 to 17 years who were prescribed an opioid after an ambulatory surgery. The QI initiative included enhanced education and a home opioid disposal kit including DisposeRX®, a medication disposal packet that renders medications inert within a polymeric gel when mixed with water. Weighted segmented regression models evaluated the association between the QI initiative and outcomes. We considered the association between the QI initiative and outcome significant if the beta coefficient for the change in intercept between the end of Phase I and the beginning of Phase II was significant. Safe opioid disposal and any opioid disposal were evaluated as secondary outcomes. RESULTS: The analyzed sample contained 161 pediatric patients in Phase I and 190 pediatric patients in Phase II. Phase II (post-QI initiative) cohort compared to Phase I cohort reported higher rates of optimal (58%, n = 111/190 vs 11%, n = 18/161) and safe (66%, n = 125/190 vs 34%, n = 55/161) opioid disposal. Weighted segmented regression analyses demonstrated significant increases in the odds of optimal (odds ratio [OR], 26.5, 95% confidence interval [CI], 4.0-177.0) and safe (OR, 4.4, 95% CI, 1.1-18.4) opioid disposal at the beginning of Phase II compared to the end of Phase I. The trends over time (slopes) within phases were nonsignificant and close to 0. The numbers needed to be exposed to achieve one new disposal event were 2.2 (95% CI, 1.4-3.7]), 3.1 (95% CI, 1.6-7.4), and 4.3 (95% CI, 1.7-13.6) for optimal, safe, and any disposal, respectively. CONCLUSIONS: A multidisciplinary approach to educating parents on the importance of safe disposal of leftover opioids paired with dispensing a convenient opioid disposal kit was associated with increased odds of optimal opioid disposal.
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Parental chronic pain is associated with adverse outcomes in children, but the mechanisms of transmission are largely untested. Mothers with chronic pain (N = 400, Mage = 40.3 years, 90.5% White) and their children (Mage = 10.33 years, 83.3% White, 50.2% female) were recruited in 2016-2018 to test longitudinal pathways of risk transmission from maternal chronic pain to children's psychological symptoms, examining roles of parenting, maternal depression, and child distress tolerance. Maternal pain was associated with positive (ß = .28) and pain-specific (ß = .10) parenting behaviors. Maternal depression was associated with lower child distress tolerance (ß = -.03), which was associated with greater child psychological symptoms (ß = -.62). Parenting and maternal pain were not prospectively associated with child outcomes. When considering the dual-generational impacts of chronic pain, physical and psychological functioning should be examined.
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Accelerometers worn by animals produce distinct behavioral signatures, which can be classified accurately using machine learning methods such as random forest decision trees. The objective of this study was to identify accelerometer signal separation among parsimonious behaviors. We achieved this objective by (1) describing functional differences in accelerometer signals among discrete behaviors, (2) identifying the optimal window size for signal pre-processing, and (3) demonstrating the number of observations required to achieve the desired level of model accuracy,. Crossbred steers (Bos taurus indicus; n = 10) were fitted with GPS collars containing a video camera and tri-axial accelerometers (read-rate = 40 Hz). Distinct behaviors from accelerometer signals, particularly for grazing, were apparent because of the head-down posture. Increasing the smoothing window size to 10 s improved classification accuracy (p < 0.05), but reducing the number of observations below 50% resulted in a decrease in accuracy for all behaviors (p < 0.05). In-pasture observation increased accuracy and precision (0.05 and 0.08 percent, respectively) compared with animal-borne collar video observations.
