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BACKGROUND: Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed. METHODS: An 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations. RESULTS: There was agreement on 94% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK. CONCLUSIONS: These expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.
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Distrofias Hereditarias de la Córnea , Queratitis , Enfermedades del Nervio Trigémino , Consenso , Córnea , Humanos , Enfermedades del Nervio Trigémino/diagnóstico , Enfermedades del Nervio Trigémino/terapiaRESUMEN
BACKGROUND: Migraine is associated with debilitating symptoms that can affect daily functioning. "My Migraine Voice" was a large, cross-sectional, multi-country online survey aimed at understanding disease burden directly from people with migraine. OBJECTIVE: This study reports on the social and economic impacts of migraine, specifically the impact on activities of daily living and the costs of migraine, from the point of view of people with migraine in the United States. METHODS: The online survey was administered to adults with a self-reported diagnosis of migraine who experienced 4 or more monthly migraine days each month for the previous 3 months. Prespecified screening quotas were used so that 90% of respondents reported current or past use of preventive migraine medication, 80% of whom switched treatment (ie, changed their prescribed preventive medication at least once). The remaining 10% were preventive treatment naïve (ie, never used any prescribed preventive medication). Burden of migraine on activities of daily living and caregivers (eg, functional limitations, fear of next migraine attack, sleep problems) and economic burden (eg, out-of-pocket costs, impact on work productivity using the validated work productivity and activity impairment questionnaire) reported by respondents from the United States are presented. Results are stratified by employment status, migraine frequency (chronic vs episodic migraine), and history of preventive treatment. RESULTS: Thousand hundred and one individuals with migraine from the United States responded to the survey. Respondents reported limitations completing daily activities during all migraine phases, including during the premonitory/aura and postdrome phases. Most (761/1101 (69%)) relied on family, friends, or others for help with daily tasks and reported being helped a median of 9 days (25th percentile 5 days, 75th percentile 15 days) within the last 3 months. Respondents with chronic migraine reported being helped for more days (median 10 days, 25th percentile 5 days, 75th percentile 23 days) in the last 3 months. Almost all (962/1101 (87%)) experienced sleep difficulties and 41% (448/1101) (48% (336/697) of those with 2 or more preventive treatment failures) were very or extremely fearful of a next migraine attack. Median (25th percentile, 75th percentile) monthly out-of-pocket costs of $90.00 ($30.00, $144.00) in doctor's fees (n = 504), $124.00 ($60.00, $234.00) in health insurance (n = 450), $40.00 ($20.00, $100.00) for prescriptions (n = 630), and $50.00 ($0.00, $100.00) for complementary therapies (n = 255) were reported. Those with 2 or more preventive treatment failures reported higher monthly out-of-pocket doctor fees (median $99.00 ($30.00, $150.00), n = 388). Among employed respondents (n = 661), migraine resulted in 22% absenteeism, 60% presenteeism, 65% work productivity loss, and 64% activity impairment. CONCLUSIONS: Migraine impacts individuals' activities of daily living, work-life, and financial status, especially individuals with high needs, namely those with 4 or more monthly migraine days and prior treatment failures. People with migraine are impaired during all migraine phases, experience fear of their next migraine attack and sleep difficulties, and pay substantial monthly out-of-pocket costs for migraine. Burden is even greater among those who have had 2 or more preventive treatment failures. Impacts of migraine extend beyond probands to caregivers who help people with migraine with daily tasks, employers who are affected by employee absenteeism, presenteeism, and reduced productivity, and society which is burdened by lost and reduced economic productivity and healthcare costs.
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Actividades Cotidianas , Costo de Enfermedad , Eficiencia , Empleo/estadística & datos numéricos , Gastos en Salud/estadística & datos numéricos , Trastornos Migrañosos , Adulto , Estudios Transversales , Personas con Discapacidad/estadística & datos numéricos , Femenino , Salud Global , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/economía , Trastornos Migrañosos/fisiopatología , Trastornos Migrañosos/psicología , Trastornos Migrañosos/terapia , Estados UnidosRESUMEN
G1 phase cell cycle proteins, such as cyclin-dependent kinase 6 (Cdk6) and its activating partners, the D-type cyclins, are important regulators of T-cell development and function. An F-box protein, called F-box only protein 7 (Fbxo7), acts as a cell cycle regulator by enhancing cyclin D-Cdk6 complex formation and stabilising levels of p27, a cyclin-dependent kinase inhibitor. We generated a murine model of reduced Fbxo7 expression to test its physiological role in multiple tissues and found that these mice displayed a pronounced thymic hypoplasia. Further analysis revealed that Fbxo7 differentially affected proliferation and apoptosis of thymocytes at various stages of differentiation in the thymus and also mature T-cell function and proliferation in the periphery. Paradoxically, Fbxo7-deficient immature thymocytes failed to undergo expansion in the thymus due to a lack of Cdk6 activity, while mature T cells showed enhanced proliferative capacity upon T-cell receptor engagement due to reduced p27 levels. Our studies reveal differential cell cycle regulation by Fbxo7 at different stages in T-cell development.
