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1.
Clin Exp Rheumatol ; 41(2): 340-347, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36861744

RESUMO

OBJECTIVES: Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in those aged above 50. It is classically heralded by weakness in the long finger flexors and quadriceps. The aim of this article is to describe five atypical cases of IBM, outlining two potential emerging clinical subsets of the disease. METHODS: We reviewed relevant clinical documentation and pertinent investigations for five patients with IBM. RESULTS: The first phenotype we describe is young-onset IBM in two patients who had symptoms since their early thirties. The literature supports that IBM can rarely present in this age range or younger. We describe a second phenotype in three middle-aged women who developed early bilateral facial weakness at presentation in tandem with dysphagia and bulbar impairment followed by respiratory failure requiring non-invasive ventilation (NIV). Within this group, two patients were noted to have macroglossia, another possible rare feature of IBM. CONCLUSIONS: Despite the classical phenotype described within the literature IBM can present in a heterogenous fashion. It is important to recognise IBM in younger patients and investigate for specific associations. The described pattern of facial diplegia, severe dysphagia, bulbar dysfunction and respiratory failure in female IBM patients requires further characterisation. Patients with this clinical pattern may require more complex and supportive management. Macroglossia is a potentially under recognised feature of IBM. The presence of macroglossia in IBM warrants further study, as its presence may lead to unnecessary investigations and delay diagnosis.


Assuntos
Transtornos de Deglutição , Macroglossia , Miosite de Corpos de Inclusão , Feminino , Humanos , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/genética , Miosite de Corpos de Inclusão/terapia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Fenótipo
2.
Liver Transpl ; 29(7): 735-744, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36747344

RESUMO

Children with rare cholestatic liver diseases, such as Alagille syndrome, progressive familial intrahepatic cholestasis, and biliary atresia typically require liver transplantation (LT). The objective of this analysis was to assess the economic burden of LT on these patients. Health care resource utilization and costs associated with pediatric LT were retrospectively assessed using insurance claims data from the US IBM MarketScan Commercial and Medicaid databases collected between October 2015 and December 2019. Inclusion criteria were as follows: ≥1 procedure code for LT, <18 years old at transplant, and ≥6 months of insurance eligibility at baseline. A cholestatic liver disease population who received LT was selected in the absence of specific diagnosis codes by excluding other severe liver conditions (ie, acute liver failure, malignancy) and by excluding severely decompensated individuals requiring ICU admission before LT. Annualized rates were reported. Over a mean study duration of 1.8 years, 53 commercially insured and 100 Medicaid-insured children received LT, with mean (SD) ages at baseline of 6.9 (6.0) and 5.7 (5.4) years, respectively. During this period, commercially insured and Medicaid-insured patients had annualized means of 65.3 and 52.8 medical visits, respectively. Most were outpatient visits, although the burden of inpatient visits was also high, with mean inpatient stays (inclusive of LT stay) of 37.2 and 31.6 days per year, respectively. Commercially insured and Medicaid-insured patients averaged US$512,124 and $211,863 in medical costs and $26,998 and $15,704 in pharmacy costs, respectively. These costs remained substantial throughout the first year after transplant. Overall, pediatric LT resulted in substantial health care resource utilization and cost burden in both commercially- and Medicaid-insured patients. Novel targeted medications that negate the need for pediatric LT could decrease the associated morbidity and costs.


Assuntos
Colestase , Transplante de Fígado , Estados Unidos/epidemiologia , Humanos , Criança , Adolescente , Medicaid , Seguro Saúde , Estudos Retrospectivos , Custos de Cuidados de Saúde , Colestase/etiologia , Colestase/cirurgia
3.
J Pediatr ; 252: 68-75.e5, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36096175

