Pharmacotherapy for ADHD in children and adolescents: A summary and overview of different European guidelines.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries.   Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. What is Known: • There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents. • Pediatricians are often involved in assessment, diagnosis and management of children with ADHD. What is New: • Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents. • Discrepancies exist primarily in terms of selection and sequencing of different medications.

[Lisdexamfetamine dimesylate: a Treatment Option for Children and Adolescents with Attention Deficit/Hyperactivity Disorder in Germany and Across Europe]. / Lisdexamfetamindimesilat: Eine Behandlungsoption für Kinder und Jugendliche mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung in Deutschland und Europa.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder - which may persist into adolescence and adulthood. Psychostimulants and atomoxetine (ATX) are frequently prescribed to treat ADHD in Germany. Lisdexamfetamine dimesylate (LDX) is the most recently approved ADHD medication in Germany and other European countries. Data used to support the European registration of LDX is summarised from three phase-3/3b studies in children and adolescents with ADHD. Short-term efficacy (study SPD489 - 325), maintenance of efficacy (study SPD489 - 326) and efficacy in patients who had previously responded inadequately to methylphenidate (MPH) treatment (study SPD489 - 317) were demonstrated. The safety and tolerability profile of LDX in all three European studies was shown to be in line with that of other psychostimulants used to treat patients with ADHD.

Design considerations for a high power, ultrabroadband optical parametric chirped-pulse amplifier.

A conceptual design of a high power, ultrabroadband optical parametric chirped-pulse amplifier (OPCPA) was carried out comparing nonlinear crystals (LBO and BBO) for 810 nm centered, sub-7.0 fs pulses with energies above 1 mJ. These amplifiers are only possible with a parallel development of kilowatt-level OPCPA-pump amplifiers. It is therefore important to know good strategies to use the available OPCPA-pump energy efficiently. Numerical simulations, including self- and cross-phase modulation, were used to investigate the critical parameters to achieve sufficient spectral and spatial quality. At high output powers, thermal absorption in the nonlinear crystals starts to degrade the output beam quality. Strategies to minimize thermal effects and limits to the maximum average power are discussed.

Long-term stabilization of high power optical parametric chirped-pulse amplifiers.

The long-term stability of optical parametric chirped-pulse amplifiers is hindered by thermal path length drifts affecting the temporal pump-to-signal overlap. A kilowatt-pumped burst amplifier is presented delivering broadband 1.4 mJ pulses with a spectral bandwidth supporting sub-7 fs pulse duration. Active temporal overlap control can be achieved by feedback of optical timing signals from cross-correlation or spectral measurements. Using a balanced optical cross-correlator, we achieve a pump-to-signal synchronization with a residual jitter of only (46 ± 2) fs rms. Additionally, we propose passive pump-to-signal stabilization with an intrinsic jitter of (7.0 ± 0.5) fs rms using white-light continuum generation.

High rate of non-eligibility: methodological factors impacting on recruitment for a multicentre, double-blind study of paediatric patients with major depressive disorder.

INTRODUCTION: This report describes difficulties encountered when attempting to recruit children and adolescents with major depression for a recent international double-blind, placebo-controlled trial (www.clinicaltrials.gov Nr. NCT00849901). METHODS: Over a 14-month period, children and adolescents with depressive symptoms were pre-screened for their eligibility for inclusion. RESULTS: 85 patients (age 7-17 years) were considered. Of these, only one was enrolled. The main reasons for non-eligibility were: failure to meet the baseline severity criterion on the primary outcome scale (clinical global impression-severity; 32.1% of the patients); requirement for immediate hospitalisation (15.4%); or the presence of an exclusionary comorbid psychiatric disorder (19.1%). DISCUSSION: The recruitment of paediatric patients with major depression was primarily limited by various inclusion and exclusion criteria. Slow recruitment of small patient samples may impact strongly on the representativeness and generalisability of research findings, and thus on analyses in evidence-based medicine and on the development and recommendations of treatment guidelines. This may impact in turn on the feasibility of the clinical development and registration process of new compounds in paediatric psychopharmacology and beyond.

[From ocular itching to eye rubbing: a review of the literature]. / Du prurit aux frottements oculaires : une revue de la littérature.

