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Biological Trace Element Research Jan 2023To date, no study has critically reviewed the current literature on the association between magnesium (Mg) and sleep health. Therefore, we carried out a systematic...
To date, no study has critically reviewed the current literature on the association between magnesium (Mg) and sleep health. Therefore, we carried out a systematic review to assess the association between Mg and sleep patterns in adults' population through observational and interventional studies. We searched for relevant studies through PubMed ( http://www.ncbi.nlm.nih.gov/pubmed ), Scopus ( http://www.scopus.com ), and ISI Web of Science ( http://www.webofscience.com ) from the earliest available date until November 2021. Eligibility criteria for study selection were guided by the following components identified using the PI(E)CO (Population, Intervention (Exposure), Comparison, Outcome) framework: P (adult population), I(E) (high dietary intake or supplementation of Mg), C (low dietary intake of Mg or placebo group), and O (sleep pattern including sleep duration, sleep-onset latency, night awakenings, sleep stages, and sleep phases). The present study involved 7,582 subjects from 9 published cross-sectional, cohort, and RCT systematically reviewed the possible links between Mg and sleep quality (daytime falling asleep, sleepiness, snoring, and sleep duration) in an adult population. Observational studies suggested an association between Mg statuses and sleep quality, while the RCTs reported contradictory findings. This systematic review revealed an association between magnesium status and sleep quality (daytime falling asleep, sleepiness, snoring, and sleep duration) according to the observational studies, while the randomized clinical trials showed an uncertain association between magnesium supplementation and sleep disorders. The association between dietary magnesium and sleep patterns needs well-designed randomized clinical trials with a larger sample size and longer follow-up time (more than 12 weeks) to further clarify the relationship.
Topics: Adult; Humans; Magnesium; Snoring; Cross-Sectional Studies; Sleepiness; Sleep
PubMed: 35184264
DOI: 10.1007/s12011-022-03162-1 -
BMC Medical Education Feb 2021It has been previously shown that a high percentage of medical students have sleep problems that interfere with academic performance and mental health. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
It has been previously shown that a high percentage of medical students have sleep problems that interfere with academic performance and mental health.
METHODS
To study the impact of sleep quality, daytime somnolence, and sleep deprivation on medical students, we analyzed data from a multicenter study with medical students in Brazil (22 medical schools, 1350 randomized medical students). We applied questionnaires of daytime sleepiness, quality of sleep, quality of life, anxiety and depression symptoms and perception of educational environment.
RESULTS
37.8% of medical students presented mild values of daytime sleepiness (Epworth Sleepiness Scale - ESS) and 8.7% presented moderate/severe values. The percentage of female medical students that presented ESS values high or very high was significantly greater than male medical students (p < 0.05). Students with lower ESS scores presented significantly greater scores of quality of life and perception of educational environment and lower scores of depression and anxiety symptoms, and these relationships showed a dose-effect pattern. Medical students reporting more sleep deprivation showed significantly greater odds ratios of presenting anxiety and depression symptoms and lower odds of good quality of life or perception of educational environment.
CONCLUSIONS
There is a significant association between sleep deprivation and daytime sleepiness with the perception of quality of life and educational environment in medical students.
Topics: Brazil; Female; Humans; Male; Perception; Quality of Life; Sleep Deprivation; Sleepiness; Students, Medical; Surveys and Questionnaires
PubMed: 33596885
DOI: 10.1186/s12909-021-02544-8 -
Pediatrics Sep 2014Chronic sleep loss and associated sleepiness and daytime impairments in adolescence are a serious threat to the academic success, health, and safety of our nation's... (Review)
Review
Chronic sleep loss and associated sleepiness and daytime impairments in adolescence are a serious threat to the academic success, health, and safety of our nation's youth and an important public health issue. Understanding the extent and potential short- and long-term repercussions of sleep restriction, as well as the unhealthy sleep practices and environmental factors that contribute to sleep loss in adolescents, is key in setting public policies to mitigate these effects and in counseling patients and families in the clinical setting. This report reviews the current literature on sleep patterns in adolescents, factors contributing to chronic sleep loss (ie, electronic media use, caffeine consumption), and health-related consequences, such as depression, increased obesity risk, and higher rates of drowsy driving accidents. The report also discusses the potential role of later school start times as a means of reducing adolescent sleepiness.
