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OBJECTIVE: To evaluate the effect of nerve decompression on pain in patients with lower extremity painful diabetic peripheral neuropathy (DPN). BACKGROUND: Currently, no treatment provides lasting relief for patients with DPN. The benefits of nerve decompression remain inconclusive. METHODS: This double-blinded, observation and same-patient sham surgery-controlled randomized trial enrolled patients aged 18 to 80 years with lower extremity painful DPN who failed 1 year of medical treatment. Patients were randomized to nerve decompression or observation group (2:1). Decompression-group patients were further randomized and blinded to nerve decompression in either the right or left leg and sham surgery in the opposite leg. Pain (11-point Likert score) was compared between decompression and observation groups and between decompressed versus sham legs at 12 and 56 months. RESULTS: Of 2987 screened patients, 78 were randomized. At 12 months, compared with controls (n=37), both the right-decompression group (n=22) and left-decompression group (n=18) reported lower pain (mean difference for both: -4.46; 95% CI: -6.34 to -2.58 and -6.48 to -2.45, respectively; P < 0.0001). Decompressed and sham legs equally improved. At 56 months, compared with controls (n=m 14), pain was lower in both the right-decompression group (n=20; mean difference: -7.65; 95% CI: -9.87 to -5.44; P < 0.0001) and left-decompression group (n=16; mean difference: -7.26; 95% CI: -9.60 to -4.91; P < 0.0001). The mean pain score was lower in decompressed versus sham legs (mean difference: 1.57 95% CI: 0.46 to 2.67; P =0.0002). CONCLUSIONS: Although nerve decompression was associated with reduced pain, the benefit of surgical decompression needs further investigation as a placebo effect may be responsible for part or all of these effects.
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Descompresión Quirúrgica , Neuropatías Diabéticas , Extremidad Inferior , Dimensión del Dolor , Humanos , Descompresión Quirúrgica/métodos , Neuropatías Diabéticas/cirugía , Neuropatías Diabéticas/complicaciones , Masculino , Persona de Mediana Edad , Femenino , Método Doble Ciego , Anciano , Adulto , Resultado del Tratamiento , Extremidad Inferior/inervación , Extremidad Inferior/cirugía , Anciano de 80 o más Años , Adolescente , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody-positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2. METHODS: This multicenter North American open-label prospective investigator-initiated study had two components: the IVIg Stabilization Period (ISP) enrolling patients already on IVIg as part of routine clinical care (Weeks -10 to -1), followed by transition of stable MG subjects to SCIg in the Experimental Treatment Period (ETP; Weeks 0 to 12). We hypothesized that >65% of patients entering the ETP would have a stable Quantitative Myasthenia Gravis (QMG) score from Week 0 to Week 12. Secondary outcome measures included other efficacy measures, safety, tolerability, IgG levels, and treatment satisfaction. RESULTS: We recruited 23 patients in the ISP, and 22 entered the ETP. A total of 12 subjects (54.5%) were female, and 18 (81.8%) were White, with mean age 51.4 ± 17 years. We obtained Week 12 ETP QMG data on 19 of 22; one subject withdrew from ETP owing to clinical deterioration, and two subjects withdrew due to dislike of needles. On primary analysis, 19 of 22 participants (86.4%, 95% confidence interval = 0.72-1.00) were treatment successes using last observation carried forward (p = 0.018). Secondary efficacy measures supported MG stability. SCIg was safe and well tolerated, and IgG levels were stable. Treatment satisfaction was comparable between ISP and ETP. CONCLUSIONS: MG patients on IVIg as part of their routine clinical care remained stable on monthly IVIg dosage, and most maintained similar disease stability on SCIg.
