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Parenteral fluid therapy in children requires careful consideration of patient-specific factors such as weight, hydration status, and concomitant disease states. Recent literature has changed the standard of care for maintenance fluids for children in the past decade and brought to light more questions. Concentrations of electrolytes in fluids and the use of balanced fluids are still controversial. This article will review the use of parenteral fluids in children, including fluid content, maintenance fluid rate, treatment of dehydration, and the basics of parenteral fluid ingredients. All pediatric patients should have a plan for fluid therapy that includes careful consideration of hydration status and individual response to therapy.
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BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs preeclamptic pregnancies. METHODS: Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum. RESULTS: Recruited subjects (n = 68) were grouped according to their blood pressure as: a) normotensive pregnancy n = 15; b) PreE with normotensive postpartum (PreE-Resolved, n = 36); c) PreE with persistent postpartum HTN (PreE-HTN, n = 17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], P < .001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, P < .001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, P < .001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, P = .001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, P = .045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, P = 0.045). Exercise duration was negatively associated with gravidity (R = -0.27, P = .029) and postpartum LV mass index (R = -0.45, P < .001), resting average E/e' (R = -0.51, P < .001), BMI (R = -0.6, P < .001) and resting SBP (R = -0.51, P < .001). CONCLUSIONS: Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.
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Medication administration via enteral feeding tubes (EFT) is a necessary practice for patients unable to swallow oral dosage forms due to a medical condition or treatment that affects the ability to swallow or the function of the gastrointestinal tract. Off-label administration of oral drug products via EFT raises concerns for pharmaceutical sponsors, regulators, and healthcare practitioners (HCPs) because of the potential risks this practice introduces to both the patient and the caregiver. These risks can be mitigated by generating data-supported instructions that patients and HCPs can use to ensure safe and accurate administration of oral drug products via EFT. This commentary presents an industry perspective on the testing that should be conducted to enable development of product-specific instructions in the labeling to support or advise against administration of oral drug products via enteral feeding tube. The proposal outlined in this commentary takes a risk-based approach, addressing recommendations from both regulatory agencies as well as considerations for expanding this testing to address needs specific to neonatal and pediatric populations.
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Nutrición Enteral , Intubación Gastrointestinal , Niño , Recién Nacido , Humanos , Administración Oral , Preparaciones Farmacéuticas , Técnicas In VitroRESUMEN
OBJECTIVE: Ethanol is a common excipient used in liquid medications to enhance solubility and inhibit -bacterial growth. While the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have released guidance for how much ethanol is acceptable in medicines, many medications contain more than the recommended amount. The objective of this study was to determine what effect these medications would have on blood alcohol concentration (BAC) for pediatric patients, defined as those medications that would increase the BAC by ≥2.5 mg/dL. METHODS: A list of medications dispensed to pediatric patients from a single hospital over a period of 4 months was obtained. The package inserts of these medications were reviewed to determine ethanol content. Typical doses were used to determine the amount of ethanol pediatric patients weighing 10, 20, and 40 kg would receive. The theoretical BAC was then calculated for each medication containing ethanol. RESULTS: Seven hundred ninety-six medications were dispensed for pediatric patients during the study period, of which 33 contained ethanol. Seven medications would be projected to increase the BAC above 2.5 mg/dL with a normal pediatric dose. CONCLUSION: While most medications do not contain ethanol, we found 7 that contained enough ethanol to potentially raise the BAC above 2.5 mg/dL. Health care practitioners should consider the ethanol content of medications prior to recommending them in children and when assessing overdoses.
