bluuebunny/crossref_metadata_2025 huggingface dataset:
0812 Inconsistent improvements of neurocognitive function after adenotonsillectomy: a pediatric sleep-disordered breathing cohort study
Authors: Huang Yu-Shu , Chin Wei-Chih
Published: May 2023

Introduction

Adenotonsillectomy (AT) is the most common surgical treatment for pediatric obstructive-sleep-apnea (OSA) with fair effectiveness. There are still controversies about the improvement of neurocognitive function after AT. This study investigates the changes of neurocognitive function after AT in preschool and school age children with OSA, including intelligence and attention, and explore the inconsistent improvements by comparing different evaluation tools.

Methods

130 children with pediatric OSA were recruited, including 30 preschool and 100 school-age children. 125 participants underwent clinical evaluation, including polysomnography (PSG), before and 1-year after AT. Preschool children received the Wechsler-Preschool-and-Primary-Scale-of-Intelligence (the revised and IV edition, WPPSI-R and WPPSI-IV) and the Conners’-Kiddie-Continuous-Performance-Test (K-CPT) while school-age children received the Wechsler-Intelligence-Scale-for-Children (the 3rd and 4th edition, WISC-III and WISC-IV), and the Conners’-continuous-performance-test-II (CPT-II), before and 1-year after AT. Questionnaires including the Obstructive-Sleep-Apnea-Questionaire-18 (OSA-18) and Child-Behavior-Checklist (CBCL) were also used. The t-test and chi-square test analysis was used to compare data between preschool and school-age children, including PSG, CPT variables, intelligence variables, OSA-18 and CBCL before and after AT, as well as group differences in changes. Correlation analysis of CPT variables were performed by using the Pearson-Correlation to investigate factors related to treatment response.

Results

No significant group difference was found except age (p=0.000) and less male gender in preschool children (p=0.049). 21.7% of preschool children had language delay, and more than 80% of all children had allergic rhinitis or high narrow palate. After AT, both groups had significant improvement in PSG and OSA-18. No significant change was found by WPPSI-IV in the preschool children and WISC-IV in the school-age children, but significant improvements were found in preschool children and school-age children by WPPSI-R and WISC-III. There were also significant improvements of CPT-II in school-age children, and the Hit-reaction-time-standard-deviation positively correlates with the improvement in PSG.

Conclusion

Besides the improvement of sleep apnea and subjective improvements of emotion and behavior, AT can be beneficial in the neurocognitive function of preschool and school-age children with OSA, including intelligence and attention. Some tools may not be sensitive enough to detect the improvement in neurocognitive function, and selection of proper evaluation tools can be important in study design.

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0872 Periodic limb movements during sleep and hypertension: A systematic review and meta-analysis
Authors: Srivali Narat , Thongprayoon Charat , Tangpanithandee Supawit , Krisanapan Pajaree , Zinchuk Andrey , Koo Brain , Cheungpasitporn Wisit
Published: May 2023

Introduction

Several studies suggest an association between periodic limb movements during sleep (PLMS) and hypertension; however, a systematic evaluation of this relationship is lacking.

Methods

We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio, comparing the risk of hypertension in persons with PLMS (defined by the level of periodic limb movements per hour of sleep depended on individual studies) versus those without PLMS. After assessing heterogeneity and bias, the pooled risk ratio and 95% confidence intervals (CIs) were determined using a random-effect, generic inverse variance method of DerSimonian and Laird.

Results

Out of 572 potentially relevant articles, six eligible cross-sectional studies were included in the data analysis which included 8,949 participants. The statistical heterogeneity of this study was insignificant, with an I2 of 0%. A funnel plot showed no publication bias. The pooled risk ratio of hypertension in patients with PLMS was 1.26 (95% CI, 1.12–1.41).

Conclusion

Our analysis demonstrates an increased hypertension risk among patients with PLMS. Prospective or interventional studies are needed to confirm this association.

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0875 Self-Reported Sleep Indices in Veterans Exposed to Deleted Uranium
Authors: Russo Anthony , Baher Ali , Gucer Patricia , Diaz-Abad Montserrat , Hines Stella , McDiarmid Melissa , Glick Danielle
Published: May 2023

Introduction

During Gulf War I, a group of veterans sustained exposure to deplete uranium (DU) through a series of “friendly fire” incidents. This resulted in both inhalational and traumatic injuries, with a subset having retained fragments and ongoing systemic exposure to DU. These veterans have undergone biennial surveillance assessments to monitor for DU-related health effects. While effects of DU on bones and kidneys have been consistently shown, less is understood about the effect of DU on sleep. In rat models, exposure to DU affected sleep architecture by increasing both sleep fragmentation and quantity of REM sleep. We therefore sought to characterize the effect of DU on self-reported sleep complaints among this unique veteran cohort.

Methods

Of a dynamic cohort of 81 DU-exposed veterans, 37 completed medical history, exposure, and sleep questionnaires and 24-hour urine uranium collections. Responses on the sleep questionnaires -which included subjective assessment of sleep quality and quantity as well as an Epworth Sleepiness Scale (ESS) score – were compared in veterans with elevated (>0.1 mcg U/g creatinine) vs low urine uranium (uU).

Results

The 37 veterans assessed were all male, mostly white, and had a mean age of 54 ± 2.8 years. 10 were identified as having elevated urine DU levels. The mean ESS score for the group overall was in the pathologic range (13 ± 4) and did not differ significantly between the high and low uU groups. The most frequent complaints in the group overall were of difficulty falling asleep, awakening frequently throughout the night, restless sleep, and frequent tossing and turning. Among all self-reported sleep indices, there were no significant differences among the two groups.

