RESUMEN
OBJECTIVE: To evaluate the safety and efficacy of abatacept treatment for refractory juvenile localized scleroderma (jLS) in a retrospective study. METHODS: A multicentre cohort study was performed to evaluate jLS subjects treated with abatacept with follow-up for 12 months to maximum of 24 months. Assessments at 6-month intervals included skin activity measures and physician global assessment of activity (PGA-A). Descriptive statistical analysis was performed. RESULTS: Eighteen subjects were studied with median age of 13.4 years, the majority had linear scleroderma subtype, and musculoskeletal involvement. All had previously failed MTX and/or mycophenolate mofetil treatment and glucocorticoids. Abatacept was added to the subject's maintenance DMARD treatment; 13 also received glucocorticoids at start of abatacept. No serious adverse events occurred. Skin activity and PGA-A scores declined in nearly all by 6 months and continued to improve from 6 to 12 months. At 12 months, 15 (83%) subjects were considered responders, two (11%) treatment failures, and one dropped out for adverse event. Response was sustained for 11 (61%) subjects to 18 months and eight (44%) to 24 months. Overall, four (22%) subjects were treatment failures and three (16.7%) discontinued abatacept for adverse event. Active musculoskeletal problems improved in most affected subjects. Ten subjects were able to discontinue initial glucocorticoid and six concomitant DMARD treatment. CONCLUSION: Abatacept was found to be safe and effective for jLS subjects refractory to standard of care treatment. Subjects experienced improvement in both skin and musculoskeletal activity. Prospective studies should be performed to more fully evaluate abatacept's efficacy.
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Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Esclerodermia Localizada/tratamiento farmacológico , Esclerodermia Sistémica/tratamiento farmacológico , Adolescente , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Ácido Micofenólico/uso terapéutico , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: Idiopathic pulmonary hemosiderosis (IPH) is one of the rarest and least understood causes of pulmonary hemorrhage in children. Illustrated by a complex case presentation, we discuss the clinical manifestations, diagnosis, pathology, proposed etiologies, and treatment of this rare disease. We also compare IPH with anti-glomerular basement membrane antibody syndrome (anti-GBM disease), another rare causes of pediatric pulmonary hemorrhage. RECENT FINDINGS: Recent retrospective studies regarding IPH along with advanced immunotherapy have led to an improved understanding of how to best treat this condition, potential associations, and improved prognosis. Pathogenesis remains unknown, but several reports have suggested involvement of the alveolar capillary basement membrane. IPH is a poorly understood disease of unknown etiology that is a diagnosis of exclusion. Our patient was diagnosed with IPH after an exhaustive workup, including lung biopsy, into other immune-mediated causes of disease. While the pathogenesis of this rare disease remains elusive, our patient's immunofluorescent staining along the alveolar basement membrane without evidence of circulating antibody to type IV collagen raises the question of an immune-mediated pathogenesis of the disease with involvement of the alveolar basement membrane.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Hemosiderosis/diagnóstico , Enfermedades Pulmonares/diagnóstico , Adolescente , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Biopsia , Diagnóstico Diferencial , Femenino , Glucocorticoides/uso terapéutico , Hemosiderosis/tratamiento farmacológico , Humanos , Enfermedades Pulmonares/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Radiografía Torácica , Pruebas de Función Respiratoria , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Hemosiderosis PulmonarRESUMEN
