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1.
J Surg Res ; 303: 499-505, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39426061

RESUMO

INTRODUCTION: Operative volume is associated with improved outcomes across many surgical specialties, but this relationship has not been illustrated clearly in trauma. This study sought to evaluate the relationship between operative trauma volume and mortality, hypothesizing that increased volume would be associated with improved survival. MATERIALS AND METHODS: The National Trauma Data Bank was queried for patients ≥18 y undergoing hemorrhage control surgery at level I or II trauma centers from 2017 to 2020. Hierarchical logistic regression was performed to evaluate the association between operative volume and in-hospital mortality, controlling for demographic and clinical characteristics. RESULTS: 55,469 patients were included and treated at 516 centers. After adjustment, the operative volume was significantly associated with reduced mortality (OR 0.999, 95% CI 0.997-0.999, P = 0.018). However, there was considerable variability in volumes, with the busiest 5% of centers performing 90-294 operations per year, compared to 7-35 in the middle 50% of centers. To evaluate whether volume exhibited a uniform effect, the top 5% of trauma centers were excluded on subset analysis, with operative volume becoming nonsignificant in the remaining 491 centers (OR 0.999, 95% CI 0.996-1.001, P = 0.274). CONCLUSIONS: Higher operative trauma volume is associated with reduced mortality for patients undergoing hemorrhage control surgery, but this mortality benefit appears to arise solely from very high-volume centers. The time-sensitive nature of hemorrhage control surgery makes centralization at this level impractical. Future efforts should focus on investigating the relationship between patient proximity to trauma centers and center volume as well as identifying modifiable factors common to high-volume centers that may be widely implemented.

2.
Int J Eat Disord ; 57(2): 376-387, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38069451

RESUMO

OBJECTIVE: This study examined the impact of the COVID-19 pandemic on healthcare engagement for anorexia nervosa (AN) and bulimia nervosa (BN) in a large, geographically diverse population. METHOD: This repeated monthly, cross-sectional study queried Military Health System records of individuals aged 10-21 before and during the pandemic (February 2019-January 2022). ICD-10 codes identified encounters for AN and BN. Monthly rates of care were modeled as the number of unique individuals with an ICD-10-identified eating disorder-related encounter per month divided by the enrolled population. Poisson regression analysis evaluated rates of care stratified by eating disorder, clinical setting, and sex. RESULTS: In a population of 1.76 million adolescents and young adults, 1629 individuals with AN or BN received care during the pre-pandemic period; 3256 received care during the pandemic. The monthly rate of care for females with AN during the pandemic increased in inpatient settings (adjusted relative risk [aRR]: 1.31 [1.16-1.49]) and outpatient settings (aRR: 1.42 [1.37-1.47]); monthly care rates in males with AN increased in the outpatient setting (aRR: 1.46 [1.28-1.67]). Females with BN had increased engagement in outpatient settings (aRR: 1.09 [1.03-1.16]); BN care for males showed no significant monthly changes during the pandemic period in either healthcare setting. DISCUSSION: With increased rates of AN and BN disorder-related care during the pandemic, screening for eating disorder symptomatology may allow for timely diagnosis and intervention in periods of heightened stress. Pandemic-related increases in healthcare engagement may strain limited resources, emphasizing a need to expand accessibility of clinical expertise. PUBLIC SIGNIFICANCE: This study indicates that monthly rates of healthcare engagement during the COVID-19 pandemic for AN and BN varied based on clinical setting and sex in an adolescent and young adult population. The increased number of individuals seeking eating disorder-related care, especially outpatient care, attributed to heightened stressors necessitates accessible professionals with eating disorder clinical expertise.


Assuntos
Anorexia Nervosa , Bulimia Nervosa , COVID-19 , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Bulimia Nervosa/diagnóstico , Bulimia Nervosa/epidemiologia , Bulimia Nervosa/terapia , Pandemias , Anorexia , Estudos Transversais , COVID-19/epidemiologia , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/epidemiologia , Anorexia Nervosa/terapia
3.
J Pediatr ; 254: 61-67.e1, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36265574

