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ABSTRACT: In our cohort of 20,947 infants aged 60 days or younger, cerebrospinal fluid Gram stain had a sensitivity of 34.3% (95% confidence interval, 28.1%-41.1%) and a positive predictive value of 61.4% (95% confidence interval, 52.2%-69.8%) for positive cerebrospinal fluid culture, suggesting that Gram stain alone may lead to both underdiagnosis and overdiagnosis of bacterial meningitis.
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Meningites Bacterianas , Líquido Cefalorraquidiano , Estudos de Coortes , Humanos , Lactente , Meningites Bacterianas/diagnóstico , Valor Preditivo dos TestesRESUMO
Despite the transient hyporeactivity of neonatal platelets, full-term neonates do not display a bleeding tendency, suggesting potential compensatory mechanisms which allow for balanced and efficient neonatal hemostasis. This study aimed to utilize small-volume, whole blood platelet functional assays to assess the neonatal platelet response downstream of the hemostatic platelet agonists thrombin and adenosine diphosphate (ADP). Thrombin activates platelets via the protease-activated receptors (PARs) 1 and 4, whereas ADP signals via the receptors P2Y1 and P2Y12 as a positive feedback mediator of platelet activation. We observed that neonatal and cord blood-derived platelets exhibited diminished PAR1-mediated granule secretion and integrin activation relative to adult platelets, correlating to reduced PAR1 expression by neonatal platelets. PAR4-mediated granule secretion was blunted in neonatal platelets, correlating to lower PAR4 expression as compared to adult platelets, while PAR4 mediated GPIIb/IIIa activation was similar between neonatal and adult platelets. Under high shear stress, cord blood-derived platelets yielded similar thrombin generation rates but reduced phosphatidylserine expression as compared to adult platelets. Interestingly, we observed enhanced P2Y1/P2Y12-mediated dense granule trafficking in neonatal platelets relative to adults, although P2Y1/P2Y12 expression in neonatal, cord, and adult platelets were similar, suggesting that neonatal platelets may employ an ADP-mediated positive feedback loop as a potential compensatory mechanism for neonatal platelet hyporeactivity.
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Plaquetas/metabolismo , Grânulos Citoplasmáticos/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Transporte Biológico , Biomarcadores , Coagulação Sanguínea , Humanos , Recém-Nascido , Integrinas/metabolismo , Ativação Plaquetária , Agregação Plaquetária , Resistência ao Cisalhamento , Trombina/metabolismoRESUMO
The RAG1/RAG2 endonuclease (RAG) initiates the V(D)J recombination reaction that assembles immunoglobulin heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires. IgH V(D)J assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor (pre-) B cells. Expression of IgH µ and IgL (Igκ or Igλ) chains generates IgM, which is expressed on immature B cells as the B-cell antigen-binding receptor (BCR). Rag expression can continue in immature B cells, allowing continued Igκ V(D)J recombination that replaces the initial VκJκ exon with one that generates a new specificity. This 'receptor editing' process, which can also lead to Igλ V(D)J recombination and expression, provides a mechanism whereby antigen encounter at the Rag-expressing immature B-cell stage helps shape pre-immune BCR repertoires. As the major site of postnatal B-cell development, the bone marrow is the principal location of primary immunoglobulin repertoire diversification in mice. Here we report that early B-cell development also occurs within the mouse intestinal lamina propria (LP), where the associated V(D)J recombination/receptor editing processes modulate primary LP immunoglobulin repertoires. At weanling age in normally housed mice, the LP contains a population of Rag-expressing B-lineage cells that harbour intermediates indicative of ongoing V(D)J recombination and which contain cells with pro-B, pre-B and editing phenotypes. Consistent with LP-specific receptor editing, Rag-expressing LP B-lineage cells have similar VH repertoires, but significantly different Vκ repertoires, compared to those of Rag2-expressing bone marrow counterparts. Moreover, colonization of germ-free mice leads to an increased ratio of Igλ-expressing versus Igκ-expressing B cells specifically in the LP. We conclude that B-cell development occurs in the intestinal mucosa, where it is regulated by extracellular signals from commensal microbes that influence gut immunoglobulin repertoires.