BACKGROUND: Our goal was to determine (a) the prevalence of multimorbidity and polypharmacy in patients with cancer and (b) the prevalence, predictability, and preventability of adverse drug reactions (ADRs) causing/contributing to hospitalization. MATERIALS AND METHODS: We conducted a 12-month prospective observational study of patients aged ≥16 years admitted to an oncology center. Older adults were aged ≥70 years. RESULTS: We enrolled 350 patients: 52.3% (n = 183) female, mean age 63.6 years (SD 12.1), 36.6% (n = 121) aged ≥70 years. Multimorbidity (≥2 conditions) was identified in 96.9%; 68% had ≥5 conditions. The median number of medications was 6 (interquartile range [IQR] 4-8); 47% were prescribed ≥6 medications and 11.4% ≥11 medications. Older adults had higher numbers of comorbid conditions (7 [IQR 5-10] vs. 5 [IQR 3-7]) and were prescribed more medications (median 7 [IQR 4-9] vs. 4 [IQR 2-7]). ADRs caused/contributed to hospitalization in 21.5% (n = 75): 35.8% (n = 72) of emergency admissions and 4.7% (n = 3) of elective admissions. The most common ADRs were neutropenia with infection (25.3%), dyspepsia/nausea/vomiting (20%), and constipation (20%). Causative medications included systemic anticancer therapies (SACTs; 53.3%), opioids (17.3%), corticosteroids (6.7%), and nonsteroidal anti-inflammatory drugs (5.3%). ADR prevalence was similar in older and younger adults secondary to SACTs (8.3% vs. 13.1%), non-cancer medications (10.7% vs. 8.3%), and both (0% vs. 1.3%). ADRs were predictable in 89.3% (n = 67), definitely avoidable in 29.3% (n = 22), and possibly avoidable in 33.3% (n = 25). No association was identified between ADRs and age, gender, daily medication number, length of stay, or death. No ADR predictor variables were identified by logistic regression. CONCLUSION: More than 21% of admissions to an oncology service are ADR-related. ADRs are caused by both SACTs and non-cancer-specific medications. The majority are predictable; ≥60% may be preventable. Patients with cancer have high levels of multimorbidity and polypharmacy, which require vigilance for related adverse outcomes. IMPLICATIONS FOR PRACTICE: A diagnosis of cancer often occurs in patients with multimorbidity and polypharmacy. Cancer can cause an altered physiological environment, placing patients at risk of drug-drug interactions, drug-disease interactions, and adverse drug reactions (ADRs). This study identified that ADRs caused or contributed to one in five hospital admissions of patients with cancer. ADRs were caused by systemic anticancer therapies (SACTs) in 53.3% of cases and non-cancer medications in 45.4% of cases, and a combination of both in 1.3%. ADRs occurred in similar frequencies in older and younger patients secondary to SACTs (8.3% vs. 13.1%, p = .295), non-SACTs (10.7% vs. 8.3%, p = .107), and a combination of both (0% vs. 1.3%, p = .240). The majority of ADRs were predictable (89.3%) and potentially preventable (62.6%). These findings support the need for increased awareness of medication-related adversity in patients with cancer and interventions to minimize their occurrence, thus supporting the American Society of Clinical Oncology guidelines that recommend adults ≥65 years of age receiving chemotherapy have geriatric assessment to identify medical and medication issues.
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Corticoesteroides/efectos adversos , Analgésicos Opioides/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Neoplasias/tratamiento farmacológico , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Analgésicos Opioides/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Interacciones Farmacológicas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/epidemiología , Neoplasias/patología , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVES: Ethanol is bactericidal against most pathogens implicated in central line-associated bloodstream infections (CLABSIs) and biofilms. Current Infectious Diseases Society of America guidelines cite insufficient evidence to support adjunctive ethanol-lock therapy (ELT) for central venous catheter (CVC) salvage in patients with CLABSI in combination with systemic antimicrobial treatment. We evaluated the safety and potential efficacy of 70% ELT for CLABSI at our institution after implementation of a hospital ELT protocol. METHODS: We collected data on all patients treated with adjunctive 70% ELT for catheter salvage from September 2009 to September 2011 and assessed clinical outcomes and adverse events associated with ELT. RESULTS: Sixty-eight hospitalized patients received 70% ELT for CVC salvage: 45 (66%) met the criteria for CLABSI. Five (11%) had persistent or recurrent bacteraemia triggering CVC removal; 28 (62%) preserved their CVC long term. There were no documented adverse events associated with ELT. DISCUSSION: Adjunctive 70% ELT is an inexpensive, well-tolerated option for CVC salvage in patients with CLABSI and warrants further investigation.
