Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España

IntroductionAlemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.ObjectiveA consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.DevelopmentA group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group.ConclusionThe present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.     

Therapeutic response to domperidone in gastroparesis: A prospective study using the GCSI‐daily diary

Common symptoms of gastroparesis include nausea, vomiting, early satiety, postprandial fullness, and upper abdominal pain. Domperidone is used for treatment of gastroparesis. Daily symptom scoring may help document efficacy.

Aim

To determine the effectiveness of domperidone for gastroparesis symptoms using the gastroparesis cardinal symptom index‐daily diary (GCSI‐DD) and to determine which symptoms improve and when with domperidone treatment.

Methods

Symptomatic patients with diabetic or idiopathic gastroparesis were enrolled. Gastric emptying was performed using 4 hour scintigraphy. GCSI‐DD recorded symptoms at baseline and during six weeks of treatment with domperidone 10 mg TID. GCSI‐DD records severity of nausea, early satiety, postprandial fullness, upper abdominal pain, overall gastroparesis symptoms on a scale of 0 (no symptom) to 4 (very severe) and records the number of vomiting episodes per day.

Results

Thirty‐four patients with gastroparesis (5 diabetic, 29 idiopathic) participated in this open label study. Treatment duration averaged 36.9 ± 7.6 days. Improvement in overall gastroparesis symptoms occurred on day 3 of treatment and maintained during the treatment. Early satiety, postprandial fullness, and overall symptom severity significantly improved from baseline to the final week of treatment (P < .05 for all), whereas nausea had borderline improvement (P = .055). Side effects included palpitations (5 patients), headache (5), breast tenderness (2), menstrual bleeding (2), dizziness (1), drowsiness (1), chest pain (1), swelling (1), constipation (1).

Conclusions

Domperidone improves symptoms of gastroparesis, reducing overall gastroparesis symptom severity and decreasing early satiety, postprandial fullness, and nausea. GCSI‐DD is useful to document efficacy of therapy for gastroparesis.     

National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors. There was consensus that placebo has a definite role in mood disorder studies. Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo. Add-on studies in which patients are randomized to standard therapy plus the investigational drug or standard therapy plus placebo are especially indicated for high-risk patients. Mood disorders in elderly and pediatric patients are understudied, and properly designed trials are urgently needed. Research is needed on the ethical conduct of studies to limit risks of medication-free intervals and facilitate poststudy treatment. Patients must fully understand the risks and lack of individualized treatment involved in research.     

Evaluating symptom outcomes in gastroparesis clinical trials: validity and responsiveness of the Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD)

Background Patient‐reported symptom scales are needed to evaluate treatments for gastroparesis. The Gastroparesis Cardinal Symptom Index‐Daily Diary (GCSI‐DD) was developed to assess daily symptoms of gastroparesis. This study evaluated the validity and responsiveness of the GCSI‐DD in patients with gastroparesis. Methods Symptomatic patients were started with a new treatment for gastroparesis. Patients completed the GCSI‐DD each evening during a baseline week and for 8 weeks of treatment. Responders were defined based on patient and clinician global rating of change. Minimal important differences (MID) were estimated based on baseline to 4 week changes in symptoms scores for small improvements. Key Results Of 69 patients participating, 46 had idiopathic, 19 diabetic, and four postfundoplication gastroparesis. Excellent test–retest reliability was seen for GCSI‐DD scores, and there were significant correlations between GCSI‐DD scores and clinician ratings of symptom severity. Responders to treatment reported improvements in nausea [effect size (ES) = 0.42, P < 0.001], postprandial fullness, ES = 0.83, P < 0.001), bloating (ES = 0.34, P < 0.001), early satiety (ES = 0.53, P < 0.001), but lower responses for upper abdominal pain (ES = 0.29), and vomiting (ES = 0.22; P = 0.119). MIDs were 0.55 for nausea, 0.97 for excessive fullness, 0.63 for bloating, 0.77 for postprandial fullness, and 0.30 for abdominal pain. A composite score of four symptoms (Composite‐1; nausea, bloating, excessive fullness, postprandial fullness) had ES of 0.61 and MID of 0.73. Composite‐2 score (nausea, early satiety, bloating, abdominal pain) had a lower ES of 0.47. Conclusions & Inferences Symptoms of early satiety, nausea, postprandial fullness, and bloating were responsive to treatment for gastroparesis. A composite of these symptoms also demonstrates validity and responsiveness to treatment for gastroparesis, and may represent an acceptable endpoint for evaluating the effectiveness of medical treatments in clinical trials for gastroparesis.     

What are the important subsets of gastroparesis?

