Effects of the active botanical blend "WKUP GT" on attention and cognitive functions after lunch in healthy volunteers.

OBJECTIVES: "WKUP GT", a low caffeine beverage consisting of carob, Guarana, Green Tea and Elderberry extracts was studied on attention and cognitive functions post-lunch in a pilot randomized double blind placebo controlled trial. METHODS: Thirty healthy volunteers were included in a crossover design trial, presenting five beverages randomly assigned to the following groups: placebo, "WKUP GT" (single, double or triple doses), or "caffeine" as an active control. Hemodynamic measurements were assessed as safety outcomes. The Cambridge Neuropsychological Test Automated Battery (CANTAB), was used to evaluate the patients when beverages were consumed 30 and 120 min after lunch (respectively Delta30 and Delta120 considering baseline). RESULTS: Drinking "caffeine" or "WKUP GT" after lunch, showed significant improvement (p < 0.05) in rapid visual information processing compared to placebo (Delta120 of "caffeine", "WKUP" single and double). In addition, improvement in Multitasking Test (Delta30 for "WKUP" double, and Delta120 for "caffeine" and "WKUP" triple compared to placebo) was observed. "WKUP" triple also showed significant improvement for "memory" when compared to placebo (Delta120). Compared to "caffeine", WKUP GT did not increase systolic blood pressure. CONCLUSION: "WKUP GT" showed improvements for attention, memory, psychomotor and executive function tasks after lunch without increase in pulse rate.

Healthcare utilization is increased in children living in urban areas, with ethnicity-related disparities: A big data analysis study.

This study aimed to investigate differences in pediatric healthcare utilization in Israel over 10 years by examining differences across populations defined by living environment and ethnicity. Data was obtained from the Clalit Health Care data warehouse, covering over 250,000 children residing in Haifa and Western Galilee districts. The population groups were categorized based on ethnicity (Jewish vs Arab) and residential settings (urban vs rural). Healthcare utilization was consistently higher among Jewish than Arab children, irrespective of the specific dimension analyzed. Additionally, urban-dwelling children exhibited higher usage rates than those residing in rural areas in all investigated dimensions. However, Jewish children showed significantly about 18% lower hospitalization rates than Arab children across all years (P < 0.001). No significant differences in hospitalizations were observed between urban and rural children (RR 0.999, CI (0.987-1.011)). Notably, the study revealed reduced antibiotic consumption and hospitalizations over the years for all populations. Additionally, we found that Arab children and those living in rural areas had reduced access to healthcare, as evidenced by 10-40% fewer physician visits, laboratory tests, and imaging (P < 0.001).    Conclusion: This study highlights the substantial population-based disparities in healthcare utilization among children in Israel despite the equalizing effect of the national health insurance law. Rural and low socioeconomic populations seem to have reduced healthcare access, showing decreased healthcare utilization. Consequently, it is imperative to address these disparities and implement targeted interventions to enhance healthcare access for Arab children and rural communities. The decline in antibiotic usage and hospitalizations suggests positive trends in pediatric health care, necessitating ongoing efforts to ensure equitable access and quality of care for all populations. What is Known: • Healthcare systems worldwide vary in coverage and accessibility, including Israel, which stands out for its diverse population. • Existing research primarily focuses on healthcare utilization among adults, leaving a need for comprehensive data on children's healthcare patterns globally. What is New: • Investigating over 250,000 children, this study reveals higher healthcare utilization among Jewish and urban children across all dimensions. • Despite Israel's national health insurance law, the study underscores the significant population-based disparities in healthcare utilization.

Medical clowns improve sleep and shorten hospitalization duration in hospitalized children.