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Antiinfecciosos Locales/administración & dosificación , Cateterismo Venoso Central/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Etanol/administración & dosificación , Sepsis/etiología , Sepsis/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Antiinfecciosos Locales/efectos adversos , Terapia Combinada , Etanol/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sepsis/diagnóstico , Sepsis/prevención & control , Resultado del Tratamiento , Adulto JovenRESUMEN
Background: Historically, resilience has often been conceptualized as the sustained lack of symptoms following trauma exposure. In line with a novel conceptualization of resilience as being dynamic over lifespan, determined by interacting biological and environmental factors, we examined the VA Mid-Atlantic Post Deployment Mental Health Repository (PDMH) comprised of 3876 US Military Veterans with and without PTSD diagnoses. Methods: We performed regression modelling to study the relationship between resilience (measured with Connor Davidson Resilience Scale; CD-RISC), posttraumatic stress disorder (PTSD) severity (Davidson Trauma Scale; DTS), social support (Medical Outcome Study Social Support Survey; MOSSS), combat exposure (Combat Exposure Scale; CES), childhood trauma (Trauma Life Events Questionnaire; TLEQ), and demographic factors. CD-RISC was positively correlated with years of education and negatively correlated with DTS, CES and TLEQ scores. Results: We found an interaction between CD-RISC and CES in predicting PTSD severity (Davidson Trauma Scale). Specifically, high resilience predicted lower PTSD symptom severity than low resilience, this relationship was amplified with increasing levels of combat exposure. Structural equation modelling (SEM) identified an optimal latent variable that represents resilience and relationships between latent variables for resilience, trauma, and illness. We derived a resilience latent variable composed of age, education level, MOSSS and race. Conclusions: Our results support a conceptualization of resilience as a multifactorial determinant that coexists with PTSD, a state rather than trait variable, and can be quantified by biological and behavioural metrics. HIGHLIGHTS: ⢠Historically, resilience has often been conceptualized as the sustained lack of symptoms following trauma exposure.⢠We examined the VA Mid-Atlantic Post Deployment Mental Health Repository (PDMH) comprised of 3876 US Military Veterans.⢠We found an interaction effect between CD-RISC and CES in predicting PTSD severity (Davidson Trauma Scale).
Antecedentes: Históricamente, la resiliencia a menudo se ha conceptualizado como la ausencia sostenida de síntomas después de la exposición al trauma. En línea con una novedosa conceptualización de la resiliencia como un fenómeno dinámico a lo largo de la vida, determinada por la interacción de factores biológicos y ambientales, examinamos el Repositorio de salud mental post-despliegue VA Mid-Atlantic (PDMH por sus siglas en ingles) compuesto por 3.876 veteranos militares de EE.UU. con y sin diagnósticos de TEPT.Métodos: Realizamos modelos de regresión para estudiar la relación entre resiliencia (medida con la Escala de resiliencia de Connor Davidson; CD-RISC por sus siglas en ingles), gravedad del trastorno de estrés postraumático (TEPT) (con Escala de Trauma de Davidson; DTS por sus siglas en ingles), apoyo social (Encuesta de Estudio de Resultados Médicos - Apoyo Social; MOSSS por sus siglas en ingles), exposición al combate (Escala de exposición al combate; CES por sus siglas en ingles), trauma infantil (Cuestionario de Eventos de vida traumáticos; TLEQ por sus siglas en ingles), y factores demográficos. CD-RISC se correlacionó positivamente con años de educación y se correlacionó negativamente con los puntajes de DTS, CES y TLEQ.Resultados: Encontramos una interacción entre CD-RISC y CES en la predicción de la gravedad del TEPT (Escala de trauma de Davidson). Específicamente, una alta resiliencia predijo menor gravedad de los síntomas de TEPT que una baja resiliencia, esta relación fue amplificada con niveles crecientes de exposición al combate. El modelo de ecuaciones estructurales (SEM por sus siglas en ingles) identificó una variable latente óptima que representa la resiliencia y las relaciones entre las variables latentes de resiliencia, trauma y enfermedad. Derivamos una variable latente de resiliencia compuesta por edad, nivel educativo, MOSSS y raza.Conclusiones: Nuestros resultados apoyan una conceptualización de la resiliencia como un determinante multifactorial que coexiste con el TEPT, una variable de estado más que de rasgo, y puede ser cuantificada con mediciones biológicas y conductuales.