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Inmunoglobulinas Intravenosas , Miastenia Gravis , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Inmunoglobulinas Intravenosas/uso terapéutico , Estudios Prospectivos , Miastenia Gravis/tratamiento farmacológico , Receptores Colinérgicos , AutoanticuerposRESUMEN
OBJECTIVES: The aim of this study was to achieve the translation and cross-cultural adaptation of the MG-QOL15R questionnaire into Spanish and the analysis of its psychometric properties. MATERIALS AND METHODS: We recruited patients with MG, ≥18 years old, whose mother tongue was Spanish. After the translation and cross-cultural adaptation of the MG-QOL15-R, the following tests were performed: internal consistency using the Cronbach-α coefficient and corrected item-total correlations; reproducibility with a test-retest analysis using intraclass correlation coefficients; and concurrent validity using Spearman's correlation coefficient of the Spanish language MG-QOL15R-S, Myasthenia Gravis Activity of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. As an approximation to construct validity, the nonparametric Mann-Whitney U test was performed between MG-QOL15R-S scores according to the Myasthenia Gravis Foundation of America classification. RESULTS: A total of 83 MG patients were enrolled, mean age 48.19 ± 17.25 years; 58 (69.9%) were women. The mean MG-QOL15R-S score was 11.3 ± 7.1. Cronbach-α coefficient was 0.92. Item-total correlation ranged between 0.43 and 0.75. Intraclass correlation coefficient was 0.80. The Spearman correlation coefficient was 0.637 (p-value < .001) for MG-ADL and 0.487 (p-value < .001) for QMG. Mann-Whitney U tests of the mean MG-QOL15R-S scores were significantly different according to the clinical severity (p-value < .001). CONCLUSIONS: The Spanish version of the MG-QOL15R is a valid and reliable instrument and potentially useful for measuring health-related quality of life in Spanish-speaking MG patients.
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Miastenia Gravis , Calidad de Vida , Adolescente , Adulto , Anciano , Femenino , Humanos , Lenguaje , Persona de Mediana Edad , Miastenia Gravis/diagnóstico , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scales were compared using the data from the Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy (MGTX) study. METHODS: Correlation between QMG and MG-ADL raw and change-from-baseline scores was calculated every 3 months for 60 months based on treatment groups and minimal manifestation status (MMS). RESULTS: QMG and MG-ADL change-from-baseline scores correlated significantly, with increasing strength of correlation over time, in both treatment groups. QMG and MG-ADL raw scores correlated significantly in both treatment groups, with increasing correlation only in the prednisone-alone group. Correlation between raw scores was weaker in patients who were in MMS, demonstrating a "floor effect" on the MG-ADL scale. Raw QMG scores could be modeled assuming a normal distribution, whereas raw MG-ADL scores could not be modeled this way. DISCUSSION: The floor effect and skewed distribution of the MG-ADL measure should be taken into account in the design of myasthenia gravis clinical trials.
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Actividades Cotidianas , Miastenia Gravis/fisiopatología , Evaluación de Resultado en la Atención de Salud , Terapia Combinada , Glucocorticoides/uso terapéutico , Humanos , Miastenia Gravis/terapia , Prednisona/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , TimectomíaRESUMEN
BACKGROUND: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS: A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS: Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).
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Glucocorticoides/administración & dosificación , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/cirugía , Prednisona/administración & dosificación , Timectomía , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/clasificación , Índice de Severidad de la Enfermedad , Método Simple Ciego , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: In this study we evaluated the safety, tolerability, and efficacy of prednisone in patients with ocular myasthenia gravis (OMG) concurrently treated with pyridostigmine. METHODS: This investigation was a randomized, double-blind, placebo-controlled trial. Participants whose symptoms failed to remit on pyridostigmine were randomized to receive placebo or prednisone, initiated at 10 mg every other day, and titrated to a maximum of 40 mg/day over 16 weeks. The primary outcome measure was treatment failure. RESULTS: Fewer subjects were randomized than the 88 planned. Of the 11 randomized, 9 completed 16 weeks of double-blind therapy. Treatment failure incidence was 100% (95% CI 48%-100%) in the placebo group (n = 5) vs. 17% (95% CI 0%-64%) in the prednisone group, P = 0.02 (n = 6). Median time to sustained minimal manifestation status (MMS) was 14 weeks, requiring an average prednisone dose of 15 mg/day. Adverse events were infrequent and generally mild in both groups. CONCLUSIONS: A strategy of low-dose prednisone with gradual escalation appears to be safe, well-tolerated, and effective in treating OMG.
