Narcolepsy Severity Scale-2 and Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and consequences in Narcolepsy type 2.

STUDY OBJECTIVES: Narcolepsy type 2 (NT2) is an understudied central disorder of hypersomnolence sharing some similarities with narcolepsy type 1 and idiopathic hypersomnia (IH). We aimed: (1) to assess systematically the symptoms in patients with NT2, with self-reported questionnaires: Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scale (NSS), IH Severity Scale (IHSS), and (2) to evaluate the responsiveness of these scales to treatment. METHODS: One hundred and nine patients with NT2 (31.4 ±â€…12.2 years old, 47 untreated) diagnosed according to ICSD-3 were selected in a Reference Center for Narcolepsy. They all completed the ESS, subgroups completed the modified NSS (NSS-2, without cataplexy items) (n = 95) and IHSS (n = 76). Some patients completed the scales twice (before/during treatment): 42 ESS, 26 NSS-2, and 30 IHSS. RESULTS: Based on NSS-2, all untreated patients had sleepiness, 58% disrupted nocturnal sleep, 40% hallucinations, and 28% sleep paralysis. On IHSS, 76% reported a prolonged nocturnal sleep, and 83% sleep inertia. In the independent sample, ESS and NSS-2 scores were lower in treated patients, with same trend for IHSS scores. After treatment, ESS, NSS-2, and IHSS total scores were lower, with a mean difference of 3.7 ±â€…4.1, 5.3 ±â€…6.7, and 4.1 ±â€…6.2, respectively. The minimum clinically important difference between untreated and treated patients were 2.1 for ESS, 3.3 for NSS-2, and 3.1 for IHSS. After treatment, 61.9% of patients decreased their ESS > 2 points, 61.5% their NSS-2 > 3 points, and 53.3% their IHSS > 3 points. CONCLUSIONS: NSS-2 and IHSS correctly quantified symptoms' severity and consequences in NT2, with good performances to objectify response to medications. These tools are useful for monitoring and optimizing NT2 management, and for use in clinical trials.

Functional recovery after ischemic stroke: Impact of different sleep health parameters.

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep.

Are the deprescribing guidelines for proton pump inhibitors in palliative care applicable? A monocentric observational study.

OBJECTIVES: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. The aim of this study was to assess the appropriateness of prescribing PPIs in the palliative care unit on admission and during hospitalisation to determine the applicability of deprescribing recommendations. METHODS: A monocentric observational study was conducted over a 6-month period in 2020 in a university palliative care unit. Data on indication, starting date, dose and posology were collected at discharge from the medical record and by contacting the prescriber. A physician and a pharmacist evaluated PPI prescription appropriateness according to guidelines. RESULTS: 131 patients (mean age: 69.5 years; 82% with cancer) were included. Prior to admission, 41% (54/131) of patients were already prescribed PPIs. During hospitalisation, 50% of prescriptions were discontinued, while 12% were initiated. The indication was known for 50% of patients on admission and 59% during their stay. Among patients with PPI prescriptions, 56% had a relevant indication on admission, and 63% during their stay. The prevalence of potential drug interactions was low (<1/10). CONCLUSIONS: While PPIs remain essential for specific indications, this study highlights their excessive prescription even during palliative care. Implementing deprescribing recommendations in this population is crucial to optimise treatment plans.

Changes in Sleep Pattern During the COVID-19 Lockdown in Patients With Narcolepsy, Idiopathic Hypersomnia, and Restless Legs Syndrome.

BACKGROUND AND OBJECTIVES: To explore the first coronavirus disease 2019 (COVID-19) lockdown effect on sleep symptoms in patients with narcolepsy, idiopathic hypersomnia (IH), and restless legs syndrome (RLS). METHODS: Between March and May 2020, a sample of adult patients regularly followed up in a Reference Hospital Sleep Unit (299 with narcolepsy, 260 with IH, and 254 with RLS) was offered an online survey assessing their sleep-wake habits, daily activities, medication intake, and validated scales: International RLS Study Group questionnaire, Narcolepsy Severity Scale (NSS), IH Severity Scale (IHSS), Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Beck Depression Inventory-II, and European Quality of Life (QoL) scale. The survey was proposed once, and the questions were answered for the prelockdown (recall of the month before the confinement) and the lockdown (time of study) periods. RESULTS: Overall, 331 patients completed the survey (response rate 40.7%): 102 with narcolepsy, 81 with IH, and 148 with RLS. All patients reported later bedtimes, with reduced differences for time in bed (TIB) and total sleep time (TST) over 24 hours between weekdays and weekends. Patients with narcolepsy spent more TIB and increased TST overnight, with more daytime napping. They had more awakenings, higher ESS scores, lower QoL, and no NSS changes. Patients with IH also increased their TIB, TST overnight and 24 hours on weekdays. Nocturnal sleep latency and the number of awakenings increased but with no change in ESS, QoL, and IHSS scores. Patients with RLS reported longer nocturnal sleep latency, more awakenings, more naps, decreased TIB, and TST overnight. RLS severity increased while QoL decreased. A significant portion of patients reported disease worsening during the lockdown (narcolepsy: 39.4%, IH: 43.6%, and RLS: 32.8%), and some patients stopped or lowered their medication (narcolepsy: 22.5%, IH: 28%, and RLS: 9.5%). DISCUSSION: During the lockdown, all patients reported later bedtimes; those with narcolepsy and IH extended their sleep duration unlike patients with RLS. These changes were often associated with negative consequences on QoL. In the current context of recurrent COVID-19 waves, the recent development of teleconsultations should enable physicians to monitor patients with chronic sleep disorders more closely and to recommend optimized sleep schedules and duration, in order to prevent psychological problems and improve their QoL.