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Acelerometría , Conducta Animal , Aprendizaje Automático , Animales , Bovinos , Acelerometría/métodos , Conducta Animal/fisiología , Grabación en Video/métodos , Masculino , Procesamiento de Señales Asistido por ComputadorRESUMEN
OBJECTIVE: Neighborhood socioeconomic status (SES) is linked to self-reported pain severity and disability but its association with evoked pain responsiveness in individuals with chronic pain remains unclear. The present study examined relations between neighborhood SES, assessed through the area deprivation index (ADI), and static and dynamic pain response indices. It was hypothesized that youth with functional abdominal pain (FAP) living in lower SES neighborhoods would exhibit lower pain threshold, lower pain tolerance, and reduced conditioned pain modulation (CPM) compared to youth living in higher SES neighborhoods. METHODS: Participants were 183 youth with FAP and their parents. Youth completed a quantitative sensory testing protocol. Family addresses were used to compute ADI scores. Thermal stimuli for pain threshold and tolerance were delivered to participants' forearms using thermodes. CPM, an index of descending pain inhibition, was determined using a thermode as test stimulus and a hot water bath as conditioning stimulus. RESULTS: As hypothesized, youth with FAP living in lower SES neighborhoods exhibited weaker CPM. Contrary to hypotheses, lower neighborhood SES was associated with neither pain thresholds nor with pain tolerance. CONCLUSIONS: These findings demonstrated the independent contribution of place of residence-an often neglected component of the biopsychosocial model-to efficiency of descending pain inhibition. Understanding the mechanisms that account for such associations between place and pain could guide the development of public health and policy initiatives designed to mitigate chronic pain risk in underserved and economically marginalized communities.
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Dolor Crónico , Dolor Abdominal , Adolescente , Dolor Crónico/psicología , Humanos , Dimensión del Dolor/métodos , Características de la Residencia , Clase SocialRESUMEN
BACKGROUND: Nausea is a common complaint among children and is particularly prevalent in children with functional abdominal pain (FAP), with nearly half of children with FAP also endorsing nausea. Dysfunction of the autonomic nervous system, which can be indexed by heart rate variability (HRV), leads to abnormalities in gastric electrical activity that are associated with GI symptoms. AIMS: To evaluate that relationship between nausea severity and HRV in adolescents and young adults with a history of FAP and to assess for sex differences. METHODS: Participants were pediatric patients with a diagnosis of FAP who were recruited from a pediatric GI clinic between 1993 and 2007 for a prospective study of the course of FAP. Study analyses focused on the cross-sectional relationship between HRV, indexed by standard deviation of the R-R interval (SDRRI) and high-frequency (HF) power, and nausea severity collected during a follow-up visit in late adolescence and young adulthood. RESULTS: Controlling for age and BMI, a significant nausea by sex interaction emerged for both SDRRI and HF power. Tests of conditional effects of nausea by sex showed that the inverse relation between nausea severity and both SDRRI and HF was significant for females but not for males. CONCLUSIONS: This is the first study to evaluate the relationship between nausea severity and HRV. Greater nausea severity was associated with lower HRV in females but not in males. Further validation of these results may provide insight into novel treatment approaches for females with nausea that target vagal tone.
