Citizen science reveals waterfowl responses to extreme winter weather.

Global climate change is increasing the frequency and severity of extreme climatic events (ECEs) which may be especially detrimental during late-winter when many species are surviving on scarce resources. However, monitoring animal populations relative to ECEs is logistically challenging. Crowd-sourced datasets may provide opportunity to monitor species' responses to short-term chance phenomena such as ECEs. We used 14 years of eBird-a global citizen science initiative-to examine distribution changes for seven wintering waterfowl species across North America in response to recent extreme winter polar vortex disruptions. To validate inferences from eBird, we compared eBird distribution changes against locational data from 362 GPS-tagged Mallards (Anas platyrhynchos) in the Mississippi Flyway. Distributional shifts between eBird and GPS-tagged Mallards were similar following an ECE in February 2021. In general, the ECE affected continental waterfowl population distributions; however, responses were variable across species and flyways. Waterfowl distributions tended to stay near wintering latitudes or moved north at lesser distances compared with non-ECE years, suggesting preparedness for spring migration was a stronger "pull" than extreme weather was a "push" pressure. Surprisingly, larger-bodied waterfowl with grubbing foraging strategies (i.e., geese) delayed their northward range shift during ECE years, whereas smaller-bodied ducks were less affected. Lastly, wetland obligate species shifted southward during ECE years. Collectively, these results suggest specialized foraging strategies likely related to resource limitations, but not body size, necessitate movement from extreme late-winter weather in waterfowl. Our results demonstrate eBird's potential to monitor population-level effects of weather events, especially severe ECEs. eBird and other crowd-sourced datasets can be valuable to identify species which are adaptable or vulnerable to ECEs and thus, begin to inform conservation policy and management to combat negative effects of global climate change.

Refractory Insomnia in an Adolescent with Total Blindness.

We present a totally blind adolescent with refractory insomnia due to a combination of Non-24 hour sleep-wake disorder and restless leg syndrome that was successfully treated with tasimelteon, iron replacement, and gabapentin. To our knowledge, this is the first published report of treatment of N24 with tasimelteon in an adolescent. In addition, this case highlights the importance of recognizing and treating multifactorial causes of insomnia.

Sleep: important considerations for the prevention of cardiovascular disease.

PURPOSE OF REVIEW: Sleep plays many roles in maintenance of cardiovascular health. This review summarizes the literature across several areas of sleep and sleep disorders in relation to cardiometabolic disease risk factors. RECENT FINDINGS: Insufficient sleep duration is prevalent in the population and is associated with weight gain and obesity, inflammation, cardiovascular disease, diabetes, and mortality. Insomnia is also highly present and represents an important risk factor for cardiovascular disease, especially when accompanied by short sleep duration. Sleep apnea is a well-characterized risk factor for cardiometabolic disease and cardiovascular mortality. Other issues are relevant as well. For example, sleep disorders in pediatric populations may convey cardiovascular risks. Also, sleep may play an important role in cardiovascular health disparities. SUMMARY: Sleep and sleep disorders are implicated in cardiometabolic disease risk. This review addresses these and other issues, concluding with recommendations for research and clinical practice.

Incidence of delirium in children with cancer.

There are limited data on the incidence of delirium in children with cancer. We performed a retrospective chart review of all pediatric oncology admissions over a 1 year period to determine the incidence of delirium in this population. We identified seven patients with delirium (10% incidence). Delirium is associated with significant morbidity and mortality, and is likely under-recognized in this population. Improved diagnosis and treatment of delirium may improve outcomes in children with cancer.

The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome.

STUDY OBJECTIVES: Children with Down syndrome (DS) are at very high risk for obstructive sleep apnea (OSA). Current OSA treatments have limited effectiveness in this population. We evaluated the effectiveness of atomoxetine and oxybutynin (ato-oxy) to treat OSA in children with Down syndrome. METHODS: Children ages 6-7 years old with Down syndrome and OSA participated in a double-blind crossover clinical trial evaluating two dose regimens of ato-oxy. Participants received low-dose ato-oxy (0.5 mg/kg atomoxetine and 5 mg oxybutynin) and high-dose ato-oxy (1.2 mg/kg atomoxetine and 5 mg oxybutynin) for 1 month in random order. The primary study outcome was change in obstructive apnea-hypopnea index. Health-related quality of life as measured by the OSA-18 as well as changes in sleep architecture were secondary outcomes. RESULTS: Fifteen participants qualified for randomization and 11 participants had complete data at all points. Baseline obstructive apnea-hypopnea index was 7.4 ± 3.7 (mean ± standard deviation), obstructive apnea-hypopnea index with low-dose ato-oxy was 3.6 ± 3.3 (P = .001 vs baseline), and obstructive apnea-hypopnea index with high-dose ato-oxy was 3.9 ± 2.8 (P = .003 vs baseline). No significant sleep architecture differences were present with ato-oxy. No significant difference in OSA-18 score was present. OSA-18 total score was 51 ± 19 at baseline, 45 ± 17 (P = .09) at the end of 4 weeks of low-dose ato-oxy, and 45 ± 16 (P = .37) at the end of high-dose ato-oxy therapy. The most common adverse effects were irritability and fatigue, and these were generally mild. CONCLUSIONS: Ato-oxy is a promising treatment for OSA in children with Down syndrome. CLINICAL TRIAL REGISTRATION: Registry: Clinicaltrials.gov; Name: Medications for Obstructive Sleep Apnea In Children With Down Syndrome (MOSAIC); URL: https://clinicaltrials.gov/ct2/show/NCT04115878; Identifier: NCT04115878. CITATION: Combs D, Edgin J, Hsu C-H, et al. The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome. J Clin Sleep Med. 2023;19(12):2065-2073.

