Levetiracetam as the first-line treatment for neonatal seizures: a systematic review and meta-analysis.

AIM: To assess the effectiveness and safety of levetiracetam when used as first-line treatment of neonatal seizures. METHOD: Four electronic databases, Medline, Embase, Web of Science, and ClinicalTrials.gov were systematically searched from inception until 20th November 2020. Randomized controlled trials (RCTs) and observational studies that included neonates born preterm and term were eligible for inclusion. The primary outcome measure was levetiracetam effectiveness, defined as seizure cessation within 24 hours of starting treatment. Secondary outcomes included short-term adverse events, mortality before discharge, and long-term neurodevelopmental outcomes. RESULTS: Fourteen studies assessing 1188 neonates were included: four RCTs, three observational trials with phenobarbital as the control arm, and seven observational studies of levetiracetam with no control arm. Pooled efficacy of levetiracetam from observational studies was 45% (95% confidence interval [CI] 34-57%) (GRADE - very low). Meta-analysis of RCTs evaluating levetiracetam versus phenobarbital showed that both were equally effective (risk ratio [95% CI] 0.6 [0.30-1.20]) (GRADE - very low). Levetiracetam resulted in a lower risk of short-term adverse events compared to phenobarbital (risk ratio [95% CI] 0.24 [0.06-0.92]) (GRADE - moderate). INTERPRETATION: Very low certainty of evidence suggests levetiracetam might not be more effective than phenobarbital. Moderate certainty of evidence indicates levetiracetam is associated with a lower risk of adverse events. Future trials on neonatal antiseizure medication therapy should include continuous electroencephalogram (EEG) monitoring as standard of care and enrol a homogenous population with similar seizure aetiology. What this paper adds Levetiracetam is effective in 45% of neonatal seizures. Levetiracetam might not be more effective than phenobarbital. Levetiracetam is likely to be safer than phenobarbital. Evidence available is limited and of very low certainty.

CPAP Therapeutic Options for Obstructive Sleep Apnea.

INTRODUCTION: There are many options available to patients who are placed on constant positive airway pressure (CPAP) for obstructive sleep apnea. Despite the success of CPAP in correcting apnea, a significant number of patients have difficulty with the therapy. A large number of those patients who have difficulty stop therapy and are often labeled as "CPAP Failure". Non-sleep specialists may view CPAP therapy as a singular course of treatment, but there are many ways CPAP may be ordered for a patient. Each patient experiences a unique set of options that constitute a unique order set. METHODS: In order to demonstrate the magnitude of the possible options, estimates of the number of unique order sets were calculated. The author chose individual order options and the number of selections possible within each option. The calculated sets included a "Generous, Limited and Minimal" number of selections for each option. Calculations were done separately for standard CPAP and for auto-adjusting CPAP. Additional calculations were performed using the number of commercially available masks in the United States. RESULTS: The maximum number of unique order sets was seen using a standard CPAP combined with commercially available masks: 49,152 unique order sets. The fewest number of unique order sets were seen with the auto-adjusting CPAP and the "Minimal" selections: 288 unique order sets. DISCUSSION: There are a large number of unique CPAP orders that a patient may experience. CPAP treatment is not a singular or simple therapy. When evaluating obstructive sleep apnea patients with histories of CPAP failure or prior difficulty with CPAP, paying close attention to the patient's treatment experiences may help explain a significant number of those patients' CPAP therapy problems.

The level of observed physical movement accompanying periodic limb movements measured in a clinical sleep population.

STUDY OBJECTIVES: Periodic limb movements (PLMs) are routinely measured during polysomnogram (PSG) testing. During the early years of sleep testing, physical movements were identified and over time, consensus ultimately led to the current definitions of movement disorders including criteria used to measure PLMs on PSG testing. There has been considerable debate about the clinical importance of the PLMs measured during PSG testing. Over the last decade, the author has observed significant variations in the actual visible physical movements observed with a PLM event. This report is the result of work to quantify the amount of movement and the frequency of movements observed among individuals who have PLMs. METHODS/PRINCIPAL FINDINGS: Consecutive PSGs performed in a suburban sleep center for an initial diagnosis of a sleep disorder were retrospectively reviewed to identify those with measured PLMs. Of 646 studies on patients >18 years, 460 met criteria for inclusion. Visual assessment of movements was carried out on all of those with PLM events measured using American Academy of Sleep Medicine guidelines. The movements were quantified based on the number of extremities observed to move. PLMs were observed in 237 of the 460 studies that met inclusion criteria (52%). As expected, the PLMs occurred more frequently in older individuals. PLMs occurred with equal frequency in both sexes. Apnea occurred with equal frequency in those with and without observed physical movements. Of those with PLMs, 62% (147) demonstrated observable physical movements. Significant movements involving three or four extremities occurred in 16% of individuals with PLMs. No physical movements were observed in 38%. CONCLUSION: In this uncontrolled, nonrandom, observational series, visual physical movements with a PLM event identify a unique subset of individuals with PLMs. The presence of any visual movements or more pronounced visual movements involving multiple extremities may represent markers for PLM disorder, for clinically significant PLMs with other disorders, or for other clinical conditions or physiologic variables.

The relation between sleep and weight in a suburban sleep center: observations and speculations on apnea and weight.

STUDY OBJECTIVES: The relationship between obstructive sleep apnea (OSA) and body weight is not clearly established. In order to describe the relationship of weight and OSA severity seen in a suburban sleep center, an observational review was performed of initial diagnostic polysomnograms (PSGs) ordered on patients with American Academy of Sleep Medicine (AASM) symptomatic indications. METHODOLOGY/PRINCIPLE FINDINGS: Initial, full-night diagnostic or initial split-night (diagnostic portion) PSGs performed for any indication on patients >18 years old were retrospectively reviewed for a two year period. All studies were performed following AASM guidelines. PSG data were reviewed for the presence and severity of apnea (no OSA - apnea hypopnea index (AHI) <5, mild - AHI 5-14, moderate - AHI 15-29, severe - AHI 30-59, and very severe - AHI >60). Data were reviewed from 629 PSGs (37% females and 63% males) of which 450 met the criteria for apnea. Studies were classified by apnea severity (196 mild, 103 moderate, 91 severe apnea and 60 with very severe apnea) and weight (body mass index (BMI)). Of those with apnea, and BMIs <25, severe or very severe apnea occurred in 22% (10/45). Three individuals with BMIs <20 had apnea, one severe. Of those with BMIs ≥40, one (1.6%) did not have apnea and 52% (31/60) had AHI >30. CONCLUSION/SIGNIFICANCE: The profile of this nonrandom series, tested because they were suspected of having a disorder of sleep, provides guidelines for physicians in their approach to symptomatic patients. Individuals with a normal BMI can have apnea, including severe apnea. Severe obesity (BMI >40) is almost always associated with apnea when symptoms are present. Obesity increases the severity of the diagnosed apnea. Excessive weight should be an indication for testing, but normal weight should not exclude individuals with appropriate symptoms. Obesity, while a major contributing factor to severity, is not the etiological cause of OSA in the majority of these patients.