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Linfócitos B/citologia , Linfócitos B/imunologia , Linhagem da Célula , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Animais , Linfócitos B/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Rearranjo Gênico do Linfócito B/genética , Vida Livre de Germes , Imunoglobulinas/genética , Imunoglobulinas/imunologia , Camundongos , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/metabolismo , Simbiose , DesmameRESUMO
BACKGROUND: The effect of temporal changes in cancer therapy on health status among childhood cancer survivors has not been evaluated. OBJECTIVE: To compare proportions of self-reported adverse health status outcomes among childhood cancer survivors across 3 decades. DESIGN: Cross-sectional. (ClinicalTrials.gov: NCT01120353). SETTING: 27 North American institutions. PARTICIPANTS: 14 566 adults, who survived for 5 or more years after initial diagnosis (median age, 27 years; range, 18 to 48 years), treated from 1970 to 1999. MEASUREMENTS: Patient report of poor general or mental health, functional impairment, activity limitation, or cancer-related anxiety or pain was evaluated as a function of treatment decade, cancer treatment exposure, chronic health conditions, demographic characteristics, and health habits. RESULTS: Despite reductions in late mortality and the proportions of survivors with severe, disabling, or life-threatening chronic health conditions (33.4% among those treated from 1970 to 1979 and 21.0% among those treated from 1990 to 1999), those reporting adverse health status did not decrease by treatment decade. Compared with survivors diagnosed in 1970 to 1979, those diagnosed in 1990 to 1999 were more likely to report poor general health (11.2% vs. 13.7%; P < 0.001) and cancer-related anxiety (13.3% vs. 15.0%; P < 0.001). From 1970 to 1979 and 1990 to 1999, the proportions of survivors reporting adverse outcomes were higher (P < 0.001) among those with leukemia (poor general health, 9.5% and 13.9%) and osteosarcoma (pain, 23.9% and 36.6%). Temporal changes in treatment exposures were not associated with changes in the proportions of survivors reporting adverse health status. Smoking, not meeting physical activity guidelines, and being either underweight or obese were associated with poor health status. LIMITATION: Considerable improvement in survival among children diagnosed with cancer in the 1990s compared with those diagnosed in the 1970s makes it difficult to definitively determine the effect of risk factors on later self-reported health status without considering their effect on mortality. CONCLUSION: Because survival rates after a diagnosis of childhood cancer have improved substantially over the past 30 years, the population of survivors now includes those who would have died in earlier decades. Self-reported health status among survivors has not improved despite evolution of treatment designed to reduce toxicities. PRIMARY FUNDING SOURCE: The National Cancer Institute.
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Nível de Saúde , Neoplasias/terapia , Autorrelato , Sobreviventes , Adulto , Criança , Doença Crônica , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Neoplasias/diagnóstico , Fatores de TempoRESUMO
Pregnancy is a particularly vulnerable period for the growing fetus, when exposure to toxic agents, especially in the early phases, can decisively harm embryo development and compromise the future health of the newborn. The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first weeks of gestation, when critical processes, like the migration and proliferation of the neural crest derived cells, start to form the ENS. Importantly, cosmetic neurotoxins can cross the placental barrier and affect the future embryo, but they are also secreted in breast milk, so babies remain exposed for longer periods, even after birth. In this review, we explore how neurotoxins contained in cosmetics and PCPs may have a role in the pathogenesis of various neurodevelopmental disorders and neurodegenerative diseases and, therefore, also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy.