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Resiliencia Psicológica , Trastornos por Estrés Postraumático , Veteranos , Demografía , Humanos , Apoyo Social , Trastornos por Estrés Postraumático/diagnóstico , Veteranos/psicologíaRESUMEN
Children with rheumatic disease have rare pulmonary manifestations that may cause significant morbidity and mortality. These children are often clinically asymptomatic until disease has significantly progressed, so they should be screened for pulmonary involvement. There has been recent recognition of a high mortality-related lung disease in systemic-onset juvenile idiopathic arthritis; risk factors include onset of juvenile idiopathic arthritis less than 2 years of age, history of macrophage activation syndrome, presence of trisomy 21, and history of anaphylactic reaction to biologic therapy. Early recognition and treatment of lung disease in children with rheumatic diseases may improve outcomes.
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Enfermedades Pulmonares/etiología , Enfermedades Reumáticas/complicaciones , Niño , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/terapia , Pruebas de Función Respiratoria , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/terapiaRESUMEN
In 2005, the Oregon Legislature passed a bill modifying the existing Psychiatric Security Review Board (PRSB) statute, creating a juvenile panel for management of juvenile insanity acquittees. Dubbed the Juvenile PSRB (JPSRB), it borrows heavily from the 30 years of experience of its adult predecessor. Statutory language was also modified to create a plea of "responsible except for insanity" for juveniles in Oregon. The authors discuss the similarities of the JPSRB to the adult PSRB system and highlight the differences that take into account the unique needs of juvenile defendants. They go on to discuss potential problems foreseen with implementation of the JPSRB system and to recommend possible solutions.
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Comités de Ética en Investigación/legislación & jurisprudencia , Defensa por Insania , Delincuencia Juvenil/legislación & jurisprudencia , Trastornos Mentales/rehabilitación , Medidas de Seguridad/legislación & jurisprudencia , Adolescente , Adulto , Niño , Internamiento Obligatorio del Enfermo Mental/legislación & jurisprudencia , Conducta Peligrosa , Humanos , Delincuencia Juvenil/rehabilitación , Tutores Legales , Trastornos Mentales/diagnóstico , OregonRESUMEN
PURPOSE: To discuss current literature evaluating the medial clavicular epiphysis to assess an individual's age using various imaging modalities. METHODS: Four scholarly research databases were searched to find studies that examined living subjects. Several articles were included that used cadavers, and a textbook was used to detail the anatomy of the clavicle. Thirty-nine articles were analyzed. RESULTS: The literature indicated that several imaging modalities, including conventional radiography, computed tomography, magnetic resonance, and sonography, are being used to evaluate the medial clavicular epiphysis to estimate an individual's age in the forensic context. In addition to multiple modalities, researchers are using various staging classification systems, ethnic groups, and interpreter criteria to establish reference data. DISCUSSION: There is a need to determine the age of individuals involved in civil and criminal proceedings who do not have valid birth date documentation. The clavicle is the last bone in the human body to complete fusion. The clavicle begins to fuse in the early teens and completes medial epiphyseal fusion in the late 20s. Clavicle fusion spans the legally significant age range of 18 through 21. Multiple variables influence the final age estimation, including interpreters' experience, the individual's socioeconomic class or area of origin, and limitations within the imaging modalities. CONCLUSION: Computed tomography is the modality of choice for forensic age estimation using the medial clavicular epiphysis. Radiologic technologists should be cognizant of current forensic age estimation practices, and future research should continue to provide reference data to improve accuracy of age estimation in those individuals who lack documentation of their date of birth.