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Dolor Abdominal/fisiopatología , Sistema Nervioso Autónomo/fisiopatología , Enfermedades Gastrointestinales/fisiopatología , Frecuencia Cardíaca/fisiología , Náusea/fisiopatología , Adolescente , Adulto , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto JovenRESUMEN
BACKGROUND: Opioid analgesics are commonly prescribed for postoperative analgesia following pediatric surgery and often result in leftover opioid analgesics in the home. To reduce the volume of leftover opioids and overall community opioid burden, the State of Tennessee enacted a policy to reduce initial opioid prescribing to a 3-day supply for most acute pain incidents. We aimed to evaluate the extent of leftover opioid analgesics following pediatric ambulatory surgeries in the context of a state-mandated restrictive opioid-prescribing policy. We also aimed to evaluate opioid disposal rates, methods of disposal, and reasons for nondisposal. METHODS: Study personnel contacted the parents of 300 pediatric patients discharged with an opioid prescription following pediatric ambulatory surgery. Parents completed a retrospective telephone survey regarding opioid use and disposal. Data from the survey were combined with data from the medical record to evaluate proportion of opioid doses prescribed that were left over. RESULTS: The final analyzable sample of 185 patients (62% response rate) were prescribed a median of 12 opioid doses (interquartile range [IQR], 12-18), consumed 2 opioid doses (IQR, 0-4), and had 10 opioid doses left over (IQR, 7-13). Over 90% (n = 170 of 185) of parents reported they had leftover opioid analgesics, with 83% of prescribed doses left over. A significant proportion (29%, n = 54 of 185) of parents administered no prescribed opioids after surgery. Less than half (42%, n = 71 of 170) of parents disposed of the leftover opioid medication, most commonly by flushing down the toilet, pouring down the sink, or throwing in the garbage. Parents retaining leftover opioids (53%, n = 90 of 170) were most likely to keep them in an unlocked location (68%, n = 61 of 90). Parents described forgetfulness and worry that their child will experience pain in the future as primary reasons for not disposing of the leftover opioid medication. CONCLUSIONS: Despite Tennessee's policy aimed at reducing leftover opioids, a significant proportion of prescribed opioids were left over following pediatric ambulatory surgeries. A majority of parents did not engage in safe opioid disposal practices. Given the safety risks related to leftover opioids in the home, further interventions to improve disposal rates and tailor opioid prescribing are warranted after pediatric surgery.
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Analgésicos Opioides/administración & dosificación , Control de Medicamentos y Narcóticos , Dolor Postoperatorio/tratamiento farmacológico , Pediatría/normas , Pautas de la Práctica en Medicina , Dolor Agudo , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Trastornos Relacionados con Opioides/prevención & control , Oxicodona/administración & dosificación , Padres , Seguridad del Paciente , Estudios Retrospectivos , Riesgo , TennesseeRESUMEN
OBJECTIVE/BACKGROUND: Sleep disturbances have been commonly reported as comorbid in youth with pain conditions, but prior research specific to functional abdominal pain (FAP) is limited. This study describes individual factors associated with increased risk for sleep disturbance and characterizes the relationship between sleep disturbance and pain-related variables. PARTICIPANTS: Participants included 278 adolescents (age 11 to 17 years, M age = 15 years; 89% Caucasian; 65% female) with FAP. METHODS: Participants reported on sleep disturbances, abdominal pain severity, functional disability, somatic symptoms, and healthcare utilization. RESULTS: Female adolescents reported greater sleep disturbance than male adolescents (t(276) = 5.52, p < .001, Cohen's d = 0.70) and increased age was associated with greater sleep disturbance (r =.20, p =.001). In hierarchical regressions controlling for age, sex, and abdominal pain, greater sleep disturbance was significantly associated with greater functional disability (ß =.32), non-gastrointestinal somatic symptoms (ß =.35), and emergency department visits (ß =.29). CONCLUSIONS: Results suggest that sleep disturbance is common and should be assessed in youth presenting with FAP and may be a potential target for intervention.
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Dolor Abdominal/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Adolescente , Niño , Comorbilidad , Femenino , Humanos , Masculino , SueñoRESUMEN
BACKGROUND: Opioid analgesics are frequently used in the home setting to manage episodic pain in youth with sickle cell disease (SCD). Given the risk of adverse side effects, including constipation and sedation, understanding factors associated with at-home opioid use is important for maximizing pain relief while minimizing negative side effects. PURPOSE: The present study aimed to evaluate the relationship between individual psychological factors (pain catastrophizing and negative affect), caregiver psychological factors (catastrophizing about child's pain and caregiver negative affect), and home opioid use in youth with SCD. METHODS: Youth with SCD (n = 32) and a caregiver (n = 28) recruited during a routine outpatient hematology visit completed electronic 14 day diaries assessing pain, opioid use, and psychological factors. RESULTS: Approximately 28% of youth (n = 9) reported pain ≥50% of diary days and a third of youth (n = 11, 34%) used opioid analgesics at least one of the diary days. The number of days opioid analgesics were used ranged from 0 to 7 (50% of diary days). Results from generalized linear mixed models indicated greater child negative affect accounted for increased odds of opioid use on a given day when accounting for pain intensity. Greater caregiver catastrophizing about children's pain was also associated with increased odds of children's opioid use. CONCLUSIONS: Child and parent psychological factors relate to child opioid use at home for SCD-related pain. Future research is warranted in larger samples to identify targets for interventions to enhance pain management while reducing opioid-related risk and side effects.