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Inhibidores de la Colinesterasa/uso terapéutico , Miastenia Gravis/tratamiento farmacológico , Bromuro de Piridostigmina/uso terapéutico , Resultado del Tratamiento , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score. METHODS: Cross-sectional data from a real-world prospective study (MRW) were combined with longitudinal data from the ADAPT trial. Outcome measures included were MG-ADL, Quantitative Myasthenia Gravis score (QMG), MG 15-item Quality of Life (MG-QOL15r) and EQ-5D-5L. Patients were categorized by their Myasthenia Gravis Foundation of America (MGFA) clinical classification. The following measurement properties were assessed: distributional characteristics, inter-item correlation, convergent, known groups and construct validity and internal factor structure. RESULTS: Correlations of items within MG-ADL dimensions were moderate, while MG-ADL correlations between comparable MG-QOL15r and QMG items were mixed. Known groups validity for the MG-ADL score was demonstrated for MGFA class. Mean MG-ADL item level scores by MGFA class demonstrated construct validity. PCA, including all four outcome measures, resulted in a nine factor solution. DISCUSSION: Psychometric properties of individual MG-ADL items were moderate to good. This study showed that the MG-ADL adequately captures the multidimensional heterogeneous nature of MG. This is, however, accompanied by mixed psychometric performance of the MG-ADL score, which may complicate health economic modelling. REGISTRATION: MyRealWorld-MG was registered on November 25, 2019, with registration numberNCT04176211. The ADAPT randomized clinical trial is registered atClinicalTrials.gov(NCT03669588).
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Background and Objectives: In 2016, a randomized controlled trial demonstrated the clinical efficacy of trans-sternal thymectomy for patients with non-thymomatous myasthenia gravis (MG). Whether large-scale changes occurred in clinical practice after this trial is unknown. Methods: We performed a retrospective longitudinal cross-sectional analysis using National Inpatient Sample (NIS) data from 2012 to 2019. Our study included hospitalized adults at least 18 years of age diagnosed with MG without an associated thymoma. We used joinpoint regression to analyze annual trends in thymectomy volume and surgical approach (minimally invasive vs trans-sternal) from 2012 to 2019. Using logistic regression models, we examined patient and hospital-level factors that may have influenced whether thymectomy was performed, such as age, sex, race, insurance payor, hospital size and teaching status, and Elixhauser Comorbidity Index. Sampling weights were applied to account for the complex survey design of NIS. Results: The total number of thymectomy procedures increased by 69.8% per year (95% CI 40.1-105.8) between 2012 and 2019. Trans-sternal thymectomies increased by 62.8% per year (95% CI 35.8-95.2) and minimally invasive thymectomies by 83.7% per year (95% CI 38.1-144.3). Thymectomies were significantly more likely to occur in 2017-2019 compared with 2012-2016 (OR 1.93, 95% CI 1.62-2.31). In a multivariable regression model, several factors decreased the odds of patients with MG having a thymectomy: older age, Black race (OR 0.62, 95% CI 0.49-0.77), female (OR 0.73, 95% CI 0.63-0.86), and higher Elixhauser Comorbidity Index. Patients in medium (OR 1.82, 95% CI 1.30-2.55) or large (OR 2.81, 95% CI 2.07-3.82) size and urban teaching hospitals (OR 6.09, 95% CI 2.65-13.97) were more likely to undergo thymectomy. Discussion: Thymectomy is being performed more frequently for non-thymomatous MG, especially after 2016 after publication of a positive phase III clinical trial. There are several disparities in thymectomy utilization that warrant further attention.
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The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy. We conclude that for patients with acetylcholine receptor antibody-positive MG and those diagnosed with thymoma, the removal of the thymus offers prominent benefits that well outweigh the potential risks. However, incidental removal of thymic tissue during other thoracic surgeries should be minimized whenever feasible.
