Applying the functional independence measure to the assessment of patients with mucopolysaccharidosis / Test de medida de independencia funcional en la evaluación de pacientes con mucopolisacaridosis

Abstract Objective: To assess the functional independence of a group of patients with mucopolysaccharidosis using the Functional Independence Measure as a tool that accomplishes this purpose. Methods: This is a cross-sectional study of patients with mucopolysaccharidosis. Our data was collected between June 2015 and July 2016. In addition to history of present illness and physical examination each study participant was asked to answer a questionnaire to specifically evaluate their functional independence using the functional independence measure. the internal consistency of the functional independence measure was assessed using Cronbach's alpha coefficient. Results: We collected data on 20 patients with mucopolysaccharidosis. The average age was 10.8 (8.67-13.03) years, the average weight was 23.6 (19.91-27.37) kg and the average height was 1 (0.83-1.17) m. The most prevalent type of mucopolysaccharidosis in the study was type VI (n= 14). The average total functional independence measure score was 104.4 (97.61-111.19), the average for the mobility domain was 73.50 (68.22-78.78) and the average for the cognitive function domain was 30.90 (28.68-33.13). The internal consistency of the entire questionnaire was 0.859, with values of 0.966 for the mobility domain and 0.624 for the cognitive function domain. Conclusion: The lowest functional independence measure scores were obtained in the following sub-domains: self-care, locomotion and cognitive function. The functional independence measure questionnaire demonstrated internal consistency for the evaluation of functional independence in patients with mucopolysaccharidosis, being able to value all the affected sub-domains separately.

Resumen Objetivo: Evaluar la independencia funcional de un grupo de pacientes con mucopolisacaridosis utilizando la Medida de Independencia Funcional como herramienta para lograr este propósito. Métodos: Este es un estudio transversal de pacientes con mucopolisacaridosis. Nuestros datos se recopilaron entre junio de 2015 y julio de 2016. Además de la historia de la enfermedad actual y el examen físico, se pidió a cada participante del estudio que respondiera un cuestionario para evaluar específicamente su independencia funcional utilizando la Medida de Independencia Funcional. la consistencia interna de la Medida de Independencia Funcional se evaluó mediante el coeficiente alfa de Cronbach. Resultados: Recopilamos datos de 20 pacientes con mucopolisacaridosis. La edad promedio fue de 10.8 (8.67-13.03) años, el peso promedio fue de 23.6 (19.91-27.37) kg y la altura promedio fue de 1 m (0.83-1.17). El tipo de mucopolisacaridosis más prevalente en el estudio fue el tipo VI (n= 14). El puntaje promedio de la medida de independencia funcional total fue 104.4 (97.61-111.19), el promedio para el dominio de movilidad fue 73.50 (68.22-78.78) y el promedio para el dominio de función cognitiva fue 30.90 (28.68-33.13). La consistencia interna de todo el cuestionario fue de 0.859, con valores de 0.966 para el dominio de movilidad y 0.624 para el dominio de función cognitiva. Conclusión: Las puntuaciones más bajas de la medida de independencia funcional se obtuvieron en los siguientes subdominios: autocuidado, locomoción y función cognitiva. El cuestionario de medida de independencia funcional demostró consistencia interna para la evaluación de la independencia funcional en pacientes con mucopolisacaridosis, pudiendo valorar todos los subdominios afectados por separado.

Applying the functional independence measure to the assessment of patients with mucopolysaccharidosis.

OBJECTIVE: To assess the functional independence of a group of patients with mucopolysaccharidosis using the Functional Independence Measure as a tool that accomplishes this purpose. METHODS: This is a cross-sectional study of patients with mucopolysaccharidosis. Our data was collected between June 2015 and July 2016. In addition to history of present illness and physical examination each study participant was asked to answer a questionnaire to specifically evaluate their functional independence using the functional independence measure. the internal consistency of the functional independence measure was assessed using Cronbach's alpha coefficient. RESULTS: We collected data on 20 patients with mucopolysaccharidosis. The average age was 10.8 (8.67-13.03) years, the average weight was 23.6 (19.91-27.37) kg and the average height was 1 (0.83-1.17) m. The most prevalent type of mucopolysaccharidosis in the study was type VI (n= 14). The average total functional independence measure score was 104.4 (97.61-111.19), the average for the mobility domain was 73.50 (68.22-78.78) and the average for the cognitive function domain was 30.90 (28.68-33.13). The internal consistency of the entire questionnaire was 0.859, with values of 0.966 for the mobility domain and 0.624 for the cognitive function domain. CONCLUSION: The lowest functional independence measure scores were obtained in the following sub-domains: self-care, locomotion and cognitive function. The functional independence measure questionnaire demonstrated internal consistency for the evaluation of functional independence in patients with mucopolysaccharidosis, being able to value all the affected sub-domains separately.

