Clinician Perspectives of Gene Therapy as a Treatment Option for Duchenne Muscular Dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a progressive, life-limiting, neuromuscular disorder. Clinicians play an important role in informing families about therapy options, including approved gene therapies and clinical trials of unapproved therapies. Objective: This study aimed to understand the perspectives of clinicians about gene therapy for DMD, which has not previously been studied. Methods: We conducted interviews with specialist clinicians treating patients with DMD in the United States (n = 8) and United Kingdom (n = 8). Interviews were completed in 2022, before any approved gene therapies, to gain insight into barriers and facilitators to implementing gene therapy and educational needs of clinicians. Results: Most respondents expressed cautious optimism about gene therapy. Responses varied regarding potential benefits with most expecting delayed progression and duration of benefit (1 year to lifelong). Concern about anticipated risks also varied; types of anticipated risks included immunological reactions, liver toxicity, and cardiac or renal dysfunction. Clinicians generally, but not uniformly, understood that gene therapy for DMD would not be curative. Most reported needing demonstrable clinical benefit to justify treatment-related risks. Conclusions: Our data demonstrate variability in knowledge and attitudes about gene therapy among clinicians who follow patients with DMD. As our knowledge base about DMD gene therapy grows, clinician education is vital to ensuring that accurate information is communicated to patients and families.

An online survey on burden of illness among families with post-stem cell transplant mucopolysaccharidosis type I children in the United States.

BACKGROUND: Severe mucopolysaccharidosis type I (also known as Hurler syndrome) is a rare devasting recessive genetic disease caused by the deficiency of an enzyme. Hematopoietic stem cell transplant is the standard of care in the United States, usually conducted before the child is 3 years of age, but little is known about the continued medical and educational needs of the child after transplant. A greater understanding of the burden of illness on the primary caregiver is also needed. Therefore, this online survey sought to gather information on the burden of severe MPS I in the United States at least 1 year after transplant. RESULTS: Thirty-two respondents reported that children with severe MPS I have significant medical and educational needs after transplant. Healthcare resource use was frequent, especially in the outpatient setting specifically for bone, cardiac, and vision complications that were not relieved by HSCT. Twenty-five percent of the children had been hospitalized at least once in the last year and two had been hospitalized twice. The most common reasons for overnight hospitalizations included orthopedic surgeries and respiratory infections. Among children ages 5 and older, only 3 of 28 (11%) were able to attend school with no special support. While caregivers were generally satisfied with the healthcare services their child receives, 69% of working caregivers reported negative impact on their ability to conduct work tasks, and 54% of caregivers did not work so that they could care for the child. CONCLUSIONS: Results suggest that severe MPS I children continue to  require medical care and special support for education. Future research on the burden of illness on families affected by severe MPS I is needed to better understand total cost of care, and to identify therapies and interventions that reduce burden of illness. Future studies that compare cost of and access to health care in different countries may provide a more global view of the burden of MPS I.

Principles for interactions with biopharmaceutical companies: the development of guidelines for patient advocacy organizations in the field of rare diseases.

BACKGROUND: Rare diseases are a global public health concern, affecting an estimated 350 million individuals. Only 5% of approximately 7000 known rare diseases have a treatment, and only about half have a patient advocacy organization. Biopharmaceutical companies face complex challenges in developing treatments for rare diseases. Patient advocacy organizations may play a major role by positively influencing research and development, clinical trials, and regulations. Thus, collaboration among patient advocacy organizations and industry is essential to bring new therapeutics to patients. METHODS: We identified an unmet need for guidelines on day-to-day decision-making by rare disease patient advocacy organizations when working with biopharmaceutical partners. We convened an Independent Expert Panel experienced in collaborations between patient advocacy organizations and biopharmaceutical companies (April 2017) to develop consensus guidelines for these relationships. The guidelines were based on an original version by the International Fibrodysplasia Ossificans Progressiva Association (IFOPA). The Expert Panel reviewed and broadened these to be applicable to all patient advocacy organizations. Comments on the draft Guidelines were provided first by Panel participants and subsequently by six independent experts from patient advocacy organizations and industry. RESULTS: The Panel comprised four experts from the rare disease community who lead patient advocacy organizations; three leaders who perform advocacy functions within biopharmaceutical companies; and two facilitators, both having leadership experience in rare diseases and industry. The finalized Guidelines consist of four main sections: Identification and Engagement With Companies, Patient Engagement and Patient Privacy, Financial Contributions, and Clinical Trial Communication and Support. The Guidelines address the daily considerations, choices, and consequences of patient advocacy organizations as they engage with biopharmaceutical companies, and offer recommendations for volunteer/paid leaders of the organizations on how to interact in a thoughtful, responsible, ethical way that engenders trust. CONCLUSIONS: These Guidelines recommend best practices and standards for interactions between patient advocacy organizations and industry that will ultimately have a positive effect on the development of novel treatments. Patient advocacy organizations will be provided free access to these Guidelines to help bring clarification to day-to-day decision-making around their interactions, and for use as a living document with the potential for regular revisions and updates.

A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.

OBJECTIVE: To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). METHODS: Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score >/=4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. RESULTS: Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer >/=1:80 and/or anti-double-stranded DNA [anti-dsDNA] >/=30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician's global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. CONCLUSION: Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.