Topics: Accidents, Traffic; Adolescent; Caffeine; Communications Media; Depression; Humans; Obesity; Sleep; Sleep Deprivation; Sleep Wake Disorders; Young Adult
PubMed: 25157012
DOI: 10.1542/peds.2014-1696 -
Chest Feb 2020Current strategies for the management of OSA reflect a one-size-fits-all approach. Diagnosis and severity of OSA are based on the apnea-hypopnea index and treatment... (Review)
Review
Current strategies for the management of OSA reflect a one-size-fits-all approach. Diagnosis and severity of OSA are based on the apnea-hypopnea index and treatment initiated with CPAP, followed by trials of alternatives (eg, oral appliances) if CPAP "fails." This approach does not consider the heterogeneity of individuals with OSA, reflected by varying risk factors, pathophysiological causes, clinical manifestations, and consequences. Recently, studies using analytic approaches such as cluster analysis have taken advantage of this heterogeneity to identify OSA phenotypes, or subtypes of patients with unique characteristics, that may enable more personalized approaches to prognostication and treatment. Examples include symptom-based subtypes such as "excessively sleepy" and "disturbed sleep" with differing impact of CPAP on symptoms and health-related quality of life. Polysomnographic subtypes, distinguished by respiratory event association with hypoxemia, arousals, or both, exhibit varying risks of cardiovascular disease and response to therapy. This review summarizes the findings from recent cluster analysis studies in sleep apnea and synthesizes common themes to describe the potential role (and limitations) of phenotypic subtypes in precision medicine for OSA. It also highlights future directions, including linking of phenotypes to clinically relevant outcomes, rigorous and transparent assessment of phenotype reproducibility, and need for tools that categorize patients into subtypes, to prospectively validate phenotype-based prognostication and treatment approaches. Finally, we highlight the critical need to include women and more racially/ethnically diverse populations in this area of research if we are to leverage the heterogeneity of OSA to improve patient lives.
Topics: Anthropometry; Arousal; Cardiovascular Diseases; Cluster Analysis; Continuous Positive Airway Pressure; Humans; Hypoxia; Phenotype; Polysomnography; Precision Medicine; Quality of Life; Risk Factors; Sleep Apnea, Obstructive; Sleepiness
PubMed: 31539538
DOI: 10.1016/j.chest.2019.09.002 -
JAMA Neurology Mar 2021Efficacy of cannabidiol has been demonstrated in seizures associated with Lennox-Gastaut and Dravet syndromes but appears not yet to have been established in conditions... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Efficacy of cannabidiol has been demonstrated in seizures associated with Lennox-Gastaut and Dravet syndromes but appears not yet to have been established in conditions with primarily focal seizures, such as tuberous sclerosis complex (TSC).
OBJECTIVE
To evaluate efficacy and safety of 25-mg/kg/day and 50-mg/kg/day cannabidiol dosages vs placebo against seizures associated with TSC.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind, placebo-controlled randomized clinical trial (GWPCARE6) enrolled patients between April 6, 2016, and October 4, 2018; follow-up was completed on February 15, 2019. The trial was conducted at 46 sites in Australia, Poland, Spain, the Netherlands, United Kingdom, and United States. Eligible patients (aged 1-65 years) were those with a clinical diagnosis of TSC and medication-resistant epilepsy who had had at least 8 TSC-associated seizures during the 4-week baseline period, with at least 1 seizure occurring in at least 3 of the 4 weeks, and were currently taking at least 1 antiepileptic medication.
INTERVENTIONS
Patients received oral cannabidiol at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or a matched placebo for 16 weeks.
MAIN OUTCOMES AND MEASURES
The prespecified primary outcome was the change from baseline in number of TSC-associated seizures for cannabidiol vs placebo during the treatment period.
RESULTS
Of 255 patients screened for eligibility, 31 were excluded and 224 were randomized. Of the 224 included patients (median [range] age, 11.4 [1.1-56.8] years; 93 female patients [41.5%]), 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo, with 201 completing treatment. The percentage reduction from baseline in the type of seizures considered the primary end point was 48.6% (95% CI, 40.4%-55.8%) for the CBD25 group, 47.5% (95% CI, 39.0%-54.8%) for the CBD50 group, and 26.5% (95% CI, 14.9%-36.5%) for the placebo group; the percentage reduction from placebo was 30.1% (95% CI, 13.9%-43.3%; P < .001) for the CBD25 group and 28.5% (95% CI, 11.9%-42.0%; nominal P = .002) for the CBD50 group. The most common adverse events were diarrhea (placebo group, 19 [25%]; CBD25 group, 23 [31%]; CBD50 group, 41 [56%]) and somnolence (placebo group, 7 [9%]; CBD25 group, 10 [13%]; CBD50 group, 19 [26%]), which occurred more frequently with cannabidiol than placebo. Eight patients in CBD25 group, 10 in CBD50 group, and 2 in the placebo group discontinued treatment because of adverse events. Twenty-eight patients taking cannabidiol (18.9%) had elevated liver transaminase levels vs none taking placebo.