Psychiatric implications of adolescent methamphetamine exposures.

OBJECTIVES: Methamphetamine abuse has reached epidemic proportions during the last decade. Abuse among adolescents is linked to increased rates of depression and suicidal ideation. Sources suggest that there is an increase rate of suicide attempts in the methamphetamine-abusing adolescent patient population. Our study seeks to examine adolescent methamphetamine exposures reported to the California Poison Control System during the past decade of suicidal ideation and suicide attempts in comparison to rates reported by population-based surveys. METHODS: The records of the California Poison Control System were searched for methamphetamine exposures from 2000 to 2009. All charts of patients identified between the ages of 11 and 18 years were reviewed and abstracted. RESULTS: The records of 293 youth between the ages of 11 and 18 years were identified and assigned levels of severity according to parameters set by the National Poison Data System Medical Outcome Criteria of the American Association of Poison Control Centers. Charts were categorized as follows: 11 as major, 52 as moderate, and 75 as minor. The remainder of the charts were not evaluated because of no effect (n = 13) or unable to follow (n = 142). In this cohort, more females were reported than males (57%). The most common presenting symptom in this patient population was agitation (39%). The most common events were suicidal ideation (31%) and suicide attempts (21%). CONCLUSIONS: In this data set, adolescent methamphetamine exposures were associated with increased rates of suicidal ideation and suicide attempts that are disproportionate to population-based surveys during the same period.

Obstructive Sleep Apnea as a Risk Factor for COVID-19 Severity-The Gut Microbiome as a Common Player Mediating Systemic Inflammation via Gut Barrier Dysfunction.

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy.

Markers of ventricular repolarization and overall mortality in sleep disordered breathing.

INTRODUCTION: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality. METHODS: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality. RESULTS: Eight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05). CONCLUSION: Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality.

A Comparison of 10% Dextrose and 50% Dextrose for the Treatment of Hypoglycemia in the Prehospital Setting.

BACKGROUND: Hypoglycemia is a frequent cause of emergency medical services (EMS) activation; however, limited evidence exists to support optimal prehospital treatment. OBJECTIVE: This study sought to compare the safety and efficacy of the administration of 10% dextrose (D10) intravenously (IV) versus 50% dextrose (D50) IV for the treatment of hypoglycemia in the prehospital setting. METHODS: This was a retrospective cohort study of patients who received IV dextrose by EMS and were transported to an academic teaching hospital emergency department between 2014 and 2017. RESULTS: Four hundred seventy-eight eligible patients were reviewed, with 161 patients receiving D10 and 150 patients receiving D50. There was no significant difference found regarding the need for dextrose retreatment prior to hospital arrival between the D10 and D50 groups (0.6% vs 2.0%; P = .565). The prehospital reassessment glucose in the D50 group was a significantly higher than the D10 group (151.9 vs 124.6 mg/dL, P = .001) and this difference was maintained on hospital arrival (129.5 vs 108.0 mg/dL, P = .011). No significant difference was found between groups with regard to hospital admission, length of stay, or in-hospital mortality. CONCLUSION: When comparing D10 with D50 for the treatment of hypoglycemia by EMS, there were no significant differences in the need for dextrose retreatment prior to hospital arrival. The use of D50 resulted in a significantly higher blood glucose concentrations both in the prehospital setting and upon hospital arrival. Further study is needed in larger patient populations to evaluate the use of D10, the need for dextrose readministration, and its impact on clinical outcomes.

The Hypoglossal Nerve Stimulation as a Novel Therapy for Treating Obstructive Sleep Apnea-A Literature Review.

