Patient-reported experience with Fabry disease and its management in the real-world setting: results from a double-blind, cross-sectional survey of 280 respondents.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with a heterogeneous clinical presentation. Patients with FD may exhibit early signs/symptoms including neuropathic pain, gastrointestinal complaints, and dermatologic manifestations. FD may ultimately progress to renal, neurologic, and cardiac dysfunction. Current treatments for FD have significantly improved the management and outcomes for patients with FD, but important clinical and convenience limitations still exist. METHODS: To illuminate the impact of FD on daily life from the patient's perspective, we asked adult patients (≥ 18 years old) with FD in the United States and Canada to complete a 33-question online survey to assess patient-reported disease severity, management, and treatment outcomes. RESULTS: A total of 280 respondents with FD completed the survey; they had a mean age of 47 years, and 68% (191/280) were women. Most were currently receiving FD treatment (84%, 234/280) with enzyme replacement therapy (ERT) (89%, 208/234) or chaperone therapy (11%, 26/234). Common symptoms included low energy/fatigue (72%, 201/280), tingling (62%, 174/280) or pain in the hands/feet (60%, 168/280), ringing in ears/hearing loss (54%, 151/280), general body pains/pain crises (51%, 143/280), and abdominal/stomach pain (50%, 140/280). More than half (51%, 144/280) of respondents reported their symptoms as bothersome (38%, 106/280) or difficult to control (14%, 38/280). Temporary symptom worsening between infusions was reported by about half of respondents: 51% (108/211) currently receiving ERT and 48% (14/29) previously receiving ERT. Only 48% (59/122) of respondents reported their symptom worsening to their physician. Of those who reported it, 41% (24/59) said that their physician prescribed medication to manage their symptoms or changed their treatment regimen. CONCLUSIONS: Our analysis highlights the gap between current standard-of-care in disease monitoring and patient perception of disease progression among patients with FD. This information may be helpful for healthcare providers and drug developers seeking to improve the care of patients with FD by addressing unmet needs of high relevance.

Symptoms and Quality of Life in Patients with Fabry Disease: Results from an International Patient Survey.

INTRODUCTION: Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A. Symptoms include neuropathic pain and gastrointestinal problems, such as diarrhoea. To inform and support the design of a Phase III clinical trial for a new oral treatment for Fabry disease, this study evaluated patients' experiences of Fabry disease symptoms, the impact of symptoms on their quality of life, and their views on participating in clinical trials. METHODS: An online survey questionnaire was distributed to patients with Fabry disease, through relevant patient organisations. The questionnaire consisted mainly of quantitative, closed questions with pre-defined response options. Fabry-specific pain intensity and its impact on quality of life were rated on a scale from 0 to 10. RESULTS: In total, 367 patients completed the survey, of whom half reported frequent pain, moderate to severe pain, and pain in their hands and feet. Pain frequency, intensity and location were similar for males and females. There was no clear association between Fabry-specific pain and the use of enzyme replacement therapy (ERT), with moderate to severe pain reported by 80.4% of participants receiving ERT and by 75.0% of participants not receiving ERT. Of participants who were receiving ERT, 35.7% said they were willing to discontinue it to take part in a clinical trial testing a new oral drug for treating Fabry disease. Gastrointestinal symptoms were more heterogeneous in nature and frequency than Fabry-specific pain, but still affected a significant proportion of participants. CONCLUSIONS: Both male and female patients with Fabry disease experience significant Fabry-specific pain, which affects their quality of life. Furthermore, frequent diarrhoea affects many patients. The symptoms occur independently of the use of ERT. This suggests the healthcare needs of patients with Fabry disease are not being fully met, and additional treatments are required to improve symptoms and quality of life. FUNDING: This study was sponsored by Actelion Pharmaceuticals Ltd. Study sponsorship was transferred to Idorsia Pharmaceuticals Ltd in July 2018.

Tormenta tiroidea durante el embarazo: reporte de caso / Thyroid storm in pregnancy: A case report