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Afecto , Analgésicos Opioides/uso terapéutico , Anemia de Células Falciformes/complicaciones , Catastrofización/psicología , Dolor/tratamiento farmacológico , Padres/psicología , Adolescente , Negro o Afroamericano , Niño , Femenino , Abuelos/psicología , Humanos , Modelos Lineales , Masculino , Dolor/etiología , Dolor/psicologíaRESUMEN
Study objectives were to examine the relationships between physical activity, pain, and psychological distress in youth 8 to 17 years of age with sickle cell disease. Participants were 206 youth with sickle cell disease (M = 11.73 years, 54.9% female, 99.5% African American). Caregivers and youth completed a clinical psychosocial screening battery. Results revealed frequent pain (37.6%), moderate median pain intensity, and elevated median pain interference in youth. Lower caregiver-reported physical activity was associated with worse pain outcomes. Increased anxiety was also associated with worse pain outcomes. A better understanding of the relationship between physical activity/inactivity and pain will guide multifactorial treatment interventions.
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Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/psicología , Ejercicio Físico/psicología , Dolor/psicología , Adolescente , Adulto , Niño , Femenino , Humanos , MasculinoRESUMEN
The incidence of Hodgkin's lymphoma (HL) is growing due to an increase in Epstein-Barr virus (EBV)-associated HL in AIDS patients. The HL tumor microenvironment is vital for the survival of the malignant Hodgkin-Reed Sternberg (HRS) cells of HL, which express the EBV protein latent membrane protein 2A (LMP2A). While previous work shows that LMP2A mimics B-cell receptor (BCR) signaling to promote the survival of HRS cells, the ability of LMP2A to establish and maintain the tumor microenvironment through the production of chemokines remains unknown. Since BCR signaling induces the production of the chemokine macrophage inflammatory protein-1α (MIP-1α), and since LMP2A is a BCR mimic, we hypothesized that LMP2A increases MIP-1α levels. A comparison of multiple LMP2A-negative and -positive cell lines demonstrates that LMP2A increases MIP-1α. Additionally, LMP2A-mutant cell lines and pharmacologic inhibitors indicate that LMP2A activates a Syk/PI3K/NF-κB pathway to enhance MIP-1α. Finally, based on the finding that an NF-κB inhibitor decreased MIP-1α RNA/protein in LMP2A-positive cells, we are the first to demonstrate that LMP2A increases the nuclear localization of the NF-κB p65 subunit using DNA-binding assays and confocal microscopy in human B cells. These findings not only have implications for the treatment of HL, but also other LMP2A-expressing B-cell tumors that overexpress NF-κB.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Enfermedad de Hodgkin/fisiopatología , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Quinasa Syk/metabolismo , Proteínas de la Matriz Viral/metabolismo , Supervivencia Celular , Humanos , Células de Reed-Sternberg/fisiologíaRESUMEN