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Quinasa 6 Dependiente de la Ciclina/inmunología , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/inmunología , Proteínas F-Box/inmunología , Linfocitos T/citología , Animales , Apoptosis , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Ciclo Celular , Diferenciación Celular , Proliferación Celular , Regulación hacia Abajo , Proteínas F-Box/genética , Femenino , Eliminación de Gen , Activación de Linfocitos , Masculino , Ratones Endogámicos C57BL , Mutación , Linfocitos T/inmunología , Timo/citología , Timo/inmunologíaRESUMEN
STATEMENT OF PROBLEMM: The dimensional stability, in particular polymerization shrinkage, of pattern resins affects the accuracy of implant prosthesis fabrication. Recently introduced photopolymerizing pattern resins are easy to use, but their shrinkage needs to be determined and compared with traditional autopolymerizing pattern resins. PURPOSE: The purpose of the study was to compare the polymerization shrinkage of photopolymerizing pattern resins with autopolymerizing pattern resins. MATERIAL AND METHODSS: Two autopolymerizing (DuraLay, GC Pattern resin) and 2 photopolymerizing (Primopattern LC Gel, Primopattern LC Paste) pattern resins were tested. The sample size was 10 for each group. Polymerization shrinkage was determined by measuring the change in area dimensions with image analysis. The percentage of volumetric shrinkage was calculated, and the results were statistically analyzed with ANOVA, followed by the Student-Newman-Keuls post hoc test (α=.05). RESULTS: The volumetric shrinkage values (%; mean ±standard deviation) for GC Pattern Resin were 5.72 ±0.89; for DuraLay, 5.07 ±1.36; for Primopattern LC Gel, 5.42 ±1.83; and for Primopattern LC Paste, 7.43 ±0.62. The volumetric shrinkage of the Primopattern LC Paste was significantly higher than that of the other 3 materials. CONCLUSIONS: The photopolymerizing pattern resin in gel form (Primopattern LC Gel) had a similar shrinkage value to the autopolymerizing pattern resins (DuraLay and GC Pattern Resin). However, the photopolymerizing pattern resin in paste form (Primopattern LC Paste) shrank significantly more than the other 3 materials tested.
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Resinas Acrílicas/química , Materiales Dentales/química , Metilmetacrilatos/química , Acrilatos/química , Algoritmos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Curación por Luz de Adhesivos Dentales , Ensayo de Materiales , Metacrilatos/química , Polimerizacion , Polimetil Metacrilato/química , Propiedades de SuperficieRESUMEN
BACKGROUND: Early transfer to specialized centers improves trauma and burn outcomes; however, overtriage can result in unnecessary burdens to patients, providers, and health systems. Our institution developed novel burn triage pathways in 2016 to improve resource allocation. We evaluated the implementation of these pathways, analyzing trends in adoption, resource optimization, and pathway reliability after implementation. METHODS: Triage pathways consist of transfer nurses (RNs) triaging calls based on review of burn images and clinical history: green pathway for direct outpatient referral, blue pathway for discussion with the on-call provider, red pathway for confirmation of transfer as requested by referring provider, and black pathway for the rapid transfer of severe burns. We used the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework to evaluate implementation. These pathways affected all acute burn referrals to our center from January 2017 to December 2019 (reach). Outcomes of interest were pathway assignment over time (adoption), changes to burn provider call volume (effectiveness), and the concordance of pathway assignment with final disposition (implementation reliability). RESULTS: Transfer RNs triaged 5,272 burn referrals between 2017 and 2019. By January 2018, >98% of referrals were assigned a pathway. In 2018-2019, green pathway calls triaged by RNs reduced calls to burn providers by a mean of 40 (SD, 11) per month. Patients in green/blue pathways were less likely to be transferred, with >85% receiving only outpatient follow-up ( p < 0.001). Use of the lower acuity pathways increased over time, with a concordant decrease in use of the higher acuity pathways. Younger adults, patients referred from Level III to Level V trauma centers and nontrauma hospitals, and patients referred by APPs were less likely to be triaged to higher acuity pathways. CONCLUSION: Implementation of highly adopted, reliable triage pathways can optimize existing clinical resources by task-shifting triage of lower acuity burns to nursing teams. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.