CONCLUSIONS AND RELEVANCE
Cannabidiol significantly reduced TSC-associated seizures compared with placebo. The 25-mg/kg/day dosage had a better safety profile than the 50-mg/kg/day dosage.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02544763.
Topics: Adolescent; Adult; Anticonvulsants; Cannabidiol; Child; Child, Preschool; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Infant; Internationality; Male; Middle Aged; Seizures; Sleepiness; Treatment Outcome; Tuberous Sclerosis; Young Adult
PubMed: 33346789
DOI: 10.1001/jamaneurol.2020.4607 -
BMJ (Clinical Research Ed.) Aug 2023To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational... (Review)
Review
OBJECTIVE
To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs).
DESIGN
Umbrella review.
DATA SOURCES
PubMed, PsychInfo, Embase, up to 9 February 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted.
RESULTS
101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive).
CONCLUSIONS
Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events.
STUDY REGISTRATION
PROSPERO CRD42018093045.
FUNDING
None.
Topics: Adolescent; Adult; Female; Humans; Infant, Newborn; Pregnancy; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Chronic Pain; Hallucinogens; Randomized Controlled Trials as Topic; Risk Assessment; Sleepiness; Systematic Reviews as Topic; Meta-Analysis as Topic; Observational Studies as Topic
PubMed: 37648266
DOI: 10.1136/bmj-2022-072348 -
The Cochrane Database of Systematic... Jan 2019This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to nervous tissue). Antiepileptic drugs have long been used in pain management. Pregabalin is an antiepileptic drug used in management of chronic pain conditions.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of pregabalin for chronic neuropathic pain in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from January 2009 to April 2018, online clinical trials registries, and reference lists.
SELECTION CRITERIA
We included randomised, double-blind trials of two weeks' duration or longer, comparing pregabalin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality and biases. Primary outcomes were: at least 30% pain intensity reduction over baseline; much or very much improved on the Patient Global Impression of Change (PGIC) Scale (moderate benefit); at least 50% pain intensity reduction; or very much improved on PGIC (substantial benefit). We calculated risk ratio (RR) and number needed to treat for an additional beneficial (NNTB) or harmful outcome (NNTH). We assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included 45 studies lasting 2 to 16 weeks, with 11,906 participants - 68% from 31 new studies. Oral pregabalin doses of 150 mg, 300 mg, and 600 mg daily were compared with placebo. Postherpetic neuralgia, painful diabetic neuropathy, and mixed neuropathic pain predominated (85% of participants). High risk of bias was due mainly to small study size (nine studies), but many studies had unclear risk of bias, mainly due to incomplete outcome data, size, and allocation concealment.Postherpetic neuralgia: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (50% vs 25%; RR 2.1 (95% confidence interval (CI) 1.6 to 2.6); NNTB 3.9 (3.0 to 5.6); 3 studies, 589 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (32% vs 13%; RR 2.5 (95% CI 1.9 to 3.4); NNTB 5.3 (3.9 to 8.1); 4 studies, 713 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (62% vs 24%; RR 2.5 (95% CI 2.0 to 3.2); NNTB 2.7 (2.2 to 3.7); 3 studies, 537 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (41% vs 15%; RR 2.7 (95% CI 2.0 to 3.5); NNTB 3.9 (3.1 to 5.5); 4 studies, 732 participants, moderate-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 16% versus 5.5%, 600 mg 25% versus 5.8%; dizziness 300 mg 29% versus 8.1%, 600 mg 35% versus 8.8%.Painful diabetic neuropathy: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (47% vs 42%; RR 1.1 (95% CI 1.01 to 1.2); NNTB 22 (12 to 200); 8 studies, 2320 participants, moderate-quality evidence), more had at least 50% pain intensity reduction (31% vs 24%; RR 1.3 (95% CI 1.2 to 1.5); NNTB 22 (12 to 200); 11 studies, 2931 participants, moderate-quality evidence), and more had PGIC much or very much improved (51% vs 30%; RR 1.8 (95% CI 1.5 to 2.0); NNTB 4.9 (3.8 to 6.9); 5 studies, 1050 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (63% vs 52%; RR 1.2 (95% CI 1.04 to 1.4); NNTB 9.6 (5.5 to 41); 2 studies, 611 participants, low-quality evidence), and more had at least 50% pain intensity reduction (41% vs 28%; RR 1.4 (95% CI 1.2 to 1.7); NNTB 7.8 (5.4 to 14); 5 studies, 1015 participants, low-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 11% versus 3.1%, 600 mg 15% versus 4.5%; dizziness 300 mg 13% versus 3.8%, 600 mg 22% versus 4.4%.Mixed or unclassified post-traumatic neuropathic pain: More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (48% vs 36%; RR 1.2 (1.1 to 1.4); NNTB 8.2 (5.7 to 15); 4 studies, 1367 participants, low-quality evidence), and more had at least 50% pain intensity