Ocular itching and eye rubbing are frequent complaints in an ophthalmology practice. Numerous studies address the consequences of eye rubbing, such as keratoconus. However, there are few studies concerning the pathophysiology of itching, its transmission pathways, or its interactions with eye rubbing. Through this literature review, we will address the various clinical, physiological and therapeutic aspects of this pair of symptoms with a variety of ocular consequences. We will then describe the state of the art in itching and scratching in dermatology, in order to draw a parallel between these two vicious cycles. A better understanding of the pathophysiology of ocular itching and eye rubbing, as well as new studies based on dermatological data, might allow more appropriate clinical management of our patients and their symptoms.

Evaluating the potential of ChatGPT-4 in ophthalmology: The good, the bad and the ugly.

There is growing interest nowadays for artificial intelligence (AI) in all medical fields. Beyond the direct medical application of AI to medical data, generative AI such as "pre-trained transformer" (GPT) could significantly change the ophthalmology landscape, opening up new avenues for enhancing precision, productivity, and patient outcomes. At present, ChatGPT-4 has been investigated in various ways in ophthalmology for research, medical education, and support for clinical decisions purposes. This article intends to demonstrate the application of ChatGPT-4 within the field of ophthalmology by employing a 'mise en abime' approach. While we explore its potential to enhance the future of ophthalmology care, we will also carefully outline its current limitations and potential risks.

Coherent spectral enhancement of carrier-envelope-phase stable continua with dual-gas high harmonic generation.

Attosecond science is enabled by the ability to convert femtosecond near-infrared laser light into coherent harmonics in the extreme ultraviolet spectral range. While attosecond sources have been utilized in experiments that have not demanded high intensities, substantially higher photon flux would provide a natural link to the next significant experimental breakthrough. Numerical simulations of dual-gas high harmonic generation indicate that the output in the cutoff spectral region can be selectively enhanced without disturbing the single-atom gating mechanism. Here, we summarize the results of these simulations and present first experimental findings to support these predictions.

Microcystic macular degeneration in autosomal hereditary optic neuropathies: A cross-sectional retrospective study.

OBJECTIVE: Patients with autosomal optic neuropathies (AON) may develop microcystic macular degeneration (MMD), observed on retinal optical coherence tomography (OCT) examination. This study aimed to report the prevalence of MMD in AON patients and to assess the consequences of MMD on retinal architecture. METHODS: Retrospective single-center study conducted between 2001 and 2018. Patients affected by AON secondary to OPA1 or WFS1 gene mutations were included. The following data were collected: visual acuity, macular volume, vitreomacular interface and presence or absence of MMD. RESULTS: Forty-two subjects (34 OPA1, 8 WFS1) were included. MMD was found in 12 (29%) patients, i.e. 6 of the 8 WFS1 patients (75%) and 6 of the 34 OPA1 patients (17%). In cases with MMD, total retinal volume was greater (P=0.02) in accordance with thickening of the inner nuclear layer (P<0.001). WFS1 subjects had the highest total retinal volume (P=0.01), in relation to a thickening of the inner plexiform layer (P=0.02), inner nuclear layer (P<0.001) and outer plexiform layer (P=0.002). MMD was significantly associated with the WFS1 mutation (P<0.001). No significant association was found between the presence of vitreomacular adhesion and MMD. CONCLUSION: MMD was found in 29% of patients affected by AON and was more frequent in cases with a WFS1 gene mutation. MMD appears to be related to primary ganglion cell degeneration and Müller cell dysfunction. The vitreomacular interface does not appear to play a role in the occurrence of MMD.

Prevalence of dysphagia in patients with muscle tension dysphonia.

BACKGROUND: It is hypothesised that patients with muscle tension dysphonia have a high prevalence of dysphagia in comparison to normative values reported in the literature. METHODS: This prospective study included 44 subjects diagnosed with muscle tension dysphonia, based on symptoms and laryngoscopic findings, and 25 control subjects with no history of dysphonia and normal laryngeal examination findings. Demographic data included age, gender and smoking history. The aetiology of muscle tension dysphonia was classified as primary or secondary. Evaluation involved the Eating Assessment Tool ('EAT-10') questionnaire. RESULTS: Patients' mean age was 45.93 ± 14.95 years, with a female to male ratio of 1.2:1. Fourteen patients had primary muscle tension dysphonia, while 30 had secondary muscle tension dysphonia. Among patients with secondary muscle tension dysphonia, Reinke's oedema was the most common aetiology. There was a significant difference in the prevalence of dysphagia between the study group and the control group (40.9 per cent vs 8 per cent respectively, p < 0.05). CONCLUSION: This study demonstrates a higher prevalence of dysphagia in patients with the presenting symptom of dysphonia and diagnosed with muscle tension dysphonia in comparison to subjects with no dysphonia.

Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study.

INTRODUCTION: Methylphenidate is the most frequently used medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in Europe. Following concerns about its safety, the European Commission called for research into the long-term effects of methylphenidate on children and adolescents with ADHD. The Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) research programme was designed to address this call. At the heart of this programme is a 2-year longitudinal naturalistic pharmacovigilance study being conducted in 27 European sites. METHODS AND ANALYSIS: 3 cohorts of children and adolescents (aged 6-17) living in the UK, Germany, Italy and Hungary are being recruited:Group 1 (Medicated ADHD): 800 ADHD medication-naive children and adolescents with a clinical diagnosis of ADHD about to start methylphenidate treatment for the first time.Group 2 (Unmedicated ADHD): 400 children and adolescents with a clinical diagnosis of ADHD who have never been treated with ADHD medication and have no intention of beginning medication.Group 3 (Non-ADHD): 400 children and adolescents without ADHD who are siblings of individuals in either group 1 or 2.All participants will be assessed 5 times during their 2-year follow-up period for growth and development, psychiatric, neurological and cardiovascular health. The primary outcome measure will be the height velocity SD score. ETHICS AND DISSEMINATION: Ethical approval for the study has been granted by the East of Scotland Research Ethics Service. Following this approval, patient information leaflets and consent forms were translated as necessary and submissions made by lead sites in each of the other 3 countries to their own ethics committees. Following ethical approval in each country, local ethical permissions at each site were sought and obtained as needed. The study's website (http://www.adhd-adduce.org/page/view/2/Home) provides information for researchers, participants and the general public. TRIAL REGISTRATION NUMBER: NCT01470261.

Exaggerated renal vasoconstriction during exercise in heart failure patients.

BACKGROUND: During static exercise in normal healthy humans, reflex renal cortical vasoconstriction occurs. Muscle metaboreceptors contribute importantly to this reflex renal vasoconstriction. In patients with heart failure, in whom renal vascular tone is already increased at rest, it is unknown whether there is further reflex renal vasoconstriction during exercise. METHODS AND RESULTS: Thirty-nine heart failure patients (NYHA functional class III and IV) and 38 age-matched control subjects (controls) were studied. Renal blood flow was measured by dynamic positron emission tomography. Graded handgrip exercise and post-handgrip ischemic arrest were used to clarify the reflex mechanisms involved. During sustained handgrip (30% maximum voluntary contraction), peak renal vasoconstriction was significantly increased in heart failure patients compared with controls (70+/-13 versus 42+/-1 U, P=0.02). Renal vasoconstriction returned to baseline in normal humans by 2 to 5 minutes but remained significantly increased in heart failure patients at 2 to 5 minutes and had returned to baseline at 20 minutes. In contrast, during post-handgrip circulatory arrest, which isolates muscle metaboreceptors, peak renal vasoconstriction was not greater in heart failure patients than in normal controls. In fact, the increase in renal vasoconstriction was blunted in heart failure patients compared with controls (20+/-5 versus 30+/-2 U, P=0.05). CONCLUSIONS: During sustained handgrip exercise in heart failure, both the magnitude and duration of reflex renal vasoconstriction are exaggerated in heart failure patients compared with normal healthy humans. The contribution of the muscle metaboreceptors to reflex renal vasoconstriction is blunted in heart failure patients compared with normal controls.

A new compact soft x-ray spectrometer for resonant inelastic x-ray scattering studies at PETRA III.

We present a newly designed compact grating spectrometer for the energy range from 210 eV to 1250 eV, which would include the Kα(1,2) emission lines of vital elements like C, N, and O. The spectrometer is based on a grazing incidence spherical varied line spacing grating with 2400 l/mm at its center and a radius of curvature of 58 542 mm. First, results show a resolving power of around 1000 at an energy of 550 eV and a working spectrometer for high vacuum (10(-4) mbar) environment without losing photon intensity.

Safety and hemodynamic effects of intravenous triiodothyronine in advanced congestive heart failure.