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Unidades de Quemados , Triaje , Adulto , Humanos , Reproducibilidad de los Resultados , Derivación y Consulta , Centros Traumatológicos , Estudios RetrospectivosRESUMEN
INTRODUCTION: No validated algorithm exists to identify patients with neuromyelitis optica spectrum disorder (NMOSD) in healthcare claims data. We developed and tested the performance of a healthcare claims-based algorithm to identify patients with NMOSD. METHODS: Using medical record data of 101 adults with NMOSD, multiple sclerosis (MS), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), we tested the sensitivity and specificity of claims-based algorithms developed through interviews with neurologists. We tested the best-performing algorithm's face validity using 2016-2019 data from IBM MarketScan Commercial and Medicare Supplemental databases. Demographics and clinical characteristics were reported. RESULTS: Algorithm inclusion criteria were age ≥ 18 years and (≥1 NMO diagnosis [or ≥ 1 transverse myelitis (TM) and ≥ 1 optic neuritis (ON) diagnosis] and ≥ 1 NMOSD drug) or (≥2 NMO diagnoses ≥90 days apart). Exclusion criteria were MS diagnosis or use of MS-specific drug after last NMO diagnosis or NMOSD drug; sarcoidosis diagnosis after last NMO diagnosis; or use of ≥1 immune checkpoint inhibitor. In medical record billing data of 50 patients with NMOSD, 30 with MS, and 21 with MOGAD, the algorithm had 82.0% sensitivity and 70.6% specificity. When applied to healthcare claims data, demographic and clinical features of the identified cohort were similar to known demographics of NMOSD. CONCLUSIONS: This clinically derived algorithm performed well in medical records. When tested in healthcare claims, demographics and clinical characteristics were consistent with previous clinical findings. This algorithm will enable a more accurate estimation of NMOSD disease burden using insurance claims datasets.
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Algoritmos , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Sensibilidad y Especificidad , Bases de Datos Factuales , Adulto Joven , Estados Unidos/epidemiología , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiologíaRESUMEN
ABSTRACT: Severe aplastic anemia (SAA) is a rare hematologic condition for which there is no clear management algorithm. A panel of 11 experts on adult and pediatric aplastic anemia was assembled and, using the RAND/University of California, Los Angeles modified Delphi panel method, evaluated >600 varying patient care scenarios to develop clinical recommendations for the initial and subsequent management of patients of all ages with SAA. Here, we present the panel's recommendations to rule out inherited bone marrow failure syndromes, on supportive care before and during first-line therapy, and on first-line (initial management) and second-line (subsequent management) therapy of acquired SAA, focusing on when transplant vs medical therapy is most appropriate. These recommendations represent the consensus of 11 experts informed by published literature and experience. They are intended only as general guidance for experienced clinicians who treat patients with SAA and are in no way intended to supersede individual physician and patient decision making. Current and future research should validate this consensus using clinical data. Once validated, we hope these expert panel recommendations will improve outcomes for patients with SAA.
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Anemia Aplásica , Consenso , Técnica Delphi , Manejo de la Enfermedad , Anemia Aplásica/terapia , Anemia Aplásica/diagnóstico , HumanosRESUMEN
PURPOSE: This review summarizes the published evidence on the clinical impact of using next-generation sequencing (NGS) tests to guide management of patients with cancer in the United States. METHODS: We performed a comprehensive literature review to identify recent English language publications that presented progression-free survival (PFS) and overall survival (OS) of patients with advanced cancer receiving NGS testing. RESULTS: Among 6,475 publications identified, 31 evaluated PFS and OS among subgroups of patients who received NGS-informed cancer management. PFS and OS were significantly longer among patients who were matched to targeted treatment in 11 and 16 publications across tumor types, respectively. CONCLUSION: Our review indicates that NGS-informed treatment can have an impact on survival across tumor types.