RESUMO

OBJECTIVE: The objective of this study was to assess the impact of treatment response to the ileal bile acid transporter inhibitor maralixibat on health-related quality of life (HRQoL) in children with Alagille syndrome. STUDY DESIGN: This analysis used data from the ICONIC trial, a phase 2 study with a 4-week double-blind, placebo-controlled, randomized drug withdrawal period in children with Alagille syndrome with moderate-to-severe pruritus. Clinically meaningful treatment response to maralixibat was defined a priori as a ≥1-point reduction in the Itch-Reported Outcome (Observer) score, from baseline to week 48. HRQoL was assessed using the Pediatric Quality of Life Inventory Generic Core, Family Impact, and Multidimensional Fatigue scale scores, which were collected via the caregiver. The minimal clinically important difference for HRQoL ranged from 4 to 5 points, depending on the scale. RESULTS: Twenty of the 27 patients (74%) included in this analysis achieved an Itch-Reported Outcome (Observer) treatment response at week 48. The mean (SD) change in Multidimensional Fatigue score was +25.8 (23.0) for responders vs -3.1 (19.8) for nonresponders (P = .03). Smaller and non-statistically significant mean changes were observed for the Pediatric Quality of Life Inventory Generic Core and Family Impact scores. Controlling for baseline Family Impact score, responders' Family Impact scores increased an average of 16.9 points over 48 weeks compared with non-responders (P = .05). Smaller and non-statistically significant point estimates were observed for the Pediatric Quality of Life Inventory Generic Core and Multidimensional Fatigue scores. CONCLUSION: The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160782.


Assuntos
Síndrome de Alagille , Qualidade de Vida , Criança , Humanos , Síndrome de Alagille/tratamento farmacológico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Prurido/tratamento farmacológico , Prurido/etiologia
4.
J Pediatr ; 253: 144-151.e1, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36179890

RESUMO

OBJECTIVE: To assess and characterize health care resource utilization (HRU) in children with the rare, genetic, multisystem disorder, Alagille syndrome. STUDY DESIGN: This retrospective analysis reviewed commercially insured and Medicaid-insured claims from October 1, 2015 to December 31, 2019 to assess HRU in patients with Alagille syndrome. As there is no specific International Classification ofDiseases-10 code for Alagille syndrome, patients were identified using the following algorithm: ≥1 claim with diagnosis code Q44.7 (other congenital malformations of the liver); <18 years of age, with no history of biliary atresia (International Classification ofDiseases-10 code: Q44.2); and ≥6 months of insurance eligibility prior to diagnosis. HRU was summarized per patient per year over all available claims postdiagnosis. RESULTS: A total of 171 commercially insured and 215 Medicaid-insured patients with Alagille syndrome were available for analysis. Annually, commercially insured and Medicaid-insured patients averaged 31 medical visits (range, 1.5-237) and 48 medical visits (range, 0.7-690), respectively. The most common visits were outpatient with the majority encompassing lab/imaging and primary care visits (commercially insured: 21 [range, 0.0-183]; Medicaid-insured: 26 [range, 0.0-609]). Inpatient visits were the highest driver of costs in both the commercial and Medicaid populations. CONCLUSIONS: Patients with Alagille syndrome have a substantial HRU burden driven largely by numerous outpatient visits and costly inpatient stays. Given the complexity and variability of Alagille syndrome presentation, patients may benefit from multidisciplinary and subspecialized care.


Assuntos
Síndrome de Alagille , Custos de Cuidados de Saúde , Criança , Estados Unidos , Humanos , Estudos Retrospectivos , Síndrome de Alagille/diagnóstico , Síndrome de Alagille/terapia , Atenção à Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Medicaid , Seguro Saúde
5.
Eur Neurol ; 85(2): 162-168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34788771

RESUMO

The neurological and psychological manifestations of trauma, confinement, and terror became apparent throughout Europe as soldiers were evacuated from the trenches of the Western Front. The response in the UK evolved as a result of the experience of medical staff embedded with the troops in base hospitals and the philosophy of those treating returned soldiers in specialist establishment. There were widely disparate approaches to the management encompassing simple supportive care, a psychanalytic approach and radical electric shock therapy. The latter was partially driven by the Queen Square experience in the UK but was also concurrently widely pursued throughout Europe. With experience, care was increasingly undertaken close to the front lines using a philosophy of immediacy and expectation of recovery. Post-war analysis was startlingly unsympathetic, yet the experiences and management of shell shock have guided psychiatric and medical understanding of functional illness and post-traumatic stress over the subsequent century. In this historical review, we have sought to present features of the UK response to the neurological manifestations of trauma, the way in which these changed as the war proceeded and the political and medical response in the aftermath of war.