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Cosméticos , Humanos , Feminino , Gravidez , Cosméticos/efeitos adversos , Neurotoxinas/toxicidade , Síndromes Neurotóxicas/etiologia , Ácidos Ftálicos/toxicidade , AnimaisRESUMO
OBJECTIVES: To ascertain prevalence of peripheral sensory and motor neuropathy, and to evaluate impairments in relation to function. DESIGN: St. Jude Lifetime Cohort Study, a clinical follow-up study designed to evaluate adverse late effects in adult survivors of childhood cancer. SETTING: A children's research hospital. PARTICIPANTS: Eligibility required treatment for an extracranial solid malignancy between 1962 and 2002, age ≥ 18 years, ≥ 10 years postdiagnosis, and no history of cranial radiation. Survivors (N=531) were included in the evaluation with a median age of 32 years and a median time from diagnosis of 25 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary exposure measures were cumulative doses of vinca-alkaloid and platinum-based chemotherapies. Survivors with scores ≥ 1 on the sensory subscale of the Modified Total Neuropathy Score were classified with prevalent sensory impairment. Those with sex-specific z scores of ≤-1.3 for dorsiflexion strength were classified with prevalent motor impairment. Participants completed the 6-minute walk test (endurance), the Timed Up & Go test (mobility), and the Sensory Organization Test (balance). RESULTS: The prevalence of sensory and motor impairment was 20% and 17.5%, respectively. Vinca-alkaloid exposure was associated with an increased risk of motor impairment (adjusted odds ratio [OR]=1.66; 95% confidence interval [CI], 1.04-2.64) without evidence for a dose response. Platinum exposure was associated with increased risk of sensory impairment (adjusted OR=1.62; 95% CI, .97-2.72) without evidence of a dose response. Sensory impairment was associated with poor endurance (OR=1.99; 95% CI, .99-4.0) and mobility (OR=1.65; 95% CI, .96-2.83). CONCLUSIONS: Vincristine and cisplatin exposure may increase risk for long-term motor and sensory impairment, respectively. Survivors with sensory impairment are at increased risk for functional performance limitations.
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Antineoplásicos/efeitos adversos , Transtornos dos Movimentos/etiologia , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Transtornos de Sensação/induzido quimicamente , Adolescente , Adulto , Carboplatina/efeitos adversos , Criança , Pré-Escolar , Cisplatino/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/epidemiologia , Neoplasias/mortalidade , Neoplasias/patologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/epidemiologia , Transtornos de Sensação/diagnóstico , Transtornos de Sensação/epidemiologia , Vimblastina/efeitos adversos , Vincristina/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: To evaluate health status and participation restrictions in survivors of childhood extremity sarcomas. DESIGN: Members of the Childhood Cancer Survivor Study cohort with extremity sarcomas who completed questionnaires in 1995, 2003, or 2007 were included. SETTING: Cohort study of survivors of extremity sarcomas. PARTICIPANTS: Childhood extremity sarcoma survivors (N=1094; median age at diagnosis, 13y (range, 0-20y); current age, 33y (range, 10-53y); 49% male; 87.5% white; 75% had lower extremity tumors) who received their diagnosis and treatment between 1970 and 1986. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence rates for poor health status in 6 domains and 5 suboptimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age. RESULTS: In adjusted models, when compared with upper extremity survivors, lower extremity survivors had an increased risk of activity limitations but a lower risk of not completing college. Compared with those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEAs) were 1.6 times more likely to report functional impairment, while those with an above-the-knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes <$20,000, unemployment, and no college degree. Those with UEAs more likely reported inactivity, unmarried status, and no college degree. Those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with an increased risk of poor mental health, functional impairment, and activity limitation. CONCLUSIONS: Treatment of lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at a 10% higher risk for not completing college. The type of local control influences health status and participation restrictions. Both of these outcomes decline with age.