Resumen ANTECEDENTES: La tormenta tiroidea es una complicación rara del hipertiroidismo, con riesgo 10 veces mayor de aparecer durante el embarazo. El término "tormenta" describe la intensidad de la manifestación clínica y la significativa concentración de tiroxina (T4) y tri-yodotironina (T3). CASO CLÍNICO: Paciente de 25 años, con embarazo de 29 semanas, control prenatal deficiente, enviada al Instituto Nacional Materno Perinatal de Lima, Perú, por taquicardia fetal. A la exploración clínica se encontró: frecuencia cardiaca de 161 latidos por minuto, frecuencia cardiaca fetal de 178; piel caliente, exoftalmos bilateral, uñas de Plumer, bocio difuso 3N bilateral, ingurgitación yugular bilateral, estertores crepitantes bilaterales de predominio en ambas bases y edema en los miembros inferiores. De acuerdo con los criterios de Burch y Wartofsky, se estimó un puntaje de 60 para establecer el diagnóstico de tormenta tiroidea. Se indicaron fármacos antitiroideos, betabloqueadores y medidas de soporte. La paciente tuvo amenaza de parto pretérmino y taquicardia fetal persistente, por lo que se programó para cesárea de urgencia. La evolución para la madre y su hijo fue satisfactoria. CONCLUSIONES: El tamizaje para hipertiroidismo en pacientes embarazadas con antecedentes personales y síntomas relacionados es la mejor medida de prevención de la tormenta tiroidea. La sospecha de tormenta tiroidea debe tratarse de manera inmediata, por un equipo multidisciplinario. El bienestar fetal debe evaluarse continuamente y estimar el tiempo de finalización del embarazo, además de considerar si existen indicaciones poco satisfactorias en cuanto al tratamiento indicado.

Abstract BACKGROUND: Thyroid storm is a rare complication of hyperthyroidism, with 10 times greater risk of developing during pregnancy. The term "storm" describes the intensity of the clinical manifestation and the significant concentration of thyroxine (T4) and tri-iodothyronine (T3). CLINICAL CASE: Woman of 25 years with a gestational age of 29 weeks with poor prenatal control, referred to our institution due to fetal tachycardia. Clinically, he had a heart rate of up to 161 per minute, a fetal heart rate of 178, hot skin, bilateral exophthalmos, Plumer's nails, bilateral 3N diffuse goiter, bilateral jugular vein enlargement, bilateral lung crepitations with predominance of bases, lower limb edema. He presented a score of 60 on the Burch and Wartofsky criteria for thyroid storm. Antithyroid drugs, beta blockers and support measures were established. Patient developed a threat of preterm delivery and persistent fetal tachycardia, so an emergency caesarean section was indicated. CONCLUSIONS: Screening for hyperthyroidism in pregnant women with a personal history and symptoms is the best measure of thyroid storm prevention. The suspicion of thyroid storm should be treated immediately by a multidisciplinary team. Fetal well-being should be evaluated continuously and determine the end of pregnancy if there are fetal indications or the mother does not respond to the treatment established.

Surgical Treatment of Chiari I Malformation.

This article is a discussion of the surgical technique for posterior fossa decompression as treatment for Chiari I malformation. It includes a brief discussion of the indications for surgical treatment as well as a discussion of the risks and benefits of bone-only decompression or decompression with accompanying duraplasty. Most of the text is dedicated to the technical description of the surgical procedure for decompression of the Chiari I malformation with particular attention to techniques aimed at avoiding common complications.

Epidemiology of fracture risk in the Women's Health Initiative.

Osteoporosis is one of the most disabling consequences of aging in women. Strategies that permit earlier identification of women at risk for fracture are needed. The Women's Health Initiative has extended our knowledge of clinical risk factors and biomarkers of fracture risk in postmenopausal women. Based upon 11 clinically available risk factors (age, race/ethnicity, self-reported health, weight, height, physical activity, parental hip fracture, fracture history after age 54, current smoking, corticosteroid use, and history of treated diabetes), an algorithm has been developed to predict 5-year hip fracture risk. Biomarkers including low vitamin D or bioavailable testosterone and/or high cystatin C or sex hormone-binding globulin also predict risk for hip fracture independent of clinical risk factors. To address the growing incidence of fractures in minority women, clinical risk factors for fracture have been identified. These data demonstrate that we can better identify women, irrespective of race or ethnicity, at risk for fracture.

Chiari I malformation and neurofibromatosis type 1.

Single case reports exist in the medical literature of patients with tonsillar ectopia, i.e., the Chiari I malformation and neurofibromatosis type 1. However, large series of patients with either of these entities have not been examined for the presence of both defects. We have retrospectively examined two large groups of pediatric patients: Group I, with the primary diagnosis of Chiari I malformation, who have undergone posterior fossa decompression for symptomatology; and Group II patients, who have been observed in our hospital's neurofibromatosis clinic for evaluation. Of 130 surgically addressed Chiari I malformations (Group I), we determined that 5.4% of these patients had the additional diagnosis of neurofibromatosis type 1. Of Group II patients (198) who underwent imaging of the brain, 8.6% were found to have a concomitant Chiari I malformation. These data suggest that Chiari I malformation and neurofibromatosis type 1 are not spurious findings but rather true associations. We hypothesize that the same early dysgenesis of mesoderm that is widely accepted as a culprit in the genesis of many Chiari I malformations is the same pathology affecting primitive development of tissues involved in many patients with neurofibromatosis type 1. Perhaps these data will aid in the determination of a genetic locus for the Chiari I malformation.