BACKGROUND: Postpartum hemorrhage is the leading cause of maternal mortality in developing countries and the primary cause of one-quarter of all maternal deaths globally. Inaccuracy in estimating blood loss obscures the diagnosis of postpartum hemorrhage and its management. OBJECTIVE: Our objective was to compare assessment of blood loss using the quantitative Triton system (Gauss Surgical, Inc, Los Altos, CA) with other measures of blood loss in women undergoing cesarean delivery. STUDY DESIGN: Women scheduled for cesarean deliveries at our facility were included. Intraoperative blood loss was measured using the Triton, which was masked to the clinical team, as well as estimated by the surgeon (subjective estimated blood loss). The relation between the 2 methods (Triton and subjective estimated blood loss) and postoperative hemoglobin as well as delta hemoglobin (postoperative minus preoperative hemoglobin) was determined using the Spearman correlation. Triton measurement and subjective estimated blood loss were compared between women with delta hemoglobin in the upper quartile (cases) vs all other quartiles (control). Prediction of delta hemoglobin in the upper quartile also was evaluated for each method, and the area under the receiver operating characteristic curves was compared. RESULTS: The trial enrolled 242 patients. The mean blood loss estimated by the Triton device was significantly lower than that estimated by clinical judgment (415.3±260.6 vs 799.6±215.6 mL, P<.01). The Triton estimate correlated best with delta hemoglobin. Seventy patients had delta hemoglobin in the upper quartile (delta hemoglobin ≥2). There was a significant difference in the Triton blood loss measurement between cases and controls but no difference with subjective estimated blood loss. Triton, but not subjective estimated blood loss, was predictive of delta hemoglobin ≥2 g/dL (Triton: area under the receiver operating characteristic curve, 0.66; 95% confidence interval, 0.58-0.74; P<.01 vs subjective estimated blood loss: area under the receiver operating characteristic curve, 0.53; 95% confidence interval, 0.45-0.61; P=.45). CONCLUSIONS: The Triton system provides a better estimate of blood loss than the visual estimate. Clinical trials to evaluate its benefit are warranted.
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Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Cesárea , Hemorragia Posparto/diagnóstico , Adulto , Femenino , Estudios de Seguimiento , Humanos , Embarazo , Estudios Prospectivos , Curva ROCRESUMEN
OBJECTIVE: To determine if prehospital identification of sepsis will affect time to Centers for Medicare and Medicaid services (CMS) sepsis core measures and improve clinical outcomes. METHODS: We conducted a retrospective cohort study among septic patients who were identified as "sepsis alerts" in the emergency department (ED). Metrics including time from ED registration to fluid resuscitation, blood cultures, serum lactate draws, and antibiotics administration were compared between those who had pre-arrival notification by EMS versus those that did not. Additionally, outcomes such as mortality and intensive care unit (ICU) admission were recorded. RESULTS: Of the 272 total patients, 162 had pre-arrival notification (prehospital sepsis alerts) and 110 did not. The prehospital sepsis alert group had significantly lower times to intravenous fluid administration (6â¯min 95%CI 4-9â¯min vs 41â¯min 95%CI 24-58â¯min, pâ¯<â¯0.001), blood cultures drawn (12â¯min 95%CI 10-14â¯min vs 34â¯min 95%CI 20-48â¯min, pâ¯=â¯0.003), lactate levels drawn (12â¯min 95%CI 10-15â¯min vs 34â¯min 95%CI 20-49â¯min, pâ¯=â¯0.003), and administration of antibiotics (33â¯min 95%CI 26-40â¯min vs 61â¯min 95%CI 44-78â¯min, pâ¯=â¯0.004). Patients with prehospital sepsis alerts also had a higher admission rate (100% vs 95%, pâ¯=â¯0.006), and a lower ICU admission rate (33% vs 52%, pâ¯=â¯0.003). There was no difference in mortality (11% vs 14%, pâ¯=â¯0.565) between groups. CONCLUSIONS: Prehospital sepsis alert notification may decrease time to specific metrics shown to improve outcomes in sepsis.