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Neoplasias , Humanos , Estados Unidos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Supervivencia sin Progresión , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Background: On-demand treatments can treat OFF episodes in Parkinson's disease, however, there is limited information regarding when to prescribe them. Objective: Develop expert consensus to determine appropriate clinical factors for considering on-demand treatments. Methods: Using a RAND/UCLA modified Delphi panel method, a panel developed consensus on the use of on-demand treatments for OFF episodes. Results: The panel agreed on-demand treatments were appropriate when OFF episodes were associated with greater functional impact and interfered with basic daily activities. The panel also agreed on-demand treatment may be appropriate for patients with morning akinesia and/or delayed ON of first levodopa dose and >1 type of OFF episode (eg, early morning OFF or wearing OFF regardless of frequency). Conclusions: Experts agreed on-demand treatment is appropriate for many patients with OFF episodes. The greater the functional impact of OFF episodes, the more likely experts agreed that on-demand treatment is appropriate to prescribe.
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Purpose: Patients with diagnosed with systemic light chain (AL) amyloidosis at advanced Mayo stages have greater morbidity and mortality than those diagnosed at non-advanced stages. Estimating service use by severity is difficult because Mayo stage is not available in many secondary databases. We used an expert panel to estimate healthcare utilization among advanced and non-advanced AL amyloidosis patients. Patients and Methods: Using the RAND/UCLA modified Delphi method, expert panelists completed 180 healthcare utilization estimates, consisting of inpatient and outpatient visits, testing, chemotherapy, and procedures by disease severity and organ involvement during two treatment phases (the 1 year after starting first line [1L] therapy and 1 year following treatment [post-1L]). Estimates were also provided for post-1L by hematologic treatment response (complete or very good partial response [CR/VGPR], partial, no response or relapse [PR/NR/R]). Areas of disagreement were discussed during a meeting, after which ratings were completed a second time. Results: During 1L therapy, 55% of advanced patients had ≥1 hospitalization and 38% had ≥2 admissions. Rates of hematopoietic stem cell transplant (HSCT) in advanced patients were 5%, while pacemaker or implantable cardioverter defibrillator (ICD) placement were 15%. During post-1L therapy, rates of hospitalization in advanced patients remained high (≥1 hospitalization: 20-43%, ≥2 hospitalizations: 10-20%), and up to 10% of advanced patients had a HSCT. Ten percent of these patients underwent pacemaker/ICD placement. Conclusion: Experts estimated advanced patients, who would not be good candidates for HSCT, would have high rates of hospitalization (traditionally the most expensive type of healthcare utilization) and other health service use. The development of new treatment options that can facilitate organ recovery and improve function may lead to decreased utilization.
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BACKGROUND: Regionalized care for burn-injured patients requires accurate triage. In 2016, we implemented a tele-triage system for acute burn consultations. We evaluated resource utilization following implementation, hypothesizing that this system would reduce short-stay admissions and prioritize inpatient care for those with higher burn severity. STUDY DESIGN: We conducted a retrospective study of all transferred patients with acute burn injuries from January 1, 2010 to December 31, 2015, and January 1, 2017 to December 31, 2019. We evaluated the proportions of short-stay admissions (discharges less than 24 hours without operative intervention, ICU admission, or concern for nonaccidental trauma) among patients transferred before (2010 to 2015) and after (2017 to 2019) triage system implementation. Multivariable Poisson regression was used to evaluate factors associated with short-stay admissions. Interrupted time series analysis was used to evaluate the effect of the triage system. RESULTS: There were 4,688 burn transfers (3,244 preimplementation and 1,444 postimplementation) in the study periods. Mean age was higher postimplementation (32 vs 29 years, p < 0.001). Median hospital length of stay (LOS) and ICU LOS were both 1 day higher, more patients underwent operative intervention (19% vs 16%), and median time to first operation was 1 day lower postimplementation. Short-stay admissions decreased from 50% (n = 1,624) to 39% (n = 561), and patients were 17% less likely to have a short-stay admission after implementation (adjusted relative risk [aRR], 0.83; 95% CI, 0.8 to 0.9). Pediatric patients younger than 15 years old composed 43% of all short-stay admissions and were much more likely than adult patients to have a short-stay admission independent of transfer timing (aRR, 2.36; 95% CI, 1.84 to 3.03). CONCLUSIONS: Tele-triage burn transfer center protocols reduced short-stay admissions and prioritized inpatient care for patients with more severe injuries. Pediatric patients remain more likely to have short-stay admission after transfer.
