Moreover, diagnosis of PLMD cannot be used when narcolepsy, restless legs syndrome (RLS), REM sleep behaviour disorder (RBD) or untreated obstructive sleep apnea (OSA) is already diagnosed, since abnormal movements during sleep are frequent in these disorders. Signs and symptoms
People with PLMD often have excessive daytime sleepiness (EDS), falling asleep during the day, trouble falling asleep at night, and difficulty staying asleep throughout the night. Patients also display involuntary limb movements that occur at periodic intervals anywhere from 20 to 40 seconds apart. They often only last the first half of the night during non-REM sleep stages. Movements do not occur during REM because of muscle atonia. PLMS can be unilateral or bilateral and not really symmetrical or simultaneous. PLMS is often a symptom of RLS but evidence for differences between those two sleep disorders was found in literature. Sleep structure differed, when RLS patients had significantly more REM sleep and less stage 1 sleep compared to PLMD patients. Besides, PLMI was significantly higher in patients with PLMD. Causes
It is mostly unknown what causes PLMD, but in many cases the patient also has other medical problems such as Parkinsons disease or narcolepsy. Medical agents must be taken into consideration: several psychopharmacological drugs (serotonergic and tricyclic antidepressants, venlafaxine and mirtazapine) heighten the risk of PLMD.
The mean effective half-life of elexacaftor, tezacaftor, and ivacaftor is 27.4 hours, 25.1 hours, and 15 hours, respectively. History
A phase III trial showed people treated with elexacaftor/tezacaftor/ivacaftor improved in FEV1 at four weeks with sustained improvement at 24 weeks. Rate of pulmonary exacerbation was 63% lower and sweat chloride concentration was 41.8 mmol/L lower. Its effectiveness is dependent on the type of CF mutations the patient has. Society and culture
Legal status
United States
The combination was approved for use in the United States in 2019 for people twelve years and older with cystic fibrosis who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is estimated to represent 90% of the cystic fibrosis population. In December 2020, after an additional clinical trial was completed, and FDA approval was expanded for 177 other cystic fibrosis mutations. FDA approval for children aged 6–11 was added in January 2021, after a third clinical trial was completed.The U.S. Food and Drug Administration (FDA) granted the application priority review, in addition to fast track, breakthrough therapy, and orphan drug designations. The drugs manufacturer Vertex Pharmaceuticals will receive a rare pediatric disease priority review voucher for having developed this therapy. Australia
In March 2021, health regulators in Australia approved trikafta for patients aged 12 years and older with at least one copy of the F508del mutation. At the end of April 2022, it was placed on PBS, thus reducing the cost from tens of thousands of dollars a month, to tens of dollars a month.