RESUMO

OBJECTIVE: To investigate why certain at-risk individuals develop celiac disease (CD), we examined the association of proton pump inhibitors (PPI), histamine-2 receptor antagonists (H2RAs), and antibiotic prescriptions in the first 6 months of life with an early childhood diagnosis of CD. STUDY DESIGN: A retrospective cohort study was performed using the Military Healthcare System database. Children with a birth record from October 1, 2001, to September 30, 2013, were identified. Outpatient prescription records were queried for antibiotic, PPI, and H2RA prescriptions in the first 6 months of life. Cox proportional hazards regression was used to calculate the hazard ratio (HR) of developing CD based on medication exposure. International Classification of Diseases, Ninth Revision, Clinical Modification codes identified children with an outpatient visit for CD. RESULTS: There were 968 524 children who met the inclusion criteria with 1704 cases of CD in this group. The median follow-up for the cohort was approximately 4.5 years. PPIs (HR, 2.23; 95% CI, 1.76-2.83), H2RAs (HR, 1.94; 95% CI, 1.67-2.26), and antibiotics (HR, 1.14; 95% CI, 1.02-1.28) were all associated with an increased hazard of CD. CONCLUSIONS: There is an increased risk of developing CD if antibiotics, PPIs and H2RAs are prescribed in the first 6 months of life. Our study highlights modifiable factors, such as medication stewardship, that may change the childhood risk of CD.


Assuntos
Antibacterianos , Doença Celíaca , Criança , Humanos , Lactente , Pré-Escolar , Estudos Retrospectivos , Antibacterianos/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Fatores de Risco
4.
J Surg Res ; 287: 142-148, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36933545

RESUMO

INTRODUCTION: Thromboelastography (TEG) is a functional test of coagulation used to guide transfusions. Despite literature supporting its utility, its use remains limited to select populations. In patients with cirrhosis, conventional coagulation tests are notoriously inaccurate, and TEG may be a better measure of coagulopathy. We aimed to assess the utilization of TEG in patients with cirrhosis to steward blood transfusions in this high-risk group. METHODS: A single-center retrospective chart review of all patients ≥18 y old with a diagnosis of liver cirrhosis who had TEG results documented in the electronic medical record from January 1 to November 1, 2021. RESULTS: There were 277 TEG results on 89 patients with cirrhosis. Overall, 91% of the TEGs performed were associated with a clinical indication for transfusion. However, of the patients who were transfused, abnormal TEG values, including elevated R time and reduced maximum amplitude, did not correspond to transfusion of indicated blood products (fresh frozen plasma and platelets). A reduction in alpha angle showed a statistically significant association with transfusion of cryoprecipitate (P < 0.05). When assessing conventional coagulation tests, abnormal values were not significantly associated with transfusion (P = 0.07). CONCLUSIONS: Despite TEG suggesting that transfusions could be avoided in many cirrhotic patients, patients are still being transfused platelets and fresh frozen plasma in the absence of evidence of coagulopathy on TEG. Our finding suggests the need for education about appropriate utilization of TEG. More research is needed to understand the role of these tests to guide transfusion practices in patients with cirrhosis.


Assuntos
Transtornos da Coagulação Sanguínea , Tromboelastografia , Humanos , Tromboelastografia/métodos , Estudos Retrospectivos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Testes de Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/terapia
5.
Arch Phys Med Rehabil ; 104(2): 237-244, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35917950

RESUMO

OBJECTIVE: To investigate the association between Service Dog Training Program (SDTP) participation and mental health care utilization. DESIGN: Retrospective cohort study. SETTING: Outpatient rehabilitation clinic at a large military treatment facility. PARTICIPANTS: Military Health System beneficiaries who attended at least 1 SDTP session at a large military treatment facility (N=597). SDTP program enrollment records identified participants. INTERVENTION: The SDTP, a unique application of animal-assisted therapy, is intended to improve the mental and cognitive health for individuals with war-related trauma. MAIN OUTCOME MEASURES: Negative binomial regression calculated the associations between the SDTP participation rate and 2 mental health care utilization outcomes: mental health encounter days and psychotropic medication months' supply. RESULTS: Most of the 597 participants were male, enlisted service members, and aged 25-34 years. Approximately 46% had a posttraumatic stress disorder diagnosis, 21% had a traumatic brain injury diagnosis, 47% had an opioid prescription, and 58% had a sleep aid prescription pre-SDTP participation. Participation was categorized into low (≤1 sessions), medium (>1 and ≤2 sessions), and high (>2 sessions) monthly participation. In adjusted analysis, high monthly SDTP participation was associated with 18% fewer post-SDTP mental health encounter days (rate ratio [RR], 0.82; 95% confidence interval [CI], 0.68-0.96) than low monthly SDTP participation. High monthly SDTP participation was also associated with a 22% fewer post-SDTP psychotropic prescription months' supply (RR, 0.78; 95% CI, 0.64-0.95) than low monthly SDTP participation in adjusted analysis. CONCLUSIONS: Results suggest that participants who attend more than 2 SDTP sessions monthly encounter mental health care differently post SDTP than participants who attended 1 or fewer monthly sessions. Adjunct therapies, such as the SDTP, may offer patients a nonstigmatizing way to engage in mental health care.


