Patient and caregiver experiences with pantothenate kinase-associated neurodegeneration (PKAN): results from a patient community survey.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disorder of PANK2, which enables mitochondrial synthesis of coenzyme A. Its loss causes neurodegeneration with iron accumulation primarily in motor-related brain areas. Symptoms include dystonia, parkinsonism, and other disabilities. PKAN has been categorized as classic PKAN, with an age of onset ≤ 10 years, rapid progression, and early disability or death; and atypical PKAN, with later onset, slower progression, generally milder, and more diverse symptom manifestations. Available treatments are mostly palliative. Information on the lived experience of patients with PKAN and their caregivers or on community-level disease burden is limited. It is necessary to engage patients as partners to expand our understanding and improve clinical outcomes. This patient-oriented research study used multiple-choice and free-form question surveys distributed by patient organizations to collect information on the manifestations and disease burden of PKAN. It also assessed respondents' experiences and preferences with clinical research to inform future clinical trials. RESULTS: The analysis included 166 surveys. Most respondents (87%) were parents of a patient with PKAN and 7% were patients, with 80% from Europe and North America. The study cohort included 85 patients with classic PKAN (mean ± SD age of onset 4.4 ± 2.79 years), 65 with atypical PKAN (13.8 ± 4.79 years), and 16 identified as "not sure". Respondents reported gait disturbances and dystonia most often in both groups, with 44% unable to walk. The classic PKAN group reported more speech, swallowing, and visual difficulties and more severe motor problems than the atypical PKAN group. Dystonia and speech/swallowing difficulties were reported as the most challenging symptoms. Most respondents reported using multiple medications, primarily anticonvulsants and antiparkinsonian drugs, and about half had participated in a clinical research study. Study participants reported the most difficulties with the physical exertion associated with imaging assessments and travel to assessment sites. CONCLUSIONS: The survey results support the dichotomy between classic and atypical PKAN that extends beyond the age of onset. Inclusion of patients as clinical research partners shows promise as a pathway to improving clinical trials and providing more efficacious PKAN therapies.

Polyisobutylene and Silicone in Warm Edge Glazing Systems-Evaluation of Long-Term Performance.

This article describes the characteristics of one type of sealing system used in warm edge glazing units and analyses the possible causes of damage. Attention was focused on the performance of the dual seal, PIB/silicone system. This type of glazing is widely used for modern curtain walls and roofs of office buildings and shopping centres. Study was focused on PIB displacement defects, which affects both the appearance and thermal performance of the curtain wall system. Wide-ranging field surveys were conducted to examine the problems identified in some office buildings. The information gathered in this way was used to identify the critical areas and causes of seal displacement in the analysed insulating glass units (IGUs). Laboratory tests were conducted on PIB and silicone seals retrieved from the removed defective units. The properties of these materials were determined and used to evaluate the applied edge sealing system and build a representative numerical model. Due to the problems encountered in deriving accurate analytical formulas, finite element (FE) approximation was used as a problem solving tool. The generated FE model and strain analysis were the key parts to obtaining a true representation of the actual behaviour of IGUs subjected to various environmental loads, taking into account the influence of the air cavity. Results of computer simulations and laboratory tests were compared for model validation. The effect of changes in ambient pressure was examined, showing the development of tensile strains in the silicone and PIB, which can lead to debonding. The greatest principal strains occur at the silicone/butyl rubber interface and this location should be considered to be the most susceptible to failure. The observations are summarised in the final conclusions. Additionally, as field study showed, after ten years in service, the percentage of damaged units is considerable. More frequent IGUs inspection should cover both appearance and thermal imaging to detect unsealed panels. From the standpoint of both durability and appearance, dual silicone/PIB should be phased out in favour of modern seal systems.