Intervention by medical clowns was proven to have a positive effect in reducing stress and anxiety, increasing cooperation and improving the child's experience prior to a medical procedure and during the various stages of hospitalization. Sleep has long been known to be essential for recovery from injury and sickness, improving immune functions, and there is an emerging understanding of the restorative role quality sleep has on health and diseases. Hospitalized children are more exposed to sleep disorders and sleep deprivation due to the hospitalized environment, anxiety, and illness. Different behavioral interventions to promote sleep were previously studied in hospitalized children, some showing potential benefits. In this study, we sought to examine the ability of medical clowns to positively impact the child's sleep during hospitalization. The study is an observational matching (case-control) interventional study which took place at the department of pediatrics in Carmel Medical Center. Forty-two hospitalized children ages 2-17 were included in two equal groups of intervention or control. Children in the control group were recruited based on a method of matching the chief complaint plus the medical diagnosis and age of the children in the intervention group in a 1:1 matching. The children's sleep parameters were objectively evaluated for two consecutive nights using an Actigraph device and subjectively by parent's questionnaire. Additional factors such as hospital length of stay and demographics were also monitored. The study group had an encounter with a medical clown (15-30 min) before bedtime on either the first or the second night, and the control group was not exposed to a medical clown at all. We then compared the data from both groups using unpaired t-tests. Hospitalized children exposed to a medical clown prior to bedtime (n = 21) and children not exposed to a medical clown (n = 21) were comparable in age and clinical characteristics. The study group had a significantly delayed wake-up time compared to the control group (06:59 ± 46 min vs. 07:26 ± 42 min, p < 0.05) (mean difference of 27 min). Night's duration (from bedtime to wake-up) was significantly longer in the study versus the control group (570 ± 76 vs. 500 ± 66.1 min, p < 0.05), a total mean increase of 70 min, and sleep efficiency were significantly increased (92.3 ± 4.6% vs. 87.9 ± 8.7%, p < 0.05). Within the clown group, when comparing nights with and without exposure to a medical clown, total sleep time was prolonged by a mean of 54 min on the night of the intervention (518 ± 74 min vs. 464 ± 59 min, p < 0.01), and the total wake time during the night were reduced (52 ± 27 min vs. 77 ± 61 min, P < 0.05), mean difference of 25 min), mainly by reduction of wake period after sleep onset (WASO) (42 ± 25 min vs. 66 ± 58 min, p < 0.05), mean difference of 24 min). Regarding general medical outcomes, hospital stay was significantly shorter in the clown group vs. control (104 ± 42 h vs. 128 ± 42 h, p < 0.05), a mean reduction of 23 h-nearly an entire day. An encounter with a medical clown before bedtime in hospitalized children positively affects sleep parameters, which may be of great importance for healing in general. The clown intervention was also shown to shorten the hospital stay. Larger scale studies are warranted to establish these findings.

COVID-19 in neonates and infants younger than 6 months - a mild viral illness.

A surge in pediatric COVID-19 cases was observed during the fifth wave (Omicron) of the COVID-19 pandemic. Little is known about the clinical features and disease course in neonates and young infants. To describe the clinical and laboratory features, disease course and complications of COVID-19 in neonates and infants younger than 6 months. A retrospective descriptive study in which data were collected from the electronic medical records of infants younger than 6 months, with positive nasal swab tests for COVID-19. Fifty-two infants younger than 6 months who tested positive for COVID-19 were admitted to our pediatric ER/department during the omicron wave of the COVID-19 pandemic, between December 2021 and December 2022. Twenty-one percent were discharged from the ER, while the others were hospitalized predominantly for observation or supportive treatment, with an average duration of hospitalization of 1.3 ± 0.7 days. No major complications were observed.   Conclusion: COVID-19 is a mild viral illness in young healthy infants with no major complications. What is Known: • Pediatric patients generally have a milder clinical presentation of COVID-19 but can also experience more severe symptoms and post-COVID phenomena. • Our knowledge of COVID-19 in neonates and young infants is limited, and guidelines for their diagnosis and management are lacking. What is New: • In neonates and young infants, COVID-19 infection is typically a mild viral illness with no major complications observed in the majority of cases. • Hospitalization may not be necessary for well-appearing infants with COVID-19, as long as their clinical and laboratory evaluations do not raise any concerns.

Medical clowning in hospitalized children: a meta-analysis.