Assuntos
Terapia Assistida com Animais , Transtornos de Estresse Pós-Traumáticos , Masculino , Humanos , Animais , Cães , Feminino , Estudos Retrospectivos , Animais de Trabalho , Transtornos de Estresse Pós-Traumáticos/psicologia , Aceitação pelo Paciente de Cuidados de Saúde
6.
Int J Vitam Nutr Res ; 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37469107

RESUMO

Vitamin B12 can lead to neurological deficits. We assessed whether the mean corpuscular volume (MCV) could be a sufficiently sensitive measurement for abnormal serum methylmalonic Acid (MMA) and total plasma homocysteine (tHCY) (biomarkers of vitamin B12 or folate deficiency) and if so, at what cutoff value. A total of 26,397 participants (12,730 males and 13,667 females) were included in the analysis. Weighted analysis was performed using NHANES data to calculate crude/adjusted associations between MCV-MMA/tHCY, using linear regression. Unadjusted odds ratios (OR) 95% CIs were estimated from logistic regression models. Receiver Operating Curve and the Youden Index were used to identify the MCV level that most accurately distinguished those with abnormal MMA and tHCY (dependent variables) from those without. A positive and significant correlation between MCV-MMA/tHCY was found in the general population between ages 18-85, 0.95 (95% C.I. 0.75-1.17) and 2.61 (95% C.I. 2.15-3.08). In pregnant women, for every unit increase in MCV there was a 19% increase in odds of abnormal MMA, OR 1.19 (95% C.I. 1.08-1.31), p=0.001 and the Area Under the Curve for MCV as a test for abnormal MMA was 78%. An MCV cutoff of 93.1 correctly identified abnormal MMA in pregnant women with 81% sensitivity and 77% specificity. In the general population the MCV test performed poorly in identifying abnormal MMA/tHCY. MCV is an inexpensive measurement that may be useful to screen asymptomatic pregnant women for vitamin B12 abnormalities. This may have a significant impact on reducing adverse neurological outcomes in their children.

7.
J Pediatr ; 236: 148-156.e3, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33991543

RESUMO

OBJECTIVE: To evaluate the relationship between parental injury and illness and disorders of gut-brain interaction (DGBI) in children. STUDY DESIGN: A self-controlled case series using data from the Military Health System Data Repository compared International Classification of Diseases, Ninth Revision-identified DGBI-related outpatient visits and prescriptions in 442 651 children aged 3-16 years in the 2 years before and the 2 years after the injury and/or illness of their military parent. Negative binomial regression was used to compare visit rates for constipation, fecal incontinence, abdominal pain, irritable bowel syndrome, and a composite of these before and after parental injury and/or illness. Logistic regression, clustered by child, compared the odds of stooling agent and antispasmodic prescription before and after parental injury and/or illness. RESULTS: In the 2 years following parental injury and/or illness, children had increased visits for DGBIs (adjusted incidence rate ratio [aIRR] 1.09; 95% CI 1.07-1.10), constipation (aIRR 1.07; 95% CI 1.04-1.10), abdominal pain (aIRR 1.09; 95% CI 1.07-1.12), and irritable bowel syndrome (aIRR 1.37; 95% CI 1.19-1.58). Following parental injury and/or illness, the odds of stooling agent prescription decreased (aOR 0.95; 95% CI 0.93-0.97) and the odds of antispasmodic prescription increased (aOR 1.26; 95% CI 1.18-1.36). CONCLUSIONS: Parental injury and/or illness is associated with increased healthcare use for DGBIs. Parental health should be considered by clinicians when assessing DGBIs, counseling patients, and formulating treatment plans.