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Unidades de Quemados , Triaje , Adulto , Humanos , Niño , Adolescente , Estudios Retrospectivos , Hospitalización , Tiempo de InternaciónRESUMEN
Immunization with Schistosoma mansoni soluble antigen preparations protects non-obese diabetic (NOD) mice against the development of type 1 diabetes. These preparations have long been known to induce Th2 responses in vitro and in vivo. Recently, two separate groups have reported that ω-1, a well-characterized glycoprotein in S. mansoni soluble egg antigens (SEA), which with IL-4 inducing principle of S. mansoni eggs (IPSE/α-1) is one of the two major glycoproteins secreted by live eggs, is a major SEA component responsible for this effect. We found that ω-1 induces Foxp3 as well as IL-4 expression when injected in vivo. We confirmed that ω-1 conditions DCs to drive Th2 responses and further demonstrated that ω-1 induces Foxp3(+) T cells from NOD mouse naïve T cells. In contrast, IPSE/α-1 did not drive Foxp3 responses. The in vitro development of Foxp3-expressing T cells by ω-1 was TGF-ß- and retinoic acid-dependent. Our work, therefore, identifies ω-1 as an important factor for the induction of Foxp3(+) T cells by SEA in NOD mice.
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Linfocitos T CD4-Positivos/metabolismo , Diabetes Mellitus Tipo 1/inmunología , Factores de Transcripción Forkhead/metabolismo , Interleucina-4/metabolismo , Schistosoma mansoni/inmunología , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/patología , Diabetes Mellitus Tipo 1/prevención & control , Proteínas del Huevo/administración & dosificación , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Proteínas del Helminto/administración & dosificación , Inmunización , Interleucina-4/genética , Interleucina-4/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Schistosoma mansoni/metabolismo , Células Th2/inmunología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Tretinoina/metabolismoRESUMEN
Zymosan is a complex fungal component shown to be capable of both promoting and suppressing the development of autoimmune disorders in mice. In this study, we show that a single injection of zymosan just prior to diabetes onset can significantly delay the progression of disease in NOD mice. Zymosan treatment of NOD mice induced the production of biologically active TGF-beta from cells infiltrating the pancreas and was associated with expansion of programmed cell death 1 ligand 1(+)TGF-beta(+) macrophages and Foxp3(+) regulatory T cells in vivo. Neutralization of either TGF-beta or programmed cell death 1 ligand 1 abrogated the protective effects of zymosan. Zymosan acted through TLR2 as well as ERK and p38 MAPK to induce macrophage secretion of TGF-beta and promotion of Foxp3(+) regulatory T cells in vitro and in vivo.
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Antígeno B7-1/fisiología , Diferenciación Celular/inmunología , Proliferación Celular , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/inmunología , Glicoproteínas de Membrana/fisiología , Péptidos/fisiología , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta/fisiología , Zimosan/administración & dosificación , Animales , Antígeno B7-H1 , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Diabetes Mellitus Tipo 1/patología , Relación Dosis-Respuesta Inmunológica , Femenino , Inmunidad Innata/efectos de los fármacos , Ratones , Ratones Endogámicos NOD , Visón , Linfocitos T Reguladores/patología , Zimosan/uso terapéuticoRESUMEN
Introduction: Simulation is increasingly being used in the preclinical years of US medical school curricula to provide experiential learning opportunities for students. However, preclinical medical students may not be able to access the full benefits of immersive simulation scenarios without an in-depth introduction to the simulation environment and manikin. An escape room may be an effective way to orient students in an interactive manner to overcome this barrier. Methods: We designed and implemented a 90-minute escape room orientation activity to address student discomfort in the simulation environment by providing a team-based, hands-on exploration of identified critical features of the room and manikin in the guise of a routine clinic visit for a patient. We surveyed learners on their confidence immediately following the escape room and on their perceptions of the session effectiveness following their first simulation. Results: A total of 148 preclinical medical students participated in the escape room activity in 30 groups of four to five persons. Of those students, 130 participated in a simulated patient case within 1 month of the escape room activity, and 89 filled out a follow-up survey. Of responding students, 80% reported that the escape room activity was highly effective or very effective in preparing them for participation in a simulated patient case. Discussion: Implementing an escape room orientation activity for preclinical medical students was effective in preparing students to participate in their first immersive simulation scenario.