reduction (34% vs 20%; RR 1.5 (1.2 to 1.9); NNTB 7.2 (5.4 to 11); 4 studies, 1367 participants, moderate-quality evidence). Somnolence (12% vs 3.9%) and dizziness (23% vs 6.2%) were more common with pregabalin.Central neuropathic pain: More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (44% vs 28%; RR 1.6 (1.3 to 2.0); NNTB 5.9 (4.1 to 11); 3 studies, 562 participants, low-quality evidence) and at least 50% pain intensity reduction (26% vs 15%; RR 1.7 (1.2 to 2.3); NNTB 9.8 (6.0 to 28); 3 studies, 562 participants, low-quality evidence). Somnolence (32% vs 11%) and dizziness (23% vs 8.6%) were more common with pregabalin.Other neuropathic pain conditions: Studies show no evidence of benefit for 600 mg pregabalin in HIV neuropathy (2 studies, 674 participants, moderate-quality evidence) and limited evidence of benefit in neuropathic back pain or sciatica, neuropathic cancer pain, or polyneuropathy.Serious adverse events, all conditions: Serious adverse events were no more common with placebo than with pregabalin 300 mg (3.1% vs 2.6%; RR 1.2 (95% CI 0.8 to 1.7); 17 studies, 4112 participants, high-quality evidence) or pregabalin 600 mg (3.4% vs 3.4%; RR 1.1 (95% CI 0.8 to 1.5); 16 studies, 3995 participants, high-quality evidence).
AUTHORS' CONCLUSIONS
Evidence shows efficacy of pregabalin in postherpetic neuralgia, painful diabetic neuralgia, and mixed or unclassified post-traumatic neuropathic pain, and absence of efficacy in HIV neuropathy; evidence of efficacy in central neuropathic pain is inadequate. Some people will derive substantial benefit with pregabalin; more will have moderate benefit, but many will have no benefit or will discontinue treatment. There were no substantial changes since the 2009 review.
Topics: Acute Disease; Adult; Analgesics; Chronic Disease; Diabetic Neuropathies; Dizziness; Humans; Neuralgia; Neuralgia, Postherpetic; Pain; Pregabalin; Randomized Controlled Trials as Topic; Sleepiness
PubMed: 30673120
DOI: 10.1002/14651858.CD007076.pub3 -
CNS Drugs Mar 2022Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not...
Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not least because the seizures are highly drug resistant, requiring multiple anti-seizure medications (ASMs), while some ASMs can exacerbate seizures. Initial treatments include the broad-spectrum ASMs valproate (VPA), and clobazam (CLB) in some regions; however, they are generally insufficient to control seizures. With this in mind, three adjunct ASMs have been approved specifically for the treatment of seizures in patients with Dravet syndrome: stiripentol (STP) in 2007 in the European Union and 2018 in the USA, cannabidiol (CBD) in 2018/2019 (in combination with CLB in the European Union) and fenfluramine (FFA) in 2020. These "add-on" therapies (mostly to VPA/CLB) are used as escalation therapies, with the choice dependent on availability in different countries, patient characteristics and caregiver preferences. Topiramate is also frequently used, with evidence of efficacy in Dravet syndrome, and there is anecdotal evidence of efficacy with bromide, which is frequently used in Germany and Japan. With a growing treatment landscape for Dravet syndrome, there can be practical challenges for clinicians, particularly with issues associated with polypharmacy. This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated. Standard laboratory and clinical parameters include blood counts, liver function tests, serum concentrations of ASMs, monitoring the growth of children, as well as weight loss and acceleration of behavioural problems. Regular cardiac monitoring is also important with FFA as it has previously been associated with cases of cardiac valve disease when used in adults at high doses (up to 120 mg/day) in combination with phentermine as a therapy for obesity. Importantly, no signs of heart valve disease have been documented to date at the low doses used in patients with developmental and epileptic encephalopathies. In addition, potential drug-drug interactions and their consequences are a key consideration in everyday practice. Interactions that potentially require dosage adjustments to alleviate adverse events include the following: STP + CLB resulting in increased plasma concentrations of CLB and its active metabolite norclobazam may increase somnolence, and an interaction with STP and VPA may increase gastrointestinal adverse events. Cannabidiol has a bi-directional interaction with CLB producing an increase in plasma concentrations of 7-OH-CBD and norclobazam resulting in the potential for increased somnolence and sedation. In addition, CBD is associated with elevations of liver transaminases particularly in patients taking concomitant VPA. The interaction between FFA and STP requires a dose reduction of FFA. Furthermore, concomitant administration of VPA with topiramate has been associated with encephalopathy and/or hyperammonaemia. Finally, we briefly describe other ASMs used in Dravet syndrome, and current key clinical trials.