Assuntos
Dor Abdominal/epidemiologia , Constipação Intestinal/epidemiologia , Saúde da Família , Incontinência Fecal/epidemiologia , Síndrome do Intestino Irritável/epidemiologia , Pais , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Família Militar , Razão de Chances , Fatores de Tempo
8.
J Sex Med ; 18(8): 1444-1454, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34247956

RESUMO

OBJECTIVE: Transgender and gender-diverse (TGD) adolescents experience increased mental health risk compared to cisgender peers. Limited research suggests improved outcomes following gender-affirmation. This study examined mental healthcare and psychotropic medication utilization among TGD youth compared to their siblings without gender-related diagnoses and explored utilization patterns following gender-affirming care. METHOD: This retrospective cohort study used military healthcare data from 2010-2018 to identify mental healthcare diagnoses and visits, and psychotropic medication prescriptions among TGD youth who received care for gender dysphoria before age 18, and their siblings. Logistic and Poisson regression analyses compared mental health diagnosis, visits, and psychotropic prescriptions of TGD youth to their siblings, and compared healthcare utilization pre- and post-initiation of gender-affirming pharmaceuticals among TGD adolescents. RESULTS: 3,754 TGD adolescents and 6,603 cisgender siblings were included. TGD adolescents were more likely to have a mental health diagnosis (OR 5.45, 95% CI [4.77-6.24]), use more mental healthcare services (IRR 2.22; 95% CI [2.00-2.46]), and be prescribed more psychotropic medications (IRR = 2.57; 95% CI [2.36-2.80]) compared to siblings. The most pronounced increases in mental healthcare were for adjustment, anxiety, mood, personality, psychotic disorders, and suicidal ideation/attempted suicide. The most pronounced increased in psychotropic medication were in SNRIs, sleep medications, anti-psychotics and lithium. Among 963 TGD youth (Mage: 18.2) using gender-affirming pharmaceuticals, mental healthcare did not significantly change (IRR = 1.09, 95% CI [0.95-1.25]) and psychotropic medications increased (IRR = 1.67, 95% CI [1.46-1.91]) following gender-affirming pharmaceutical initiation; older age was associated with decreased care and prescriptions. CONCLUSION: Results support clinical mental health screening recommendations for TGD youth. Further research is needed to elucidate the longer-term impact of medical affirmation on mental health, including family and social factors associated with the persistence and discontinuation of mental healthcare needs among TGD youth. Hisle-Gorman E, Schvey NA, Adirim TA, et al. Mental Healthcare Utilization of Transgender Youth Before and After Affirming Treatment. J Sex Med 2021;18:1444-1454.


Assuntos
Disforia de Gênero , Pessoas Transgênero , Transexualidade , Adolescente , Idoso , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos
9.
J Surg Res ; 266: 361-365, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34087619

RESUMO

BACKGROUND: Tracheostomy improves outcomes for critically ill patients requiring prolonged mechanical ventilation. Data are limited on the use and benefit of tracheostomies for intubated, critically ill coronavirus disease 2019 (COVID-19) patients. During the surge in COVID 19 infections in metropolitan New York/New Jersey, our hospital cared for many COVID-19 patients who required prolonged intubation. This study describes the outcomes in COVID-19 patients who underwent tracheostomy. METHODS: We present a case series of patients with COVID-19 who underwent tracheostomy at a single institution. Tracheostomies were performed on patients with prolonged mechanical ventilation beyond 3 wk. Patient demographics, medical comorbidities, and ventilator settings prior to tracheostomy were reviewed. Primary outcome was in-hospital mortality. Secondary outcomes included time on mechanical ventilation, length of ICU and hospital stay, and discharge disposition. RESULTS: Fifteen COVID-19 patients underwent tracheostomy at an average of 31 d post intubation. Two patients (13%) died. Half of our cohort was liberated from the ventilator (8 patients, 53%), with an average time to liberation of 14 ± 6 d after tracheostomy. Among patients off mechanical ventilation, 5 (63%) had their tracheostomies removed prior to discharge. The average intensive care length of stay was 47 ± 13 d (range 29-74 d) and the average hospital stay was 59 ± 16 d (range 34-103 d). CONCLUSIONS: This study reports promising outcomes in COVID-19 patients with acute respiratory failure and need for prolonged ventilation who undergo tracheostomy during their hospitalization. Further research is warranted to establish appropriate indications for tracheostomy in COVID-19 and confirm outcomes.