Assuntos
Distúrbios de Guerra , Neurologia , Transtornos de Estresse Pós-Traumáticos , Distúrbios de Guerra/história , História do Século XX , Humanos , Transtornos de Estresse Pós-Traumáticos/história , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Reino Unido , I Guerra Mundial
6.
BMJ Neurol Open ; 3(1): e000096, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079936

RESUMO

BACKGROUND: Daclizumab is an anti-CD25 monoclonal antibody developed for the treatment of relapsing remitting multiple sclerosis, which was withdrawn worldwide in March 2018, due to emerging serious immune-mediated systemic andcentral nervous system adverse events. We report a case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis occurring 14 weeks after stopping daclizumab, which responded to the proteasome inhibitor bortezomib. METHODS: Following lack of effective clinical response to first line (corticosteroid, plasma exchange, intravenous immunoglobulin) and second line (rituximab) treatments, bortezomib therapy was commenced. The patient received six cycles of bortezomib treatment. RESULTS: Clinical improvement was noted 4 weeks after the first of six cycles of bortezomib and the patient experienced sustained clinical improvement. CONCLUSION: Our case provides further class IV evidence of the use of bortezomib therapy for treatment refractory anti-NMDAR encephalitis.

7.
Neurol Clin Pract ; 11(1): 18-24, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33968468

RESUMO

BACKGROUND: Recovery from Guillain-Barré syndrome (GBS) may be protracted, and patients may need prolonged ventilatory support. We present clinical data from a tertiary referral weaning center managing patients with GBS requiring prolonged ventilatory support. METHODS: A retrospective review of patients managed in a 34-bed specialist ventilator weaning facility in London, United Kingdom, between 2006 and 2017. Data including demographics, initial presentation, and ventilatory support were collected. Functional recovery and outcome data were collected between 12 months and 3 years following disease onset. RESULTS: Twenty-nine patients with severe GBS requiring prolonged ventilation were included. In several patients, coexisting conditions or complications affected the course. Seventy-six percent (n = 22) were successfully weaned from invasive ventilation with a median time to tracheostomy decannulation of 193 days (range: 49-527 days). Use of noninvasive ventilation (NIV), as part of the weaning program, was applied in 59% (13/22), with 14% (3/22) requiring long-term nocturnal NIV. Twenty-four percent (7/29) were not decannulated, with 14% (4/29) supported on long-term invasive ventilation. Forty-five percent (10/22) weaned from invasive ventilation were able to achieve short distance-assisted ambulation. Mortality at 36 months was 17% (5/29), with 3 of these deaths occurring in patients invasively ventilated during their acute admission. CONCLUSIONS: GBS with severe respiratory muscle weakness and bulbar dysfunction may require prolonged invasive ventilation. However, there is potential for complete weaning from invasive mechanical ventilatory support with associated function recovery. These data highlight the importance of maintaining ongoing support and rehabilitation for patients with GBS requiring prolonged ventilation.

9.
Brain ; 143(10): 3104-3120, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32637987

RESUMO

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.


Assuntos
Infecções por Coronavirus , Doenças do Sistema Nervoso , Pandemias , Pneumonia Viral , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Londres/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/epidemiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
10.
JAMA Netw Open ; 2(11): e1915374, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31730182

RESUMO

Importance: Individuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD. Objective: To estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD. Design, Setting, and Participants: Cohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018. Main Outcomes and Measures: Life expectancy, quality-adjusted life expectancy, and projected lifetime income. Results: The estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates. Conclusions and Relevance: In this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.


Assuntos
Anemia Falciforme/epidemiologia , Renda , Expectativa de Vida , Anos de Vida Ajustados por Qualidade de Vida , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Previsões , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Estados Unidos/epidemiologia , Adulto Jovem
11.
JAMA Netw Open ; 2(9): e1912014, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31553471

RESUMO

Importance: The BCG vaccine is currently the only approved tuberculosis vaccine and is widely administered worldwide, usually during infancy. Previous studies found increased rates of lymphoma and leukemia in BCG-vaccinated populations. Objective: To determine whether BCG vaccination was associated with cancer rates in a secondary analysis of a BCG vaccine trial. Design, Setting, and Participants: Retrospective review (60-year follow-up) of a clinical trial in which participants were assigned to the vaccine group by systematic stratification by school district, age, and sex, then randomized by alternation. The original study was conducted at 9 sites in 5 US states between December 1935 and December 1998. Participants were 2963 American Indian and Alaska Native schoolchildren younger than 20 years with no evidence of previous tuberculosis infection. Statistical analysis was conducted between August 2018 and July 2019. Interventions: Single intradermal injection of either BCG vaccine or saline placebo. Main Outcomes and Measures: The primary outcome was diagnosis of cancer after BCG vaccination. Data on participant interval health and risk factors, including smoking, tuberculosis infection, isoniazid use, and other basic demographic information, were also collected. Results: A total of 2963 participants, including 1540 in the BCG vaccine group and 1423 in the placebo group, remained after exclusions. Vaccination occurred at a median (interquartile range) age of 8 (5-11) years; 805 participants (52%) in the BCG group and 710 (50%) in the placebo group were female. At the time of follow-up, 97 participants (7%) in the placebo group and 106 participants (7%) in the BCG vaccine group could not be located; total mortality was 633 participants (44%) in the placebo group and 632 participants (41%) in the BCG group. The overall rate of cancer diagnosis was not significantly different in BCG vaccine vs placebo recipients (hazard ratio, 0.82; 95% CI, 0.66-1.02), including for lymphoma and leukemia. The rate of lung cancer was significantly lower in BCG vs placebo recipients (18.2 vs 45.4 cases per 100 000 person-years; hazard ratio, 0.38; 95% CI, 0.20-0.74; P = .005), controlling for sex, region, alcohol overuse, smoking, and tuberculosis. Conclusions and Relevance: Childhood BCG vaccination was associated with a lower risk of lung cancer development in American Indian and Alaska Native populations. This finding has potentially important health implications given the high mortality rate associated with lung cancer and the availability of low-cost BCG vaccines.


