Low Doses of Melatonin to Improve Sleep in Children with ADHD: An Open-Label Trial

Objective. Only a few studies assessing the sleep effects of low doses of melatonin (aMT) have been performed in the past, most of them in adults, and only one in subjects with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to provide evidence of the changes induced by aMT doses as low as 1 mg in the sleep pattern of pediatric patients with ADHD under treatment with methylphenidate (MPH). Methods. Children and adolescents (7–15 years) with ADHD who were receiving extended-release MPH were recruited. A seven-week sleep diary was collected prior to starting a four-week treatment with 1 mg of aMT (30 min before bedtime). Seven-day actigraphic assessments of sleep were performed before and after treatment. Results. Twenty-seven patients (17 males, 62.96%) participated in the study, who had been receiving MPH for 1.57 (1.11) months. A significant increase in sleep duration (TST) was observed after one month of treatment (463 (49) min to 485 (41) min; p < 0.040), with nonsignificant improvements in sleep-onset latency (SOL), nocturnal awakenings, or sleep efficiency. Only minor adverse effects were reported. Conclusion. Low doses of melatonin (1 mg) are able to increase TST in children and adolescents with ADHD receiving treatment with psychostimulants, with an adequate tolerability profile. Further placebo-controlled trials adjusting the time of aMT administration to the individual circadian profile should explore the effects of low doses of this hormone to shorten SOL in this population of patients

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome–gut–brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (!-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the !-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD

Actigraphic sleep assessment in children with sleep disorders and attention deficit/hyperactivity (ADHD): Role of melatonin and omega-3 fatty acids

Los trastornos del sueño constituyen uno de los motivos de consulta más frecuentes en Pediatría, con una prevalencia que oscila entre el 13-27% según las distintas series consultadas, en referencia a niños con edades comprendidas entre 4 y 12 años. Por otra parte, es sobradamente conocida su participación como una comorbilidad en niños que son diagnosticados, según criterios establecidos por la 5ª edición del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-5), de un trastorno por déficit de atención y/o hiperactividad (TDAH), con el que se asocia hasta en un 55% de los casos. Comorbilidad que puede ser primaria, pero que en ocasiones puede ser secundaria al efecto de la medicación psicoestimulante (Metilfenidato/ MTF). En la actualidad se están desarrollando y ensayando nuevos compuestos con menores efectos adversos como posibles terapias para el TDAH y sus comorbilidades, entre los cuales cabe destacar los ácidos grasos omega (ω)-3 por sus posibles beneficios a nivel cognitivo y del aprendizaje, y la melatonina por sus efectos inductores del sueño, de sincronización de ritmos biológicos y protección neuronal. Con estos antecedentes nos propusimos en el presente proyecto los objetivos que describimos a continuación: a) Definir los patrones de sueño-vigilia y su relación con la variación circadiana en la excreción de 6-sulfatoximelatonina (6s-aMT) en orina en 2 grupos de pacientes. Un grupo de niños normales, sin trastornos endocrinológicos ni de sueño (Grupo Control: G-C), y otro grupo de niños con diversos trastornos de sueño, según la Clasificación Internacional de Trastornos de Sueño (CITS) (Grupo con Trastornos del Sueño: G-TS). b) Comprobar la utilidad de un ensayo terapéutico con melatonina en aquellos pacientes del G-TS en quienes se demostró una escasa producción de 6s-aMT o una alteración en su secreción. c) Evaluar la eficacia terapéutica y el perfil de seguridad a corto plazo de un tratamiento combinado de MTF, melatonina y ácidos grasos ω-3 en una muestra de pacientes con TDAH, monitorizando el perfil sérico de ácidos grasos y los cambios experimentados en el patrón de sueño por medio de actigrafía y la aplicación de un modelo de red neuronal.Sleep disorders are one of the most frequent reasons for consulting the paediatrician, with a prevalence ranging between 13% and 27% in children aged 4 to 12 years, depending on the different reviewed reports. Moreover, it is well-known their participation as a comorbidity in children diagnosed with Attention Deficit/Hyperactivity Disorder (ADHD) according to the criteria established by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Sleeps disorders and ADHD are found together in 55% of cases. This comorbidity may be primary or secondary, as a consequence of the effect produced by psychostimulant medication (Methylphenidate/MPH). At present, new chemical compounds with less adverse effects are being developed to be used as possible therapies for ADHD and related comorbidities. Among them, it should be mentioned the omega (ω)-3 fatty acids, due to their possible beneficial effects on cognition and health, and the melatonin, on account of its functions as a sleep inductor, a synchroniser of biological rhythms and a neuronal protector1. Under these premises, the present project was developed with the following aims: a) To define the sleep-wake patterns and its association with the circadian variation of urinary 6-sulfatoxymelatonin (aMT6s) levels in 2 groups of patients. One group of healthy children (Control Group: C-G), who did not have any sleep difficulties nor endocrine problems. The other group was composed of children diagnosed with different sleep disorders according to the International Classification of Sleep Disorders (ICSD) (Group with Sleep Disorders: SD-G). b) To analyse the efficacy of a therapeutic trial with melatonin in those patients of SD-G who showed a low production or a disordered secretion of aMT6s. c) To assess the short-term efficacy and the tolerability of a therapeutic combination of MPH, melatonin and ω-3 fatty acids in patients with ADHD. Serum fatty acid profile was monitored and changes in sleep patterns were analysed by using the actigraphy and a neural network model.Tesis Univ. Granada. Programa Oficial de Doctorado en Medicina Clínica y Salud Públic

