Some aspects of the glass transition of polyvinylpyrrolidone depending on the molecular mass.

Amorphous polymers currently have a wide range of applications, including the production of amorphous solid dispersions in the pharmaceutical industry. This application requires knowledge of the kinetic parameters of the glass transition process, which are the key to the formation of the end product. In the present work, we have thoroughly investigated the glass transition in the biocompatible polymer polyvinylpyrrolidone as a function of the polymer molecular mass, using differential scanning calorimetry, fast scanning calorimetry, and broadband dielectric spectroscopy. We have determined the dependence of the difference between the isobaric specific heat capacities of the liquid and the glass on the dynamic glass transition temperature, volume, and number of particles included in the cooperatively rearranging regions. A linear dependence between the shift factor from the Frenkel-Kobeko-Reiner equation and the molecular mass of polyvinylpyrrolidone was established. The results of the present work help in choosing the optimal excipient for the development of solid dispersions based on amorphous polymers.

The Impact of Upcoming Treatments in Huntington's Disease: Resource Capacity Limitations and Access to Care Implications.

BACKGROUND: The most advanced disease-modifying therapies (DMTs) in development for Huntington's disease (HD) require intrathecal (IT) administration, which may create or exacerbate bottlenecks in resource capacity. OBJECTIVE: To understand the readiness of healthcare systems for intrathecally administered HD DMTs in terms of resource capacity dynamics and implications for patients' access to treatment. METHODS: Forty HD centres across 12 countries were included. Qualitative and quantitative data on current capacity in HD centres and anticipated capacity needs following availability of a DMT were gathered via interviews with healthcare professionals (HCPs). Data modelling was used to estimate the current capacity gap in HD centres. RESULTS: From interviews with 218 HCPs, 25% of HD centres are estimated to have the three components required for IT administration (proceduralists, nurses and facilities). On average, 114 patients per centre per year are anticipated to receive intrathecally administered DMTs in the future. At current capacity, six of the sampled centres are estimated to be able to deliver DMTs to all the anticipated patients based on current resources. The estimated waiting time for IT administration at current capacity will average 60 months (5 years) by the second year after DMT availability. CONCLUSION: Additional resources are needed in HD centres for future DMTs to be accessible to all anticipated patients. Timely collaboration by the HD community will be needed to address capacity gaps. Healthcare policymakers and payers will need to address costs and navigate challenges arising from country- or region-specific healthcare delivery schemes.

Criteria for the diagnosis of neurosyphilis in cerebrospinal fluid: relationships with intrathecal immunoglobulin synthesis and blood-cerebrospinal fluid barrier dysfunction.

BACKGROUND: The origin of cerebrospinal fluid (CSF) syphilis antibodies (intrathecal or blood-derived) is in doubt. Little is known about CSF test behavior under the condition of physiological or disturbed functioning of blood-CSF barrier (BCB) and intrathecal immunoglobulin (Ig) production. METHODS: We collected 126 serum/CSF pairs from patients with serological evidence of syphilis. We explored the relationships between the established facts of intrathecal Ig synthesis and/or BCB dysfunction and the results of CSF diagnostic tests: the Treponema pallidum hemagglutination (TPHA) test, the fluorescent treponemal antibody absorption (FTA-Abs) test, the Venereal Disease Research Laboratory (VDRL) test, and white blood cell counts. We checked the criteria used either to support or refute the diagnosis of neurosyphilis. RESULTS: Reactive CSF-VDRL tests, elevated CSF-white blood cell counts, and elevated CSF-TPHA titers/indices were associated with the signs of intrathecal Ig synthesis, whereas nonreactive CSF-fluorescent treponemal antibody absorption, nonreactive CSF-TPHA tests, and CSF-TPHA titers from 1:4 to 1:160 were associated with cases where the intrathecal synthesis was not detected. There were some peculiarities of the tests toward BCB dysfunction.Most of reactive CSF-VDRL test samples and CSF samples with pleocytosis were also meeting at least 1 of the CSF-TPHA titer/indices-based criteria. T. pallidum hemagglutination indices were in no better conformity with the facts of intrathecal immune response than CSF-TPHA titers. CONCLUSIONS: Our findings have shown that all the examined criteria for the diagnosis of neurosyphilis in CSF are different assessment tools of intrathecal humoral immune activity and support the hypothesis that high CSF treponemal-specific antibody titers are a consequence of inflammatory pathology of the central nervous system.