Sleep problems and circadian rhythm functioning in autistic children, autism with co-occurring attention deficit hyperactivity disorder, and typically developing children: A comparative study.

LAY ABSTRACT: Sleep problems are common in autism spectrum disorder (ASD) and different factors can contribute to its occurrence in this population. Misalignment of the biological clock (our circadian system) has been described as one possible explanation. While there is a body of research on sleep problems, relatively less is known about circadian functioning and the specific population of autistic children with co-occurring attention deficit hyperactivity disorder (ADHD). Using an ambulatory circadian monitoring (ACM) system, which resembles a common watch, we gathered sleep parameters and the different rhythms obtained from measuring motor activity, light exposure and distal temperature in 87 autistic children and adolescents, 27 of whom were diagnosed with co-occurring ADHD, and 30 neurotypical children and adolescents as a comparison group. Autistic children and, especially, those with co-occurring ADHD showed greater motor activity during sleep which would be worth studying in future projects which could better define this restless sleep. Of note, we observed an atypical pattern of wrist temperature, with higher values in neurotypical children, followed by autistic children and, ultimately, those with co-occurring ADHD. Temperature is one of the most valuable factors evaluated here as it is closely connected to sleep-wakefulness and the hormone melatonin. Its special pattern during day and nighttime would support the hypothesis of an atypical secretion of melatonin in autistic individuals which would also link with the higher presence of sleep problems in this neurodevelopmental condition.

Cost-effectiveness of omalizumab for the treatment of severe pediatric allergic asthma-Results of a real-life study in Spain.

BACKGROUND: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective. METHODS: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab. RESULTS: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively. CONCLUSION: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment.

[Oral desensitization with Ketocal® in an infant with ketogenic diet and cow's milk protein allergy]. / Desensibilización con Ketocal® en lactante con dieta cetogénica y alergia a proteínas de leche de vaca.

Introduction: Introduction: ketogenic diet is a treatment with proven efficacy in drug-refractory childhood epilepsy. Cow's milk protein allergy may be a limitation for treating infants with ketogenic diet, as they need a product that contains cow's milk protein (Ketocal®). Case report: we report the case of an infant with a drug-refractory epileptic encephalopathy and IgE-mediated cow's milk protein allergy, who started a classic ketogenic diet. Oral desensitization was achieved with Ketocal 3:1®, allowing its use in the diet and achieving a clinical improvement with seizure control. Discussion: a patient with epilepsy and cow's milk protein allergy can benefit from the ketogenic diet, since it is possible to perform an oral immunotherapy with Ketocal®, also achieving a probable resolution of his/her allergy.

Introducción: Introducción: la dieta cetogénica es un tratamiento con eficacia demostrada en la epilepsia infantil refractaria a fármacos. La alergia a la proteína de leche de vaca puede ser una limitación para tratar a lactantes con dieta cetogénica, ya que necesitan un producto que contiene proteínas de leche de vaca (Ketocal®). Caso clínico: presentamos el caso de un lactante con una encefalopatía epiléptica refractaria a fármacos y alergia a las proteínas de leche de vaca IgE mediada al que se quiere instaurar una dieta cetogénica clásica. Se consigue la desensibilización con Ketocal 3:1®, pudiendo utilizarlo en la dieta y logrando una mejoría clínica con el control de las crisis. Discusión: un paciente con epilepsia y alergia a las proteínas de leche de vaca puede beneficiarse de la dieta cetogénica, ya que es posible realizar una inmunoterapia oral con Ketocal® y conseguir, además, una probable resolución de su alergia.

Is it necessary to perform a follow-up study after adenotonsillectomy in all children with moderate-severe obstructive sleep apnoea?

Hypertrophy of adenotonsillar tissue is the most common cause of OSAS in otherwise healthy children, and therefore adenotonsillectomy is the first line treatment. Scientific societies recommend nocturnal follow-up PSG to assess for residual OSAS in children with preoperative evidence for moderate to severe OSAS, obesity, craniofacial anomalies that obstruct the upper airway and neurological disorders, based on the increasing trend of publications reporting residual OSAS after adenotonsillectomy. Follow-up PSG values in children with a pre-operative diagnosis of severe OSAS were analysed retrospectively, and compared to the parents' impression after ENT surgery. The study population included 41 healthy children with severe OSAS and adenotonsillar surgery. The percentage of children with normal PSG parameters (AHI < 2/h) after adenotonsillectomy was 80.48%. A very good correlation was observed between the parents' perception after treatment and the follow-up PSG parameters, specifically when the parents perceived that the patient had shown "complete resolution" (no snoring or apnoea), 90.62% of the children had an AHI < 2/h in the follow-up PSG, the maximum residual AHI being 2.6/h. In healthy children with no underlying pathology, the information provided by the parents on clinical progression after surgery could be useful and might enable the selection of those patients who require a follow-up study, avoiding overload in sleep units.

Is it necessary to perform a follow-up study after adenotonsillectomy in all children with moderate-severe obstructive sleep apnoea? / ¿Es necesario repetir el estudio de sueño de control a todos los niños con SAHOS moderado-severo tras la cirugía?