BACKGROUND: Medical clowning has been proven effective in reducing pain, anxiety, and stress in many sporadic, usually small-scale studies. Our meta-analysis aims to evaluate the efficiency of medical clowns in reducing pain and anxiety in hospitalized pediatric patients and their parents in different medical fields. METHODS: A thorough literature search was conducted from different databases, and only randomized controlled trials (RCTs) were included with children aged 0 to 18 years old. A total of 18 studies were included, and statistical analysis was performed on the combined data. RESULTS: A total of 912 children (14 studies) showed significantly reduced anxiety when procedures were performed with a medical clown compared with the controls (- 0.76 on anxiety score, P < 0.001). Preoperative anxiety was lower in 512 children (nine studies) with clown interventions than in the controls (- 0.78, P < 0.001). The pain scale was completed by 338 participants (six studies), indicating a trend toward reduced pain during procedures performed while the clown was acting compared to controls (- 0.49, P = 0.06). In addition, medical clown significantly (- 0.52, P = 0.001) reduced parental anxiety in 489 participants in ten studies; in six of the ten studies, with a total of 380 participants, medical clown significantly reduced parental preoperative anxiety (P = 0.02). CONCLUSION: Medical clowns have substantial positive and beneficial effects on reducing stress and anxiety in children and their families in various circumstances in pediatrics.

Inhaled Nitric Oxide for the Treatment of Acute Bronchiolitis: A Multicenter Randomized Controlled Clinical Trial to Evaluate Dose Response.

Rationale: Inhaled nitric oxide (iNO) has potential antiinflammatory, antimicrobial, and antiviral properties for patients with lower respiratory tract infections. Objectives: We compared the safety and efficacy of iNO administered in two concentrations in addition to standard supportive treatment (SST) compared with SST alone with the aim of improving clinical outcomes of infants with bronchiolitis. Methods: In this prospective, multicenter, double-blind, randomized controlled study, 89 infants hospitalized with moderate to severe bronchiolitis were randomly assigned to three treatment groups: 150 ppm NO plus SST (group 1), 85 ppm NO plus SST (group 2), and the control treatment (O2/air plus SST) (group 3). Treatment was given for 40 minutes, four times each day, for up to 5 days. The primary endpoint was time to reach "fit for discharge." This was a composite endpoint composed of both reaching a sustained oxygen saturation ≥92% on room air and reaching a clinical score ⩽5. Secondary endpoints included time to reach sustained oxygen saturation ≥92% on room air, time to clinical score ⩽5, and time to hospital discharge. Safety was assessed by the number of treatment-related adverse events (AEs) or serious AEs. Time-to-event efficacy outcomes were analyzed using a Cox proportional hazards regression model. Hazard ratios (HR) describe how many times more likely an individual is to experience an event, if such an individual receives NO rather than the control treatment during the observational period. Results: Group 1 demonstrated significant efficacy for time to reach fit to discharge compared with groups 2 (HR, 2.11; P = 0.041) and 3 (HR, 2.32; P = 0.049). Group 1 also demonstrated significant efficacy for time to hospital discharge compared with groups 2 (HR, 2.01; P = 0.046) and 3 (HR, 2.28; P = 0.043). No significant differences were observed between groups 2 and 3 for either endpoint. There were no differences between treatment groups in time to reach a clinical score ⩽5. The iNO therapy was well tolerated, with no treatment-related serious AEs. Conclusions: Treatment with high-dose intermittent iNO at 150 ppm showed reduced time to clinical improvement compared with 85 ppm or control treatment of hospitalized infants with acute bronchiolitis. The 150-ppm iNO dose is well tolerated, with significant benefit compared with both standard therapy and 85 ppm iNO, improving respiratory outcomes and reducing length of stay. Clinical trial registered with www.clinicaltrials.gov (NCT04060979).

Management of obstructive sleep apnea in Europe - A 10-year follow-up.

OBJECTIVE: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time. METHODS: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice. RESULTS: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). CONCLUSION: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.

Detection of Common Arrhythmias by the Watch-PAT: Expression of Electrical Arrhythmias by Pulse Recording.