OBJETIVO: Evaluar la independencia funcional de un grupo de pacientes con mucopolisacaridosis utilizando la Medida de Independencia Funcional como herramienta para lograr este propósito. MÉTODOS: Este es un estudio transversal de pacientes con mucopolisacaridosis. Nuestros datos se recopilaron entre junio de 2015 y julio de 2016. Además de la historia de la enfermedad actual y el examen físico, se pidió a cada participante del estudio que respondiera un cuestionario para evaluar específicamente su independencia funcional utilizando la Medida de Independencia Funcional. la consistencia interna de la Medida de Independencia Funcional se evaluó mediante el coeficiente alfa de Cronbach. RESULTADOS: Recopilamos datos de 20 pacientes con mucopolisacaridosis. La edad promedio fue de 10.8 (8.67-13.03) años, el peso promedio fue de 23.6 (19.91-27.37) kg y la altura promedio fue de 1 m (0.83-1.17). El tipo de mucopolisacaridosis más prevalente en el estudio fue el tipo VI (n= 14). El puntaje promedio de la medida de independencia funcional total fue 104.4 (97.61-111.19), el promedio para el dominio de movilidad fue 73.50 (68.22-78.78) y el promedio para el dominio de función cognitiva fue 30.90 (28.68-33.13). La consistencia interna de todo el cuestionario fue de 0.859, con valores de 0.966 para el dominio de movilidad y 0.624 para el dominio de función cognitiva. CONCLUSIÓN: Las puntuaciones más bajas de la medida de independencia funcional se obtuvieron en los siguientes subdominios: autocuidado, locomoción y función cognitiva. El cuestionario de medida de independencia funcional demostró consistencia interna para la evaluación de la independencia funcional en pacientes con mucopolisacaridosis, pudiendo valorar todos los subdominios afectados por separado.

Influence of Corneal Opacity on Intraocular Pressure Assessment in Patients with Lysosomal Storage Diseases.

AIMS: To investigate an influence of mucopolysaccharidosis (MPS)- and Morbus Fabry-associated corneal opacities on intraocular pressure (IOP) measurements and to evaluate the concordance of the different tonometry methods. METHODS: 25 MPS patients with or without corneal clouding, 25 Fabry patients with cornea verticillata ≥ grade 2 and 25 healthy age matched controls were prospectively included into this study. Outcome measures: Goldmann applanation tonometry (GAT); palpatory assessment of IOP; Goldmann-correlated intraocular pressure (IOPg), corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF) and corneal hysteresis (CH) assessed by Ocular Response Analyzer (ORA); central corneal thickness (CCT) and density assessed with Pentacam. Statistical analysis was performed using linear mixed effect models and Spearman correlation coefficients. The concordance between tonometry methods was assessed using Bland-Altman analysis. RESULTS: There was no relevant difference between study groups regarding median GAT, IOPg, IOPcc and CCT measurements. The limits of agreement between GAT and IOPcc/IOPg/palpatory IOP in MPS were: [-11.7 to 12.1mmHg], [-8.6 to 15.5 mmHg] and [- 5.4 to 10.1 mmHg] respectively. Limits of agreement were less wide in healthy subjects and Fabry patients. Palpatory IOP was higher in MPS than in healthy controls and Fabry patients. Corneal opacity correlated more strongly with GAT, IOPg, CH, CRF, CCT and corneal density in MPS (r = 0.4, 0.5, 0.5, 0.7, 0.6, 0.6 respectively) than in Fabry patients (r = 0.3, 0.2, -0.03, 0.1, 0.3, -0.2 respectively). In contrast, IOPcc revealed less correlation with corneal opacity than GAT in MPS (r = 0.2 vs. 0.4). CONCLUSIONS: ORA and GAT render less comparable IOP-values in patients suffering from MPS-associated corneal opacity in comparison to Fabry and healthy controls. The IOP seems to be overestimated in opaque MPS-affected corneas. GAT, IOPg and biomechanical parameters of the cornea correlate more strongly with the corneal clouding than IOPcc in MPS patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01695161.

Multidetector computed tomography (MDCT) for preoperative airway assessment in children with mucopolysaccharidoses.