Conclusion

In this group of DU-exposed veterans, excessive daytime sleepiness and several other sleep complaints were observed. Although there were no differences in the frequency or severity of self-reported sleep indices among this group of DU-exposed veterans, the group was overall pathologically sleepy. More work is needed to further characterize the possible impact of DU exposure on sleep.

Support (if any)

Funded by the US Department of Veterans Affairs and supported by the University of Maryland General Clinical Research Center.
0878 Sleep Measures Worsen for Individuals who are Obese but Improve for Individuals who are not Obese from 60-90days after Stroke
Authors: Klingman Karen , Duncan Pamela , Billinger Sandra , Bartsch Bria , Moores Sasha , DeBlois Amy , Valastro Daniel , Fulk George
Published: May 2023

Introduction

Goals of post-stroke rehabilitation include recovery of physical function which, in turn, relies on motor learning to relearn functional skills. Given the known association between motor learning and sleep, it is important to understand if sleep is related to characteristics of persons with stroke (PwS) during the subacute timeframe (60–90 days following stroke) to potentially guide interventions. Obesity is a known risk-factor for stroke and therefore prevalent among PwS. The purpose of this study was to determine if there are differences between changes in objectively measured sleep parameters across the 60-90 day post-stroke period that correspond to different levels of body mass index (BMI).

Methods

PwS received standard of care for post-stroke physical rehabilitation, and wore wrist actigraphy for 3-9nights at 60 and 90 days post-stroke, with no additional interventions. Total sleep time (TST), time in bed (TIB), sleep efficiency (SE), sleep latency (SL), wake after sleep onset (WASO), number of awakenings (NWAK) and average time per awakening (TPA) were obtained from the actigraphy software for each night, and average nightly values determined. Participants were categorized into two groups based on BMI (< 30 and >=30). Changes were calculated as 90-day minus 60-day values. Independent samples t-tests were performed to determine if there were differences in changes in sleep parameters between BMI groups.

Results

The PwS sample (n=31, 52% female, average age 66.7years, range 44–85+) included n=13 with BMI >=30. Independent t-tests found a significant difference in change in SE (6.9%, p=0.016) and change in NWAK (6.3, p=0.003) between the two groups. For those with BMI>=30 SE and NWAK worsened from 60-90-days following stroke (-4.2% and 2counts), whereas for those with BMI< 30 SE and NWAK improved (+2.7% and -4.3counts). No significant differences were found between groups for changes in TST, TIB, SL, WASO or TPA.

Conclusion

Without sleep-related interventions, sleep characteristics worsen for PwS who are obese in the subacute post-stroke recovery phase, but improves for PwS who are not obese. There may be opportunities to explore sleep-related interventions for PwS who are obese.

Support (if any)

This study was supported by NINR Award Number R01 NR018979.
0887 Divergent Slow wave sleep and Alzheimer's disease Plasma Biomarkers’ Associations in Black and White Cognitive Normal Older-Adults
Authors: Azad Dishari , White Payton , Cesar Oliver , Kovbasyuk Zanatta , Gonzalez Moses , Wahab Ariana , Mullins Anna , Kam Korey , Parekh Ankit , Rapoport David , Ayappa Indu , Jean-Louis Girardin , Varga Andrew , Osorio Ricardo , Bubu Omonigho
Published: May 2023

Introduction

We determined whether slow wave sleep is associated with plasma levels of Aβ40, Aβ42, Aβ42/Aβ40, Tau, tau/Aβ42 and NfL and whether this relationship differed between Blacks/African-Americans and non-Hispanic Whites.

Methods

This was a cross-sectional analysis of baseline data from 171 community-dwelling cognitively normal older-adults, participating in ongoing NYU studies on memory, sleep and aging. Non-rapid eye movement sleep (NREM) slow wave sleep (SWS) duration was calculated from 2 nights of in-lab NPSGs. Plasma Aβ40, Aβ42, Tau and NfL were determined using single molecule array (SIMOA). Associations of NREM SWS duration and plasma AD biomarker levels were assessed using adjusted generalized linear models and Pearson correlation analysis after data normalization. Analyses were adjusted for age, sex, BMI, race, and education.

Results

Of the 171 subjects (128 non-Hispanic Whites and 43 Blacks/African-Americans), 112 (65.5%) were females, and mean (SD) age was 68.6 (6.6) years, BMI was 27.6 (6.1) kg/m**2, and education was 16.9 (2.1). There were no racial differences in age, sex, BMI, NREM SWS and AHI4%. Compared to non-Hispanic Whites, Blacks/African-Americans had significantly lower years of education (14.2 vs. 17.2, p <.01), plasma Aβ40 (248.3 vs. 262.5 pg/ml) and NfL levels (11.4 vs. 15.2 pg/ml) p<.05 for both. There were no significant racial differences in levels of plasma Aβ42, Aβ42/Aβ40, Tau, Tau/Aβ40 and Tau/Aβ42 (p>.05 for all). NREM SWS duration was not associated with plasma Aβ42, Aβ40 or tau in the overall sample (p>.05 for all). However, in non-Hispanic Whites, NREM SWS negatively correlated with plasma Aβ42 (r=-0.28, p<=0.05), plasma Aβ40 (r=-0.087, p=0.72), though not significant, and plasma Tau (r=-0.153, p=0.27), though not significant. In Black/African-Americans, NREM SWS positively correlated with plasma Aβ42 (r=0.48, p=0.05), plasma Aβ40 levels (r=0.32, p=0.04), and plasma Tau levels (r=0.52, p=0.04). NREM SWS was not associated with plasma tau/Aβ42, plasma tau/Aβ40 or plasma NfL in the overall sample and across racial subgroups.

Conclusion

Race-specific divergent associations between NREM SWS and plasma Aβ42, Aβ40 & Tau may suggest differences in SDOH factors and mechanisms that could influence sleep and AD-risk in older-adults.