Assuntos
COVID-19/complicações , Intubação Intratraqueal/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/terapia , Traqueostomia/estatística & dados numéricos , COVID-19/mortalidade , COVID-19/terapia , Cuidados Críticos/métodos , Cuidados Críticos/estatística & dados numéricos , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Intubação Intratraqueal/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Traqueostomia/efeitos adversos , Resultado do Tratamento , Desmame do Respirador/estatística & dados numéricos
10.
J Surg Res ; 253: 100-104, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32339786

RESUMO

BACKGROUND: Osteopenia is common in the elderly, increasing their risk of sustaining cervical fractures after ground level falls (GLFs). We sought to examine the incidence of blunt cerebrovascular injury (BCVI) and subsequent stroke in elderly GLF patients as compared with other higher injury mechanisms. MATERIALS AND METHODS: The Trauma Quality Improvement Program database (2011-2016) was used to identify blunt trauma patients with isolated (other body region abbreviated injury scale <3) cervical spine (C1-C7) fractures. Patients were stratified into three groups: nonelderly patients (<65) with all mechanisms of injury, elderly patients (≥65) with GLF, and elderly patients with all other mechanism of injury. Multivariable logistic regression was used to determine predictors for BCVI, stroke, spinal cord injury, and acute kidney injury. RESULTS: Seventeen thousand six hundred twenty-eight patients with cervical spine injuries were identified. BCVI was highest in the <65 group (0.8%) and lowest in elderly patients with GLF (0.3%, P = 0.001). When controlling for other factors, elderly patients with GLF were less likely to sustain BCVI (adjusted odds ratio: 0.46, P = 0.03) but had comparable rates of stroke attributable to BCVI (18.2% versus 6.5%, P = 0.184) and comparable rate of acute kidney injury compared with elderly patients with other mechanism of injury. CONCLUSIONS: In elderly patients with isolated cervical spine fracture after GLF, BCVI occurs less frequently but is associated with a comparable rate of stroke as compared with other mechanisms. Low injury mechanism should not preclude BCVI screening in the presence of cervical spine fractures.


Assuntos
Acidentes por Quedas , Traumatismo Cerebrovascular/epidemiologia , Vértebras Cervicais/lesões , Traumatismos Cranianos Fechados/epidemiologia , Fraturas da Coluna Vertebral/complicações , Acidente Vascular Cerebral/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Traumatismo Cerebrovascular/etiologia , Feminino , Traumatismos Cranianos Fechados/etiologia , Humanos , Incidência , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Centros de Traumatologia/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto Jovem
11.
J Pediatr ; 207: 148-153, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30528571

RESUMO

OBJECTIVE: To evaluate the impact of prematurity on fracture by age 5, controlling for medications and comorbidities of prematurity. STUDY DESIGN: We performed a retrospective cohort study of infants born in Military Treatment Facilities in 2009-2010 with ≥5 years of follow-up care. Gestational age, low birth weight, comorbidities of prematurity (osteopenia, necrotizing enterocolitis, chronic lung disease, and cholestasis) and fractures were identified by International Classification of Disease, 9th Edition, codes. Pharmaceutical records identified treatment with caffeine, diuretics, postnatal corticosteroids, and antacids. Poisson regression analysis determined fracture rate by 5 years of life. RESULTS: There were 65 938 infants born in 2009-2010 who received care in the military health system for ≥5 years, including 3589 born preterm; 165 born at ≤286/7 weeks of gestation, 380 born at 29-316/7 weeks of gestation, and 3044 born at 32-366/7 weeks of gestation. Preterm birth at any gestational age was not associated with fracture rate in adjusted models. The fracture rate was increased with cholestasis, proton pump inhibitor exposure, and male sex. CONCLUSIONS: Prematurity was not associated with fracture rate. Neonatal cholestasis and proton pump inhibitor treatment were associated with increased fractures by age 5.