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Extremidades , Nível de Saúde , Sarcoma/fisiopatologia , Sobreviventes/estatística & dados numéricos , Atividades Cotidianas , Adolescente , Adulto , Criança , Intervalos de Confiança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
IMPORTANCE: Adult survivors of childhood cancer are known to be at risk for treatment-related adverse health outcomes. A large population of survivors has not been evaluated using a comprehensive systematic clinical assessment to determine the prevalence of chronic health conditions. OBJECTIVE: To determine the prevalence of adverse health outcomes and the proportion associated with treatment-related exposures in a large cohort of adult survivors of childhood cancer. DESIGN, SETTING, AND PARTICIPANTS: Presence of health outcomes was ascertained using systematic exposure-based medical assessments among 1713 adult (median age, 32 [range, 18-60] years) survivors of childhood cancer (median time from diagnosis, 25 [range, 10-47] years) enrolled in the St Jude Lifetime Cohort Study since October 1, 2007, and undergoing follow-up through October 31, 2012. MAIN OUTCOMES AND MEASURES: Age-specific cumulative prevalence of adverse outcomes by organ system. RESULTS: Using clinical criteria, the crude prevalence of adverse health outcomes was highest for pulmonary (abnormal pulmonary function, 65.2% [95% CI, 60.4%-69.8%]), auditory (hearing loss, 62.1% [95% CI, 55.8%-68.2%]), endocrine or reproductive (any endocrine condition, such as hypothalamic-pituitary axis disorders and male germ cell dysfunction, 62.0% [95% CI, 59.5%-64.6%]), cardiac (any cardiac condition, such as heart valve disorders, 56.4% [95% CI, 53.5%-59.2%]), and neurocognitive (neurocognitive impairment, 48.0% [95% CI, 44.9%-51.0%]) function, whereas abnormalities involving hepatic (liver dysfunction, 13.0% [95% CI, 10.8%-15.3%]), skeletal (osteoporosis, 9.6% [95% CI, 8.0%-11.5%]), renal (kidney dysfunction, 5.0% [95% CI, 4.0%-6.3%]), and hematopoietic (abnormal blood cell counts, 3.0% [95% CI, 2.1%-3.9%]) function were less common. Among survivors at risk for adverse outcomes following specific cancer treatment modalities, the estimated cumulative prevalence at age 50 years was 21.6% (95% CI, 19.3%-23.9%) for cardiomyopathy, 83.5% (95% CI, 80.2%-86.8%) for heart valve disorder, 81.3% (95% CI, 77.6%-85.0%) for pulmonary dysfunction, 76.8% (95% CI, 73.6%-80.0%) for pituitary dysfunction, 86.5% (95% CI, 82.3%-90.7%) for hearing loss, 31.9% (95% CI, 28.0%-35.8%) for primary ovarian failure, 31.1% (95% CI, 27.3%-34.9%) for Leydig cell failure, and 40.9% (95% CI, 32.0%-49.8%) for breast cancer. At age 45 years, the estimated cumulative prevalence of any chronic health condition was 95.5% (95% CI, 94.8%-98.6%) and 80.5% (95% CI, 73.0%-86.6%) for a serious/disabling or life-threatening chronic condition. CONCLUSIONS AND RELEVANCE: Among adult survivors of childhood cancer, the prevalence of adverse health outcomes was high, and a systematic risk-based medical assessment identified a substantial number of previously undiagnosed problems that are more prevalent in an older population. These findings underscore the importance of ongoing health monitoring for adults who survive childhood cancer.
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Doença Crônica/epidemiologia , Neoplasias/epidemiologia , Sobreviventes , Adolescente , Adulto , Estudos de Coortes , Sistema Endócrino/fisiopatologia , Feminino , Nível de Saúde , Coração/fisiopatologia , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Segunda Neoplasia Primária/epidemiologia , Sistema Nervoso/fisiopatologia , Prevalência , Medição de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
Chest tubes account for a large proportion of postoperative pain after cardiothoracic operations. The objective of this study was to develop a novel, cost-effective, easy-to-use, lidocaine-eluting coating to reduce pain associated with postoperative chest tubes. A lidocaine-eluting hydrogel was developed by dispersing lidocaine-loaded nanoparticles in an aqueous solution containing gelatin (5%). Glutaraldehyde (1%) was added to crosslink the gelatin into a hydrogel. The hydrogel was dehydrated, resulting in a thin, stable polymer. Sterile lidocaine hydrogel-coated silicone discs and control discs were prepared and surgically implanted in the subcutaneous space of C57B6 mice. Using von Frey filaments, mice underwent preoperative baseline pain testing, followed by pain testing on post-procedure day 1 and 3. On post-procedure day 1, mice implanted with control discs demonstrated no change in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 2.4-fold (P = 0.36) and 4.7-fold (P = 0.01) increase in pain tolerance, respectively. On post-procedure day 3, mice implanted with control discs demonstrated a 0.7-fold decrease in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 1.8-fold (P = 0.88) and 8.4-fold (P = 0.02) increase in pain tolerance, respectively. Our results demonstrate successful development of a lidocaine-eluting chest tube with hydrogel coating, leading to improved pain tolerance in vivo. The concept of a drug-eluting drain coating has significant importance due to its potential universal application in a variety of drain types and insertion locations.