Background: The WatchPAT (WP) device was shown to be accurate for the diagnosis of sleep apnea and is widely used worldwide as an ambulatory diagnostic tool. While it records peripheral arterial tone (PAT) and not electrocardiogram (ECG), the ability of it to detect arrhythmias is unknown and was not studied previously. Common arrhythmias such as atrial fibrillation (AF) or premature beats may be uniquely presented while recording PAT/pulse wave. Purpose: To examine the potential detection of common arrhythmias by analyzing the PAT amplitude and pulse rate/volume changes. Patients and Methods: Patients with suspected sleep disordered breathing (SDB) were recruited with preference for patients with previously diagnosed AF or congestive heart failure (CHF). They underwent simultaneous WP and PSG studies in 11 sleep centers. A novel algorithm was developed to detect arrhythmias while measuring PAT and was tested on these patients. Manual scoring of ECG channel (recorded as part of the PSG) was blinded to the automatically analyzed WP data. Results: A total of 84 patients aged 57±16 (54 males) participated in this study. Their BMI was 30±5.7Kg/m2. Of them, 41 had heart failure (49%) and 17 (20%) had AF. The sensitivity and specificity of the WP to detect AF segments (of at least 60 seconds) were 0.77 and 0.99, respectively. The correlation between the WP derived detection of premature beats (events/min) to that of the PSG one was 0.98 (p<0.001). Conclusion: The novel automatic algorithm of the WP can reasonably detect AF and premature beats. We suggest that when the algorithm raises a flag for arrhythmia, the patients should shortly undergo ECG and/or Holter ECG study.

Improvement in BMI z-score following adenotonsillectomy in adolescents aged 12-18 years: a retrospective cohort study.

BACKGROUND: Characteristics of obstructive sleep apnea (OSA) changes with age. Infants, toddlers and prepubertal children with OSA are usually underweight and may suffer from failure to thrive (FTT). Adenotonsillectomy (T&A) is the first line of treatment for OSA in childhood. In adults OSA is commonly associated with obesity and the metabolic syndrome. The change in body mass index (BMI) in adolescents with OSA following T&A was only sporadically studied. Thus, we peruse to examine the BMI z-score change following T&A in adolescents. METHODS: Clalit Health Services is the largest health care organization in Israel with the largest patient registry (more than 50% of the population). Two hundred and forty two adolescents aged 12-18 who underwent T&A between 2006 and 2015 were identified in the Clalit registry and their characteristics including height and weight were retrieved. The BMI z-score of these adolescents at baseline (up to 3 months prior to T&A) and during the consecutive 3 years after T&A were analyzed and compared. RESULTS: Changes in BMI Z-score were observed to all directions following T&A with overall small increase, not statistically significant (P = 0.26) from a median of 0.79 prior to T&A to a median of 0.835 after it. There was a minimal trend toward BMI z-score reduction in overweight children (n = 74) from 1.508 to 1.48 following T&A (p = NS), and in obese children (n = 33) from 2.288 to 2.000 (P = 0.06, 2 tailed). Interestingly thin individuals (n = 6) increased their BMI z-score following T&A from - 2.4 to - 0.59 (p = 0.046). CONCLUSIONS: Adolescents show variable changes in their BMI z-score following T&A. In this aspect their BMI z-score change is closer to the change seen in adults treated for OSA and not that of young children. The changes observed show a trend toward normalization of the BMI z-score such that overweight children tend to decrease their BMI z-score while thin individuals tend to increase it.

Watch-PAT is Useful in the Diagnosis of Sleep Apnea in Patients with Atrial Fibrillation.

