Project description:The conceptual shift of our understanding of migraine from a vascular disorder to a brain disorder has dramatically altered the approach to the development of new medicines in the field. Current pharmacologic treatments of acute migraine consist of nonspecific and relatively specific agents. Migraine-specific drugs comprise two classes, the ergot alkaloid derivatives and the triptans, serotonin 5-HT(1B/1D) receptor agonists. The ergots, consisting of ergotamine and dihydroergotamine (DHE), are the oldest specific antimigraine drugs available and are considered relatively safe and effective. Ergotamine has been used less extensively because of its adverse effects; DHE is better tolerated. The triptan era, beginning in the 1990s, was a period of considerable change, although these medicines retained vasoconstrictor actions. New methods of delivering older drugs include orally inhaled DHE and the transdermal formulation of sumatriptan, both currently under study. Novel medicines being developed are targeted at neural sites of action. Serotonin 5-HT(1F) receptor agonists have proven effective in phase II studies and have no vascular actions. Calcitonin gene-related peptide (CGRP) receptor antagonists are another promising nonvasoconstrictor approach to treating acute migraine. Olcegepant (BIBN4096BS) and telcagepant (MK-0974) have been shown to be safe and effective in phase I, II, and (for telcagepant) phase III clinical trials. Other targets under investigation include glutamate (AMPA/kainate), TRPV1, prostanoid EP4, and nitric oxide synthase. With new neural targets and the potential for therapeutic advances, the next era of antimigraine medications is near.
Project description:ObjectiveTo test the hypothesis that ineffective acute treatment of episodic migraine (EM) is associated with an increased risk for the subsequent onset of chronic migraine (CM).MethodsIn the American Migraine Prevalence and Prevention Study, respondents with EM in 2006 who completed the Migraine Treatment Optimization Questionnaire (mTOQ-4) and provided outcome data in 2007 were eligible for analyses. The mTOQ-4 is a validated questionnaire that assesses treatment efficacy based on 4 aspects of response to acute treatment. Total mTOQ-4 scores were used to define categories of acute treatment response: very poor, poor, moderate, and maximum treatment efficacy. Logistic regression models were used to examine the dichotomous outcome of transition from EM in 2006 to CM in 2007 as a function of mTOQ-4 category, adjusting for covariates.ResultsAmong 5,681 eligible study respondents with EM in 2006, 3.1% progressed to CM in 2007. Only 1.9% of the group with maximum treatment efficacy developed CM. Rates of new-onset CM increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. In the fully adjusted model, the very poor treatment efficacy group had a more than 2-fold increased risk of new-onset CM (odds ratio = 2.55, 95% confidence interval 1.42-4.61) compared to the maximum treatment efficacy group.ConclusionInadequate acute treatment efficacy was associated with an increased risk of new-onset CM over the course of 1 year. Improving acute treatment outcomes might prevent new-onset CM, although reverse causality cannot be excluded.
Project description:There is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bisphosphonates, 6 hydroxymethyl-glutaryl CoA reductase inhibitors, anticoagulants and hyperbaric oxygen, and terms related to these MESH terms. A randomized controlled trial showed that osteonecrosis can be prevented by intermittent, instead of continuous, corticosteroid administration. The studies on interventions after onset of osteonecrosis were of low-quality evidence. Seven pediatric acute lymphoblastic leukemia studies described non-surgical interventions; bisphosphonates (n=5), hyperbaric oxygen therapy (n=1), or prostacyclin analogs (n=1). Safety and efficacy studies are lacking. Five studies focused on surgical interventions; none was of sufficient quality to draw definite conclusions. In conclusion, preventing osteonecrosis is feasible in a proportion of the pediatric acute lymphoblastic leukemia patients by discontinuous, instead of continuous, steroid scheduling. The questions as to how to treat childhood acute lymphoblastic leukemia patients with osteonecrosis cannot be answered as good-quality studies are lacking.
Project description:After the triptans, a calcitonin gene-related peptide blocker (telcagepant) is the first acute medicine that has been developed primarily for treatment of acute migraine. Otherwise, the new drugs have been developed first for other purposes, like anticonvulsants, antihypertensives and antidepressants used for migraine prophylaxis. For acute attacks, a new way to administer a traditional drug like dihydroergotamine is under way, and documentation of efficacy in migraine has been gained for some commonly used painkillers and anti-inflammatory drugs, and for some herbal extracts. Based on insights into the basic pathophysiological mechanisms of the disorder, some drugs have been developed which seem promising in early phase II studies (NOS inhibitors and 5HT1F-receptor agonists). In the future, development and enhancements of existing medicines must be accompanied by increased efforts to develop truly new migraine drugs based on knowledge of the pathophysiology if one wishes to reduce substantially the great burden migraine poses on patients and society.