Support (if any)

AASMBTS#231-BS-20, NIAK23AG068534A, AARG-D- 21-848397, BFFA2022033S
0917 A Hybrid Cognitive Behavioral Therapy for Insomnia (CBT-I) Improves Access and Patient Engagement
Authors: Roth Alicia , Kane Alexa , Drerup Michelle
Published: May 2023

Introduction

Despite CBTI being the gold standard for insomnia treatment, numerous barriers need to be overcome in order for the field of sleep medicine to utilize CBTI as the front-line treatment. We investigated if a hybrid intervention combining groups, telehealth, and 1-on-1 visits would provide greater access to CBTI than the traditional model of in-person 1-on-1 sessions.

Methods

Patients receiving CBTI in 2019 (in person, 1-on-1 visits, n=200) were compared to patients receiving CBTI in 2021 (CBTInitiate=hybrid telehealth/in-person, group/1-on-1 visits, n=299). In CBTInitiate, the first 1-on-1 follow-up session was replaced by a 60-minute telehealth group session that introduced sleep psychoeducation and stimulus control followed by 1-on-1 sessions. CBTInitiate (2021) was compared with traditional-CBTI (2019) on wait times (between consultation and initial follow up session; CBTInitiate and 1-on-1 follow-up) utilizing multivariate linear regression with age as a covariate. Treatment completer status (≥ 3 visits) was also compared between groups utilizing chi-square test and two-sample t-test.

Results

Dependent variables were log-transformed to meet normality assumptions. Age significantly differed between groups (Hybrid-CBTI=55.59; traditional-CBTI=51.87; t=2.763, p=.006) and was included as a covariate. CBTI type significantly predicted wait time to first follow-up (overall: R2=.25, F(2, 496)=.83.30, p<.001; β=-.50, p<.001). Back-transformation to estimated means show CBTInitiate patients had a shorter wait time to first follow-up (x̄=11.16 days) than traditional-CBTI (x̄=31.24 days). Age was not a significant predictor (β=-.03, p=.385). CBTI type also significantly predicted wait time from new evaluation to first 1-on-1 follow-up (overall: R2=.04, F(2,452)=8.99, p=<.001; β=.194, p<.001). Age was not a significant predictor (β=-.06, p=.229). However, CBTInitiate had a longer wait time (x̄=38.76 days) than traditional-CBTI (x̄=31.27days) for a 1-on-1 appointment.

Conclusion

The CBTInitiate model addresses systemic, patient, and provider-level barriers to implementing CBTI as the gold-standard treatment for insomnia. The implementation of CBTInitiate significantly decreased wait times to begin CBTI and increased patients completing treatment compared to a traditional care model. Future areas for investigation include CBTInitiate’s impact on healthcare costs and insomnia treatment outcomes.

Support (if any)

None
0976 Central Sleep Apnea (CSA) following treatment with Non-Positive Airway Pressure (PAP) Modalities
Authors: Ramo Kathreen al , Vijayakumar Punitha , Kapish Neeraj
Published: May 2023

Introduction

Emergence or worsening of CSA following non- PAP therapies has not been well studied. We present two cases of CSA following treatment of OSA; one with mandibular advancing device (MAD) and other with hypoglossal nerve stimulation (HGNS).

Report of case(s)

Case 1: A78 y/o male presented with CPAP intolerance and seeking HGNS for OSA treatment. His AHI was 25 with an O2 nadir of 76%. Following a comprehensive evaluation including sleep endoscopy, he was deemed a good candidate for HGNS. Per protocol, his HGNS was activated, PSG done after an interval period during which his stimulation was titrated from 0-2.3V. His AHI remained elevated (50 – 163) at all voltage settings with emergence of CSA at 2.3 & 2.4 V. Due to tongue discomfort, his stimulation parameters were changed and HSAT was done to re-assess his breathing. Home study showed persistent severe sleep apnea- central & obstructive with periodic breathing and desaturations to 70s. Case 2: A 28-y/o male with OSA AHI of 20.2 and O2 nadir of 82%. He was intolerant of CPAP; hence MAD was pursued. PSG done showed MAD was ineffective as his AHI was elevated at 26.8 with elevated CAI (associated with desaturations). A repeat study at home was done following adjustments to the MAD showed a higher index with pAHI of 37.7, predominantly central in nature with periodic breathing. Patient is awaiting a CPAP titration but has returned back to PAP therapy with good tolerance and resolution of his residual symptoms including daytime hypersomnolence.

Conclusion

These two cases highlight that CSA can be associated with non-PAP therapies and symptomatic improvement alone may not be an effective approach. Testing following initiation of treatment would allow for more effective management especially when patient is symptomatic or treatment is suspected to be ineffective.

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0987 Asking the Right Questions: A Case of Restless Legs Syndrome and Spinal Muscular Atrophy
Authors: Brown Peomia , Greer Meredith
Published: May 2023

Introduction

The association between iron deficiency and restless legs syndrome (RLS) is well established. However, there is limited data on the association between motor neuron diseases such as spinal muscular atrophy (SMA) and RLS. A forty-three-year-old with Type 2 SMA presented to clinic for management of chronic respiratory failure. She had recently undergone surgery and chemotherapy for newly diagnosed anal cancer. However, she reported persistent abdominal pain, anorexia, weight loss, and rectal bleeding. She reported “muscle twitching” and bilateral lower extremity pain and tingling that was worse at night. Her husband would awaken every 2 hours to massage her legs. She assumed these symptoms had emerged as a result of an increase in motor function due to risdiplam, a survival motor neuron 2 splicing modifier drug. Further questioning led to the diagnosis of RLS. Bloodwork revealed severe iron deficiency anemia (hemoglobin of 6.0 g/dL, iron 13 mcg/dL, and ferritin 3 ng/ml). She received a blood transfusion and underwent sigmoidoscopy for evaluation of cancer recurrence given the report of bleeding. Fortunately, her cancer remained in remission. Her symptoms of RLS significantly improved after blood transfusions and iron supplementation.