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Servicios Médicos de Urgencia/métodos , Sepsis/diagnóstico , Sepsis/terapia , Tiempo de Tratamiento , Anciano , Antibacterianos/uso terapéutico , Cultivo de Sangre , Centers for Medicare and Medicaid Services, U.S. , Femenino , Fluidoterapia , Adhesión a Directriz , Hospitalización/estadística & datos numéricos , Humanos , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Sepsis/mortalidad , Estados Unidos/epidemiologíaRESUMEN
Objective: To apply a biopsychosocial framework to understand factors influencing pain in survivors of pediatric cancer to inform pain prevention efforts and highlight the need for interdisciplinary care. Method: This topical review draws from both pediatric cancer survivorship research and chronic noncancer pain research to illustrate how components of a preventative model can be applied to pain in survivorship. Results: Pain is a common experience among long-term survivors of pediatric cancer. The pain experience in survivorship can be conceptualized in terms of biological disease and treatment factors, cognitive and affective factors, and social and contextual factors. We review literature pertinent to each of these biopsychosocial factors and tailor an existing public health prevention framework for pain in survivors of pediatric cancer. Conclusions: Classifying survivors of pediatric cancer into pain risk categories based on their daily experiences of pain, pain-related functional impairment, and distress could help guide the implementation of pain-related prevention and intervention strategies in this population. Future research is needed to establish the efficacy of screening measures to identify patients in need of psychosocial pain and pain-related fear management services, and interdisciplinary pediatric chronic pain management programs in survivors of pediatric cancer.
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Supervivientes de Cáncer , Neoplasias , Dolor/prevención & control , Prevención Secundaria/métodos , Niño , HumanosRESUMEN
BACKGROUND & AIMS: Nausea is common among children with functional abdominal pain (FAP). We evaluated the relation of nausea to short- and long-term morbidity in pediatric patients with FAP. METHODS: We performed a prospective study of 871 children with FAP (age, 8-17 y) seen in a pediatric gastroenterology practice; follow-up data were collected from 392 of the patients at 8.7 ± 3.3 years later. Participants were defined as having significant nausea if they reported nausea "a lot" or "a whole lot" within the past 2 weeks. Validated questionnaires assessed abdominal pain, gastrointestinal and somatic symptoms, and depression. Baseline measures, anxiety, and the Rome III criteria were assessed in the follow-up evaluation. RESULTS: At baseline, 44.8% of the patients reported significant nausea. Those with nausea reported worse abdominal pain, gastrointestinal symptoms, somatic symptoms, and depression than those without nausea (P < .001 for all). When the children had reached young adulthood, those with nausea in childhood continued to have more severe gastrointestinal (P < .001) and somatic symptoms (P = .003) than patients without nausea in childhood, as well as higher levels of anxiety (P = .02) and depression (P = .02). In the follow-up evaluation, somatic symptoms, depression, and anxiety remained significant after controlling for baseline abdominal pain severity. CONCLUSIONS: Pediatric patients with FAP and nausea have more severe short- and long-term gastrointestinal and somatic symptoms than patients with FAP without nausea, as well as reductions in mental health and daily function. Pediatric patients with FAP and nausea therefore need intensive treatment and follow-up evaluation.
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Dolor Abdominal , Ansiedad/patología , Depresión/patología , Enfermedades Gastrointestinales/patología , Estado de Salud , Náusea , Adolescente , Ansiedad/epidemiología , Niño , Depresión/epidemiología , Femenino , Estudios de Seguimiento , Enfermedades Gastrointestinales/epidemiología , Humanos , Masculino , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Objective: Evaluate psychometric properties of a measure of adolescents' observations of parental pain behaviors and use this measure to test hypotheses regarding pain-specific social learning. Methods: We created a proxy-report of the Patient Reported Outcomes Measurement Information System (PROMIS) Pain BehaviorShort Form (PPB) for adolescents to report on parental pain behaviors, which we labeled the PPB-Proxy. Adolescents (n = 138, mean age = 14.20) with functional abdominal pain completed the PPB-Proxy and a parent completed the PPB. Adolescents and their parents completed measures of pain and disability during the adolescent's clinic visit for abdominal pain. Adolescents subsequently completed a 7-day pain diary period. Results: The PPB-Proxy moderately correlated with the PPB, evidencing that adolescents observe and can report on parental pain behaviors. Both the PPB-Proxy and PPB significantly correlated with adolescents' pain-related disability. Conclusions: Parental modeling of pain behaviors could represent an important target for assessment and treatment in pediatric chronic pain patients.