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BACKGROUND: The current standard of care in the treatment of children with physical trauma presenting to non-designated pediatric trauma centers is consultation with a pediatric trauma center by telephone. This includes contacting a pediatric trauma specialist and transferring any child with a potentially serious injury to a regionalized level I pediatric trauma center. This approach to care frequently results in medically unnecessary transfers and may place undue burdens on families. A newer model of care, the "Virtual Pediatric Trauma Center" (VPTC), uses telemedicine to make the expertise of a level I pediatric trauma center virtually available to any hospital. While the use of the VPTC model of care is increasing, there have been no studies comparing the VPTC to standard care of injured children at non-designated trauma centers with respect to patient- and family-centered outcomes. The goal of this study is to compare the current standard of care to the VPTC with respect to family-centered outcomes developed by parents and community advisory boards. METHODS: We will use a stepped-wedge trial design to enroll children with physical trauma presenting to ten hospitals, including level II, level III, and non-designated trauma centers. The primary outcome measures are parent/family experience of care and distress 3 days following injury. Secondary aims include 30-day healthcare utilization, parent/family out-of-pocket costs at 3 days and 30 days after injury, transfer rates, and parent/family distress 30 days following injury. We expect at least 380 parents/families of children will be eligible for the study following an emergency department physician's request for a level I pediatric trauma center consultation. We will evaluate parent/family experience of care and distress using previously validated instruments, healthcare utilization by family recollection and medical record abstraction, and out-of-pocket costs using standard economic analyses. DISCUSSION: We expect that the findings from this study will inform other level I pediatric trauma centers and non-pediatric trauma centers on how to improve their systems of care for injured children. The results will help to optimize communication, confidence, and shared decision-making between parents/families and clinical staff from both the transferring and receiving hospitals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04469036. Registered July 13, 2020 before start of inclusion.
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Telemedicina , Centros de Traumatologia , Criança , Humanos , Atenção à Saúde , Estudos Prospectivos , Padrão de CuidadoRESUMO
Background: This article describes factors related to adoption, implementation, and effectiveness of the Virtual Pediatric Trauma Center intervention, which uses telehealth for trauma specialist consultations for seriously injured children. We aimed at (1) measuring RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) implementation outcomes and (2) identifying PRISM (Practical, Robust, Implementation, and Sustainability Model) contextual factors that influenced the implementation outcomes. Methods: This interim implementation evaluation of our telehealth trial used a convergent mixed-methods design. The quantitative component was a cross-sectional analysis of pediatric trauma encounters using electronic health records. The qualitative component was a thematic analysis of written and verbal feedback from providers and family advisory board meetings. We compared the quantitative and qualitative data by synthesizing them in a joint display table, organized by RE-AIM dimensions. We categorized these key findings into the PRISM domains. Results: During the first 10 months of this trial, 246 subjects were randomized, with 177 assigned to standard care and 69 assigned to telehealth. Four referring sites transitioned from standard care into their intervention period. PRISM contextual factors that influenced RE-AIM implementation outcomes included the following findings: Providers struggle to remember, interpret, and navigate intervention workflows; providers have preconceived ideas about the intervention purpose; the intervention mitigates parents' anxieties about the transfer process. Discussion: This study revealed implementation challenges that influence the overall success of this telehealth trial. Early identification of these challenges allows our team the opportunity to address them now to optimize the intervention reach, adoption, and implementation. This early action will ultimately enhance the success of our trial and the ability of our intervention to achieve broad impact.
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OBJECTIVES: To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection. METHODS: In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively. RESULTS: Of all infants included, 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] <14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with >28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43). CONCLUSIONS: A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.