Obstructive sleep apnea (OSA) is a common sleep disorder that affects all age groups and is associated with many co-morbid diseases (especially cardiovascular diseases). Continuous positive airway pressure (CPAP) is the gold standard for treating OSA. However, adherence to PAP therapy has been a major challenge with an estimated adherence between 20% and 80%. Mandibular advancement devices (MAD) are a good alternative option if used in the appropriate patient. MAD are most effective in mild and moderate OSA but not severe OSA. Surgical options are invasive, not appropriate for severe OSA, and associated with pain and long healing time. Hypoglossal nerve stimulation (HGNS), or upper airway stimulation (UAS), is a novel therapy in treating moderate and severe degrees of OSA in patients who cannot tolerate CPAP therapy. We reviewed the MEDLINE (PubMed) database. The search process yielded 303 articles; 31 met the inclusion and exclusion criteria and were included. We concluded that hypoglossal nerve stimulation is a very effective and novel alternative therapy for moderate and severe OSA in patients who cannot tolerate CPAP therapy. Adherence to HGNS is superior to CPAP. However, more developments are needed to ensure the highest safety profile.

Matrix metalloproteinase-9 as a messenger in the cross talk between obstructive sleep apnea and comorbid systemic hypertension, cardiac remodeling, and ischemic stroke: a literature review.

STUDY OBJECTIVES: OSA is a common sleep disorder. There is a strong link between sleep-related breathing disorders and cardiovascular and cerebrovascular diseases. Matrix metalloproteinase-9 (MMP-9) is a biological marker for extracellular matrix degradation, which plays a significant role in systemic hypertension, myocardial infarction and postmyocardial infarction heart failure, and ischemic stroke. This article reviews MMP-9 as an inflammatory mediator and a potential messenger between OSA and OSA-induced comorbidities. METHODS: We reviewed the MEDLINE database (PubMed) for publications on MMP-9, OSA, and cardiovascular disease, identifying 1,592 studies and including and reviewing 50 articles for this work. RESULTS: There is strong evidence that MMP-9 and tissue inhibitor of metalloproteinase-1 levels are elevated in patients with OSA (mainly MMP-9), systemic hypertension, myocardial infarction, and postmyocardial infarction heart failure. Our study showed variable results that could be related to the sample size or to laboratory methodology. CONCLUSIONS: MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1, are a common denominator in OSA, systemic hypertension, myocardial infarction, and heart failure. This characterization makes MMP-9 a target for developing novel selective inhibitors that can serve as adjuvant therapy in patients with OSA, which may ameliorate the cardiovascular and cerebrovascular mortality associated with OSA.

Differences in sleep timing and related effects between African Americans and non-Hispanic Whites.

STUDY OBJECTIVES: Prior studies have shown a morning chronotype for African Americans compared with non-Hispanic Whites, yet self-reported sleep timing is delayed in African Americans compared with Whites. METHODS: We analyzed data from the Multi-Ethnicity Study of Atherosclerosis, a multisite community-based cohort. Self-reported and actigraphic sleep timing, chronotype measured by the modified Horne-Östberg Morningness-Eveningness Questionnaire, and risk of depression measured by the Center for Epidemiologic Studies Depression scale were examined using nonparametric approaches and linear or logistic regression while comparing between African Americans and Whites and evaluating the effects of delayed sleep phase. RESULTS: In 1,401 participants, there was no difference in chronotype between African Americans and Whites. African Americans were 80% more likely to report a delayed sleep phase (defined as bedtime after midnight) on weekdays and 50% more likely on weekends than were Whites. Actigraphic data showed similar results. Actigraphic midsleep time was delayed 38 minutes on weekdays and 24 minutes on weekends in African Americans compared with Whites. Stratified analysis by chronotype showed that African Americans with a morning or intermediate chronotype had a significantly delayed sleep phase compared with Whites, but there was no difference between African Americans and Whites with an evening chronotype. Delayed sleep phase was associated with depression, but this relationship was only significant in White participants. CONCLUSIONS: African Americans had a delayed sleep phase compared with Whites that was more pronounced in individuals with a morning or intermediate chronotype. Consequences of delayed sleep phase may vary by race and ethnicity.

Atezolizumab and Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma: Pharmacokinetic and Safety Assessments Based on Hepatic Impairment Status and Geographic Region.