Report of case(s)

n/a

Conclusion

RLS is a complex sensorimotor syndrome. The diagnosis of RLS is clinical, relying on diagnostic criteria that requires lower extremity movement. The case is a reminder of the variable presentation of RLS in individuals with neuromuscular disorders, including SMA. How are symptoms of restless legs disclosed in patients with the inability to move and with potentially altered sensorium? The focus of the patient encounter could have anchored on the common and expected sequalae of SMA, chronic respiratory failure. Unfortunately, anchoring bias would have delayed the diagnosis and treatment of what could have been a potentially fatal disease – metastatic cancer. Ironically, the patient’s longing for motor function repressed her ability to lament. To the patient, symptoms of frequent nighttime awakenings and limb discomfort were perceived as a desired side effect of a medication that would increase movement. This case emphasizes the importance of the patient interview and its value of uncovering subtle complaints that may broaden the differential diagnosis and guide further work-up.

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0994 Neuroblastoma as the Initial Manifestation of Familial PHOX2B NPARM Positive Congenital Central Hypoventilation Syndrome
Authors: Fiala Kaylene , Amos Louella , D'Andrea Lynn
Published: May 2023

Introduction

Congenital Central Hypoventilation Syndrome (CCHS) is a genetic disorder of the autonomic nervous system caused by mutations in the PHOX2B gene. Children with CCHS often present as neonates in hypoxemic, hypercarbic respiratory failure. Most causative mutations are de novo Polyalanine Repeat Mutations (PARMs). Non-Polyalanine Repeat Mutations (NPARMs) have been associated with more severe disease, specifically the need for 24-hour ventilatory support, Hirschsprung disease, and neural crest tumors; however, NPARMs may have variable expressivity and incomplete penetrance, resulting in delayed or atypical presentations. We report a toddler with maxillary sinus neuroblastoma, which led to the diagnosis of familial PHOX2B NPARM positive CCHS.

Report of case(s)

A two-year-old boy presented with right-sided facial swelling. A facial CT uncovered a right maxillary sinus lytic lesion, and biopsy confirmed neuroblastoma. After full recovery from the procedure, he had persistent nocturnal hypoxemia and hypercapnia requiring bilevel positive airway pressure (PAP) during sleep, raising concern for CCHS. Genetic testing revealed a novel PHOX2B NPARM, c.428dup, which likely causes a frameshift and premature protein termination (p.Val144Glyfs*34). His maternal grandfather, mother and brothers tested positive for the same mutation. Family history revealed that his maternal grandfather and maternal great-uncles had frequent childhood apneic spells associated with syncope, his maternal grandfather is currently on nocturnal bilevel PAP, and his mother almost drowned as a younger child while having a breath-holding contest under water. His six-year-old brother underwent polysomnography which showed hypoventilation, now managed with bilevel PAP. His five-year-old brother also underwent polysomnography and does not require nocturnal ventilatory support at this time.

Conclusion

We report a rare case of familial PHOX2B NPARM positive CCHS which initially presented as maxillary sinus neuroblastoma. Additionally, the child and his family display varying disease severity despite having the same NPARM, highlighting the variable expressivity in this novel NPARM.

Support (if any)

None
1046 Severe hypoventilation in a child with rapid onset weight gain
Authors: Zaman Jefrina , Bhamrah Paul , Koothirezhi Rupa , Liendo Cesar , Monceaux Brittany , Chernyshev Oleg
Published: May 2023

Introduction

Pediatric sleep-related hypoventilation is a clinical pattern in which ventilatory insufficiency occurs in the setting of either severe OSA (obstructive hypoventilation) or obesity hypoventilation (sleep related hypoventilation). We are reporting a case describing the management of overlapping obstructive hypoventilation due to uncontrolled severe OSA and pediatric obesity hypoventilation syndrome.

Report of case(s)

The patient is a full term African American 5 y/o male with past medical history of obesity and prediabetes who was referred to discuss sleep related problems after rapid onset of weight gain.He gained 76 lbs over 8-month period; during this time his aunt noticed apneic events with the development of loud snoring.Initial workup was negative for abnormal findings,MRI w/w/o was unremarkable and TSH, cortisol, GH, IGF-1 and prolactin were all within normal limits. X-ray bone age study showed skeletal age appropriate for patient's chronologic age.Upper airway exam showed severe tonsillar hypertrophy 3+ with Mallampati class 4.The diagnostic PSG demonstrated the presence of 12 obstructive, 151 central, and 61 mixed apneas.There were 214 hypopneas resulting in an Apnea\Hypopnea Index of 60.5 events per hour.Mean oxygen saturation was 91.3%.The lowest oxygen saturation during sleep was 64.0%.Time spent ≤88% oxygen saturation was 119.7 minutes (26.2%). End tidal CO2 range was between 50-100 mmHg for 30% of study.The titration study revealed that the optimal treatment modality was BiPAP ST.

Conclusion

This case focuses on a five-year-old male who experienced rapid onset weight gain and presented with snoring, excessive daytime sleepiness and apneic events and was found to have profound hypoventilation with hypopnea predominant severe obstructive sleep apnea.The initial differential diagnosis of pediatric sleep-related hypoventilation includes ROHHAD, congenital central hypoventilation syndrome, primary central sleep apnea and obesity hypoventilation syndrome.The most common cause of hypoventilation during sleep in children remains OSA.The stepwise approach to management in such a case includes tonsillectomy with adenoidectomy,along with use of BiPAP. After the T&A the patient should have repeat PSG with capnography, if hypercarbia persists on post procedure PSG, he will need to continue BiPAP therapy with appropriate weight loss program. Early recognition evaluation, and treatment of obstructive sleep apnea in the pediatric population is imperative to prevent long-term consequences.