Assuntos
Vacina BCG/uso terapêutico , Indígenas Norte-Americanos , Inuíte , Neoplasias Pulmonares/etiologia , Tuberculose/prevenção & controle , Vacina BCG/efeitos adversos , Fatores de Confusão Epidemiológicos , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Vacinação
12.
Neurology ; 93(9): e895-e907, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31391248

RESUMO

OBJECTIVE: To investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for 2 major forms of motor neuron disorders: spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS). METHODS: We applied quantitative 3-point Dixon and semiquantitative T1-weighted and short tau inversion recovery (STIR) imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n = 21) and SBMA (n = 21), alongside healthy controls (n = 16). Acquired images were analyzed for the presence of fat infiltration or edema as well as specific patterns of muscle involvement. Quantitative MRI measurements were correlated with clinical measures of disease severity in ALS and SBMA. RESULTS: Quantitative imaging revealed significant fat infiltration in bulbar (p < 0.001) and limb muscles in SBMA compared to controls (thigh: p < 0.001; calf: p = 0.001), identifying a characteristic pattern of muscle involvement. In ALS, semiquantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Finally, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA. CONCLUSIONS: Our findings show that muscle MRI differentiates between SBMA and ALS and correlates with disease severity, supporting its use as a diagnostic tool and biomarker for disease progression. This highlights the clinical utility of muscle MRI in motor neuron disorders and contributes to establish objective outcome measures, which is crucial for the development of new drugs.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Atrofia Muscular Espinal/diagnóstico por imagem , Estudos de Casos e Controles , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
13.
J Pediatr ; 212: 102-110.e5, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230888

RESUMO

OBJECTIVE: To determine the risk of bacterial meningitis in infants aged 29-90 days with evidence of urinary tract infection (UTI). METHODS: PubMed (MEDLINE), Embase, and the Cochrane Library were systematically searched for studies reporting rates of meningitis in infants aged 29-90 days with abnormal urinalysis or urine culture. Observational studies in infants with evidence of UTI who underwent lumbar puncture (LP) reporting age-specific event rates of bacterial meningitis and sterile cerebrospinal fluid pleocytosis were included. Prevalence estimates for bacterial meningitis in infants with UTI were pooled in a random effects meta-analysis. RESULTS: Three prospective and 17 retrospective cohort studies were included in the meta-analysis. The pooled prevalence of concomitant bacterial meningitis in infants with UTI was 0.25% (95% CI, 0.09%-0.70%). Rates of sterile pleocytosis ranged from 0% to 29%. Variation in study methods precluded calculation of a pooled estimate for sterile pleocytosis. In most studies, the decision to perform a LP was up to the provider, introducing selection bias into the prevalence estimate. CONCLUSIONS: The risk of bacterial meningitis in infants aged 29-90 days with evidence of UTI is low. A selective approach to LP in infants identified as low risk for meningitis by other clinical criteria may be indicated.