Topics: Adult; Anticonvulsants; Cannabidiol; Child; Clobazam; Drug Therapy, Combination; Epilepsies, Myoclonic; Epileptic Syndromes; Fenfluramine; Humans; Sleepiness; Spasms, Infantile; Topiramate
PubMed: 35156171
DOI: 10.1007/s40263-022-00898-1 -
Annals of Neurology Mar 2019Solriamfetol (JZP-110) is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects. This phase 3 study (NCT02348593) evaluated the safety... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Solriamfetol (JZP-110) is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects. This phase 3 study (NCT02348593) evaluated the safety and efficacy of solriamfetol in narcolepsy.
METHODS
Patients with narcolepsy with mean sleep latency <25 minutes on the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS) score ≥10, and usual nightly sleep ≥6 hours were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Coprimary endpoints were change from baseline to week 12 in MWT and ESS. Improvement on the Patient Global Impression of Change (PGI-C) was the key secondary endpoint.
RESULTS
Safety and modified intention-to-treat populations included 236 and 231 patients, respectively. Solriamfetol 300 and 150 mg were positive on both coprimary endpoints. Least squares mean (standard error [SE]) changes from baseline were 12.3 (SE = 1.4) and 9.8 (SE = 1.3) minutes for solriamfetol 300 and 150 mg on the MWT, respectively, versus 2.1 (SE = 1.3) minutes for placebo, and -6.4 (SE = 0.7) for 300 mg and -5.4 (SE = 0.7) for 150 mg on the ESS versus -1.6 (SE = 0.7) for placebo (all p < 0.0001). At week 12, higher percentages of patients treated with solriamfetol 150 mg (78.2%) and 300 mg (84.7%) reported PGI-C improvement relative to placebo (39.7%; both p < 0.0001). Adverse events ≥5% across all solriamfetol doses included headache (21.5%), nausea (10.7%), decreased appetite (10.7%), nasopharyngitis (9.0%), dry mouth (7.3%), and anxiety (5.1%).
INTERPRETATION
Solriamfetol has the potential to be an important therapeutic option for the treatment of impaired wakefulness and excessive sleepiness in patients with narcolepsy. ANN NEUROL 2019;85:359-370.
Topics: Adult; Carbamates; Double-Blind Method; Female; Humans; Male; Middle Aged; Narcolepsy; Phenylalanine; Sleep Latency; Sleepiness; Treatment Outcome; Wakefulness-Promoting Agents; Young Adult
PubMed: 30694576
DOI: 10.1002/ana.25423 -
American Journal of Respiratory and... Aug 2019Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have...
Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have different cardiovascular consequences. To characterize OSA symptom subtypes and assess their association with prevalent and incident cardiovascular disease in the Sleep Heart Health Study. Data from 1,207 patients with OSA (apnea-hypopnea index ≥ 15 events/h) were used to evaluate the existence of symptom subtypes using latent class analysis. Associations between subtypes and prevalence of overall cardiovascular disease and its components (coronary heart disease, heart failure, and stroke) were assessed using logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether subtypes were associated with incident events, including cardiovascular mortality. Four symptom subtypes were identified (disturbed sleep [12.2%], minimally symptomatic [32.6%], excessively sleepy [16.7%], and moderately sleepy [38.5%]), similar to prior studies. In adjusted models, although no significant associations with prevalent cardiovascular disease were found, the excessively sleepy subtype was associated with more than threefold increased risk of prevalent heart failure compared with each of the other subtypes. Symptom subtype was also associated with incident cardiovascular disease ( < 0.001), coronary heart disease ( = 0.015), and heart failure ( = 0.018), with the excessively sleepy again demonstrating increased risk (hazard ratios, 1.7-2.4) compared with other subtypes. When compared with individuals without OSA (apnea-hypopnea index < 5), significantly increased risk for prevalent and incident cardiovascular events was observed mostly for patients in the excessively sleepy subtype. OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.
Topics: Aged; Cardiovascular Diseases; Cluster Analysis; Cohort Studies; Coronary Disease; Female; Heart Failure; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Sleep Apnea, Obstructive; Sleepiness; Stroke
PubMed: 30764637
DOI: 10.1164/rccm.201808-1509OC