BACKGROUND: Early diagnosis and treatment of sleep apnea in patients with atrial fibrillation (AF) is critical. The WatchPAT (WP) device was shown to be accurate for the diagnosis of sleep apnea; however, studies using the WatchPAT device have thus far excluded patients with arrhythmias due to the potential effect of arrhythmias on the peripheral arterial tonometry (PAT) amplitude and pulse rate changes. PURPOSE: To examine the accuracy of the WP in detecting sleep apnea in patients with AF. PATIENTS AND METHODS: Patients with AF underwent simultaneous WP and PSG studies in 11 sleep centers. PSG scoring was blinded to the automatically analyzed WP data. RESULTS: A total of 101 patients with AF (70 males) were recruited. Forty-six had AF episodes during the overnight sleep study. A significant correlation was found between the PSG-derived AHI and the WP- derived AHI (r=0.80, p<0.0001). There was a good agreement between PSG-derived AHI and WP-derived AHI (mean difference of AHI: -0.02±13.2). Using a threshold of AHI ≥15 per hour of sleep, the sensitivity and specificity of the WP were 0.88 and 0.63, respectively. The overall accuracy in sleep staging between WP and PSG was 62% with Kappa agreement of 0.42. CONCLUSION: WP can detect sleep apnea events in patients with AF. AF should not be an exclusion criterion for using the device. This finding may be of even greater importance in the era of the COVID19 epidemic, when sleep labs were closed and most studies were home based.

Author Correction: Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Distinguish Obstructive and Central Sleep Apnea by Portable Peripheral Arterial Tonometry.

Sleep apnea has a very high prevalence in the general population. Sleep apnea can be the cause for cardiovascular disorders. An increased risk for suffering from hypertension, stroke, and myocardial infarction had been shown in large studies, like the Sleep Heart Health Study. Sleep related breathing disorders and sleep apnea had been diagnosed in sleep laboratories with polysomnography in the past. Today in view of the high prevalence of sleep disordered breathing, home sleep apnea testing (HSAT) has become the accepted test for the diagnosis of sleep apnea, if there are no other comorbidities, and if a high pretest probability was confirmed by a sleep physician. For home sleep apnea testing, the number of sensors needed should be reduced. Some methods use indirect means to derive features to detect sleep apnea and hypopnea events. A very well developed method is peripheral arterial tonometry (PAT). This method records the pulse wave on a finger and derives sleep and sleep apnea feature. The PAT method has been tested under many conditions. As an indirect method, it was long seen as a limitation that obstructive and central sleep apnea events could not be distinguished. A new multicenter trial was set up to develop algorithms, which could distinguish central and obstructive apnea events with sufficient accuracy.

Inhaled nitric oxide therapy in acute bronchiolitis: A multicenter randomized clinical trial.

Currently, there are no approved treatments for infants with acute bronchiolitis, the leading cause for hospitalization of infants worldwide, and thus the recommended approach is supportive. Inhaled Nitric oxide (iNO), possesses anti-viral properties, improves oxygenation, and was shown to be safe in infants with respiratory conditions. Hospitalized infants with acute bronchiolitis were therefore recruited to a prospective double-blinded, multi-center, randomized controlled pilot study. They received intermittent high dose iNO (160 ppm) plus oxygen/air for 30 min or oxygen/air alone (control), five times/day, up to 5 days. Sixty-nine infants were enrolled. No difference was observed in frequencies of subjects with at least one Adverse Event (AE) in iNO (44.1%) vs. control (55.9%); neither was Methemoglobin >7% safety threshold. No drug-related serious AEs (SAEs) were reported. Analysis of Per-Protocol population revealed that length of stay (LOS), time to SpO2 ≥92%, and time to mTal clinical score ≤5 improved by 26.7 ± 12.7 (Welch's t-test p = 0.04), 20.8 ± 8.9 (p = 0.023), and 14.6 ± 9.1 (p = 0.118) hours, respectively, in the iNO group compared to the control. Overall, high dose iNO (160ppm) was safe, well-tolerated, reduced LOS and showed rapid improvement of oxygen saturation, compared to the standard therapy. Further investigation in larger cohorts is warranted to validate these encouraging efficacy outcomes. (Trial registration: NCT03053388).

Brief digital sleep questionnaire powered by machine learning prediction models identifies common sleep disorders.