Hypertrophy of adenotonsillar tissue is the most common cause of OSAS in otherwise healthy children, and therefore adenotonsillectomy is the first line treatment. Scientific societies recommend nocturnal follow-up PSG to assess for residual OSAS in children with preoperative evidence for moderate to severe OSAS, obesity, craniofacial anomalies that obstruct the upper airway and neurological disorders, based on the increasing trend of publications reporting residual OSAS after adenotonsillectomy. Follow-up PSG values in children with a pre-operative diagnosis of severe OSAS were analysed retrospectively, and compared to the parents' impression after ENT surgery. The study population included 41 healthy children with severe OSAS and adenotonsillar surgery. The percentage of children with normal PSG parameters (AHI <2/h) after adenotonsillectomy was 80.48%. A very good correlation was observed between the parents' perception after treatment and the follow-up PSG parameters, specifically when the parents perceived that the patient had shown «complete resolution¼ (no snoring or apnoea), 90.62% of the children had an AHI <2/h in the follow-up PSG, the maximum residual AHI being 2.6/h. In healthy children with no underlying pathology, the information provided by the parents on clinical progression after surgery could be useful and might enable the selection of those patients who require a follow-up study, avoiding overload in sleep units.

Omalizumab outcomes for up to 6 years in pediatric patients with severe persistent allergic asthma.

BACKGROUND: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. METHODS: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period. RESULTS: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. CONCLUSION: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Postoperative complications after adenotonsillectomy in two paediatric groups: Obstructive sleep apnoea syndrome and recurrent tonsillitis. / Complicaciones postoperatorias tras adenoamigdalectomía en 2 grupos de pacientes pediátricos: síndrome de apnea-hipopnea del sueño e infecciones de repetición.

INTRODUCTION AND OBJECTIVES: Adenotonsillectomy is a surgery to treat recurrent tonsillitis or obstructive sleep apnoea syndrome (OSAS). It is considered a safe procedure, with few complications. Moreover, patients over 3 years and without comorbidities do not present a higher rate of respiratory adverse events after the immediate postoperative period, and do not need systematic admission to a paediatric intensive care unit (PICU), regardless of their OSAS severity. The aim of this study is to reanalyse the situation, including patients under the age of 3 years, for whom there are fewer available data, to confirm that this trend has not changed. METHODS: A retrospective observational study was performed, including all adenotonsillectomised children in our hospital over 5 years. RESULTS: 418 adenotonsillectomised children were included, 56.7% due to recurrent tonsillitis, and 43.3% because of OSAS. Only 24 patients (5%7%) experienced adverse events, of whom 1.2% had vomiting, 3.1% bleeding, and 1.4% respiratory events. All the respiratory events occurred in the operating theatre or in the post-anaesthetic unit, most frequently in children with severe OSAS, while the tonsillitis group had more bleeding (P=.046). No differences in complications were observed according to age (P=0.174), but the group of patients under three years was relatively small. CONCLUSIONS: No differences were found in the percentage of complications between the two groups. Although the OSAS group exhibited more respiratory events, these occurred in the immediate postoperative period; otherwise, there was a higher risk of bleeding in the tonsillitis group. These results support the findings indicating that routine PICU admission is not required for these patients.

Central sleep apnea in children with obstructive sleep apnea syndrome and improvement following adenotonsillectomy.

BACKGROUND: Although the pathogenesis of central and obstructive events seems to be different, these two entities may somehow be related. We aimed to determine whether, as reported in previous research, the number of central sleep apnea (CSA) cases in a population of children with obstructive sleep apnea syndrome (OSAS) was greater than in patients without obstructive events, and if CSA worsens with increasing OSAS severity. As a second objective, we analyzed changes in central apnea index (CAI) after adenotonsillar surgery compared to changes when no surgery has been performed. METHODS: We retrospectively reviewed nocturnal polysomnography (PSG) data from children between 1 and 14 years of age with no neurological conditions or syndromes. Patients with CAI values greater than 5 per hour were diagnosed as having CSA. Improvements of greater than 50% in CAI on repeat PSG were considered to represent a real change. RESULTS: Data were available from 1279 PSG studies, resulting in 72 children with a CAI greater than 5 per hour (5.6%). Patients with OSAS showed a higher CAI (2.16) compared with those without OSAS (1.17), and this correlation increased with higher degrees of obstructive apnea severity. When adenotonsillectomy was performed due to OSAS, the CAI decreased by 1.37. The average decrease in PSG values was only 0.38 in cases where no surgery was performed. CONCLUSION: The results of this study suggest that although CSA is perceived to be mostly associated with central nervous system ventilatory control, there may be a connection with airway obstruction and in children with CSA and OSA diagnosis adenotonsillectomy may improve both conditions.

Can pulse transit time be useful for detecting hypertension in patients in a sleep unit?