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Estudiantes de Medicina , Curriculum , Humanos , Aprendizaje , Aprendizaje Basado en Problemas , Encuestas y CuestionariosRESUMEN
Intravascular lithotripsy (IVL) is associated with excellent angiographic and short-term results in patients with calcified lesions requiring percutaneous coronary intervention. We conducted a 1-year follow up of a retrospective cohort of 47 patients (61 lesions) who underwent IVL. The primary outcome was target vessel revascularization (TVR) at 1-year from index procedure. Four percent of patients required TVR within 1 year; 96% who underwent IVL remained free from repeat intervention on the same vessel. One patient suffered a myocardial infarction; the culprit vessel had not been previously treated with IVL. IVL is an effective and durable modality for treatment of highly calcified coronary lesions in high-risk patients.
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Litotricia , Intervención Coronaria Percutánea , Calcificación Vascular , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Calcificación Vascular/diagnóstico , Calcificación Vascular/terapia , Intervención Coronaria Percutánea/métodos , Litotricia/efectos adversos , Litotricia/métodosRESUMEN
The RAND/UCLA modified Delphi panel method is a formal group consensus process that systematically and quantitatively combines expert opinion and evidence by asking panelists to rate, discuss, then re-rate items. The method has been used to develop medical society guidelines, other clinical practice guidelines, disease classification systems, research agendas, and quality improvement interventions. Traditionally, a group of experts meet in person to discuss results of a first-round survey. After the meeting, experts complete a second-round survey used to develop areas of consensus. During the COVID-19 pandemic, this aspect of the method was not possible. As such, we have adapted the method to conduct virtual RAND/UCLA modified Delphi panels. In this study, we present a targeted literature review to describe and summarize the existing evidence on the RAND/UCLA modified Delphi panel method and outline our adaptation for conducting these panels virtually. Transitioning from in-person to virtual meetings was not without challenges, but there have also been unexpected advantages. The method we describe here can be a cost-effective and efficient alternative for researchers and clinicians.
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Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Pediatric-onset MS (POMS), defined as onset of MS before 18 years of age, is estimated to account for 2% to 5% of the MS population worldwide. Objectives: To conduct a literature review focused on the healthcare resource utilization and cost as well as quality-of-life (QOL) outcomes among patients with POMS. Methods: We conducted a systematic literature review of English-language studies published after September 2010 in MEDLINE and Embase to describe the global economic healthcare resource utilization and costs and humanistic (QOL) burden in patients with POMS. Results: We found 11 studies that reported on healthcare resource utilization, cost, or insurance coverage and 36 studies that reported on QOL outcomes in patients with POMS. Patients with POMS had higher rates of primary care visits (1.41 [1.29-1.54]), hospital visits (10.74 [8.95-12.90]), and admissions (rate ratio, 4.27 [2.92-6.25];OR, 15.2 [12.0-19.1]) compared with healthy controls. Mean per-patient costs in the United States were $5907 across all settings per year of follow-up between 2002 and 2012; mean costs per hospital stay were $38â¯543 (in 2015 USD) between 2004 and 2013. Three studies reported psychosocial scores between 71.59 and 79.7, and 8 studies reported physical health scores between 74.62 to 82.75 using the Pediatric Quality of Life Measurement Model (PedsQLTM). Twelve studies used the PedsQL™ Multidimensional Fatigue Scale. Mean scores on the self-reported general fatigue scale ranged from 63.15 to 78.5. Quality-of-life scores were lower than those of healthy controls. Discussion: Our review presents a uniquely broad and recent overview of the global economic and humanistic burden of patients with POMS. Additional research on healthcare resource utilization and cost would provide a more robust understanding of the economic burden in this population. Conclusions: Healthcare resource utilization and costs are high in this population, and patients report reduced QOL and significant fatigue compared with healthy children and adolescents.
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The immunomodulatory effect of Schistosoma mansoni antigens has often been attributed to interaction with PRR expressed on APC. Our previous work has shown that S. mansoni-soluble egg antigen (SEA) can induce, together with a Th2 response, TGF-ß-dependent Foxp3 expression in naïve CD4(+) T cells from NOD mice. We found that SEA can directly upregulate the expression of surface-bound TGF-ß in purified CD4(+) T cells in the absence of accessory cell interactions. In this study, we show that the C-type lectin receptors DEC-205 and galectin-3 were involved in the direct interaction between S. mansoni antigens and CD4(+) T cells. SEA was able to enhance CD4(+) T-cell secretion of bioactive TGF-ß in response to TLR2 ligand stimulation, in the absence of APC. We also show that TLR2 expressed on CD4(+) T cells was important for the Foxp3 expression induced by SEA.