INTRODUCTION: We developed and validated an abbreviated Digital Sleep Questionnaire (DSQ) to identify common societal sleep disturbances including insomnia, delayed sleep phase syndrome (DSPS), insufficient sleep syndrome (ISS), and risk for obstructive sleep apnea (OSA). METHODS: The DSQ was administered to 3799 community volunteers, of which 2113 were eligible and consented to the study. Of those, 247 were interviewed by expert sleep physicians, who diagnosed ≤2 sleep disorders. Machine Learning (ML) trained and validated separate models for each diagnosis. Regularized linear models generated 15-200 features to optimize diagnostic prediction. Models were trained with five-fold cross-validation (repeated five times), followed by robust validation testing. ElasticNet models were used to classify true positives and negatives; bootstrapping optimized probability thresholds to generate sensitivities, specificities, accuracies, and area under the receiver operating curve (AUC). RESULTS: Compared to reference subgroups, physician-diagnosed sleep disorders were marked by DSQ evidence of sleeplessness (insomnia, DSPS, OSA), sleep debt (DSPS, ISS), airway obstruction during sleep (OSA), blunted circadian variability in alertness (DSPS), sleepiness (DSPS and ISS), increased alertness (insomnia) and global impairment in sleep-related quality of life (all sleep disorders). ElasticNet models validated each diagnosis with high sensitivity (80-83%), acceptable specificity (63-69%), high AUC (0.80-0.85) and good accuracy (agreement with physician diagnoses, 68-73%). DISCUSSION: A brief DSQ readily engaged and efficiently screened a large population for common sleep disorders. Powered by ML, the DSQ can accurately classify sleep disturbances, demonstrating the potential for improving the sleep, health, productivity and safety of populations.

Detecting central sleep apnea in adult patients using WatchPAT-a multicenter validation study.

STUDY OBJECTIVES: To assess the accuracy of WatchPAT (WP-Itamar-Medical, Caesarea, Israel) enhanced with a novel systolic upstroke analysis coupled with respiratory movement analysis derived from a dedicated snoring and body position (SBP) sensor, to enable automated algorithmic differentiation between central sleep apnea (CSA) and obstructive sleep apnea (OSA) compared with simultaneous in-lab sleep studies with polysomnography (PSG). METHODS: Eighty-four patients with suspected sleep-disordered breathing (SDB) underwent simultaneous WP and PSG studies in 11 sleep centers. PSG scoring was blinded to the automatically analyzed WP data. RESULTS: Overall WP apnea-hypopnea index (AHI; mean ± SD) was 25.2 ± 21.3 (range 0.2-101) versus PSG AHI 24.4 ± 21.2 (range 0-110) (p = 0.514), and correlation was 0.87 (p < 0.001). Using a threshold of AHI ≥ 15, the sensitivity and specificity of WP versus PSG for diagnosing sleep apnea were 85% and 70% respectively and agreement was 79% (kappa = 0.867). WP central AHI (AHIc) was 4.2 ± 7.7 (range 0-38) versus PSG AHIc 5.9 ± 11.8 (range 0-63) (p = 0.034), while correlation was 0.90 (p < 0.001). Using a threshold of AHI ≥ 15, the sensitivity and specificity of WP versus PSG for diagnosing CSA were 67% and 100% respectively with agreement of 95% (kappa = 0.774), and receiver operator characteristic (ROC) area under the curve of 0.866, (p < 0.01). Using a threshold of AHI ≥ 10 showed comparable overall sleep apnea and CSA diagnostic accuracies. CONCLUSIONS: These findings show that WP can accurately detect overall AHI and effectively differentiate between CSA and OSA.

Increased Risk for Cancer in Young Patients with Severe Obstructive Sleep Apnea.

