Genomic tool may predict MS severity
Monash University researchers have used data from the MSBase registry to develop a genome-based tool that can predict the course of multiple sclerosis.
Led by Dr Vilija Jokubaitis (PhD) of the Department of Neuroscience, an international team used a genome-wide association study and machine learning approaches to assess the genetic contribution to longitudinally defined MS severity phenotypes in 1,813 people with relapse-onset MS.
No variants with moderate to large effect sizes were identified, but clinical outcomes in MS were found to be associated with multiple genetic loci of small effect sizes.
Using a machine learning approach incorporating over 62,000 variants and demographic variables available at MS disease onset, they could predict severity with an area under the receiver operator curve (AUROC) of 0.87 (95% CI 0.83 – 0.91). The classification algorithm had 86% sensitivity and 88% specificity, with a positive predictive value (PPV) of 89% and negative predictive value (NPV) of 85%.
“This approach, if externally validated, could quickly prove useful for clinical stratification at MS onset,” they wrote in a paper published on the preprint server medRxiv.
The analysis also found evidence to support CNS and mitochondrial involvement in determining MS severity, they added, with an overrepresentation of genes expressed in the cerebellum relating to mitochondrial function, synaptic plasticity, cellular senescence, calcium and the g-protein receptor signalling pathway.
Antiseizure medication adjustment needed in pregnancy
Some women with epilepsy may need dose adjustments of their antiseizure medications during pregnancy to counter declines in plasma levels that can occur from the first trimester, US researchers say.
A University of Pittsburg study of 430 women with epilepsy found that those taking lamotrigine, levetiracetam, lacosamide, oxcarbazepine, and zonisamide experienced significant decreases in dose-normalised concentrations during pregnancy.
Dose-normalised concentrations also decreased for carbamazepine but remained stable for unbound carbamazepine and carbamazepine-10,11-epoxide, according to findings published in JAMA Neurology.
The researchers said pregnancy was a challenging time for balancing the goal of seizure control and avoiding exposure of the fetus to anti-seizure medications. Pregnancy-induced pharmacokinetic changes caused by decreased protein binding, altered hepatic metabolism, increased kidney blood flow could both increase or decrease levels of antiseizure medications, they said.
The findings showed that changes in levels of medications such as lamotrigine and levetiracetam occurred early in pregnancy ( first trimester), “which suggests that it is not sufficient to wait until later in pregnancy to consider therapeutic drug monitoring and dose changes,” the authors said.
Male doctors won’t shed facial hair for N95 masks
Almost half the male hospital staff required to wear a P2/N95 respirator during the COVID-19 pandemic have beards or facial hair that would potentially render them ineffective, an audit carried out in a Victorian tertiary centre has found.
Despite successfully completing fit testing with a clean shaven face in the preceding year, 45% of the 110 male staff working in three critical areas of a hospital (ICU, ED and operating theatres) were observed to have beards or to not be clean shaven in the face seal zone of their respirators.
Writing in the journal Infection, Disease and Health, the study authors said it was imperative that clinical staff were clean shaven in the face seal zone of their respirators so they are fit-for-purpose and ready to respond during periods of significant community transmission of COVID-19.
“Health care organisations allowing employees to have facial hair where N95 protection is required may be breaching their duty of care under OHS laws,” they wrote.
Male staff “experiencing a loss of identity or significant skin irritation with daily shaving should be supported so that their respiratory protection is optimised, not only to protect themselves from harm, but also to safeguard those they work with and care for,” they added.