Assuntos
Fraturas Ósseas/epidemiologia , Recém-Nascido de Baixo Peso , Doenças do Prematuro/epidemiologia , Recém-Nascido Prematuro , Medição de Risco/métodos , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Idade Gestacional , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Serviços de Saúde Militar/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
12.
PLoS Genet ; 12(4): e1005848, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27120463

RESUMO

Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS). The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ) families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026). VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering) protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway.


Assuntos
Autofagia/genética , Efeito Fundador , Genes Recessivos , Leucoencefalopatias/genética , Mutação , Proteínas de Transporte Vesicular/genética , Adulto , Sequência de Aminoácidos , Animais , Morte Celular/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Proteínas de Transporte Vesicular/química , Adulto Jovem
13.
Pediatr Res ; 84(2): 190-198, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29538366

RESUMO

BACKGROUND: We explored the association of 29 previously reported neonatal, perinatal, and prenatal conditions, and exposures with later diagnosis of autism spectrum disorder (ASD) in a large sample of children followed over multiple years. METHODS: A retrospective case-cohort study was formed using the Military Health System database. Cases were identified by International Classification of Diseases, Ninth Revision codes for ASD between 2000 and 2013, and were matched 3:1 with controls on sex, date of birth, and enrollment time frame. Exposures included 29 conditions previously associated with ASD; 17 prenatal conditions and their pharmaceutical treatment, 5 perinatal conditions, and 6 neonatal conditions. RESULTS: A total of 8,760 children diagnosed with ASD between the ages of 2 and 18 years were matched with 26,280 controls. ASD is associated with maternal mental illness, epilepsy, obesity, hypertension, diabetes, polycystic ovary syndrome, infection, asthma, assisted fertility, hyperemesis, younger maternal age, labor complications, low birth weight, infant infection, epilepsy, birth asphyxia, and newborn complications. The greatest increased risk was associated with infant epilepsy (odds ratio (OR) 7.57 (5.68-10.07)), maternal mental health (OR 1.80 (1.65-1.96)), and epilepsy (OR 1.60 (1.02-2.50)) medications. CONCLUSION: ASD is associated with a range of prenatal, perinatal, and neonatal factors, with the highest magnitude associations with maternal medication use and neonatal seizure.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/etiologia , Mães , Convulsões/complicações , Adulto , Transtorno do Espectro Autista/complicações , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido , Masculino , Exposição Materna , Militares , Neonatologia/métodos , Gravidez , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
14.
J Allergy Clin Immunol ; 138(4): 1142-1151.e2, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27484032

RESUMO

BACKGROUND: Primary immunodeficiency diseases (PIDDs) are inherited disorders of the immune system. The most severe form, severe combined immunodeficiency (SCID), presents with profound deficiencies of T cells, B cells, or both at birth. If not treated promptly, affected patients usually do not live beyond infancy because of infections. Genetic heterogeneity of SCID frequently delays the diagnosis; a specific diagnosis is crucial for life-saving treatment and optimal management. OBJECTIVE: We developed a next-generation sequencing (NGS)-based multigene-targeted panel for SCID and other severe PIDDs requiring rapid therapeutic actions in a clinical laboratory setting. METHODS: The target gene capture/NGS assay provides an average read depth of approximately 1000×. The deep coverage facilitates simultaneous detection of single nucleotide variants and exonic copy number variants in one comprehensive assessment. Exons with insufficient coverage (<20× read depth) or high sequence homology (pseudogenes) are complemented by amplicon-based sequencing with specific primers to ensure 100% coverage of all targeted regions. RESULTS: Analysis of 20 patient samples with low T-cell receptor excision circle numbers on newborn screening or a positive family history or clinical suspicion of SCID or other severe PIDD identified deleterious mutations in 14 of them. Identified pathogenic variants included both single nucleotide variants and exonic copy number variants, such as hemizygous nonsense, frameshift, and missense changes in IL2RG; compound heterozygous changes in ATM, RAG1, and CIITA; homozygous changes in DCLRE1C and IL7R; and a heterozygous nonsense mutation in CHD7. CONCLUSION: High-throughput deep sequencing analysis with complete clinical validation greatly increases the diagnostic yield of severe primary immunodeficiency. Establishing a molecular diagnosis enables early immune reconstitution through prompt therapeutic intervention and guides management for improved long-term quality of life.