INTRODUCTION: Phase 1b GO30140 and phase 3 IMbrave150 studies evaluated first-line atezolizumab + bevacizumab for unresectable hepatocellular carcinoma (HCC). Here, we evaluated pharmacokinetics (PK) and safety by hepatic impairment status and geographic region. METHODS: Patients received atezolizumab 1,200 mg + bevacizumab 15 mg/kg IV every 3 weeks. Drug concentrations were evaluated by descriptive statistics and population PK. PK and adverse event frequencies were evaluated by hepatic impairment status and region. RESULTS: 323 IMbrave150 patients and 162 GO30140 patients were PK evaluable. Compared with IMbrave150 patients who had normal hepatic function per the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria (n = 123), patients with mild impairment (n = 171) had a geometric mean ratio (GMR) of 0.92 for cycle 1 atezolizumab area under the concentration-time curve (AUC); patients with moderate impairment (n = 27) had a GMR of 0.88. Patients in Asia ([n = 162] vs. outside [n = 161]) had a GMR of 1.25 for cycle 1 atezolizumab AUC. Compared with GO30140 patients who had normal hepatic function (NCI-ODWG [n = 61]), patients with mild impairment (n = 92) had a GMR of 0.97 for cycle 1 peak bevacizumab concentrations; those with moderate impairment (n = 9) had a GMR of 0.94. Patients in Asia (n = 111) versus outside Asia (n = 51) had a GMR of 0.94 for cycle 1 peak bevacizumab concentration. PK results were generally comparable when evaluated based on additional hepatic functional definitions (Child-Pugh or albumin/bilirubin criteria) or study enrollment in Japan. No associations between atezolizumab PK and HCC etiology were seen. Adverse event frequencies were similar across evaluated groups. CONCLUSIONS: IMbrave150 and GO30140 patients with unresectable HCC had varying baseline hepatic impairment and high enrollment from Asia. PK data demonstrated considerable exposure overlap across groups. Treatment was tolerable across groups. No need for dose adjustment based on mild or moderate hepatic impairment or region is recommended based on this analysis.

Association Between Sleep Disturbances With Neurodevelopmental Problems and Decreased Health-Related Quality of Life in Children With Fontan Circulation.

Background Children with Fontan circulation are known to be at increased risk for neurodevelopmental problems and decreased health-related quality of life (HRQOL), but many factors that may contribute to this risk are unknown. Sleep disturbances may be one previously unidentified factor that contributes to this risk. Methods and Results We analyzed data from the Pediatric Heart Network Fontan cross-sectional study to evaluate associations between a parent or child report of sleep disturbance with reported neurodevelopmental concerns and HRQOL in 558 children with Fontan circulation. Parent-reported sleep disturbance was present in 11% of participants and child-reported sleep disturbance was present in 15%. Parent-reported sleep disturbance was associated with a significantly higher risk of attention problems, anxiety, depression, behavioral problems, and developmental delay (P<0.001 for all). Similarly, parent-reported disturbance was associated with decreased HRQOL on both parent and child-reported HRQOL (P<0.001 for most domains). Child-reported sleep disturbances were associated with increased odds of anxiety, depression, and attention problems as well as worse HRQOL. These associations were present even after adjustment for cardiac, demographic, and socioeconomic factors that may affect HRQOL and neurodevelopmental status. Conclusions Sleep disturbances in children with Fontan circulation are associated with an increased risk of neurodevelopmental problems as well as reduced HRQOL compared with those without sleep disturbance. Better understanding of sleep disturbances is needed in children with Fontan circulation, as sleep disturbances may represent a reversible cause of neurodevelopmental problems and decreased HRQOL in this population.

OSA and Neurocognitive Impairment in Children With Congenital Heart Disease.

BACKGROUND: Children with congenital heart disease (CHD) have an increased risk of neurocognitive impairment. No prior studies have evaluated the role of OSA, which is associated with neurocognitive impairment in children without CHD. RESEARCH QUESTION: Is OSA is associated with neurocognitive impairment in children with CHD? STUDY DESIGN AND METHODS: Children aged 6 to 17 years with corrected moderate to complex CHD without syndromes that may affect neurocognition were recruited from the pediatric cardiology clinic. Participants underwent home sleep testing and neurocognitive testing, including a validated Intellectual Quotient (IQ) test as well as validated tests of memory (Paired Associates Learning test), executive function (Intra-Extra Dimensional set shift test), and attention (Simple Reaction Test) from the CANTAB neurocognitive testing battery. RESULTS: Complete results were available for 30 children. Seventeen children (57%) were found to have OSA. Total IQ was markedly lower in children with CHD and comorbid OSA compared with children with CHD without comorbid OSA (mean, 86 ± 12 vs 98 ± 11; P = .01). Children with CHD and OSA did significantly worse on the Paired Associates Learning test, with a median of eight total errors (interquartile range [IQR], 2.25-15) compared with children with CHD without OSA (median total errors, 2, IQR, 1-8; P = .02). INTERPRETATION: Children with CHD and comorbid OSA have impaired neurocognition compared with children with CHD without comorbid OSA. OSA may be a reversible cause of neurocognitive impairment in children with CHD. Further research is needed to evaluate the effects of OSA treatment on neurocognitive impairment in children with CHD.