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G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibits stress granule assembly and interacts with G3BP1/2 via an ITFG motif, including residue F17, in the N protein. Prior studies examining the impact of the G3PB1-N interaction on SARS-CoV-2 replication have produced inconsistent findings, and the role of this interaction in pathogenesis is unknown. Here, we use structural and biochemical analyses to define the residues required for G3BP1-N interaction and structure-guided mutagenesis to selectively disrupt this interaction. We find that N-F17A mutation causes highly specific loss of interaction with G3BP1/2. SARS-CoV-2 N-F17A fails to inhibit stress granule assembly in cells, has decreased viral replication, and causes decreased pathology in vivo. Further mechanistic studies indicate that the N-F17-mediated G3BP1-N interaction promotes infection by limiting sequestration of viral genomic RNA (gRNA) into stress granules.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , ADN Helicasas/metabolismo , ARN Helicasas/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Virulencia , ARN Guía de Sistemas CRISPR-Cas , Proteínas de la Nucleocápside , Replicación Viral , ARN Viral/genéticaRESUMEN
The administration of medications to children has been a challenge for parents and caregivers for generations. Pharmaceutical companies have often overcome the difficulties of weight-based dosing and the -inability of most young children to swallow solid dosage forms by creating oral liquids. While oral liquids -offer advantages in terms of dose flexibility, swallowability, and ease of administration for young children and patients with enteral tubes, they have been plagued by issues such as taste, volume, and texture, to name a few. While the recommendations for broader use of oral syringes can help with the issue of measuring accuracy and incremental dosing, the issues of poor taste and frequently unacceptable volumes for doses remain a problem. New oral dosage forms which have begun to enter the United States marketplace have the potential to improve adherence and acceptability of oral medications for children, but come with their own unique challenges.
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Stress granule formation is triggered by the release of mRNAs from polysomes and is promoted by the action of the RNA-binding proteins G3BP1/2. Stress granules have been implicated in several disease states, including cancer and neurodegeneration. Consequently, compounds that limit stress granule formation or promote their dissolution have potential as both experimental tools and novel therapeutics. Herein, we describe two small molecules, G3BP inhibitor a and b (G3Ia and G3Ib), designed to bind to a specific pocket in G3BP1/2 that is targeted by viral inhibitors of G3BP1/2 function. In addition to disrupting the co-condensation of RNA, G3BP1, and caprin 1 in vitro, these compounds inhibit stress granule formation in cells treated prior to or concurrent with stress and dissolve pre-existing stress granules. These effects are consistent across multiple cell types and a variety of initiating stressors. Thus, these compounds represent powerful tools to probe the biology of stress granules and hold promise for therapeutic interventions designed to modulate stress granule formation.
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ADN Helicasas , ARN Helicasas , Gránulos de Estrés , ADN Helicasas/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , ARN Helicasas/genética , Proteínas con Motivos de Reconocimiento de ARN/genéticaRESUMEN
PURPOSE: A decline in youth running was observed at the start of the COVID-19 pandemic. We investigated whether the resumption of organized running after social distancing restrictions changed running habits or injury frequency in adolescent runners. METHODS: Adolescents (age = 16.1 [2.1] y) who participated in long-distance running activities completed an online survey in the Spring and Fall of 2020. Participants self-reported average weekly running habits and whether they sustained an injury during the Fall 2020 season. Poisson regression models and 1-way analysis of variance compared running habits while Fisher exact test compared differences in frequencies of injuries during Fall 2020 among season statuses (full, delayed, and canceled). RESULTS: All runners, regardless of season status, increased weekly distance during Fall 2020. Only runners with a full Fall 2020 season ran more times per week and more high-intensity runs per week compared with their Spring 2020 running habits. There were no differences in running volume or running-related injury frequency among Fall 2020 season statuses. CONCLUSIONS: There were no significant differences in running-related injury (RRI) frequency among runners, regardless of season status, following the resumption of cross-country. Health care providers may need to prepare for runners to increase running volume and intensity following the resumption of organized team activities.
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COVID-19 , Carrera , Humanos , Adolescente , Pandemias , Estudios Prospectivos , Factores de Riesgo , HábitosRESUMEN
Medication prescriptions for both children and adults often require the patient's current weight to determine a safe and effective dose. Medication orders in the inpatient setting typically require a patient weight be recorded prior to order verification. However, in the ambulatory setting a very different standard exists; weights are not required on prescriptions and are rarely provided by practitioners. Without this information, the community pharmacist must either ask the caregiver, who may not know an accurate weight, or simply assume that the prescriber used a current and accurate weight and calculated the dose correctly. Standard doses are prescribed for most adult prescriptions, which makes it possible for the pharmacist to identify a dosing error. Without a current patient weight, the pharmacist is not able to provide the same level of patient care to pediatric patients or adults whose prescriptions require weight-based doses. The Pediatric Pharmacy Association recommends that patient weight, recorded in kilograms, be required on all medication prescriptions in both the inpatient and outpatient settings.