Assuntos
Análise de Sequência de DNA , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/genética , Adolescente , Criança , Feminino , Variação Genética , Humanos , Masculino , Patologia Molecular/normas , Patologia Molecular/tendências
15.
Genet Med ; 18(5): 513-21, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26402642

RESUMO

PURPOSE: Next-generation sequencing (NGS) has been widely applied to clinical diagnosis. Target-gene capture followed by deep sequencing provides unbiased enrichment of the target sequences, which not only accurately detects single-nucleotide variations (SNVs) and small insertion/deletions (indels) but also provides the opportunity for the identification of exonic copy-number variants (CNVs) and large genomic rearrangements. METHOD: Capture NGS has the ability to easily detect SNVs and small indels. However, genomic changes involving exonic deletions/duplications and chromosomal rearrangements require more careful analysis of captured NGS data. Misaligned raw sequence reads may be more than just bad data. Some mutations that are difficult to detect are filtered by the preset analytical parameters. "Loose" filtering and alignment conditions were used for thorough analysis of the misaligned NGS reads. Additionally, using an in-house algorithm, NGS coverage depth was thoroughly analyzed to detect CNVs. RESULTS: Using real examples, this report underscores the importance of the accessibility to raw sequence data and manual review of suspicious sequence regions to avoid false-negative results in the clinical application of NGS. Assessment of the NGS raw data generated by the use of loose filtering parameters identified several sequence aberrations, including large indels and genomic rearrangements. Furthermore, NGS coverage depth analysis identified homozygous and heterozygous deletions involving single or multiple exons. CONCLUSION: Our results demonstrate the power of deep NGS in the simultaneous detection of point mutations and intragenic exonic deletion in one comprehensive step.Genet Med 18 5, 513-521.


Assuntos
Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação INDEL/genética , Algoritmos , Variações do Número de Cópias de DNA/genética , Éxons , Doenças Genéticas Inatas/patologia , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala/tendências , Homozigoto , Humanos , Polimorfismo de Nucleotídeo Único/genética , Deleção de Sequência/genética
16.
J Pediatr ; 178: 183-187.e1, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27592097

RESUMO

OBJECTIVES: To assess for an increased risk of obesity, type 2 diabetes mellitus, hypertension, hyperlipidemia, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis in children with autism spectrum disorders (ASD). Additionally, to determine the rates of prescribed treatment for obesity-related metabolic disorders and to determine whether treatment with psychotropic medications is associated with the development of obesity for children with ASD. STUDY DESIGN: A retrospective 1:5 case-control study was performed by use of the Military Health System database from October 2000 to September 2013. For children with ASD and matched controls, International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for obesity, type 2 diabetes mellitus, hypertension, hyperlipidemia, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, and prescriptions were obtained. Conditional logistic regression determined ORs and 95% CIs. RESULTS: A total of 48 762 individuals with ASD and 243 810 matched controls were identified. Children with ASD had significantly greater odds of having obesity (OR 1.85; 95% CI 1.78-1.92), having obesity-related disorders, and being prescribed a medication when they had these diseases. In children with ASD, mood stabilizers, antipsychotics, antiepileptic drugs, and selective serotonin reuptake inhibitors were associated with obesity. CONCLUSIONS: Children with ASD have an increased risk of obesity and obesity-related metabolic disorders. They are more likely to be prescribed medications to treat these complications, suggesting they may have more severe disease. There is a significant association between the use of some psychotropic categories and a diagnosis of obesity, suggesting that obesity in children with ASD may be partially iatrogenic.


Assuntos
Transtorno do Espectro Autista/complicações , Doenças Metabólicas/complicações , Obesidade/complicações , Adolescente , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Criança , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Masculino , Doenças Metabólicas/epidemiologia , Obesidade/epidemiologia , Psicotrópicos/uso terapêutico , Estudos Retrospectivos
17.
J Pediatr Gastroenterol Nutr ; 63(4): e69-73, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27276430