Assuntos
Meningites Bacterianas/epidemiologia , Infecções Urinárias/epidemiologia , Antibacterianos/administração & dosagem , Humanos , Lactente , Recém-Nascido , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/etiologia , Medição de Risco , Punção Espinal/efeitos adversos , Infecções Urinárias/microbiologia
14.
Mil Med ; 184(11-12): 820-825, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31090905

RESUMO

INTRODUCTION: Rhabdomyolysis is often encountered in austere environments where the diagnosis can be challenging due to the expense or unavailability of creatine phosphokinase (CPK) testing. CPK concentration ≥5,000 U/L has previously been found to be a sensitive marker for progression to renal failure. This study sought to propose a model utilizing an alternate biomarker to allow for the diagnosis and monitoring of clinically significant rhabdomyolysis in the absence of CPK. MATERIALS AND METHODS: We performed a retrospective chart review of 77 patients admitted to a tertiary medical center with a primary diagnosis of rhabdomyolysis. A linear regression model with aspartate aminotransferase (AST) as the independent variable was developed and used to predict CPK ≥5,000 U/L on admission and CPK values on subsequent hospital days. The study was approved and monitored by the Institutional Review Board at Walter Reed National Military Medical Center. RESULTS: Ln(AST) explained over 80% of the variance in ln(CPK) (adjusted R2 = 0.802). The diagnostic accuracy to predict CPK ≥5,000 U/L was high (AUC 0.959; 95% CI: 0.921-0.997, P < 0.001). A cut point of AST ≥110 U/L in our study population had a 97.1% sensitivity and an 85.7% specificity for the detection of a CPK value ≥5,000 U/L. The agreement between actual CPK and predicted CPK for subsequent days of hospitalization was fair with an intraclass correlation coefficient of 0.52 (95% CI: 0.38-0.63). The developed model based on day 1 data tended to overpredict CPK values on subsequent hospital days. CONCLUSIONS: We propose a threshold concentration of AST that has an excellent sensitivity for detecting CPK concentration ≥5,000 U/L on day of admission in a patient population with a diagnosis of rhabdomyolysis. A formula with a fair ability to predict CPK levels based on AST concentrations on subsequent hospital days was also developed.


Assuntos
Creatina Quinase/análise , Rabdomiólise/diagnóstico , Rabdomiólise/terapia , Adulto , Aspartato Aminotransferases/análise , Aspartato Aminotransferases/sangue , Biomarcadores/análise , Biomarcadores/sangue , Creatina Quinase/sangue , Creatina Quinase Forma MB/análise , Creatina Quinase Forma MB/sangue , Feminino , Humanos , Modelos Lineares , Masculino , Prontuários Médicos/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Rabdomiólise/sangue , Estados Unidos
16.
Int J Gynecol Pathol ; 38(5): 449-458, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30028355

RESUMO

TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; overexpression, wild-type, and null. These stratified staining patterns are routinely utilized in subtyping ovarian cancer subtypes. Three ovarian cancer cell lines were used in the construction of an immunohistochemical p53 expression pattern control panel that highlight respective TP53 mutation status. The cell line control panel sections demonstrated consistent clean and easily interpretable p53 immunohistochemical staining. Procured resection, biopsy, and cytologic specimens were submitted along with either standard control tissue or a p53 cell line control panel to pathologists of varying experience for interrater reliability analysis. Individual interrater reliability was near-perfect and was improved with the p53 cell line control panel when compared with the tissue control. The cell line control panel demonstrated decreased misinterpretation of null expression pattern as wild-type. Next-generation sequencing analysis was performed on the cell lines and select cases, in which there was discordance in p53 expression pattern interpretation. Next-generation sequencing analysis demonstrated low-frequency variant mutations in some cases in which there was reviewer discordance. This study suggests the addition of a p53 cell line expression pattern control panel could potentially increase p53 interpretation accuracy for ovarian cancer subtypes. We developed a cell line-based p53 control panel that has the potential to increase individual interrater reliability for p53 immunohistochemical expression pattern determination, support immunohistochemical optimization, and direct submission of difficult to interpret p53 staining cases to next-generation sequencing.


Assuntos
Neoplasias Ovarianas/química , Proteína Supressora de Tumor p53/análise , Linhagem Celular Tumoral , Feminino , Genes p53 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Mutação
18.
Pain Manag ; 8(4): 287-295, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29898645

RESUMO

AIM: The purpose of this randomized, single-blind trial was to evaluate the efficacy of battlefield acupuncture in reducing postoperative pain and opioid consumption after adult tonsillectomy. METHODS: Adult participants undergoing a tonsillectomy were randomized to either receive auricular 'battlefield' acupuncture or not. Groups were compared using the Wilcox rank sum test, Fisher's exact test and a generalized estimating equations model for post-discharge pain scores. RESULTS: Statistically significant difference was not noted for morphine equivalent opioid use, nor was there any difference noted in the pain scores between the control group and treatment group. CONCLUSION: Acupuncture is cheap, safe and effective in many settings. Peri-operative battlefield auricular acupuncture did not reduce postoperative pain or opioid consumption in this study.