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G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules.
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Stress granule formation is triggered by the release of mRNAs from polysomes and is promoted by the action of the paralogs G3BP1 and G3BP2. G3BP1/2 proteins bind mRNAs and thereby promote the condensation of mRNPs into stress granules. Stress granules have been implicated in several disease states, including cancer and neurodegeneration. Consequently, compounds that limit stress granule formation or promote their dissolution have potential as both experimental tools and novel therapeutics. Herein, we describe two small molecules, referred to as G3BP inhibitor a and b (G3Ia and G3Ib), designed to bind to a specific pocket in G3BP1/2 that is known to be targeted by viral inhibitors of G3BP1/2 function. In addition to disrupting co-condensation of RNA, G3BP1, and caprin 1 in vitro, these compounds inhibit stress granule formation in cells treated prior to or concurrent with stress, and dissolve pre-existing stress granules when added to cells after stress granule formation. These effects are consistent across multiple cell types and a variety of initiating stressors. Thus, these compounds represent ideal tools to probe the biology of stress granules and hold promise for therapeutic interventions designed to modulate stress granule formation.
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BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a leading cause of cirrhosis, strongly associates with the metabolic syndrome, an insulin-resistant proinflammatory state that disrupts energy balance and promotes progressive liver degeneration. We aimed to define the role of Smoothened (Smo), an obligatory component of the Hedgehog signaling pathway, in controlling hepatocyte metabolic homeostasis and, thereby, susceptibility to NASH. METHODS: We conditionally deleted Smo in hepatocytes of healthy chow-fed mice and performed metabolic phenotyping, coupled with single-cell RNA sequencing (RNA-seq), to characterize the role of hepatocyte Smo in regulating basal hepatic and systemic metabolic homeostasis. Liver RNA-seq datasets from 2 large human cohorts were also analyzed to define the relationship between Smo and NASH susceptibility in people. RESULTS: Hepatocyte Smo deletion inhibited the Hedgehog pathway and promoted fatty liver, hyperinsulinemia, and insulin resistance. We identified a plausible mechanism whereby inactivation of Smo stimulated the mTORC1-SREBP1c signaling axis, which promoted lipogenesis while inhibiting the hepatic insulin cascade. Transcriptomics of bulk and single Smo-deficient hepatocytes supported suppression of insulin signaling and also revealed molecular abnormalities associated with oxidative stress and mitochondrial dysfunction. Analysis of human bulk RNA-seq data revealed that Smo expression was (1) highest in healthy livers, (2) lower in livers with NASH than in those with simple steatosis, (3) negatively correlated with markers of insulin resistance and liver injury, and (4) declined progressively as fibrosis severity worsened. CONCLUSIONS: The Hedgehog pathway controls insulin sensitivity and energy homeostasis in adult livers. Loss of hepatocyte Hedgehog activity induces hepatic and systemic metabolic stress and enhances susceptibility to NASH by promoting hepatic lipoxicity and insulin resistance.
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Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Resistencia a la Insulina/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Hepatocitos/metabolismo , Insulina/metabolismoRESUMEN
Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.
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Cojera Animal , Osteoartritis , Ratas , Animales , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Osteoartritis/complicaciones , Dolor/complicaciones , Modelos Anatómicos , Evaluación de Resultado en la Atención de SaludRESUMEN
Therapeutic alliance has been defined as building rapport between provider and patient in order to enhance patient motivation to improve outcomes. The purpose of this systematic review was to identify factors that patients look for that help build a strong therapeutic alliance in their pediatric sports or orthopedics healthcare provider, to identify if these factors differ across healthcare professions, and to identify any differences in therapeutic alliance between patients and their provider regarding in-person and telehealth visits. Scientific databases were searched from inception until August 2022. The search strategy resulted in 2195 articles with 11 studies included in the final analysis. The main attributes adolescents look for in their pediatric sports healthcare provider were shared decision making and understanding patients' sports and goals. These factors were found to differ among parents, sex, race, and socioeconomic status. The top factors improving therapeutic alliance in telehealth were having an already established relationship with the provider, visits lasting longer than 30 min, and having an English-speaking provider for English-speaking patients. The available literature highlights factors that contribute to the development of a stronger therapeutic alliance in the pediatric sports and orthopedics population. As these factors differ among adolescents, parents, sex, race, and socioeconomic status, this review provides insight in what patients and families look for in their provider when seeking care.