BACKGROUND: Several studies in animal models and human with obstructive sleep apnea syndrome (OSAS) demonstrated an increase in cancer aggressiveness and mortality. However, there is a need for further clinical evidence supporting a correlation between OSAS and cancer incidence. OBJECTIVES: To reveal whether OSAS presence and severity is correlated with cancer incidence in a large homogenous patients' cohort. METHODS: We analyzed a cohort of over 5,000 concurrently enrolled patients, age > 18, with suspected OSAS, from a tertiary medical academic center. Patients underwent whole night polysomnography, the gold standard diagnostic tool for OSAS, and were classified for severity according to the Apnea Hypopnea Index (AHI). Data on cancer incidence were obtained from the Israel National Cancer Registry. A multivariate Cox proportional-hazards analysis, adjusted for age, gender, and BMI, was performed to estimate the hazard-ratio of new cancer incidence. RESULTS: Among 5,243 subjects with a median follow-up of 5.9 years, 265 were diagnosed with cancer. The most prevalent cancers were prostate (14.7%), hematological (12.8%), urothelial (9.4%), colorectal (9%), and breast (8.3%). In subjects who were diagnosed at age below 45 years (n = 1,533), a high AHI (> 57/h) was significantly associated with cancer (HR 3.7, CI 1.12-12.45, p = 0.008). CONCLUSIONS: Patients younger than 45 with severe OSAS have a significantly higher all-type cancer incidence than the general population. These results should encourage clinicians to detect and diagnose young patients with suspected OSAS and to recommend cancer screening methods in this high-risk population.

Assistance of Medical Clowns Improves the Physical Examinations of Children Aged 2-6 Years.

BACKGROUND: A good physical exam is necessary to help pediatricians make the correct diagnosis and can save unnecessary imaging or invasive procedures. Distraction by medical clowns may create the optimal conditions for a proper physical examination. METHODS: Children aged 2-6 years who required physical examination in the pediatric emergency department were recruited and randomly assigned to one of two groups: physical exam by a pediatrician in the presence of caregivers vs. physical exam with the assistance of a medical clown. Outcome measures consisted of the level of child's discomfort, anxiety, and the quality of the physical examination. RESULTS: Ninety three children participated. Mean age was 3.3 ± 3.6 years (range 2-6). The duration of the physical exam was similar between the clown and control groups (4.6 ± 1.4 minutes vs. 4.5 ± 1.1 minutes (P = 0.64). The duration of discomfort was shorter in the clown group (0.2 ± 0.6 minutes) than the control group(1.6 ± 2.0 minutes, P = 0.001). In the medical clown group, 94% of pediatricians reported that the medical clown improved their ability to perform a complete physical examination. A trend of less hospitalization in the medical clown group was also noticed (11.3% in the medical clown group vs. 18.3% in the control group, P = 0.1); however, further study is required to verify this observation. CONCLUSIONS: Integration of a medical clown in physical examination improves the overall experience of the child and the caregivers and helps the pediatrician to perform a complete physical examination.

[EARLY DETECTION OF ENDOTHELIAL DYSFUNCTION IN CHILDREN WITH AUTOIMMUNE DISEASES BY A NOVEL NONINVASIVE TECHNIQUE].

INTRODUCTION: Atherosclerosis is emerging as one of the most important causes of morbidity and mortality among patients with different rheumatologic disease. Endothelial dysfunction may be an early sign of atherosclerosis. OBJECTIVES: To evaluate the occurrence of endothelial dysfunction in children with autoimmune diseases, including juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and dermatomyositis, using a novel noninvasive technique. METHODS: The study group consisted of 24 children with autoimmune diseases, and was compared to a control group of 17 healthy, age- and BMI-matched controls. Endothelial function was assessed by a noninvasive technology that captures a beat-to-beat plethysmographic recording of the finger arterial pulse-wave amplitude with pneumatic probes, utilizing a Peripheral Arterial Tonometry (PAT) device. RESULTS: In the study group, 7 out of the 24 (29%) patients had evidence of impaired endothelial function, compared to 1 out of 17 (6%) children in the control group (p <0.05). Thirty-three per cent of our patients with SLE and 23% of patients with JIA had impaired endothelial function. There were no differences between the two groups of patients with and without endothelial dysfunction as to age, body mass index, fasting glucose level, triglycerides, cholesterol, and dose and duration of steroid treatment. The patients with normal endothelial function had higher systolic blood pressure compared with the group with impaired endothelial function (112.82 ± 7.65 vs13.88 ± 104.85 respectively, p=0.04). CONCLUSIONS: Children with autoimmune diseases may have a high tendency to develop endothelial dysfunction. Larger studies are needed to confirm our findings and to explore the influence of endothelial dysfunction on the development of atherosclerosis in young children.

Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference.

BACKGROUND AND OBJECTIVES: The orally active dual OX1R and OX2R antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults. PATIENTS AND METHODS: Prospective, randomized, double-blind, placebo-controlled, active referenced trial in male and female adults aged 18-64 years with chronic, primary insomnia. Patients were randomized 1:1:1:1 to receive placebo, almorexant 100 mg, almorexant 200 mg, or zolpidem 10 mg (active reference) for 16 days. Primary efficacy assessments were objective (polysomnography-measured) and subjective (patient-recorded) wake time after sleep onset (WASO). Further sleep variables were also evaluated. RESULTS: From 709 randomized patients, 707 (mean age 45.4 years; 61.7% female) received treatment and 663 (93.8%) completed the study. A significant decrease versus placebo in median objective WASO was observed with almorexant 200 mg at the start and end of randomized treatment (-26.8 min and -19.5 min, respectively; both p < 0.0001); subjective WASO also decreased over the two-week treatment period (p = 0.0006). Objective and subjective total sleep time (TST) were increased with almorexant 200 mg (p < 0.0001). Almorexant 200 mg significantly reduced objective and subjective latency to persistent sleep and latency to sleep onset at initiation of therapy, and provided longer duration of sleep stages with no suppression of slow-wave sleep. No impaired next-day performance, rebound insomnia, or withdrawal effects were observed. Adverse events were similar with almorexant and placebo. CONCLUSION: Almorexant reduced time to sleep onset and maintained sleep without residual effects on next-day performance or safety concerns. This study provides further support for the role of the endogenous orexin system in insomnia disorder. CLINICALTRIALS. GOV REGISTRATION: NCT00608985.

Fear of clowns in hospitalized children: prospective experience.

Medical clowns (MC) have become an integral part of the pediatric staff of hospital wards. While several studies have demonstrated the huge benefits of MC, there are almost no data regarding fear of clowns, a known phenomenon that means an irrational fear of clowns. In the current study, we sought to examine the prevalence of fear of clowns in pediatrics wards, and to characterize the affected children. The clinical work of three certified MCs was prospectively assessed. Every child with fear of clowns was noted, data were retrieved from the medical records, and the parents/child completed a specific questionnaire with a research assistant. Fear of clowns was defined as crying, anxiety response or effort to avoid contact with the MCs in small children, while in older children, it was determined if the child either reported fear of MCs or made actions to avoid clowns' intervention. A total of 1160 children participated in the study. All were hospitalized in the department of pediatrics or the pediatric emergency medicine department at Carmel Medical Center, and were exposed to a MC intervention session. Of the 1160 children, 14 children experienced fear of clowns (1.2%). The average age of children who experienced fear of clowns was 3.5 years (range 1-15). Interestingly, most of the children demonstrating fear of clowns were girls (12 out of 14, 85.7%). We found no association between fear of clowns and specific diagnosis, fever, clinical appearance, religion, or ethnicity. CONCLUSION: The prevalence of fear of clowns in the general pediatric hospitalized population was 1.2%, with a significant predominance of girls (85.7%). Children who experienced significant fear of clowns also experienced significant fear of encountering or thinking about a MC visit. Fear of clowns can affect children at any age (range 1-15), any ethnicity, religion, or degree of illness. Further large scale studies are required to better understand this unique phenomenon of fear of clowns. What is Known: • Fear of clowns is a phenomenon known for more than several decades and related to the increased use of clowns as negative characters in horror movies and TV shows. • The increased use of medical clowns in hospital wards and corridors increases the significance of defining and characterizing this phenomenon in hospital wards. What is New: • The study is novel by giving new data related to the extent of fear of clowns in pediatrics wards and giving demographic characteristic of children experiencing fear of clowns.