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Miastenia Gravis , Timectomía , Timoma , Timo , Neoplasias del Timo , Humanos , Timectomía/efectos adversos , Timectomía/métodos , Miastenia Gravis/cirugía , Timo/cirugía , Neoplasias del Timo/cirugía , Neoplasias del Timo/complicaciones , Timoma/cirugía , Timoma/complicaciones , Complicaciones Posoperatorias/etiología , Enfermedades Autoinmunes/cirugíaRESUMEN
Neuromuscular clinicians are frequently asked to evaluate patients referred for asymptomatic elevations in creatine kinase (CK), a catalytic enzyme that combines creatine and ATP to form phosphocreatine and ADP. This reaction is crucial for cellular energy generation and metabolism. This laboratory finding, often referred to in simplified lexicon as asymptomatic hyperCKemia, continues to generate controversy at several levels, including definition, the extent of evaluation, and the yield of diagnostic testing. In this review, we summarize the literature based on series of patients with asymptomatic hyperCKemia and provide a rational clinical approach to reveal identifiable underlying causes.
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Enfermedades Asintomáticas , Creatina Quinasa/sangre , Enfermedades Metabólicas/diagnóstico , Enfermedades Musculares/diagnóstico , Diagnóstico Diferencial , Humanos , Enfermedades Metabólicas/sangre , Valores de ReferenciaRESUMEN
Peripheral neuropathy is a common neurological disorder. There may be important differences and similarities in the diagnosis of peripheral neuropathy between North America (NA) and South America (SA). Neuromuscular databases were searched for neuropathy diagnosis at two North American sites, University of Kansas Medical Center and University of Texas Southwestern Medical Center, and one South American site, Federal Fluminense University in Brazil. All patients were included into one of the six major categories: immune-mediated, diabetic, hereditary, infectious/inflammatory, systemic/metabolic/toxic (not diabetic) and cryptogenic. A comparison of the number of patients in each category was made between North America and South America databases. Total number of cases in North America was 1090 and in South America was 1034 [immune-mediated: NA 215 (19.7%), SA 191 (18%); diabetic: NA 148 (13.5%), SA 236 (23%); hereditary: NA 292 (26.7%), SA 103 (10%); infectious/inflammatory: NA 53 (4.8%), SA 141 (14%); systemic/metabolic/toxic: NA 71 (6.5%), SA 124 (12%); cryptogenic: NA 311 (28.5%), SA 239 (23%)]. Some specific neuropathy comparisons were hereditary neuropathies [Charcot-Marie-Tooth (CMT) cases] in NA 246/292 (84.2%) and SA 60/103 (58%); familial amyloid neuropathy in SA 31/103 (30%) and none in NA. Among infectious neuropathies, cases of human T-lymphotropic virus type 1 (HTLV-1) neuropathy in SA were 36/141(25%), Chagas disease in SA were 13/141(9%) and none for either in NA; cases of neuropathy due to leprosy in NA were 26/53 (49%) and in SA were 39/141(28%). South American tertiary care centers are more likely to see patients with infectious, diabetic and hereditary disorders such as familial amyloid neuropathies. North American tertiary centers are more likely to see patients with CMT. Immune neuropathies and cryptogenic neuropathies were seen equally in North America and South America.