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Ortopedia , Telemedicina , Alianza Terapéutica , Adolescente , Niño , Personal de Salud , HumanosRESUMEN
INTRODUCTION: Sport specialization has been shown to have negative effects on athletes but has not been studied within rock climbing. This study seeks to evaluate the proportion and impact of specialization in pediatric climbers. METHODS: Climbers (ages 8-18 y) were recruited from throughout the United States to complete a 1-time survey regarding climbing experience, training patterns, and injury history. The main outcome of proportion of climbers suffering an injury was assessed within the last 12 mo and within their entire climbing experience (defined as "lifetime" injury). Early specialization was defined as exclusive participation in climbing, with training for >8 moâ§y-1, prior to age 12 y (late specialization if after age 12 y). RESULTS: Participants (n=111, 14±3 y [mean±SD], 69 females) were high-level climbers. Fifty-five percent of participants specialized in climbing, and 69% of those specialized early. Hand and ankle injuries occurred most commonly. Seventy-eight percent of late specialized climbers had a lifetime injury. Late specialized climbers were 1.6 times (95% CI: 1.1-2.3) more likely than early specialized climbers to have had a lifetime injury and 1.8 times (95% CI: 1.1-2.8) more likely to have had an injury in the last 12 mo. No difference in overuse injuries was found between specialization groups. CONCLUSIONS: Early specialization is common among youth climbers but was not associated with an increase in injuries. Late specialization was associated with a higher likelihood of having had a climbing injury in the last 12 mo and during an entire climbing career.
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Traumatismos en Atletas , Trastornos de Traumas Acumulados , Montañismo , Deportes , Adolescente , Atletas , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/etiología , Niño , Trastornos de Traumas Acumulados/epidemiología , Trastornos de Traumas Acumulados/etiología , Femenino , Humanos , Montañismo/lesiones , Encuestas y Cuestionarios , Estados UnidosRESUMEN
CONTEXT: Strength ratios are important because imbalances in opposing muscle groups can cause articular instability and subsequently increase the risk of musculoskeletal injury (MSKI). Therefore, the purpose of this study was to evaluate the association between lower extremity (LE) musculoskeletal isometric strength ratios and the history of LE MSKI. PARTICIPANTS: One hundred eighty-two NCAA Division 1 soccer, football, volleyball, and basketball athletes. INTERVENTIONS: All isometric strength assessments were measured bilaterally using a handheld dynamometer. Strength assessments included: ankle inversion/eversion, ankle dorsiflexion/plantarflexion, knee flexion/extension, hip abduction/adduction, and hip external/internal rotation. LE MSKI history was collected through self-report; a report of the LE MSKI sustained in the one year prior to testing were collected. RESULTS: The hip external/internal rotation ratio was statistically significant for side to side differences in the non-injured (NINJ) group (p = 0.001). The dominant leg of the NINJ group had a mean external/internal rotation ratio of 1.109 ± 0.221, and the non-dominant leg had a mean ratio of 1.177 ± 0.208. CONCLUSIONS: There were no statistically significant differences between the injured (INJ) and NINJ groups. This could indicate that injury history does not play a role in current strength ratios and could suggest that the athletes in the INJ group are performing successful rehabilitation for their injuries.