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Herpes Simples/diagnóstico , Fatores Etários , Temperatura Corporal , Estudos de Casos e Controles , Serviço Hospitalar de Emergência , Exantema/epidemiologia , Feminino , Herpes Simples/epidemiologia , Humanos , Lactente , Recém-Nascido Prematuro , Leucocitose/líquido cefalorraquidiano , Masculino , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Convulsões/epidemiologia , Sensibilidade e Especificidade , Trombocitopenia/epidemiologiaRESUMO
OBJECTIVE: The validity of the Cognitive Performance Scale (CPS) embedded in the Resident Assessment Instrument-Mental Health (RAI-MH) was evaluated among adult psychiatric inpatients. METHODS: The CPS is a brief measure of cognitive performance, with scores ranging from 0 (intact) to 6 (very severe impairment). The CPS scores were compared with the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scores for 215 adult psychiatric inpatients. RESULTS: The CPS scores were significantly correlated with MMSE scores (r = -0.69, P < 0.001) and MoCA scores (r = -0.69, P < 0.001). Higher scores on the CPS were associated with greater functional impairment, older age, and a greater prevalence of dementia diagnoses than lower CPS scores. CONCLUSIONS: Pilot data show the CPS is a valid screening measure of cognitive performance among adult psychiatric inpatients. Additional research is needed to replicate our study using a larger sample with more diverse mental health conditions.
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Transtornos Cognitivos/diagnóstico , Hospitalização , Programas de Rastreamento , Entrevista Psiquiátrica Padronizada/estatística & dados numéricos , Testes Neuropsicológicos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
The Institute of Medicine (2001) identifies equity as one of six essential components of health-care quality. However, many health-care organizations lack a formal method to deeply understand and evaluate diverse patient and family experiences. Understanding care experiences of patients and families from minority racial and ethnic groups is essential to improving pervasive health disparities and to making health care more equitable. This article describes the creation of a toolkit aimed at strengthening health-care organizations' abilities to advance health equity through patient and family advisory councils (PFACs). This resource, cocreated with representatives from diverse PFACs, identifies and promotes strategies to recruit and retain diverse representation in advisory councils.
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Comitês Consultivos/normas , Etnicidade , Família , Equidade em Saúde/normas , Grupos Minoritários , Defesa do Paciente/normas , Pacientes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
Although neonatal herpes simplex virus (HSV) causes significant morbidity, utilization of the cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) test remains variable. Our objective was to examine the association of CSF HSV PCR testing with length of stay (LOS) in a 20-center retrospective cohort of hospitalized infants aged ≤60 days undergoing evaluation for meningitis after adjustment for patient-level factors and clustering by center. Of 20,496 eligible infants, 7,399 (36.1%) had a CSF HSV PCR test performed, and 46 (0.6% of those tested) had a positive test. Infants who had a CSF HSV PCR test performed had a 23% longer hospital LOS (incident rate ratio 1.23; 95% CI: 1.14-1.33). Targeted CSF HSV PCR testing may mitigate the impact on LOS for low-risk infants.
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Herpes Simples/líquido cefalorraquidiano , Tempo de Internação/estatística & dados numéricos , Meningite/diagnóstico , Complicações Infecciosas na Gravidez/líquido cefalorraquidiano , Simplexvirus/isolamento & purificação , Serviço Hospitalar de Emergência , Feminino , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Meningite/virologia , Reação em Cadeia da Polimerase/estatística & dados numéricos , Estudos RetrospectivosRESUMO
BACKGROUND: Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed. METHODS: We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture. The primary outcome was the proportion of encounters in which HSV infection was identified. Secondary outcomes included frequency of central nervous system (CNS) and disseminated HSV, and HSV testing and treatment patterns. RESULTS: Of 26 533 eligible encounters, 112 infants had HSV identified (0.42%, 95% confidence interval [CI]: 0.35%-0.51%). Of these, 90 (80.4%) occurred in weeks 1 to 4, 10 (8.9%) in weeks 5 to 6, and 12 (10.7%) in weeks 7 to 9. The median age of HSV-infected infants was 14 days (interquartile range: 9-24 days). HSV infection was more common in 0 to 28-day-old infants compared with 29- to 60-day-old infants (odds ratio 3.9; 95% CI: 2.4-6.2). Sixty-eight (0.26%, 95% CI: 0.21%-0.33%) had CNS or disseminated HSV. The proportion of infants tested for HSV (35%; range 14%-72%) and to whom acyclovir was administered (23%; range 4%-53%) varied widely across sites. CONCLUSIONS: An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.