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Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/epidemiología , Bases de Datos Factuales , Humanos , América del Norte/epidemiología , América del Sur/epidemiologíaRESUMEN
OBJECTIVE: High-dose prednisone use, lasting several months or longer, is the primary initial therapy for myasthenia gravis (MG). Upwards of a third of patients do not respond to treatment. Currently no biomarkers can predict clinical responsiveness to corticosteroid treatment. We conducted a discovery-based study to identify treatment responsive biomarkers in MG using sera obtained at study entry to the thymectomy clinical trial (MGTX), an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone. METHODS: We applied ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry to obtain comparative serum metabolomic and lipidomic profiles at study entry to correlate with treatment response at 6 months. Treatment response was assessed using validated outcome measures of minimal manifestation status (MMS), MG-Activities of Daily Living (MG-ADL), Quantitative MG (QMG) score, or a strictly defined composite measure of response. RESULTS: Increased serum levels of phospholipids were associated with treatment response as assessed by QMG, MMS, and the Responders classification, but all measures showed limited overlap in metabolomic profiles, in particular the MG-ADL. A panel including histidine, free fatty acid (13:0), γ-cholestenol and guanosine was highly predictive of the strictly defined treatment response measure. The AUC in Responders' prediction for these markers was 0.90 irrespective of gender, age, thymectomy or baseline prednisone use. Pathway analysis suggests that xenobiotic metabolism could play a major role in treatment resistance. There was no association with outcome and gender, age, thymectomy or baseline prednisone use. INTERPRETATION: We have defined a metabolomic and lipidomic profile that can now undergo validation as a treatment predictive marker for MG patients undergoing corticosteroid therapy. Metabolomic profiles of outcome measures had limited overlap consistent with their assessing distinct aspects of treatment response and supporting unique biological underpinning for each outcome measure. Interindividual variation in prednisone metabolism may be a determinate of how well patients respond to treatment.
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Actividades Cotidianas , Miastenia Gravis , Humanos , Prednisona/efectos adversos , Glucocorticoides/uso terapéutico , Miastenia Gravis/tratamiento farmacológico , Terapia Combinada , Timectomía/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate patient attitudes and beliefs toward thymectomy for myasthenia gravis (MG). METHODS: The Myasthenia Gravis Foundation of America administered a questionnaire to the MG Patient Registry, an ongoing longitudinal survey of adult MG patients. Questions assessed reasons for or against thymectomy and how hypothetical scenarios would have affected their decision. RESULTS: Of 621 respondents, 190 (31%) reported a history of thymectomy. Of those who underwent thymectomy for nonthymomatous MG, 97 (51.6%) ranked symptom improvement as most important and 100 (53.2%) ranked reducing medication as least important. Among 431 nonthymectomy patients, the most frequent reason for not undergoing thymectomy was that their doctor did not discuss it (152 of 431 = 35.2%) and 235 (56.8%) said that they would have considered it more strongly if their doctor spent more time discussing it. CONCLUSIONS: Thymectomies are motivated more by symptoms than by medication, and a lack of neurologist discussion is the most common barrier to thymectomy.
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Conocimientos, Actitudes y Práctica en Salud , Miastenia Gravis , Pacientes , Sistema de Registros , Encuestas y Cuestionarios , Timectomía , Datos de Salud Recolectados Rutinariamente , Miastenia Gravis/epidemiología , Miastenia Gravis/cirugía , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Timoma/epidemiología , Objetivos , Receptores Colinérgicos/inmunología , Autoanticuerpos/análisisRESUMEN
INTRODUCTION: Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase. Late-onset Pompe disease is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders. METHODS: Objective is to propose consensus-based treatment and management recommendations for late-onset Pompe disease. METHODS: A systematic review of the literature by a panel of specialists with expertise in Pompe disease was undertaken. CONCLUSIONS: A multidisciplinary team should be involved to properly treat the pulmonary, neuromuscular, orthopedic, and gastrointestinal elements of late-onset Pompe disease. Presymptomatic patients with subtle objective signs of Pompe disease (and patients symptomatic at diagnosis) should begin treatment with enzyme replacement therapy (ERT) immediately; presymptomatic patients without symptoms or signs should be observed without use of ERT. After 1 year of ERT, patients' condition should be reevaluated to determine whether ERT should be continued.
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Consenso , Enfermedad del Almacenamiento de Glucógeno Tipo II/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Guías como Asunto , Bases de Datos Bibliográficas/estadística & datos numéricos , Progresión de la Enfermedad , Enfermedad del Almacenamiento de Glucógeno Tipo II/historia , Historia del Siglo XX , HumanosRESUMEN
The recommendations for clinical research standards published in 2000 by a task force of the Medical Scientific Advisory Board (MSAB) of the Myasthenia Gravis Foundation of America (MGFA) were largely successful in introducing greater uniformity in the recording and reporting of MG clinical trials. Recognizing that changes in clinical trial design and implementation may increase the likelihood that new therapies are developed for MG, the MGFA MSAB Task Force here presents updated recommendations for the design and implementation of clinical trials in MG, including (a) the use of a quantitative measure, such as the MG-Composite, that is weighted for clinical significance and incorporates patient reported outcomes; (b) consideration of nontrial strategies; and (c) development of biomarkers that support mechanistic studies of pharmacotherapies. The hope is that these updated task force recommendations will expedite the development and acceptance of more effective and less noxious therapies for MG.