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Baloncesto , Traumatismos de la Pierna , Fútbol , Atletas , Baloncesto/lesiones , Humanos , Articulación de la Rodilla/fisiología , Extremidad Inferior , Fuerza Muscular/fisiología , Fútbol/lesionesRESUMEN
Stress injuries involving the epiphyseal-physeal-metaphyseal complex affecting the extremities of child and adolescent athletes were first described in the early 1950s. Initially observed in Little League baseball players, these injuries are now known to affect skeletally immature athletes in a variety of sports that involve high-impact repetitive overuse activities. Collectively known as primary periphyseal stress injuries, they may affect the long bones around the shoulder, elbow, wrist, hand, hip, knee, ankle, and foot of young athletes. These injuries respond well to timely treatment and relative rest, while non-compliance with non-operative treatment can produce skeletal growth disruption and resultant limb deformity. A major concern raised from the existing literature on primary periphyseal stress injuries is the long history of inconsistent and imprecise terminology used to describe these injuries. A variety of terms have been used to describe primary periphyseal stress injuries, including those which potentially misinform regarding who may be affected by these injuries and the true nature and pathophysiologic mechanisms involved. These imprecisions and inconsistencies arise, at least in part, from a misunderstanding or incomplete understanding of the nature and mechanism of primary periphyseal stress injuries. In this article, we examine the inconsistent and imprecise nomenclature historically used to describe primary periphyseal stress injuries. We also offer a novel framework for understanding the pathophysiologic mechanisms behind these injuries, and provide suggestions for more standard use of terminology and further research moving forward.
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Traumatismos en Atletas , Béisbol , Trastornos de Traumas Acumulados , Deportes , Adolescente , Atletas , Béisbol/lesiones , Niño , HumanosRESUMEN
BACKGROUND: Overuse injuries are common in sporting children and adolescents. These injuries are a particular concern when they involve the epiphyseal-physeal-metaphyseal (EPM) complex given their potential to disturb skeletal growth. Specifically, the limits of mechanical tolerance of the EPM complex to repetitive stress may be exceeded by the intense and continuous training characteristic of many youth sports today. OBJECTIVE: This article describes the present status of knowledge on the occurrence and outcome of primary periphyseal stress injuries (PPSIs) affecting the EPM complex in the extremities of children and adolescents involved in youth sports. METHODS: A comprehensive review of the sports medicine literature was conducted to determine the nature and extent of PPSIs affecting the EPM complex of the extremities among youth sports participants and the potential for consequent skeletal growth disturbance and resultant limb deformity associated with these injuries. RESULTS: Our initial search uncovered 128 original published scientific articles reporting relevant data on PPSIs. There were 101 case reports/series, 19 cross-sectional, 1 case-control, and 7 cohort studies with relevant data. The case reports/series studies reported 448 patients with PPSIs involving the extremities. Children and adolescents representing a variety of high impact repetitive youth sports activities-including baseball, badminton, climbing, cricket, dance, gymnastics, rugby, soccer, swimming, tennis, and volleyball-may sustain PPSIs involving the shoulder, elbow, hand and wrist, knee, and ankle and foot. Although incidence data from prospective cohort studies are lacking, data arising from cross-sectional studies suggest that PPSIs may be common in select groups of youth athletes-including the shoulder in baseball players (0-36.6%), wrist in gymnasts (10-83%) and platform divers (52.6%), and fingers in rock climbers (5-58%). Notably, not all stress-related skeletal changes detected on imaging were symptomatic in these studies. When diagnosed and treated with an appropriate period of rest and rehabilitation, most patients studied were able to return to their sport activities. However, our data also show that 57/448 PPSIs (12.7%) produced growth disturbance, and that 28/448 patients (6.2%) underwent surgery for their injuries. Absence of treatment, delayed presentation and diagnosis, and non-compliance with a rest regimen were common in cases that produced growth disturbance. CONCLUSIONS: PPSIs may affect the extremities of children and adolescents engaged in a variety of youth sports, especially at advanced levels of training and competition. Most skeletally immature patients with PPSIs respond well to timely treatment; however, in extreme cases, PPSIs can progress to produce skeletal growth disruption which may necessitate surgical intervention. Clearly, establishing the early diagnosis of PPSIs and providing timely treatment of these injuries are needed to ensure the skeletal health of youth sports participants. Rigorous prospective longitudinal epidemiological and imaging studies designed to provide incidence rates of PPSIs and to determine the effect of PPSIs on long-term skeletal health are also necessary.