RESUMO

OBJECTIVES: Eosinophilic esophagitis (EoE) can present as food selectivity or feeding disorders in children. Children with autism spectrum disorders (ASDs) commonly demonstrate behavioral food selectivity in type and texture, which often leads to the diagnosis of feeding disorder. We sought to evaluate the association of ASD with EoE. METHODS: A retrospective matched case-cohort study was performed using the Military Health System database from October 2008 to September 2013. We performed a 1:5 case-control match by age, sex, and enrollment timeframe. Feeding disorders, EoE, and atopic disorders were defined using diagnostic and procedure codes. RESULTS: There were 45,286 children with ASD and 226,430 matched controls. EoE was more common in children with ASD (0.4%) compared with controls (0.1%). Feeding disorders were associated with EoE in both children with ASD and controls. Feeding disorders also had a higher odds ratio for EoE compared with other atopic conditions, among both children with ASD (7.17, 95% confidence interval [CI] 4.87-10.5) and controls (11.5, 95% CI 7.57-17.5). Compared with controls with a feeding disorder, children with ASD and a feeding disorder had no difference in the rate of diagnosed EoE (0.85, 0.95% CI 0.39-1.88). CONCLUSIONS: Children with ASD are more likely to be diagnosed with EoE compared with controls; however, among children with feeding disorders, there is no difference in the odds of EoE. A diagnosis of feeding disorder was strongly associated with EoE. Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE.


Assuntos
Transtorno do Espectro Autista/complicações , Esofagite Eosinofílica/etiologia , Transtornos de Alimentação na Infância/etiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Bases de Dados Factuais , Esofagite Eosinofílica/diagnóstico , Transtornos de Alimentação na Infância/diagnóstico , Feminino , Humanos , Masculino , Razão de Chances , Estudos Retrospectivos , Fatores de Risco
19.
J Pediatr ; 165(5): 1034-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25128162

RESUMO

OBJECTIVE: To determine the effect of intimate partner violence (IPV) on birth outcomes and infant hospitalization. STUDY DESIGN: Hospitalization records for the first 4 months of life for infants born in the Military Health System in 2006-2007 were linked to Family Advocacy Program-substantiated cases of IPV among military parents. Adverse outcomes were identified using International Classification of Diseases, Ninth Revision codes. Logistic regression modeling calculated the OR of children exposed to IPV experiencing adverse outcomes. RESULTS: A total of 204,546 infants were born during the study period. Among these, 173,026 infants (85%) were linked to active duty military parents. 31,603 infants (18%) experienced adverse outcomes, and 3059 infants (1.8%) were born into families with IPV. The infants exposed to IPV had a 31% increased odds of experiencing adverse outcomes compared with infants without known IPV exposure. IPV exposure increased the odds of the following outcomes: prematurity (OR, 1.45; 95% CI, 1.29-1.62), low birth weight (OR, 1.57; 95% CI, 1.25-1.97), respiratory problems (OR, 1.17; 95% CI, 1.04-1.32), neonatal hospitalization (OR, 1.39; 95% CI, 1.20-1.61), and postneonatal hospitalization (OR, 1.52; 95% CI, 1.29-1.81). After controlling for prematurity and demographic variables, IPV exposure was associated with low birth weight (OR, 1.52; 95% CI, 1.16-1.99), neonatal hospitalization (OR, 1.24; 95% CI, 1.02-1.49), and postneonatal hospitalization (OR, 1.27; 95% CI, 1.03-1.56). CONCLUSION: Infants exposed to IPV are more likely to experience adverse birth outcomes and infant hospitalization. Routinely addressing IPV during prenatal and early pediatric visits may potentially prevent these adverse outcomes.


Assuntos
Doenças do Recém-Nascido/etiologia , Resultado da Gravidez , Parceiros Sexuais , Maus-Tratos Conjugais/estatística & dados numéricos , Adulto , Criança , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Gravidez , Comportamento Sexual/estatística & dados numéricos , Estados Unidos
20.
Artigo em Inglês | MEDLINE | ID: mdl-39238092

RESUMO

ABSTRACT: Acute kidney injury is associated with poor outcomes in the trauma and emergency general surgery population, and recent consensus definitions have allowed for significant advances in defining the burden of disease. The current definitions rely on overall functional measures (i.e., serum creatinine and urine output), which can be confounded by a variety of clinical factors. Biomarkers are increasingly being investigated as more direct diagnostic assays for the diagnosis of acute kidney injury and may allow earlier detection and more timely therapeutic intervention. Etiologies fall into two general categories: disorders of renal perfusion and exposure to nephrotoxic agents. Therapy is largely supportive, and prevention offers the best chance to decrease clinical impact.

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