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Dolor Crónico/psicología , Conducta de Enfermedad , Relaciones Padres-Hijo , Aprendizaje Social , Adolescente , Niño , Femenino , Humanos , Masculino , Padres/psicología , PsicometríaRESUMEN
OBJECTIVE: To determine the utility of a prehospital sepsis screening protocol utilizing systemic inflammatory response syndrome (SIRS) criteria and end-tidal carbon dioxide (ETCO2). METHODS: We conducted a prospective cohort study among sepsis alerts activated by emergency medical services during a 12 month period after the initiation of a new sepsis screening protocol utilizing ≥2 SIRS criteria and ETCO2 levels of ≤25 mmHg in patients with suspected infection. The outcomes of those that met all criteria of the protocol were compared to those that did not. The main outcome was the diagnosis of sepsis and severe sepsis. Secondary outcomes included mortality and in-hospital lactate levels. RESULTS: Of 330 sepsis alerts activated, 183 met all protocol criteria and 147 did not. Sepsis alerts that followed the protocol were more frequently diagnosed with sepsis (78% vs 43%, P < .001) and severe sepsis (47% vs 7%, P < .001), and had a higher mortality (11% vs 5%, P = .036). Low ETCO2 levels were the strongest predictor of sepsis (area under the ROC curve (AUC) of 0.99, 95% CI 0.99-1.00; P < .001), severe sepsis (AUC 0.80, 95% CI 0.73-0.86; P < .001), and mortality (AUC 0.70, 95% CI 0.57-0.83; P = .005) among all prehospital variables. Sepsis alerts that followed the protocol had a sensitivity of 90% (95% CI 81-95%), a specificity of 58% (95% CI 52-65%), and a negative predictive value of 93% (95% CI 87-97%) for severe sepsis. There were significant associations between prehospital ETCO2 and serum bicarbonate levels (r = 0.415, P < .001), anion gap (r = -0.322, P < .001), and lactate (r = -0.394, P < .001). CONCLUSION: A prehospital screening protocol utilizing SIRS criteria and ETCO2 predicts sepsis and severe sepsis, which could potentially decrease time to therapeutic intervention.
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Dióxido de Carbono/metabolismo , Servicios Médicos de Urgencia/métodos , Sepsis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Sensibilidad y Especificidad , Sepsis/metabolismo , Sepsis/mortalidad , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/metabolismo , Adulto JovenRESUMEN
Epstein-Barr virus Latent Membrane Protein 2A (LMP2A) is expressed in EBV-infected B cells in the germinal center, a site of significant apoptosis induced by engagement of Fas on activated B cells. Signals from the B cell receptor (BCR) protect germinal center B cells from Fas-mediated apoptosis, and since LMP2A is a BCR mimic, we hypothesized that LMP2A would also protect B cells from Fas-mediated apoptosis. Surprisingly, latently-infected human and murine B cell lines expressing LMP2A were more sensitive to Fas-mediated apoptosis, as determined by increases in Annexin-V staining, and cleavage of caspase-8, -3 and PARP. Additional studies show that LMP2A-expressing B cell lines demonstrate a Lyn- and Syk-dependent increase in sensitivity to Fas-mediated apoptosis, due to an LMP2A-dependent enhancement in Fas expression. These findings demonstrate the ability for LMP2A to directly increase a pro-apoptotic molecule and have implications for EBV latency as well as the treatment of EBV-associated malignancies.