INTRODUCTION: Pulse transit time (PTT) is the time that a pulse wave takes to travel between two different arterial points, and may be useful in estimating blood pressure. This noninvasive technique, which does not add any cost to the procedure, offers the advantage of avoiding 'arousals' during sleep measurement as occurs with ambulatory blood pressure monitoring (ABPM). We aim to confirm the usefulness of PTT for the detection of hypertension, and to study the correlation between both measurements. METHODS: Prospective observational study in a multidisciplinary sleep unit. We recruited 30consecutive patients attending a sleep clinic and ran a baseline polysomnography followed by an ABPM the following day. Average systolic and diastolic blood pressure (SBP, DBP) by PTT were calculated and compared with ABMP results. In accordance with international guidelines, patients with mean nocturnal ABMP ≥ 120/70 mmHg were diagnosed as having arterial hypertension. RESULTS: Mean age of 60years; 66% male, 80% suffered from sleep apnoea (OSAS). Taking the ABPM as the reference technique, we found that the diagnostic sensitivity of PTT is 85% with a specificity of 88% in the case of SBP, with a positive predictive value of 85% and negative predictive value of 88%. By studying the relationship between mean SBP measured by ABPM and PTT, we found a linear correlation coefficient (R) of 0.88, showing a distribution of all subjects with a difference of between ±15mmHg between tests. There is also a positive correlation between mean DBP measured for the two tests, with a weaker linear correlation. CONCLUSIONS: Pulse transit time shows a strong correlation with blood pressure (measured by ABPM). PTT provides continuous, non-invasive, cuffless blood pressure monitoring free of additional cost and could be an alternative for screening hypertension.

High-sensitivity C-reactive protein is a good marker of cardiovascular risk in obese children and adolescents.

OBJECTIVE: We intend to assess the utility of the high-sensitivity C-reactive protein (hs-CRP) as a marker of cardiovascular risk in obese children and adolescents. METHODS: The study included children and adolescents between 6 and 18 years of age with a body mass index (BMI) higher than 2 SDS. All the patients had their blood pressure taken and hs-CRP, hepatic function, lipid profile and uric acid were determined after 12 h of fasting. Likewise, an oral glucose tolerance test was performed, determining basal glucose and insulin levels, and after stimulus. We considered the presence of metabolic syndrome when the obese children and teenagers showed at least two of the following conditions: decreased high density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, hypertension or alteration in glucose metabolism. RESULTS: Out of the 115 obese children studied, 24% showed signs of metabolic syndrome. Those with metabolic syndrome presented higher levels of hs-CRP (mean: 3.8 mg/l; 95% CI: 2.8-4.8) in comparison with the obese patients who did not show signs of metabolic syndrome (mean: 2 mg/l; 95% CI: 1.5-2.5). After a multivariate analysis, the variables that appear to influence the changes in hs-CRP were BMI, triglycerides and HDL-cholesterol levels. CONCLUSION: The hs-CRP is a useful tool for early diagnosis of cardiovascular risk in obese children and teenagers.

[Prevalence of tuberculosis infection in BCG-vaccinated and unvaccinated Mediterranean schoolchildren]. / Prevalencia de infección por tuberculosis en una población escolar mediterránea (con y sin vacunación antituberculosa).

OBJECTIVE: To determine the prevalence of tuberculous infection in schoolchildren in the province of Malaga, Spain, and to evaluate its relation to sociodemographic variables. POPULATION AND METHODS: Tuberculin skin tests were used to screen 6-year-olds in their first year of primary school in this cross-sectional study of the prevalence of infection, with calculation of 95% confidence interval (CI). Children who had not been vaccinated against tuberculosis at birth were considered to have a positive test result if they had an induration of >or=5 mm. Those who had received bacillus Calmette-Guerin (BCG) vaccination at birth were considered to have a positive test result if they had an induration size of >10 mm or >15 mm, depending on whether they came from a country with a high or low prevalence of tuberculosis, respectively. RESULTS: The prevalence of infection in the group of unvaccinated children was 1.16% (95% CI, 0.69%-1.63%). No statistically significant differences were found for any of the sociodemographic variables analyzed. The prevalence of infection in the BCG-vaccinated children was 6.66% (95% CI, 5.55%-7.77%). CONCLUSIONS: The prevalence of tuberculosis infection in our area is slightly higher than that reported after other studies conducted in Spain. This could indicate that tuberculosis continues to be a public health problem in the province of Malaga. Infection in the subgroup of BCG-vaccinated children, however, was lower than that observed in studies of immigrants in Spain who had been immunized at birth. This is probably because the majority of immigrants in our area come from countries with a low incidence of tuberculosis.

Renal failure and acquired hypothyroidism.

The effects of thyroid metabolism on renal function in children are barely referred to in the literature. Primary hypothyroidism is known to be associated with a consistent elevation in serum creatinine levels. This is essentially because of the hypodynamic state that occurs in hypothyroidism, leading to a reduced glomerular filtration rate and hypercreatinemia. A teenager who developed renal failure due to primary hypothyroidism is reported. He displayed diverse serum biochemistry anomalies with an unremarkable physical examination. Thyroxine replacement therapy completely restored the euthyroid state and renal function. We propose, in accordance with other authors, measurement of thyrotropin levels in patients with hypercreatinemia.