Depressive Symptoms and Suicidal Thoughts in Restless Legs Syndrome.

BACKGROUND: Whether depression and suicide thoughts relate to restless legs syndrome (RLS) or comorbidities associated with RLS remain unclear. OBJECTIVES: To determine frequency of depressive symptoms and suicidal thoughts in patients with RLS and their change after RLS treatment, associated clinical and polysomnographic factors, and current major depressive episode (MDE) frequency and suicide risk in RLS. METHODS: Overall, 549 untreated patients with RLS and 549 age-, sex-, and education level-matched controls completed a standardized evaluation, including the Beck Depression Inventory-II that has one item on suicide thoughts. Patients underwent a polysomnographic recording and completed the Urgency, Premeditation, Perseverance, Sensation Seeking Impulsive Behavior scale. In a subgroup of 153 patients, current MDE and suicide risk were assessed with the face-to-face Mini-International Neuropsychiatric Interview (MINI). A subgroup of 152 patients were evaluated in untreated and treated conditions. RESULTS: The frequency of depressive symptoms (32.5%) and suicidal thoughts (28%) was 10-fold and 3-fold higher, respectively, in patients with RLS than controls. Current MDE (10.5%) and suicidal risk (19.9%) (MINI) were also high. Moderate-to-severe depressive symptoms were associated with young age, female sex, insomnia symptoms, and urgency dimension. The suicide risk was associated with depression, impulsiveness, and RLS severity. RLS treatment improved depressive symptoms but not suicidal thoughts. CONCLUSION: The rate of depressive symptoms, depression, and suicidal thoughts/risk was higher in patients with RLS, with key associations with insomnia symptoms, urgency dimension, and RLS severity. These results emphasize the importance of detecting these symptoms in current practice and of evaluating their change after treatment, especially in young women, to improve RLS management. © 2022 International Parkinson and Movement Disorder Society.

Nitrogen starvation reveals the mitotic potential of mutants in the S/MAPK pathways.

The genetics of quiescence is an emerging field compared to that of growth, yet both states generate spontaneous mutations and genetic diversity fueling evolution. Reconciling mutation rates in dividing conditions and mutation accumulation as a function of time in non-dividing situations remains a challenge. Nitrogen-starved fission yeast cells reversibly arrest proliferation, are metabolically active and highly resistant to a variety of stresses. Here, we show that mutations in stress- and mitogen-activated protein kinase (S/MAPK) signaling pathways are enriched in aging cultures. Targeted resequencing and competition experiments indicate that these mutants arise in the first month of quiescence and expand clonally during the second month at the expense of the parental population. Reconstitution experiments show that S/MAPK modules mediate the sacrifice of many cells for the benefit of some mutants. These findings suggest that non-dividing conditions promote genetic diversity to generate a social cellular environment prone to kin selection.

Quiescence unveils a novel mutational force in fission yeast.

To maintain life across a fluctuating environment, cells alternate between phases of cell division and quiescence. During cell division, the spontaneous mutation rate is expressed as the probability of mutations per generation (Luria and Delbrück, 1943; Lea and Coulson, 1949), whereas during quiescence it will be expressed per unit of time. In this study, we report that during quiescence, the unicellular haploid fission yeast accumulates mutations as a linear function of time. The novel mutational landscape of quiescence is characterized by insertion/deletion (indels) accumulating as fast as single nucleotide variants (SNVs), and elevated amounts of deletions. When we extended the study to 3 months of quiescence, we confirmed the replication-independent mutational spectrum at the whole-genome level of a clonally aged population and uncovered phenotypic variations that subject the cells to natural selection. Thus, our results support the idea that genomes continuously evolve under two alternating phases that will impact on their size and composition.

New 17-methyl-13-octadecenoic and 3,16-docosadienoic acids from the sponge Polymastia penicillus.

The phospholipid fatty acid composition of the North-East Atlantic sponge Polymastia penicillus (South Brittany, France) was investigated. Sixty fatty acids (FA) were identified as methyl esters (FAME) and N-acyl pyrrolidides (NAP) by gas chromatography-mass spectrometry (GC/MS), including eight Delta5,9 unsaturated FA and three long-chain 2-hydroxylated FA. The major phospholipid FA were palmitic (14.3% of the total FA mixture), vaccenic (12.7%), 15(Z)-docosenoic (13.4%) and 5(Z),9(Z)-hexacosadienoic (13.3%) acids. In addition to the iso- and anteiso-branched saturated FA, several unusual short-chain branched saturated FA were identified. In addition to the known Delta5,9 FA, and interestingly regarding their identification by GC-MS as N-acyl pyrrolidides, was the co-occurrence of unusual FA possessing a Delta3, Delta4 and Delta5 double bond such as iso-4-pentadecenoic, iso-5-heptadecenoic, anteiso-5-heptadecenoic and two new compounds, not hitherto found in nature, namely 17-methyl-13-octadecenoic (0.8%) and 3,16-docosadienoic (1.1%) acids.