RESUMO
Background: Clinically meaningful endpoints for respiratory syncytial virus (RSV) treatment trials are lacking for hematopoietic cell transplant (HCT) recipients. We evaluated supplemental oxygen use among HCT recipients with RSV infection. Methods: Subjects were grouped according to the presence of upper respiratory tract infection (URTI) without lower respiratory tract infection (LRTI), URTI progressing to LRTI, and LRTI at presentation. LRTI was defined as a positive lower respiratory tract sample with or without radiographic abnormality (defined as proven or probable LRTI, respectively) or a positive upper respiratory tract sample with radiographic abnormality (possible LRTI). Supplemental oxygen-free days were defined as any day while alive after diagnosis of RSV infection during which ≤2 L of supplemental oxygen per minute was received. Results: Among 230 patients, supplemental oxygen use by day 28 after the first diagnosis of RSV infection was lowest in patients presenting with URTI (31 of 197 [16%]). Supplemental oxygen use was lower in patients with possible LRTI (12 of 45 [27%]) than in those with proven/probable LRTI (29 of 42 [69%]). Patients presenting with proven/probable LRTI had a median of 16 fewer supplemental oxygen-free days than those presenting with URTI (P < .0001). Death only occurred among patients with proven/probable LRTI (11 of 42 [26%]). Conclusions: Confirmation of RSV infection in the lower respiratory tract provides prognostic information that may help prioritize therapies. Supplemental oxygen-free days as a clinical endpoint may allow smaller sample sizes for trials evaluating RSV antivirals.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Oxigenoterapia , Infecções por Vírus Respiratório Sincicial/etiologia , Infecções por Vírus Respiratório Sincicial/terapia , Vírus Sincicial Respiratório Humano , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Oxigenoterapia/métodos , Respiração Artificial , Testes de Função Respiratória , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/mortalidade , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The epidemiology of herpes zoster (HZ) in contemporary autologous hematopoietic cell transplant (HCT) recipients, and the impact of acyclovir (ACV)/valacyclovir (VACV) prophylaxis, is not well described. In this observational study from 2002 to 2010, we retrospectively identified 1000 varicella zoster virus (VZV)-seropositive autologous HCT recipients with up to 5 years of follow-up. The incidence of HZ and use of ACV/VACV prophylaxis were determined through review of medical records and mailed questionnaires. Risk factors for HZ were determined by multivariable Cox regression. Over a period of 5 years after autologous HCT, 194 patients developed at least 1 HZ episode, with a cumulative incidence of 21%; 159 of 194 (82%) were not on prophylaxis at the time of HZ. A second episode of HZ occurred in 31 of 194 (16%) patients. Patients taking ACV/VACV had reduced risk for HZ (adjusted hazard ratio [aHR], .59; 95% confidence interval [CI], .37 to .91), whereas those older than the median age (≥55.5 years) had increased risk (aHR, 1.42; 95% CI, 1.05 to 1.9). Disseminated VZV was reported in 8% and postherpetic neuralgia in 13% of patients. We demonstrate a high burden of HZ late after autologous HCT, despite long-term antiviral prophylaxis. Improved prevention strategies are needed to provide sustained protection against HZ after autologous HCT.