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Eye movements during phasic versus tonic rapid eye movement sleep are biomarkers of dissociable electroencephalogram processes for the consolidation of novel problem-solving skills
Authors: van den Berg Nicholas H , Gibbings Aaron , Baena Daniel , Pozzobon Alyssa , Al-Kuwatli Julia , Ray Laura B , Fogel Stuart M
Published: May 2023

The hallmark eye movement (EM) bursts that occur during rapid eye movement (REM) sleep are markers of consolidation for procedural memory involving novel cognitive strategies and problem-solving skills. Examination of the brain activity associated with EMs during REM sleep might elucidate the processes involved in memory consolidation, and may uncover the functional significance of REM sleep and EMs themselves. Participants performed a REM-dependent, novel procedural problem-solving task (i.e. the Tower of Hanoi; ToH) before and after intervals of either overnight sleep (n = 20) or a daytime 8-hour wake period (n = 20). In addition, event-related spectral perturbation of the electroencephalogram (EEG) time-locked to EMs occurring either in bursts (i.e. phasic REM), or in isolation (i.e. tonic REM), were compared to sleep on a non-learning control night. ToH improvement was greater following sleep compared to wakefulness. During sleep, prefrontal theta (~2–8 Hz) and central-parietal-occipital sensorimotor rhythm (SMR) activity (~8–16 Hz) time-locked to EMs, were greater on the ToH night versus control night, and during phasic REM sleep, were both positively correlated with overnight memory improvements. Furthermore, SMR power during tonic REM increased significantly from the control night to ToH night, but was relatively stable from night to night during phasic REM. These results suggest that EMs are markers of learning-related increases in theta and SMR during phasic and tonic REM sleep. Phasic and tonic REM sleep may be functionally distinct in terms of their contribution to procedural memory consolidation.
Efficacy of once-nightly sodium oxybate (FT218) in narcolepsy type 1 and type 2: post hoc analysis from the Phase 3 REST-ON Trial
Authors: Dauvilliers Yves , Roth Thomas , Bogan Richard , Thorpy Michael J , Morse Anne Marie , Roy Asim , Dubow Jordan , Gudeman Jennifer
Published: May 2023

Study Objectives

Post hoc analyses from the phase 3 REST-ON trial evaluated efficacy of extended-release once-nightly sodium oxybate (ON-SXB; FT218) vs placebo for daytime sleepiness and disrupted nighttime sleep in narcolepsy type 1 (NT1) and 2 (NT2).

Methods

Participants were stratified by narcolepsy type and randomized 1:1 to ON-SXB (4.5 g, week 1; 6 g, weeks 2–3; 7.5 g, weeks 4–8; and 9 g, weeks 9–13) or placebo. Assessments included mean sleep latency on Maintenance of Wakefulness Test (MWT) and Clinical Global Impression-Improvement (CGI-I) rating (coprimary endpoints) and sleep stage shifts, nocturnal arousals, and patient-reported sleep quality, refreshing nature of sleep, and Epworth Sleepiness Scale (ESS) score (secondary endpoints) separately in NT1 and NT2 subgroups.

Results

The modified intent-to-treat population comprised 190 participants (NT1, n = 145; NT2, n = 45). Significant improvements were demonstrated with ON-SXB vs placebo in sleep latency for NT1 (all doses, p < .001) and NT2 (6 and 9 g, p < .05) subgroups. Greater proportions of participants in both subgroups had CGI-I ratings of much/very much improved with ON-SXB vs placebo. Sleep stage shifts and sleep quality significantly improved in both subgroups (all doses vs placebo, p < .001). Significant improvements with all ON-SXB doses vs placebo in refreshing nature of sleep (p < .001), nocturnal arousals (p < .05), and ESS scores (p ≤ .001) were reported for NT1 with directional improvements for NT2.

Conclusions

Clinically meaningful improvements of a single ON-SXB bedtime dose were shown for daytime sleepiness and DNS in NT1 and NT2, with less power for the limited NT2 subgroup.
Evaluating the temperature preferences of sexually mature Duroc, Landrace, and Yorkshire boars
Authors: Raber Victoria L , Pritchett Rebecca K , Robbins Lindsey A , Stewart Kara R , Gaskill Brianna N , Green-Miller Angela R , Johnson Jay S
Published: May 2023

An accurate understanding of boar temperature preferences may allow the swine industry to design and utilize environmental control systems in boar facilities more precisely. Therefore, the study objective was to determine the temperature preferences of sexually mature Duroc, Landrace, and Yorkshire boars. Eighteen, 8.57 ± 0.10-mo-old boars (N = 6 Duroc, 6 Landrace, and 6 Yorkshire; 186.25 ± 2.25 kg) were individually tested in thermal apparatuses (12.20 m × 1.52 m × 1.86 m) that allowed free choice of their preferred temperature within a 8.92 to 27.92 ºC range. For analyses, the apparatuses were divided into five thermal zones (3.71 m2/thermal zone) with temperature recorded 1.17 m above the floor in the middle of each zone. Target temperatures for thermal zones 1 to 5 were 10, 15, 20, 25, and 30 ºC, respectively. All boars were given a 24-h acclimation phase followed by a 24-h testing phase within the thermal apparatuses. Daily feed allotments (3.63 kg/d) were provided to each boar and all boars were allowed to consume all feed prior to entering the thermal apparatus. Water was provided ad libitum within the thermal apparatuses with 1 waterer per thermal zone. During testing, boars were video recorded continuously to evaluate behavior (inactive, active, or other), posture (lying, standing, or other), and thermal zone the boar occupied. All parameters were recorded in 15 min intervals using instantaneous scan sampling. Data were analyzed using GLM in JMP 15. For the analyses, only time spent lying or inactive were used because they were observed most frequently (lying 80.02%, inactive 77.64%) and were deemed to be associated with comfort based on previous research. Percent time spent active (19.73%) or standing (15.87%) were associated with latrine or drinking activity and were too low to accurately analyze as an indicator of thermal preference. Breed did not affect temperature preference (P > 0.05). A cubic regression model determined that boars spent the majority of their time inactive at 25.50 ºC (P < 0.01) and lying (both sternal and lateral) at 25.90 ºC (P < 0.01). These data suggest that boar thermal preferences did not differ by breed and that boars prefer temperatures at the upper end of current guidelines (10.00 to 25.00 ºC).
Cardioprotective role of the coenzyme Q10 and coconut oil in acute aluminum phosphide poisoning: a randomized controlled clinical trial
Authors: Elsharkawy Rasha E , Ghonem Mona M , El-Sarnagawy Ghada N , Nagy Ayman A , Heshmat Mona M
Published: May 2023