Hemocromatosis: presentación de dos casos clinicos / Hemochromatosis: Clinic presentation of two cases

Presentamos dos casos de hemocromatosis, uno de ellos en etapas avanzadas de la enfermedad con disfunción multiorgánica y asociada a tuberculosis hepatocelular. El otro caso, hallazgo casual en etapas tempranas de la enfermedad, recibió orientación médica oportuna y temprana para planificar la progresión de la enfermedad. Recordamos la triada clásica pero tardía: diabetes mellitus, cirrosis e hiperpigmentación cutánea; otros hallazgos importantes son: la insuficiencia cardiaca, la artropatía y el hipogonadismo. El tratamiento consiste en disminuir la carga sérica y los depósitos de hierro, con flebotomías programadas monitorizando la concentración sanguínea de este elemento y los niveles de ferritina. La desferroxamina es una alternativa terapéutica interesante en las personas que no son candidatas a flebotomías.

Estudio químico-microbiológico comparativo de dos soluciones propuestas para la desinfección de endoscopios / Comparative chemical-microbiological study of two solutions for endoscopes desinfections

Se evaluó desde el punto de vista químico-microbiológico la actividad germicida de una solución propuesta para la desinfección del instrumental de endoscopia, (peróxido de hidrógeno al 7 porciento. Se tomó como solución de referencia el glutaraldehído al 2 porciento. Las soluciones fueron ensayadas a las concentraciones propuestas por los fabricantes y se expusieron frente al instrumental durante 20 min, tiempo indicado por los mismos. Se obtuvo como resultado de la valoración microbiológica que la solución de peróxido de hidrógeno al 7 porciento brinda un 100 porciento de inhibición de unidades formadoras de colonias microbianas comparadas con la solución de glutaraldehído al 2 porciento la cual ofrece un 100 porciento de inhibición. Como resultado de los ensayos químicos de compatibilidad de materiales en los cuales se desarrollaron pruebas de corrosión, enfrentamiento de las soluciones a diferentes polímeros y a 2 clases de cristales resultaron satisfactorios para las soluciones propuestas(AU)

Estudio químico-microbiológico comparativo de dos soluciones propuestas para la desinfección de endoscopios / Comparative chemical-microbiological study of two solutions for endoscopes desinfections

Se evaluó desde el punto de vista químico-microbiológico la actividad germicida de una solución propuesta para la desinfección del instrumental de endoscopia, (peróxido de hidrógeno al 7 porciento. Se tomó como solución de referencia el glutaraldehído al 2 porciento. Las soluciones fueron ensayadas a las concentraciones propuestas por los fabricantes y se expusieron frente al instrumental durante 20 min, tiempo indicado por los mismos. Se obtuvo como resultado de la valoración microbiológica que la solución de peróxido de hidrógeno al 7 porciento brinda un 100 porciento de inhibición de unidades formadoras de colonias microbianas comparadas con la solución de glutaraldehído al 2 porciento la cual ofrece un 100 porciento de inhibición. Como resultado de los ensayos químicos de compatibilidad de materiales en los cuales se desarrollaron pruebas de corrosión, enfrentamiento de las soluciones a diferentes polímeros y a 2 clases de cristales resultaron satisfactorios para las soluciones propuestas

Dispositivos médicos de uso único reprocesados por esterilización química mediante óxido de etileno / Medical equipment of unique use reprocessed by chemical sterilization with ethylene oxide

Se determinaron los valores de concentración de residuos de óxido de etileno en dispositivos médicos de uso único procesados cuatro veces mediante la esterilización química con este gas como agente esterilizante. Las evaluaciones fueron realizadas a catéteres utilizados en maniobras semicríticas con riesgo de contacto con tejido estéril. La extracción de los residuales fue realizada por medio de solventes orgánicos y su determinación cuantitativa mediante un método espectrofotométrico. Se observó la disminución de los niveles de residuos en un tiempo mínimo de tres días después de una primera reesterilización del dispositivo, se comprobó el incremento en la concentración de residuos por adhesión a la superficie del material en sucesivas reesterilizaciones de un mismo dispositivo. Se observó deterioro del material después de la tercera reesterilización, invisible a simple vista, lo que trae como consecuencia riesgos en la funcionalidad del dispositivo y de infección para el paciente(AU)

Dispositivos médicos de uso único reprocesados por esterilización química mediante óxido de etileno / Medical equipment of unique use reprocessed by chemical sterilization with ethylene oxide

Se determinaron los valores de concentración de residuos de óxido de etileno en dispositivos médicos de uso único procesados cuatro veces mediante la esterilización química con este gas como agente esterilizante. Las evaluaciones fueron realizadas a catéteres utilizados en maniobras semicríticas con riesgo de contacto con tejido estéril. La extracción de los residuales fue realizada por medio de solventes orgánicos y su determinación cuantitativa mediante un método espectrofotométrico. Se observó la disminución de los niveles de residuos en un tiempo mínimo de tres días después de una primera reesterilización del dispositivo, se comprobó el incremento en la concentración de residuos por adhesión a la superficie del material en sucesivas reesterilizaciones de un mismo dispositivo. Se observó deterioro del material después de la tercera reesterilización, invisible a simple vista, lo que trae como consecuencia riesgos en la funcionalidad del dispositivo y de infección para el paciente