Most patients with advanced congestive heart failure have altered thyroid hormone metabolism. A low triiodothyronine level is associated with impaired hemodynamics and is an independent predictor of poor survival. This study sought to evaluate safety and hemodynamic effects of short-term intravenous administration of triiodothyronine in patients with advanced heart failure. An intravenous bolus dose of triiodothyronine, with or without a 6- to 12-hour infusion (cumulative dose 0. 1 5 to 2.7 microg/kg), was administered to 23 patients with advanced heart failure (mean left ventricular ejection fraction 0.22 +/- 0.01). Cardiac rhythm and hemodynamic status were monitored for 12 hours, and basal metabolic rate by indirect calorimetry, echocardiographic parameters of systolic function and valvular regurgitation, thyroid hormone, and catecholamine levels were measured at baseline and at 4 to 6 hours. Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect. Acute intravenous administration of triiodothyronine is well tolerated in patients with advanced heart failure, establishing the basis for further investigation into the safety and potential hemodynamic benefits of longer infusions, combined infusion with inotropic agents, oral triiodothyronine replacement therapy, and new triiodothyronine analogs.

Studies on the action of nystatin on cultured rat myocardial cells and cell membranes, isolated rat hearts, and intact rats.

The action of nystatin, a polyene antibiotic, was studied in rat myocardial cells, isolated rat hearts, and intact rats. Myocardial cells responded to 10 and 25 micrograms nystatin/ml with arrhythmias that could be minimized by elevated concentrations of K+ and Mg2+ or reversed by washing the cells. Similarly, the isolated heart responded to 100 micrograms nystatin/ml with arrhythmias that could be tempered by addition of elevated concentrations of K+ and Mg2+. The i.v. injection of the drug caused heart failure in intact animals at the 4-mg/kg dose level. At the subcellular level, nystatin made the myocardial cell membranes more rigid, as measured by electron spin resonance spectrometry. These findings indicate a parallel between physiocochemical changes caused by nystatin in the myocardial cell membrane and the biological changes caused by this drug in myocardial cells, isolated heart, and heart of the intact animal.

Exaggerated muscle mechanoreflex control of reflex renal vasoconstriction in heart failure.

In heart failure (HF) patients, reflex renal vasoconstriction during exercise is exaggerated. We hypothesized that muscle mechanoreceptor control of renal vasoconstriction is exaggerated in HF. Nineteen HF patients and nineteen controls were enrolled in two exercise protocols: 1) low-level rhythmic handgrip (mechanoreceptors and central command) and 2) involuntary biceps contractions (mechanoreceptors). Renal cortical blood flow was measured by positron emission tomography, and renal cortical vascular resistance (RCVR) was calculated. During rhythmic handgrip, peak RCVR was greater in HF patients compared with controls (37 +/- 1 vs. 27 +/- 1 units; P < 0.01). Change in (Delta) RCVR tended to be greater as well but did not reach statistical significance (10 +/- 1 vs. 7 +/- 0.9 units; P = 0.13). RCVR was returned to baseline at 2-3 min postexercise in controls but remained significantly elevated in HF patients. During involuntary muscle contractions, peak RCVR was greater in HF patients compared with controls (36 +/- 0.7 vs. 24 +/- 0.5 units; P < 0.0001). The Delta RCVR was also significantly greater in HF patients compared with controls (6 +/- 1 vs. 4 +/- 0.6 units; P = 0.05). The data suggest that reflex renal vasoconstriction is exaggerated in both magnitude and duration during dynamic exercise in HF patients. Given that the exaggerated response was elicited in both the presence and absence of central command, it is clear that intact muscle mechanoreceptor sensitivity contributes to this augmented reflex renal vasoconstriction.

Examination of the protective effect of ICRF-187 and dimethyl sulfoxide against acetaminophen-induced hepatotoxicity in Syrian golden hamsters.

The protective activity of 1,2-bis(3,5-dioxopiperazin-l-yl)propane (ICRF-187) and dimethyl sulfoxide (DMSO) was tested against acetaminophen-induced hepatotoxicity. Male Syrian golden hamsters injected intraperitoneally between 18:00 h and 20:00 h for 2 consecutive days with acetaminophen (N-acetyl-p-aminophenol) (300 mg/kg) displayed signs of hepatotoxicity as evidenced by increases in enzyme activity and cellular damage. Forty-eight hours after the second acetaminophen dose, the activities of serum glutamic-pyruvic transaminase and alkaline phosphatase were increased compared with levels found in hamsters given only saline. In addition, hepatocellular necrosis was evident in acetaminophen-treated animals. ICRF-187 (300 mg/kg) given 1 h before acetaminophen attenuated the increases in enzyme activities, and both DMSO (7.3 g/kg) and ICRF-187 reduced the incidence and severity of acetaminophen-induced hepatocellular injury. Both ICRF-187 and DMSO are capable of altering free radical-mediated toxicity in other experimental systems. Whether these compounds reduce acetaminophen-induced liver toxicity by a similar mechanism remains to be determined.