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Ensayos Clínicos como Asunto/normas , Miastenia Gravis/terapia , Proyectos de Investigación/normas , Comités Consultivos , Biomarcadores , Humanos , Evaluación de Resultado en la Atención de Salud , Sociedades Médicas , Estados UnidosRESUMEN
Myasthenia gravis (MG) is the most common disorder of the neuromuscular junction (NMJ), with an estimated prevalence between 25 and 142 per million. It characteristically presents with fatigable weakness, often initially involving the ocular muscles and manifesting as intermittent ptosis and diplopia. Ultimately, the disease generalizes in two-thirds of patients, leading to weakness of bulbar, neck, limb, and respiratory muscles. The majority of patients with generalized MG, and roughly half of patients with purely ocular disease, harbor antibodies to skeletal muscle nicotinic acetylcholine receptors. A subset of patients with generalized disease have antibodies to muscle-specific receptor tyrosine kinase (MuSK). Acetylcholinesterase inhibitors are often the first modality of therapy for MG. As an immune-mediated disorder, MG can respond to several immunosuppressive agents, such as corticosteroids, azathioprine, mycophenolate mofetil, and cyclosporin. Thymectomy is a key component of management in appropriately chosen MG patients and those with thymoma. Newer or alternative immunotherapies including tacrolimus, rituximab, methotrexate, and complement inhibiting agents are an area of active investigation.
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Miastenia Gravis/terapia , Corticoesteroides/uso terapéutico , Algoritmos , Animales , Inhibidores de la Colinesterasa/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Inmunoterapia , Miastenia Gravis/patología , TimectomíaRESUMEN
Idiopathic neuropathy, now designated as chronic idiopathic axonal polyneuropathy (CIAP), is a major public health problem in the United States. The disorder affects an estimated 5-8 million Americans, comprising about one-third of patients with neuropathy, based on data from referral centers. Typically, patients develop symptoms in the sixth decade or older. The onset is insidious, with numbness, paresthesias, and pain appearing over months to years. Although strength is generally preserved, the sensory loss and pain can be disabling. The clinical approach to this condition has evolved in important ways over the years, enabling improved diagnosis and characterization of this population. Current work has focused on identifying modifiable risk factors that may be associated with idiopathic neuropathy. The results may suggest that an underlying mechanism such as oxidative stress contributes to the development of CIAP.
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Polineuropatías , HumanosRESUMEN
INTRODUCTION: The aim of this analysis was to examine the performance of the Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL) during a multicenter scale validation study. METHODS: Consecutive MG patients were assessed with several MG outcome measures, including the MG-ADL. Statistical tests included descriptive analysis, Pearson correlation, and sensitivity/specificity. RESULTS: Eighty-seven patients completed the MG-ADL, MG Composite (MGC), and MG 15-item Quality of Life scale (MG-QOL15) on the first visit, and 76 returned for the second visit. At the first visit, there was a strong positive correlation between MG-ADL and MGC (r = 0.85, P < 0.0001) and MG-QOL15 (r = 0.76, P < 0.0001). Correlation of the delta MG-ADL score and physician impression of change between the visits was strong (r = 0.70, P < 0.0001). A 2-point improvement in the MG-ADL best predicted clinical improvement. Test-retest analysis demonstrated a high reliability coefficient. CONCLUSIONS: The MG-ADL correlates strongly with newer, validated MG outcome measures. A 2-point improvement in the MG-ADL indicates clinical improvement. The MG-ADL is useful as a research tool and in routine clinical management.