Aluminum phosphide (ALP)-induced cardiotoxicity is a major cause of high mortality rates. As there is no specific antidote, restoring cardiac hemodynamics is the cornerstone for saving patients. Based on oxidative stress theory in acute ALP poisoning, we examined the cardioprotective role of coconut oil and Coenzyme Q10 (COQ10) in ALP poisoning, focusing on their antioxidant capacity. This study was a randomized, controlled, single-blind, phase II clinical trial conducted at Tanta Poison Control Center over 1 year. Eighty-four ALP poisoned patients received supportive treatment and were randomly allocated to three equal groups. Gastric lavage was performed using sodium bicarbonate 8.4% with saline in group I. Alternatively, group II received 50 ml coconut oil, and group III initially received 600 mg CoQ10 dissolved in 50 ml coconut oil; and repeated 12 hours later. In addition to patient characteristics, clinical, laboratory, electrocardiography (ECG), and total antioxidant capacity (TAC) data were recorded and repeated 12 hours later. Patient outcomes were evaluated. There was no significant difference among groups considering patient characteristics, initial cardiotoxicity severity, vital, laboratory data, ECG changes, and TAC. However, 12 hours post-admissions, group III was significantly improved in all clinical, laboratory, and ECG parameters than comparable groups. Significant correlations were observed between elevated TAC in groups II and III with hemodynamic, serum troponin, and ECG variables. Accordingly, the need for intubation, mechanical ventilation, and the total vasopressor dose was significantly decreased in group III compared with other groups. Therefore, coconut oil and COQ10 are promising cardioprotective adjuvant therapy ameliorating the ALP-induced cardiotoxicity.
Rating System for Phytophthora Root Rot Influences Quantitative Trait Locus Detection and Reveals Incomplete Dominance and Duplicative Recessive Epistatic Gene Action in Capsicum annuum
Authors: Barchenger Derek W. , Hsu Yu-ming , Liao Kuei-Jr , Lines Caleb L. , Lin Shih-wen , Wang Yen-wei , Lin Tsung-han , Huang Shu-mei , Lozada Dennis N. , Bosland Paul W.
Published: May 2023

Phytophthora capsici is one of the most devastating pathogens facing pepper ( Capsicum annuum) producers worldwide. Numerous factors, such as the race of the pathogen, the growing environment, and the source of resistance, have resulted in an overall lack of widely applicable molecular markers associated with resistance. Our objective was to determine the effect of the rating system on quantitative trait locus (QTL) detection and understand inheritance patterns of host resistance that can influence selection and molecular marker accuracy. We evaluated an F2:11 recombinant inbred line population screened against the highly virulent strain (Pc134) and scored using two widely used methods, developed by Bosland and Lindsey and by Black. The rating system developed by Bosland and Lindsey resulted in slightly higher logarithm of odds for the QTL on chromosome 5, and we detected a QTL on chromosome 12 uniquely using this rating system. A QTL on chromosome 10 was detected using both rating systems, but Black resulted in considerably higher logarithm of odds for this QTL compared with the Bosland and Lindsey system. Molecular markers developed were nominally better at accurately predicting the phenotype than previously published molecular markers but did not completely explain resistance in our validation populations. The inheritance pattern of resistance in one of our F2 populations did not significantly deviate from a 7:9 segregation ratio, indicating duplicative recessive epistasis. However, these results could be confounded by the presence of incomplete gene action, which was found through the improved selection accuracy when the phenotypes of heterozygous individuals were grouped with those with susceptible alleles.
High-Quality Genome of the Tree Pathogen Phytophthora plurivora—A Novel Resource for Epidemiological Research
Authors: Tsykun T. , Mishra B. , Ploch S. , Briseño R. I. Alcalá , Prospero S. , Grünwald N. J. , Thines M.
Published: May 2023