Assuntos
Acupuntura Auricular/métodos , Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/terapia , Tonsilectomia/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento
19.
Neurology ; 89(19): 2010-2016, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29030450

RESUMO

OBJECTIVE: To examine whether blast exposure alone and blast-associated concussion result in similar neurologic and mental health symptoms. METHODS: A 14-item questionnaire was administered to male US Marines on their return from deployment in Iraq and/or Afghanistan. RESULTS: A total of 2,612 Marines (median age 22 years) completed the survey. Of those, 2,320 (88.9%) reported exposure to ≥1 blast during their current and/or prior deployments. In addition, 1,022 (39.1%) reported ≥1 concussion during the current deployment, and 731 (28.0%) had experienced at least 1 prior lifetime concussion. Marines were more likely to have sustained a concussion during the current deployment if they had a history of 1 (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0) or ≥1 (OR 2.3, 95% CI 1.7-3.0) prior concussion. The most common symptoms were trouble sleeping (38.4%), irritability (37.9%), tinnitus (33.8%), and headaches (33.3%). Compared to those experiencing blast exposure without injury, Marines either experiencing a concussion during the current deployment or being moved or injured by a blast had an increased risk of postinjury symptoms. CONCLUSIONS: There appears to be a continuum of increasing total symptoms from no exposure to blast exposure plus both current deployment concussion and past concussion. Concussion had a greater influence than blast exposure alone on the presence of postdeployment symptoms. A high blast injury score can be used to triage those exposed to explosive blasts for evaluation.


Assuntos
Traumatismos por Explosões/complicações , Concussão Encefálica/etiologia , Síndrome Pós-Concussão/etiologia , Adulto , Campanha Afegã de 2001- , Concussão Encefálica/diagnóstico , Cefaleia/etiologia , Humanos , Guerra do Iraque 2003-2011 , Humor Irritável/fisiologia , Masculino , Militares/estatística & dados numéricos , Síndrome Pós-Concussão/diagnóstico , Distúrbios do Início e da Manutenção do Sono/etiologia , Zumbido/etiologia , Adulto Jovem
20.
Mil Med ; 182(7): e1908-e1912, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28810989

RESUMO

BACKGROUND: To compare the circumference measurement (CM) body composition method and 8-point segmental bioelectrical impedance analysis (DSM-BIA) to dual energy X-ray absorptiometry (DEXA) in military members. OBJECTIVE: The objective was to compare three body composition methods. Our hypothesis was the CM is as accurate as DSM-BIA and DEXA in assessing body fat percentage (%BF). DESIGN: Cross sectional, observational study. PARTICIPANTS/SETTING: Healthy active duty military males and nonpregnant females. Seventy-six participants (mean age 35.0 ± 9.7 years, mean body mass index 28.9 ± 4.7 kg/m2), outpatient clinic setting was used. STATISTICAL ANALYSES: Agreement between DEXA and the other two methods was examined using an intraclass correlation coefficient (ICC) using the two-way random method with absolute agreement. Repeated measures analysis of covariance was used to examine the effect of gender and waist circumference on differences in %BF. RESULTS: The agreement of DSM-BIA with DEXA for females was ICC = 0.93 (95% confidence interval [CI]: 0.87-0.96) and for males, ICC = 0.89 (95% CI: 0.78-0.94). For the agreement of CM with DEXA, the ICC for females was 0.83 (95% CI: 0.71-0.91) and for males the ICC = 0.72 (95% CI: 0.49-0.85). For females with smaller waists (<81.3 cm), the DSM-BIA underestimated the DEXA measurement by a mean of 1.6% (95% CI: 0.5-2.6%). For males with larger waists (≥95.3 cm), the DSM-BIA overestimated the DEXA measurement by a mean of 2.6% (95% CI: 0.9-4.3%). For females with larger waists (≥81.3 cm), the CM overestimated the DEXA %BF by an average of 2.4% (95% CI: 0.7-4.1%). CONCLUSION: There was good agreement between the three methods assessed in this study. Both waist circumference and gender had an effect on the accuracy of the DSM-BIA and CM measurements.


Assuntos
Impedância Elétrica , Circunferência da Cintura , Absorciometria de Fóton/métodos , Tecido Adiposo , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
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