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Herpes Simples/diagnóstico , Meningite/virologia , Simplexvirus/isolamento & purificação , Líquido Cefalorraquidiano/microbiologia , Líquido Cefalorraquidiano/virologia , Estudos Transversais , Feminino , Herpes Simples/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Meningite/diagnóstico , Razão de Chances , Estudos RetrospectivosRESUMO
BACKGROUND: With the advent of "omics" (e.g. genomics, transcriptomics, proteomics and phenomics), studies can produce enormous amounts of data. Managing this diverse data and integrating with other biological data are major challenges for the bioinformatics community. Comprehensive new tools are needed to store, integrate and analyze the data efficiently. DESCRIPTION: The PhenoGen Informatics website http://phenogen.uchsc.edu is a comprehensive toolbox for storing, analyzing and integrating microarray data and related genotype and phenotype data. The site is particularly suited for combining QTL and microarray data to search for "candidate" genes contributing to complex traits. In addition, the site allows, if desired by the investigators, sharing of the data. Investigators can conduct "in-silico" microarray experiments using their own and/or "shared" data. CONCLUSION: The PhenoGen website provides access to tools that can be used for high-throughput data storage, analyses and interpretation of the results. Some of the advantages of the architecture of the website are that, in the future, the present set of tools can be adapted for the analyses of any type of high-throughput "omics" data, and that access to new tools, available in the public domain or developed at PhenoGen, can be easily provided.
Assuntos
Sistemas de Gerenciamento de Base de Dados , Bases de Dados Genéticas , Genômica , Internet , Perfilação da Expressão Gênica , Locos de Características QuantitativasRESUMO
Daily moderate exercise (DME) and stress management are underemphasized in the care of patients with lupus nephritis (LN) due to a poor comprehensive understanding of their potential roles in controlling the inflammatory response. To investigate these effects on murine LN, disease progression was monitored with either DME or social disruption stress (SDR) induction in NZM2410/J mice, which spontaneously develop severe, early-onset LN. SDR of previously established social hierarchies was performed daily for 6 days and DME consisted of treadmill walking (8.5 m/min for 45 min/day). SDR significantly enhanced kidney disease when compared to age-matched, randomly selected control counterparts, as measured by histopathological analysis of H&E staining and immunohistochemistry for complement component 3 (C3) and IgG complex deposition. Conversely, while 88% of non-exercised mice displayed significant renal damage by 43 weeks of age, this was reduced to 45% with exercise. DME also reduced histopathology in kidney tissue and significantly decreased deposits of C3 and IgG complexes. Further examination of renal infiltrates revealed a macrophage-mediated inflammatory response that was significantly induced with SDR and suppressed with DME, which also correlated with expression of inflammatory mediators. Specifically, SDR induced IL-6, TNF-α, IL-1ß, and MCP-1, while DME suppressed IL-6, TNF-α, IL-10, CXCL1, and anti-dsDNA autoantibodies. These data demonstrate that psychological stressors and DME have significant, but opposing effects on the chronic inflammation associated with LN; thus identifying and characterizing stress reduction and a daily regimen of physical activity as potential adjunct therapies to complement pharmacological intervention in the management of autoimmune disorders, including LN.
RESUMO
To determine age-stratified prevalence of concomitant bacterial meningitis in infants ≤60 days with a urinary tract infection, we performed a 23-center, retrospective study of 1737 infants with urinary tract infection. Concomitant bacterial meningitis was rare, but more common in infants 0-28 days of age [0.9%; 95% confidence interval (CI): 0.4%-1.9%) compared with infants 29-60 days of age (0.2%; 95% CI: 0%-0.8%).
Assuntos
Meningites Bacterianas/complicações , Meningites Bacterianas/epidemiologia , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meningites Bacterianas/microbiologia , Prevalência , Estudos Retrospectivos , Infecções Urinárias/microbiologiaRESUMO
We describe a case where a patient presented with acute angiotensin-converting enzyme inhibitor (ACE-I) induced angioedema without signs or symptoms of upper airway edema beyond lip swelling. Point-of-care ultrasound (POCUS) was used as an initial diagnostic test and identified left-sided subglottic upper airway edema that was immediately confirmed with indirect fiberoptic laryngoscopy. ACE-I induced angioedema and the historical use of ultrasound in evaluation of the upper airway is briefly discussed. To our knowledge, POCUS has not been used to identify acute upper airway edema in the emergency setting. Further investigation is needed to determine if POCUS is a sensitive and specific-enough tool for the identification and evaluation of acute upper airway edema.