Role of Omega-3 Fatty Acids as Non-Photic Zeitgebers and Circadian Clock Synchronizers

Omega-3 fatty acids (&omega;-3 FAs) are well-known for their actions on immune/inflammatory and neurological pathways, functions that are also under circadian clock regulation. The daily photoperiod represents the primary circadian synchronizer (&lsquo;zeitgeber&rsquo;), although diverse studies have pointed towards an influence of dietary FAs on the biological clock. A comprehensive literature review was conducted following predefined selection criteria with the aim of updating the evidence on the molecular mechanisms behind circadian rhythm regulation by &omega;-3 FAs. We collected preclinical and clinical studies, systematic reviews, and metanalyses focused on the effect of &omega;-3 FAs on circadian rhythms. Twenty animal (conducted on rodents and piglets) and human trials and one observational study providing evidence on the regulation of neurological, inflammatory/immune, metabolic, reproductive, cardiovascular, and biochemical processes by &omega;-3 FAs via clock genes were discussed. The evidence suggests that &omega;-3 FAs may serve as non-photic zeitgebers and prove therapeutically beneficial for circadian disruption-related pathologies. Future work should focus on the role of clock genes as a target for the therapeutic use of &omega;-3 FAs in inflammatory and neurological disorders, as well as on the bidirectional association between the molecular clock and &omega;-3 FAs

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome&ndash;gut&ndash;brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (&omega;-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the &omega;-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications.

Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome-gut-brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the ω-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD

Etelcalcetide and Paricalcitol in Chronic Kidney Disease: When the Target Is Inflammation

Introduction: secondary hyperparathyroidism (SHP) is frequent in patients with chronic kidney disease (CKD), particularly in those in dialysis. To treat this complication, the current options available include phosphorus restriction, phosphate binders, the inhibition of parathyroid hormone (PTH) synthesis and secretion by the supplementation of vitamin D or VDR activators, or the use of calcimimetics. Beyond the control of PTH, the effects of the treatment of SHP on other biomarkers of risk may represent an additional benefit for this population. In this study, we explore the benefits of current SHP treatment options, mainly paricalcitol and/or etelcalcetide in the inflammatory state of hemodialysis (HD) patients. Results: the study finally included 142 maintenance HD patients (5 patients were excluded) followed for 6 months (dialysis vintage 26 ± 30 months, mean age 70 years old, 73% women, 81% Spanish white, 47% diabetic). In this case, 52 patients were on regular treatment with paricalcitol for SHP and 25 patients were eligible to initiate etelcalcetide. The baseline serum levels of Ca, P, PTH, Ferritin, albumin, C-reactive protein (CRP), and other variables were measured. We found serum PTH levels showed an improvement after the treatment with etelcalcetide again paricalcitol and no treatment (p n = 11) receiving paricalcitol + etelcalcetide compared to paricalcitol or etelcalcetide alone. The proportion of patients with CRP within target ranges (≤1.0 mg/dL) increased significantly after combined treatment (p Conclusions: etelcalcetide proved to safely reduce the PTH levels without significant adverse events and the possibility of a synergic anti-inflammatory effect with the simultaneous use of Paricalcitol in HD patients

Early monitoring of fatty acid profile in children with attention deficit and/or hyperactivity disorder under treatment with omega-3 polyunsaturated fatty acids

BACKGROUND: Cognitive effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) might make them helpful in attention deficit/hyperactivity disorder (ADHD). However, the results derived from supplementation studies in children depend on the respective combinations and the study period. We aimed to investigate the serum fatty acid profile, attention scores and the tolerability in a group of ADHD children after receiving methylphenidate (MPH) and ω-3 PUFAs for 1 month. METHODS: A combination of MPH (1 mg/kg/day) and eicosapentaenoic (EPA, 70 mg/day) + docosahexaenoic acids (DHA, 250 mg/day) was administered to 40 ADHD children (7-15 years). An analysis of serum fatty acids by gas chromatography and an assessment of attention by using the Magallanes Scale of Visual Attention (MSVA) were carried out before and after 1 month of treatment. RESULTS: Our data revealed significant decreases of several ω-6 PUFAs, like arachidonic acid (P<0.0259). EPA and DHA concentrations increased by 27% and 3% respectively, and the ω-6/ω-3 index slightly decreased. The quality of attention significantly increased (P<0.026) and an improvement of ADHD core symptoms was reported both by parents and by teachers. No severe side effects occurred. CONCLUSIONS: Results demonstrate that the combination of MPH and EPA+DHA at the tested doses has positive clinical effects and an adequate safety profile. Therefore, our study suggests that ω-3 PUFAs may represent a feasible and a safe adjuvant therapy in children with ADHD and might enhance the effects of MPH. Further long-term follow-up studies are required to confirm these initial findings.Peer Reviewe

Role of the Nephrologist in Non-Kidney Solid Organ Transplant (NKSOT)

Background: Chronic kidney disease (CKD) is a common complication of a non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in the Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD); increased serum creatinine ≥50%; renal replacement therapy (RRT); and death in the pre-transplant, peri-transplant, and post-transplant periods. Results: 74 patients were studied (7 heart transplants, 34 liver transplants, and 33 lung transplants). Patients who were not followed-up by a nephrologist in the pre-transplant (p p < 0.046) periods and those who had the longest time until an outpatient clinic follow-up (HR 1.032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred a higher risk than a liver or heart transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxicity, and the number of hospital admissions were significantly associated with a creatinine increase ≥50% and developing ESKD. Conclusions: Early and close follow-up by a nephrologist was associated with a decrease in the worsening of renal function