Phytophthora plurivora can affect a range of ecologically and silviculturally important tree species, including European beech ( Fagus sylvatica), a common late successional tree species native to Europe. Here, we report on the high-quality genome of P. plurivora strain TJ71 (CBS 124093). We sequenced it using Oxford Nanopore MinION and PacBio Sequel II long-read sequencing with 80× coverage, chromatin conformation capture (Hi-C) sequencing with 400× coverage, and DNBSEQ 150-bp paired-end short reads sequencing with 200× coverage. This complex sequencing approach allowed for assembly of the genome at the chromosome level. Specifically, the P. plurivora genome resulted in 18 scaffolds of 47 Mbp total size with 95% completeness of the eukaryotic gene set as implemented in BUSCO. This is a considerable improvement relative to the previous NCBI reference genome of P. plurivora (NMPK00000000.1) with ∼41 Mbp organized in 1,898 scaffolds with 93.8% eukaryotic BUSCO completeness. This high-quality genome provides a valuable resource for further evolutionary, epidemiological, and population genomic studies.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Prevalence and Characteristics of Diagnostic Error in Pediatric Critical Care: A Multicenter Study*
Authors: Cifra Christina L. , Custer Jason W. , Smith Craig M. , Smith Kristen A. , Bagdure Dayanand N. , Bloxham Jodi , Goldhar Emily , Gorga Stephen M. , Hoppe Elizabeth M. , Miller Christina D. , Pizzo Max , Ramesh Sonali , Riffe Joseph , Robb Katharine , Simone Shari L. , Stoll Haley D. , Tumulty Jamie Ann , Wall Stephanie E. , Wolfe Katie K. , Wendt Linder , Ten Eyck Patrick , Landrigan Christopher P. , Dawson Jeffrey D. , Reisinger Heather Schacht , Singh Hardeep , Herwaldt Loreen A.
Published: May 2023

OBJECTIVES:

Effective interventions to prevent diagnostic error among critically ill children should be informed by diagnostic error prevalence and etiologies. We aimed to determine the prevalence and characteristics of diagnostic errors and identify factors associated with error in patients admitted to the PICU.

DESIGN:

Multicenter retrospective cohort study using structured medical record review by trained clinicians using the Revised Safer Dx instrument to identify diagnostic error (defined as missed opportunities in diagnosis). Cases with potential errors were further reviewed by four pediatric intensivists who made final consensus determinations of diagnostic error occurrence. Demographic, clinical, clinician, and encounter data were also collected.

SETTING:

Four academic tertiary-referral PICUs.

PATIENTS:

Eight hundred eighty-two randomly selected patients 0–18 years old who were nonelectively admitted to participating PICUs.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of 882 patient admissions, 13 (1.5%) had a diagnostic error up to 7 days after PICU admission. Infections (46%) and respiratory conditions (23%) were the most common missed diagnoses. One diagnostic error caused harm with a prolonged hospital stay. Common missed diagnostic opportunities included failure to consider the diagnosis despite a suggestive history (69%) and failure to broaden diagnostic testing (69%). Unadjusted analysis identified more diagnostic errors in patients with atypical presentations (23.1% vs 3.6%, p = 0.011), neurologic chief complaints (46.2% vs 18.8%, p = 0.024), admitting intensivists greater than or equal to 45 years old (92.3% vs 65.1%, p = 0.042), admitting intensivists with more service weeks/year (mean 12.8 vs 10.9 wk, p = 0.031), and diagnostic uncertainty on admission (77% vs 25.1%, p < 0.001). Generalized linear mixed models determined that atypical presentation (odds ratio [OR] 4.58; 95% CI, 0.94–17.1) and diagnostic uncertainty on admission (OR 9.67; 95% CI, 2.86–44.0) were significantly associated with diagnostic error.

CONCLUSIONS:

Among critically ill children, 1.5% had a diagnostic error up to 7 days after PICU admission. Diagnostic errors were associated with atypical presentations and diagnostic uncertainty on admission, suggesting possible targets for intervention.
Transversus thoracic muscle plane block for pain during cardiac surgery: a systematic review and meta-analysis
Authors: Xue Jian-jun , Cui Yi-yang , Busse Jason W. , Ge Long , Zhou Ting , Huang Wei-hua , Ding Sheng-shuang , Zhang Jie , Yang Ke-hu
Published: May 2023

Study Objective:

The role of transversus thoracic muscle plane blocks (TTMPBs) during cardiac surgery is controversial. We conducted a systematic review to establish the effectiveness of this procedure.

Design:

Systematic review. We searched PubMed, Embase, Web of Science, CENTRAL, WanFang Data, and the China National Knowledge Infrastructure to June 2022, and followed the GRADE approach to evaluate the certainty of evidence.

Study Eligibility Criteria:

Eligible studies enrolled adult patients scheduled to undergo cardiac surgery and randomized them to receive a TTMPB or no block/sham block.

Main Results:

Nine trials that enrolled 454 participants were included. Compared to no block/sham block, moderate certainty evidence found that TTMPB probably reduces postoperative pain at rest at 12h (weighted mean difference [WMD] −1.51 cm on a 10 cm visual analogue scale for pain, 95% CI -2.02 to -1.00; risk difference [RD] for achieving mild pain or less (≤3 cm), 41%, 95%CI 17 to 65) and 24h (WMD −1.07 cm, 95%CI −1.83 to −0.32; RD 26%, 95%CI 9 to 37). Moderate certainty evidence also supported that TTMPB probably reduces pain during movement at 12h (WMD -3.42 cm, 95%CI −4.47 to −2.37; RD 46%, 95%CI 12 to 80) and at 24h (WMD −1.73 cm, 95%CI −3.24 to −0.21; RD 32%, 95%CI 5 to 59), intraoperative opioid use (WMD −28 milligram morphine equivalent [MME], 95%CI −42 to −15), postoperative opioid consumption (WMD −17 MME, 95%CI −29 to −5), postoperative nausea and vomiting (absolute risk difference 255 less per 1000 persons, 95%CI 140 to 314), and ICU length of stay (WMD −13 h, 95%CI −21 to −6).

Conclusion:

Moderate certainty evidence showed TTMPB during cardiac surgery probably reduces postoperative pain at rest and with movement, opioid consumption, ICU length of stay, and the incidence of nausea and vomiting.
Rural-urban differences in characteristics, postoperative outcomes, and costs for patients undergoing knee arthroplasty: a national retrospective propensity score matched cohort study
Authors: Long Huizhong , Xie Dongxing , Chen Hu , Wei Jie , Li Xiaoxiao , Wang Haibo , Zeng Chao , Lei Guanghua
Published: May 2023

Background:

The rural-urban disparities in postoperative complications and costs among patients undergoing knee arthroplasty (KA) have not been thoroughly explored. This study aimed to determine whether such differences exist in this patient population.