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Linfocitos B/inmunología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas de la Matriz Viral/inmunología , Receptor fas/metabolismo , Familia-src Quinasas/metabolismo , Animales , Apoptosis , Linfocitos B/citología , Linfocitos B/metabolismo , Línea Celular , Activación Enzimática , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/patogenicidad , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Ratones , Mutación , Proteínas Tirosina Quinasas/genética , Receptores de Antígenos de Linfocitos B/metabolismo , Quinasa Syk , Proteínas de la Matriz Viral/genética , Familia-src Quinasas/genéticaRESUMEN
Advanced sensor technology is widely used in aquatic monitoring and research. Most applications focus on temporal variability, whereas spatial variability has been challenging to document. We assess the capability of water chemistry sensors embedded in a high-speed water intake system to document spatial variability. This new sensor platform continuously samples surface water at a range of speeds (0 to >45 km h(-1)) resulting in high-density, mesoscale spatial data. These novel observations reveal previously unknown variability in physical, chemical, and biological factors in streams, rivers, and lakes. By combining multiple sensors into one platform, we were able to detect terrestrial-aquatic hydrologic connections in a small dystrophic lake, to infer the role of main-channel vs backwater nutrient processing in a large river and to detect sharp chemical changes across aquatic ecosystem boundaries in a stream/lake complex. Spatial sensor data were verified in our examples by comparing with standard lab-based measurements of selected variables. Spatial fDOM data showed strong correlation with wet chemistry measurements of DOC, and optical NO3 concentrations were highly correlated with lab-based measurements. High-frequency spatial data similar to our examples could be used to further understand aquatic biogeochemical fluxes, ecological patterns, and ecosystem processes, and will both inform and benefit from fixed-site data.
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Monitoreo del Ambiente/instrumentación , Lagos/análisis , Limnología/instrumentación , Ríos/química , Dióxido de Carbono/análisis , Ecosistema , Concentración de Iones de Hidrógeno , Hidrología , Lagos/química , Nitratos/análisis , Compuestos Orgánicos/análisisRESUMEN
In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3'-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC.
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Neoplasias Colorrectales/tratamiento farmacológico , Oligonucleótidos/uso terapéutico , Homeostasis del Telómero/efectos de los fármacos , Proteínas de Unión a Telómeros/metabolismo , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/fisiopatología , Células HT29 , Humanos , Homeostasis del Telómero/genéticaRESUMEN
Though there is growing awareness of the overrepresentation of autistic patients in chronic pain clinics, potential adaptations for the assessment and treatment of chronic pain in this population have not yet been established. To address this gap, a retrospective review of electronic medical records and discussions by an interdisciplinary pain treatment team were summarized to inform potential biopsychosocial factors affecting the presentation, assessment, and treatment of chronic pain in autistic youth. Our sample included a record review of 95 patients receiving treatment in an interdisciplinary outpatient pediatric pain clinic. Results indicated that 9% (n = 9) of the patients presented to the clinic with a prior diagnosis of autism, but an additional 21% (n = 20) were identified as likely meeting criteria for autism based on the clinical assessment of the developmental history, behaviors observed during the clinical encounter(s), and expert clinical judgment, suggesting that the prevalence rate of autism may be closer to 30% in our outpatient pediatric pain clinic. Over half (52%) of the autistic youth presented to the clinic with widespread pain, 60% identified as female, and 6% identified as gender expansive or transgender. Qualitative insights revealed that most of the autistic patients had co-occurring sensory-processing challenges and difficulty in describing their pain, emotions, and somatic experiences and exhibited cognitive inflexibility and social challenges. We summarize our team's clinical reflections on how autism-relevant biopsychosocial vulnerability factors may contribute to the experience of pain in autistic youth and propose treatment targets and adaptations for the assessment and treatment of pain in this population. Finally, we recommend the need for interventions focused on sensorimotor integration, especially for autistic youth, and describe how pain clinics may be particularly helpful for identifying and supporting autistic females, for whom the potential role of autism in pain experiences had not been considered until receiving treatment in our clinic.