Asunto(s)
Antígenos Helmínticos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Factores de Transcripción Forkhead/biosíntesis , Proteínas del Helminto/inmunología , Schistosoma mansoni/inmunología , Receptor Toll-Like 2/metabolismo , Animales , Antígenos CD/inmunología , Antígenos CD/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/parasitología , Linfocitos T CD4-Positivos/patología , Células Cultivadas , Femenino , Factores de Transcripción Forkhead/genética , Galectina 3/inmunología , Galectina 3/metabolismo , Interacciones Huésped-Patógeno , Inmunomodulación , Lectinas Tipo C/inmunología , Lectinas Tipo C/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Noqueados , Antígenos de Histocompatibilidad Menor , Receptores de Superficie Celular/inmunología , Receptores de Superficie Celular/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/inmunología , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling and destruction that leads to severe disability. There are no clear guidelines regarding the order of therapies. Gathering data on treatment patterns outside of a clinical trial setting can provide useful context for clinicians. Objectives: To assess real-world treatment persistence in early-line abatacept versus tumor necrosis factor-inhibitors (TNFi) treated patients with RA complicated by poor prognostic factors (including anti-cyclic citrullinated peptide antibodies [ACPA] and rheumatoid factor [RF] seropositivity). Methods: We performed a multi-center retrospective medical record review. Adult patients with RA complicated by poor prognostic factors were treated with either abatacept or TNFis as the first biologic treatment at the clinic. Poor prognostic factors included ACPA+, RF+, increased C-reactive protein levels, elevated erythrocyte sedimentation rate levels, or presence of joint erosions. We report 12-month treatment persistence, time to discontinuation, reasons for discontinuation, and risk of discontinuation between patients on abatacept versus TNFi. Select results among the subgroup of ACPA+ and/or RF+ patients are presented. Results: Data on 265 patients (100 abatacept, 165 TNFis) were collected. At 12 months, 83% of abatacept patients were persistent versus 66.1% of TNFi patients (P=0.003). Median time to discontinuation was 1423 days for abatacept versus 690 days for TNFis (P=0.014). In adjusted analyses, abatacept patients had a lower risk of discontinuing index treatment due to disease progression (0.3 [95% confidence interval (CI): 0.1-0.6], P=0.001). Among the subgroup of ACPA+ and/or RF+ patients (55 abatacept, 108 TNFis), unadjusted 12-month treatment persistence was greater (83.6% versus 64.8%, P=0.012) and median time to discontinuation was longer (961 days versus 581 days, P=0.048) in abatacept versus TNFi patients. Discussion: Patients with RA complicated by poor prognostic factors taking abatacept, including the subgroup of patients with ACPA and RF seropositivity, had statistically significantly higher 12-month treatment persistence and a longer time to discontinuation than patients on TNFis. Conclusions: In a real-world setting, RA patients treated with abatacept were more likely to stay on treatment longer and had a lower risk of discontinuation than patients treated with TNFis.
RESUMEN
STUDY OBJECTIVE: Patients with sickle cell disease (SCD) have many emergency department visits because of painful vaso-occlusive episodes (VOE). Guidelines recommend treatment within 30 minutes of triage, but this is rarely achieved in clinical practice. Our goal was to develop an order set that is being implemented in the ED to facilitate and standardize emergency care for SCD patients in acute pain from VOEs presenting to the emergency department (ED) in New York City (NYC). METHODS: Using a RAND/University of California, Los Angeles modified Delphi panel, we convened a multidisciplinary panel and reviewed evidence on how to best manage SCD pain in the ED. Panelists collaboratively developed then rated 202 items that could be included in an ED order set. RESULTS: A consensus order set, a practical how-to guide for managing SCD pain in the ED, was developed based on items that received high median ratings. CONCLUSIONS: The management of acute pain experienced during VOEs is critical to patients with SCD; ED order sets, such as this one, can help standardize pain management, including at triage, evaluation, discharge, and follow-up care. After implementation in NYC EDs, studies to examine changes in quality care metrics (eg, wait times, readmissions) are planned.