BACKGROUND: Accumulation of glycosaminoglycans is known to cause significant problems in the anesthetic management of children with mucopolysaccharidoses (MPS). Clinical and standard radiological evaluation may convey insufficient information about the upper airway and trachea in children with MPS. Multidetector computed tomography (MDCT) images have been used to define the central airway and previous studies have recommended this tool to assess the airway of children who are considered at risk of difficult intubation. However, MDCT has not been recommended in MPS children. The aim of this clinical scenario study was to verify whether information from MDCT reconstruction of the airway is useful in airway management planning of children with MPS. METHODS: In a two phase questionnaire-based study, 26 pediatric anesthesiologists were asked to produce airway management plans for 5 children with MPS. An initial plan for airway control was reported after assessment of standard preoperative anesthetic charts. A subsequent airway strategy was then described after reviewing tracheal MDCT images of each patient. RESULTS: MDCT images provided additional clinically-relevant information in 87% (95% CI: 79-92%) of the evaluations. Reduction of tracheal size was the most common finding provided by the MDCT images. After reviewing the MDCT images, anesthesiologists changed their primary airway device selection in 21% of the evaluations (P=0.01). CONCLUSION: Airway reconstruction using MDCT images from a previous CT scan may provide a useful assessment tool for preoperative airway evaluation and planning in MPS children.

A systematic review of the clinical effectiveness and cost-effectiveness of enzyme replacement therapies for Fabry's disease and mucopolysaccharidosis type 1.

OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of the administration of intravenous enzyme replacement therapy (ERT) to symptomatic patients for the prevention of long-term damage and symptoms in Fabry's disease and in mucopolysaccharidosis type 1 (MPS1). DATA SOURCES: Electronic databases from inception up to mid-2004. Contact with clinical experts. REVIEW METHODS: Relevant studies were identified and assessed using recommended quality criteria. RESULTS: The results suggested beneficial effects of ERT for Fabry's disease on measures of pain, cardiovascular function and some end-points reflecting neurosensory function. Renal function appeared to be stabilised by ERT. At present there are no utility-related health-related quality of life data on which to assess the relative health gain of ERT in MPS1. In order to be able to demonstrate the full extent of health gain from treatment, it was necessary to review the natural history of untreated patients in each disease in order to try to estimate the health loss prevented. The published information for Fabry's disease tallied with descriptions of a multi-system, life-threatening disorder particularly involving kidney, heart and brain with individual patients exhibiting many manifestations. The fragmentary information reviewed in 16 studies relevant to the natural history of MPS1 did not generate a coherent picture of disease progression and could provide little added value to published narrative reviews. For Fabry's disease, the mean cost per patient (50 kg) treated is around pounds sterling 85,000 per annum in England and Wales. The cost per patient varies considerably by dose. No published evidence reporting an economic evaluation of ERT for Fabry's disease was identified by this review. A dynamic decision model was constructed based on a birth cohort of male patients who are followed up until death. Owing to lack of information reported in the literature, many assumptions had to be applied. The key assumptions were that ERT returns patients to full health and a normal life expectancy. As far as possible, all assumptions favoured rather than detracted from the value of ERT. ERT was assumed to restore patients to full health in the base case. The estimated incremental cost-effectiveness ratio (ICER) in the base case was pounds sterling 252,000 per QALY (agalsidase beta). Univariate sensitivity analysis around the key assumptions produced ICERs ranging from pounds sterling 602,000 to pounds sterling 241,000. The base case unit cost of ERT was taken as pounds sterling 65.1/mg based on the cost of agalsidase beta. The unit cost would have had to be reduced to pounds sterling 9 to obtain an ICER of pounds sterling 30,000 per QALY. For MPS1, the mean cost per child patient (20 kg) treated is approximately pounds sterling 95,000 and an adult (70 kg) around pounds sterling 335,000 per annum in England and Wales. The cost per patient varies considerably by dose. There is no published evidence reporting an economic evaluation of ERT for MPS1 and no study was identified that reported the quality of life of MPS1 patients within a utility format. Furthermore, no or minimal information of the severity and rate of change of clinical manifestations of disease or the impact of ERT on these factors was identified. Information on the effect of ERT on mortality is also lacking owing to the relatively short time that the treatment has been available. Given this lack of data, it was not possible to develop a cost-effectiveness model of ERT treatment for MPS1 as the model would consist almost completely of assumptions based on no published evidence, leading to an incremental cost per QALY result that would be meaningless. CONCLUSIONS: Although ERT for treating the 'average' patient with Fabry's disease exceeds the normal upper threshold for cost-effectiveness seen in NHS policy decisions by over sixfold, and the value for MPS1 is likely to be of a similar order of magnitude, clinicians and the manufacturers argue that, as the disease is classified as an orphan disease under European Union legislation, it has special status, and the NHS has no option but to provide ERT. More information is required before the generalisability of the findings can be determined. Although data from the UK have been used wherever possible, this was very thin indeed. Nonetheless, even large errors in assumptions made will not reduce the ICER to anywhere near the upper level of treatments usually considered cost-effective. In order to overcome limited evidence on the natural history of the disease and the clinical effectiveness of the intervention, the establishment of disease-specific data registries is suggested to facilitate the process of technology assessment and improving patient care. These registries should attempt to include all affected patients in the UK, and collect longitudinal patient level data on clinically relevant problems, interventions received and quality of life in a utility format.