Assuntos
Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/prevenção & controle , Valina/análogos & derivados , Feminino , Herpes Zoster/tratamento farmacológico , Herpes Zoster/epidemiologia , Herpes Zoster/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética , Pré-Medicação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante Autólogo , Valaciclovir , Valina/uso terapêuticoRESUMO
Background: Stiff person syndrome (SPS) is a rare slowly progressive autoimmune neuronal hyperexcitability disease with very-high GAD-65 antibody titers that most commonly presents above the age of 20, with muscle stiffness, painful muscle spasms, slow gait, and falls leading to disability. In other autoimmune disorders, late-onset disease has different symptom-spectrum and outcomes, but there is no information regarding late-onset SPS (LOSPS). Objective: Highlight delayed diagnosis and poor tolerance or incomplete response to therapies of patients with LOSPS and outline how best to increase disease awareness early at onset. Design A retrospective chart reviewMethods: We reviewed GAD-positive SPS patients with symptom onset above age 60, identified among 54 SPS patients, examined, treated and followed-up by the same clinicians, focused on clinical presentation, misdiagnoses, response and tolerance to therapies, and evolved disability. Results: Nine patients had LOSPS with symptom onset at median age of 61 years (range 60-78), and current median age of 73. The median time from symptom onset to SPS diagnosis was 3 years; prior to diagnosis, five patients were treated for lumbosacral radiculopathies (one with laminectomy), two for Parkinson's disease, one for multiple sclerosis, and another for cerebellar degeneration. Progressive decline occurred rapidly in all patients; at time of diagnosis, six patients were already using a cane or walker and two were wheelchair-bound. Tolerance and response to treatment were limited; two patients did not respond to IVIg, two discontinued IVIg despite early response due to comorbidities (cardiac disease, thrombosis), four others partially responded to IVIg and one to rituximab; several could not tolerate high doses of oral antispasmodics due to somnolence; and two patients died. Conclusions: LOSPS is almost always misdiagnosed for other similar conditions commonly seen in the elderly. Patients with LOSPS decline quickly to clinically severe disease due to delayed treatment initiation, poor response or tolerance, other comorbidities, and possibly immunosenescence. Increased awareness that SPS can occur in the elderly mimicking other disorders is important for early diagnosis and treatment, even necessitating earlier immunotherapy initiation, compared to their younger counterparts, to prevent faster-evolving severe disability.
RESUMO
Introduction: The growing years are paramount for bone growth and mineral accrual. Children with long-term neurological condition (LTNC) have multiple risk factors for poor bone health and fragility fractures. In Singapore, this has not been studied systematically. Therefore, we aimed to evaluate the risk factors associated with fragility fractures in children with LTNC. Methods: In this study, the search for fragility fractures was done by a retrospective review of patients with LTNC on follow-up in the paediatric neurology clinic and patients who presented with fracture to the paediatric orthopaedic clinic. Information on patients' demographics, medical history, intervention, biochemical bone markers and fracture history was collected. Results: In a tertiary clinic population of 136 patients with LTNC, 65% were dependent on mobility (Gross Motor Function Classification System [GMFCS] V), 60% were underweight and 60% were fed via gastrostomy or nasogastric tube, or were on oral pureed diet. Furthermore, 60% were on anticonvulsants. The fracture rate was 3% in this population and was associated with low-impact activities such as transfer and dressing. Only 7.4% and 33% of the patients had undergone measurements of vitamin D and calcium levels, respectively. Conclusion: The local prevalence of fragility fractures in children with LTNC on follow-up at the neurology clinic was found to be 3%. Risk factors identified were limited ambulation and compromised nutritional status associated with feeding difficulty. Recommendations to optimise bone health in children with LTNC were made. These include promoting weight-bearing activities, looking out for underweight children, avoiding vitamin D deficiency and ensuring adequate calcium intake.
Assuntos
Densidade Óssea , Fraturas Ósseas , Humanos , Criança , Cálcio , Magreza/complicações , Magreza/epidemiologia , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVES: IVIg has been the preferred immunotherapy in stiff-person syndrome (SPS) based on a 3-month controlled trial, but whether it is also effective in inducing long-term benefits or arresting disease progression is unknown. The information is needed because SPS is a progressively disabling disease and IVIg is liberally used as chronic therapy without efficacy data. The present study explores the long-term effects of IVIg in the largest cohort of well-characterized patients with SPS followed by the same clinicians over 10 years. METHODS: Data of 36 patients (32 glutamic acid decarboxylase [GAD] positive), diagnosed and treated with monthly maintenance IVIg by the same neurologists, were analyzed. Response was assessed by physician-observed changes, patients' reports of symptom improvement, modified Rankin Scale (mRS) scores, and dependency trials evaluating symptom recurrence after stopping IVIg, prolonging infusion frequency, decreasing monthly dose, or wearing-off effects in between doses. Clinically meaningful long-term response was defined by improved mRS scores, improvement in physician-assessed stiffness, balance and gait, and functional decline with dependency trials. RESULTS: Twenty-four of 36 (67%) patients had clinically meaningful response over a median 40-month period. Patients with improved mRS scores by 1-2 points manifested improved gait, posture, balance and decreased stiffness, spasms, and startle response; some patients using a wheelchair and those ambulating with devices walked unassisted. In 25% of responders, treatment benefit was sustained for a 40-month median period, but in 29.1%, it declined over a 39-month period; 12.5% exhibited a conditioning effect. Three of 5 patients with cerebellar GAD-SPS variant also improved over time. The 12 patients who did not respond the first 3 months remained unresponsive even if IVIg continued for several months. DISCUSSION: This is a large study in 36 patients with SPS demonstrating that monthly maintenance IVIg therapy offers long-term benefits in 67% of patients for a median 3.3-year period. Because 29.1% experienced diminishing benefit over time due to disease progression, the study highlights the need for more effective therapies.