Project description:The treatment of hypertension in children and adolescents has been markedly changed in recent years by several factors, including the publication of new consensus recommendations, the obesity epidemic, and the increased availability of information on efficacy and safety of antihypertensive medications in the young. In this review we present an updated approach to the outpatient management of hypertension in the child or adolescent, utilizing representative cases to illustrate important principles as well as possible controversies.
Project description:The goal of this observational population-based cohort study is to investigate the clinical characteristics and outcomes of children and adolescents with primary gastrointestinal malignancies registered in the publicly available Surveillance, Epidemiology, and End Results (SEER) 17 database during 2000-2019.
Project description:ObjectiveChallenging development tasks, problematic social environments and psychiatric disorder can result in crisis leading to an emergency consultation at child and adolescent psychiatry (CAP). The study aims to describe a representative clinical sample of patients seeking help at an acute CAP outpatient clinic.MethodsData from the initial assessment tool for CAP and data gained from the hospital IT-System were analyzed. The study site is the only hospital in the country of Salzburg in Austria with a specialized emergency unit for CAP patients.ResultsOut of the 257 patients, 53.7% were female. Boys significantly more often presented with externalizing symptoms and because of external factors. Girls significantly more often reported the presence of suicidal thoughts. Symptoms that led to consultation often were present for more than a week prior to consultation, in some cases even longer than 6 months. 51% of the children and adolescents were treated at the inpatient unit, 43% at the closed unit, where they stayed for a mean of 3 nights.ConclusionsMany patients, who attended the child and adolescent psychiatry emergency showed a long duration of presenting symptoms. Suicidal tendency was a common reason for consultation and often led to a closed inpatient treatment. Developing concepts for acute situations-like primary, secondary and tertiary suicide prevention-as well as improving the easier access to child and adolescent psychiatric services seems necessary.
Project description:BACKGROUND:There is a significant unmet need for new, effective and well tolerated acute migraine treatments. A recent study has demonstrated that a novel remote electrical neuromodulation (REN) treatment provides superior clinically meaningful pain relief with a low rate of device-related adverse events. The results reported herein compare the efficacy of REN with current standard of care in the acute treatments of migraine. METHODS:We performed a post-hoc analysis on a subgroup of participants with migraine from a randomized, double-blind, parallel-group, sham-controlled, multicenter study on acute care. The original study included a 2-4?weeks run-in phase, in which migraine attacks were treated according to patient preference (i.e., usual care) and reported in an electronic diary; next, participants entered a double-blind treatment phase in which they treated the attacks with an active or sham device. The efficacy of REN was compared to the efficacy of usual care or pharmacological treatments in the run-in phase in a within-subject design that included participants who treated at least one attack with the active REN device and reported pain intensity at 2?h post-treatment. RESULTS:Of the 252 patients randomized, there were 99 participants available for analysis. At 2?h post-treatment, pain relief was achieved in 66.7% of the participants using REN versus 52.5% participants with usual care (p?<?0.05). Pain relief at 2?h in at least one of two attacks was achieved by 84.4% of participants versus 68.9% in usual care (p?<?0.05). REN and usual care were similarly effective for pain-free status at 2?h. The results also demonstrate the non-inferiority of REN compared with acute pharmacological treatments and its non-dependency on preventive medication use. CONCLUSION:REN is an effective acute treatment for migraine with non-inferior efficacy compared to current acute migraine therapies. Together with a very favorable safety profile, these findings suggest that REN may offer a promising alternative for the acute treatment of migraine and could be considered first line treatment in some patients. TRIAL REGISTRATION:ClinicalTrials.gov NCT03361423 . Registered 18 November 2017.
Project description:It is well-known that between 40 and 50% of patients taking antidepressants do not respond to treatment or relapse. Genome wide gene expression studies can help us to understand better the response to antidepressants, revealing the effects of both genetic background and environmental/epigenetic factors. We used microarrays to detail the response to Fluoxetine in children and adolescents, analysing the expression just before intake of drug and 8 weeks after starting the treatment.