Material and methods:

The study was conducted using data from the national Hospital Quality Monitoring System of China. Hospitalized patients undergoing KA from 2013 to 2019 were enrolled. Patient and hospital characteristics were compared between rural and urban patients, and differences in postoperative complications, readmissions, and hospitalization costs were analyzed using propensity score matching.

Results:

Of the 146,877 KA cases analyzed, 71.4% (104,920) were urban patients and 28.6% (41,957) were rural patients. Rural patients tended to be younger (64.4±7.7 y vs. 68.0±8.0 y; P<0.001) and had fewer comorbidities. In the matched cohort of 36,482 participants per group, rural patients were found to be more likely to experience deep vein thrombosis (OR: 1.31, 95% CI: 1.17-1.46; P<0.001) and require RBC transfusion (OR: 1.38, 95% CI: 1.31-1.46; P<0.001). However, they had a lower incidence of readmission within 30 days (OR: 0.65, 95% CI: 0.59-0.72; P<0.001) and readmission within 90 days (OR: 0.61, 95% CI: 0.57-0.66; P<0.001) than their urban counterparts. In addition, rural patients incurred lower hospitalization costs than urban patients (57,396.2 Chinese Yuan [CNY] vs. 60,844.3 CNY; P<0.001).

Conclusion:

Rural KA patients had different clinical characteristics compared with urban patients. While they had a higher likelihood of deep vein thrombosis and RBC transfusion following KA than urban patients, they had fewer readmissions and lower hospitalization costs. Targeted clinical management strategies are needed for rural patients.
Does major pathological response after neoadjuvant Immunotherapy in resectable non-small-cell lung cancers predict prognosis? a systematic review and meta-analysis
Authors: Chen Yujia , Qin Jianjun , Wu Yajing , Lin Qiang , Wang Jianing , Zhang Wei , Liang Fei , Hui Zhouguang , Zhao Min , Wang Jun
Published: May 2023

Objective:

Overall survival (OS) is the gold-standard outcome measure for phase 3 trials, but the need for long follow-up period can delay the translation of potentially effective treatment to clinical practice. The validity of Major Pathological Response (MPR) as a surrogate of survival for non small cell lung cancer (NSCLC) after neoadjuvant immunotherapy remains unclear.

Methods:

Eligibility was resectable stage I-III NSCLC and delivery of PD-1/PD-L1/CTLA-4 inhibitors prior to resection; other forms/modalities of neoadjuvant and/or adjuvant therapies were allowed. Statistics utilized the Mantel-Haenszel fixed-effect or random-effect model depending on the heterogeneity (I2).

Results:

Fifty-three trials (7 randomized, 29 prospective nonrandomized, 17 retrospective) were identified. The pooled rate of MPR was 53.8%. Compared to neoadjuvant chemotherapy, neoadjuvant chemo-immunotherapy achieved higher MPR (OR 6.19, 4.39–8.74, P<0.00001). MPR was associated with improved DFS/PFS/EFS (HR 0.28, 0.10–0.79, P=0.02) and OS (HR 0.80, 0.72–0.88, P＜0.0001). Patients with stage III (vs I/II) and PD-L1 ≥1% (vs <1%) more likely achieved MPR (OR 1.66,1.02–2.70, P=0.04; OR 2.21,1.28–3.82, P=0.004).

Conclusions:

The findings of this meta-analysis suggest that neoadjuvant chemo-immunotherapy achieved higher MPR in NSCLC patients，and increased MPR might be associated with survival benefits treated with neoadjuvant immunotherapy. It appears that the MPR may serve as a surrogate endpoint of survival to evaluate neoadjuvant immunotherapy.
Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicenter cohort study
Authors: Ren YouLiang , Liu Lei , Sun Dong , Zhang ZhengDong , Li Meng , Lan Xu , Ni JiangDong , Yan MingMing , Huang Wei , Liu ZiMing , Peng Aqin , Zhang YanLong , Jiang Nan , Song KeGuan , Huang ZhiPeng , Bi Qing , Zhang Jun , Yang Qun , Yang Jun , Liu Yi , Fu Wei , Tian XiaoBin , Wang YuanZheng , Zhong WanRun , Song XingHua , Abudurexiti Abuduxukuer , Xia ZhiLin , Jiang Qing , Shi HongFei , Liu XiMing , Wang GuoDong , Hu YunSheng , Zhang YunFei , Yin GuoYong , Fan Jin , Feng ShiQing , Zhou XianHu , Li ZhengDao , He WenBin , Weeks Jason , Schwarz Edward M. , Kates Stephen L. , Huang Lei , Chai YiMin , Yu Bin , Xie Zhao , Deng ZhongLiang , Xie Chao
Published: May 2023

Background:

Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China.

Methods:

The study was approved by the Institutional Research Board (IRB), and 3,526 PTRLO patients were identified from 212,394 traumatic limb fracture patients at 21 hospitals between January 1st, 2008- December 31st, 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors, and antibiotic resistance and sensitivity.

Results:

The IR of PTRLO increased gradually from 0.93%–2.16% (Z=14.392, P<0.001). Monomicrobial infection (MI, 82.6%) was significantly higher than polymicrobial infection (PI, 17.4%) (P<0.001). The IR of Gram-Positive (GP) & Gram-Negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP versus GN’s composition did not show any significance (Z=+/-1.1918, P>0.05). The most prevalent Gram-positive strains were MSSA (17.03%), MRSA (10.46%), E. faecalis (5.19%), and S. epidermidis (4.87%). In contrast, the dominant strains Gram-negative strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E.coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for PI include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities.

Conclusions:

This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).