Assuntos
Rigidez Muscular Espasmódica , Estudos de Coortes , Progressão da Doença , Glutamato Descarboxilase , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Rigidez Muscular Espasmódica/diagnóstico , Rigidez Muscular Espasmódica/tratamento farmacológicoRESUMO
Recent advances in high-throughput experiments and systems biology approaches have resulted in hundreds of publications identifying "immune signatures". Unfortunately, these are often described within text, figures, or tables in a format not amenable to computational processing, thus severely hampering our ability to fully exploit this information. Here we present a data model to represent immune signatures, along with the Human Immunology Project Consortium (HIPC) Dashboard ( www.hipc-dashboard.org ), a web-enabled application to facilitate signature access and querying. The data model captures the biological response components (e.g., genes, proteins, cell types or metabolites) and metadata describing the context under which the signature was identified using standardized terms from established resources (e.g., HGNC, Protein Ontology, Cell Ontology). We have manually curated a collection of >600 immune signatures from >60 published studies profiling human vaccination responses for the current release. The system will aid in building a broader understanding of the human immune response to stimuli by enabling researchers to easily access and interrogate published immune signatures.
Assuntos
Software , Biologia de Sistemas , Vacinação , Humanos , MetadadosRESUMO
Deep posterior compartment syndrome is an extremely rare complication of ankle fracture and the few reported cases in the literature show that it is usually diagnosed late. Anterior and deep posterior compartment syndromes have been described with variable manifestations according to the compartment affected. We present a case of deep posterior compartment syndrome isolated to the disputed distal "subcompartment" of the leg, which had a very subtle and late presentation and was missed. The diagnosis of compartment syndrome was confirmed on MRI scan. Subsequently the patient developed a flexor hallucis longus muscle contracture that was managed nonoperatively.
Assuntos
Traumatismos do Tornozelo/complicações , Síndromes Compartimentais/diagnóstico , Fraturas Ósseas/complicações , Contratura Isquêmica/diagnóstico , Músculo Esquelético/patologia , Adulto , Síndromes Compartimentais/etiologia , Diagnóstico Tardio , Feminino , Humanos , Contratura Isquêmica/etiologia , Imageamento por Ressonância Magnética , NecroseRESUMO
A meta-analysis assessed the behavioral impact of and psychological processes associated with presenting words connected to an action or a goal representation. The average and distribution of 352 effect sizes (analyzed using fixed-effects and random-effects models) was obtained from 133 studies (84 reports) in which word primes were incidentally presented to participants, with a nonopposite control group, before measuring a behavioral dependent variable. Findings revealed a small behavioral priming effect (dFE = 0.332, dRE = 0.352), which was robust across methodological procedures and only minimally biased by the publication of positive (vs. negative) results. Theory testing analyses indicated that more valued behavior or goal concepts (e.g., associated with important outcomes or values) were associated with stronger priming effects than were less valued behaviors. Furthermore, there was some evidence of persistence of goal effects over time. These results support the notion that goal activation contributes over and above perception-behavior in explaining priming effects. In summary, theorizing about the role of value and satisfaction in goal activation pointed to stronger effects of a behavior or goal concept on overt action. There was no evidence that expectancy (ease of achieving the goal) moderated priming effects. (PsycINFO Database Record
Assuntos
Comportamento , Priming de Repetição , Logro , Humanos , Testes de Associação de PalavrasRESUMO
This paper presents a summary of the conclusions drawn from a meta-analysis of the behavioral impact of presenting words connected to an action or a goal representation (Weingarten et al., 2016). The average and distribution of 352 effect sizes from 133 studies (84 reports) revealed a small behavioral priming effect (dFE = 0.332, dRE = 0.352), which was robust across methodological procedures and only minimally biased by the publication of positive (vs. negative) results. More valued behavior or goal concepts (e.g., associated with important outcomes or values) were associated with stronger priming effects than were less valued behaviors. In addition, opportunities for goal satisfaction appeared to decrease priming effects.