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Determinación de la Edad por el Esqueleto/métodos , Clavícula/diagnóstico por imagen , Diagnóstico por Imagen/métodos , Epífisis/diagnóstico por imagen , Cadáver , HumanosRESUMEN
: Breast cancer patients are living longer with the disease than ever before. According to the National Cancer Institute, more than 3 million women in the United States are currently living with a breast cancer diagnosis, and many seek care in nononcology settings, whether for treatment, acute symptoms and complaints related to their cancer diagnosis, or unrelated concerns. Yet many nononcology providers are unfamiliar with the various oral agents used to treat breast cancer, and their possible adverse effects and drug interactions. It is imperative that all providers be aware of these agents and know when a patient is currently taking or has taken them. This article provides an overview of the most common oral treatments for breast cancer and discusses common adverse effects and management.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Seguridad del Paciente , Administración Oral , Antineoplásicos/administración & dosificación , Antineoplásicos/clasificación , Educación Continua , Femenino , Humanos , Estados UnidosRESUMEN
The ability of microtubules of the mitotic apparatus to control the positioning and initiation of the cleavage furrow during cytokinesis was first established from studies on early echinoderm embryos. However, the identity of the microtubule population that imparts cytokinetic signaling is unclear. The two main--and not necessarily mutually exclusive--candidates are the central spindle and the astral rays. In the present study, we examined cytokinesis in ammonia-activated sea urchin eggs, which lack paternally derived centrosomes and undergo mitosis mediated by unusual anastral, bipolar mini-spindles. Live cell imaging and immunolabeling for microtubules and the centralspindlin constituent and kinesin-related protein, MKLP1, demonstrated that furrowing in ammonia-activated eggs was associated with aligned arrays of centralspindlin-linked, opposed bundles of antiparallel microtubules. These autonomous, zipper-like arrays were not associated with a mitotic apparatus, but did possess characteristics similar to the central spindle region of control, fertilized embryos. Our results highlight the self-organizing nature of the central spindle region and its ability to induce cytokinesis-like furrowing, even in the absence of a complete mitotic apparatus.
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Citocinesis/fisiología , Microtúbulos/metabolismo , Óvulo/citología , Huso Acromático/metabolismo , Animales , Mitosis/efectos de los fármacos , Mitosis/fisiología , Óvulo/efectos de los fármacos , Erizos de Mar/citología , Erizos de Mar/embriologíaRESUMEN
This commentary describes the functioning of the Oregon Psychiatric Security Review Board (PSRB) from 1978 through 2011, when the Oregon Legislature altered the authority of the PSRB in regard to certain hospitalized insanity acquittees. Following the Hinckley verdict, the American Psychiatric Association recognized the PSRB as a possible future model for the management and treatment of insanity acquittees. The commentary provides an overview of the board from administrative and empirical viewpoints over this 34-year period and discusses the changes made in PSRB statutes in 2012 and the implication of these changes for the future management of insanity acquittees in Oregon.
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Comités Consultivos , Internamiento Obligatorio del Enfermo Mental/legislación & jurisprudencia , Crimen , Psiquiatría Forense/legislación & jurisprudencia , Humanos , Oregon , Trastornos PsicóticosRESUMEN
BACKGROUND: Frailty is a state of increased vulnerability to health-related stressors and can be measured by summing the number of frailty characteristics present in an individual. Discharge institutionalization (rather than discharge to home) represents disease burden and functional dependence after hospitalization. Our aim was to determine the relationship between frailty and need for postoperative discharge institutionalization. STUDY DESIGN: Subjects ≥ 65 years undergoing major elective operations requiring postoperative ICU admission were enrolled. Discharge institutionalization was defined as need for institutionalized care at hospital discharge. Fourteen preoperative frailty characteristics were measured in 6 domains: comorbidity burden, function, nutrition, cognition, geriatric syndromes, and extrinsic frailty. RESULTS: A total of 223 subjects (mean age 73 ± 6 years) were studied. Discharge institutionalization occurred in 30% (n = 66). Frailty characteristics related to need for postoperative discharge institutionalization included: older age, Charlson index ≥ 3, hematocrit <35%, any functional dependence, up-and-go ≥ 15 seconds, albumin <3.4 mg/dL, Mini-Cog score ≤ 3, and having fallen within 6 months (p < 0.0001 for all comparisons). Multivariate logistic regression retained prolonged timed up-and-go (p < 0.0001) and any functional dependence (p < 0.0001) as the variables most closely related to need for discharge institutionalization. An increased number of frailty characteristics present in any one subject resulted in increased rate of discharge institutionalization. CONCLUSIONS: Nearly 1 in 3 geriatric patients required discharge to an institutional care facility after major surgery. The frailty characteristics of prolonged up-and-go and any functional dependence were most closely related to the need for discharge institutionalization. Accumulation of a higher number of frailty characteristics in any one geriatric patient increased their risk of discharge institutionalization.