RESUMO
BACKGROUND: Although cytomegalovirus viral load is commonly used to guide pre-emptive therapy in the post-transplantation setting, few data are available correlating viraemia with clinical endpoints. We therefore investigated the association between cytomegalovirus viral load and mortality in the first year after haemopoietic stem cell transplantation. METHODS: In this retrospective cohort study, we included patients from the Fred Hutchinson Cancer Research Center, WA, USA, who received an allogeneic haemopoietic stem cell transplantation between Jan 1, 2007, and Feb 28, 2013, were cytomegalovirus seropositive or had a seropositive donor, and underwent weekly plasma cytomegalovirus monitoring by PCR through to day 100 post-transplantation. Cox proportional hazards models were used to estimate the association of cytomegalovirus viral load at different thresholds with overall mortality by 1 year post-transplantation, adjusting for the use of pre-emptive therapy and other factors such as neutropenia, and graft-versus-host disease. FINDINGS: Of the 1037 patients initially selected for inclusion in this cohort, 87 (8%) patients were excluded because of missing cytomegalovirus testing and 24 (2%) were excluded because of their participation in cytomegalovirus prophylaxis trials. In the remaining 926 patients included in this study, the cumulative overall mortality was 30·0% (95% CI 26·9-33·0) 1 year after haemopoietic stem cell transplantation. 95 patients developed cytomegalovirus disease; death was directly attributable to cytomegalovirus disease in three (1%) of 263 patients who died in the first year after transplantation. A cytomegalovirus viral load of 250 IU/mL or greater was associated with increased risk of early (day 0-60 post-transplantation) death (adjusted hazard ratio [HR] 19·8, 95% CI 9·6-41·1). The risk was attenuated after day 60 (adjusted HR 1·8, 95% CI 1·3-2·3). Similar associations were noted for higher cytomegalovirus viral load thresholds. INTERPRETATION: Cytomegalovirus viraemia is associated with an increased risk of overall mortality in the first year after haemopoietic stem cell transplantation, independent of the use of pre-emptive therapy, and with evidence of a positive dose-response relationship. These data indicate the suitability of viral load as a surrogate clinical endpoint for clinical trials for cytomegalovirus vaccines, biologics, and drugs. FUNDING: Merck and Co, National Institutes of Health.
Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Adolescente , Adulto , Doadores de Sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias/mortalidade , Neoplasias/terapia , Neoplasias/virologia , Estudos Retrospectivos , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Missed appointments complicate primary care services. OBJECTIVE: To determine factors associated with missed pediatric appointments. DESIGN/METHODS: A convenience sample of 1537 patients who missed appointments were called and 386 (25%) families completed the 26-item survey. Those with high no-show rates were compared with the rest using χ(2) and Fisher's exact tests. Initial covariates with P < .2 were included in a multivariate logistic regression model. RESULTS: Common reasons for missing appointments were the following: forgot (27%), transportation problems (21%), and time off of work (14%). The high no-show group had more African Americans (P = .030) and older patients (P = .003). Higher no-show rates correlated with well child visits (P = .029) and perception of "excellent health" (P = .022). In the logistic regression model, well child appointments (odds ratio = 2.56) and increasing age in years (odds ratio = 1.11) were associated with higher no-show rates. CONCLUSIONS: Efforts to decrease no-show rates should target older patients and well child visits.