Gastroparesis is often divided into subsets based on etiology and pathophysiology; however, the utility of these subsets in the diagnosis and treatment of gastro-paresis is not well defined. The objectives are to consider the subsets of gastroparesis from the perspectives of etiology and pathogenesis, pathophysiology, histopathology, and clinical associations, with particular focus on similarities and differences between diabetic and idiopathic gastroparesis and consideration of the potential subset of painful gastroparesis. We conclude that idiopathic and diabetic gastroparesis has similar initial presentations and manifestations, except that idiopathic gastroparesis tends to be associated more frequently with pain. Myopathic disorders are uncommon. Extrinsic denervation was considered the most common etiology; however, with the decline in surgery for peptic ulceration and in-depth study of full-thickness gastric biopsies, the most common intrinsic defects are being recognized in the interstitial cells of Cajal (ICC-opathy) and with immune infiltration and neuronal changes (intrinsic neuropathic gastroparesis). Histomorphological differences at the microscopic level between diabetic and idiopathic gastroparesis are still of unclear significance. Two gastroparesis subsets worthy of special mention, because they are potentially reversible with identification of the cause, are postviral gastroparesis, which has a generally good prognosis, and iatrogenic gastroparesis, especially in patients with non-surgical gastroparesis, such as diabetics exposed to incretins such as pramlintide and exenatide.     

Methods of gastric electrical stimulation and pacing: a review of their benefits and mechanisms of action in gastroparesis and obesity

Abstract  Development of gastric electrical stimulation techniques for treatment of gastric dysmotility syndromes and obesity has been a long-standing goal of investigators and clinicians. Depending on stimulus parameters and sites of stimulation, such methods have a range of theoretical benefits including entrainment of intrinsic gastric electrical activity, eliciting propagating contractions and reducing symptomatology in patients with gastroparesis and reducing appetite and food intake in individuals with morbid obesity. Additionally, gastric stimulation parameters have extragastrointestinal effects including alteration of systemic hormonal and autonomic neural activity and modulation of afferent nerve pathways projecting to the central nervous system that may represent important mechanisms of action. Numerous case series and smaller numbers of controlled trials suggest clinical benefits in these two conditions, however better controlled trials are mandated to confirm their efficacy. Current research is focusing on novel stimulation methods to better control symptoms in gastroparesis and promote weight reduction in morbid obesity.     

Atherothrombotic carotid disease: towards a consensus on its prevention

This consensus document was one of the objectives of the I Meeting of the Spanish Society of Angiology and Vascular Surgery, the Spanish Interventional Neuroradiology Group of the Spanish Society of Neuroradiology, and the Cerebrovascular Disease Study Group of the Spanish Society of Neurology, which was held in October 2002 in Cordoba. Atherosclerosis is a chronic vascular disease of true epidemic proportions. It is the first cause of death in developed countries and responsible for one quarter of documented deaths worldwide. Atherothrombotic ischemic stroke, transient ischemic attack and atherothrombotic origin symptomatic or asymptomatic peripheral arterial disease are all associated with a high risk of vascular death, myocardial infarction and recurrent stroke. In this context, vascular disease represents a serious public health problem, particularly if we take into account current forecasts on population ageing. The prevention of atherosclerosis - and its consequences, if its clinical manifestations are already apparent - is therefore a priority. This multidisciplinary consensus document draws on the different medical specialties dealing with these patients and combines efforts to obtain the greatest possible benefit as regards this disease's management. The consensus document makes a global analysis of atherosclerosis prevention, basically in terms of therapeutic objectives, lifestyle change measures, high bloodpressure management, dyslipidemia, other vascular risk factors and platelet antiaggregation. Emphasis is placed on the frequent coexistence of cerebrovascular and peripheral arterial involvement, and the methods of detecting silent involvement. Lastly, consensus is reached on the diagnostic methods and specific management of atherothrombotic carotid disease, including the benefits and risks of and indications for carotid endarterectomy, and the current role of carotid angioplasty.     

Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part II

OBJECTIVE: To develop treatment recommendations for the use of antipsychotic medications for children and adolescents with serious psychiatric disorders and externalizing behavior problems. METHOD: Using a combination of evidence- and consensus-based methodologies, recommendations were developed in six phases as informed by three primary sources of information: (1) current scientific evidence (published and unpublished), (2) the expressed needs for treatment-relevant information and guidance specified by clinicians in a series of focus groups, and (3) consensus of clinical and research experts derived from a formal survey and a consensus workshop. RESULTS: Fourteen treatment recommendations on the use of atypical antipsychotics for aggression in youth with comorbid psychiatric conditions were developed. Each recommendation corresponds to one of the phases of care (evaluation, treatment, stabilization, and maintenance) and includes a brief clinical rationale that draws upon the available scientific evidence and consensus expert opinion derived from survey data and a consensus workshop. CONCLUSION: Until additional research from controlled trials becomes available, these evidence- and consensus-based treatment recommendations may be a useful approach to guide the use of antipsychotics in youth with aggression.     

Documento de revisión y actualización de la cefalea por uso excesivo de medicación (CUEM)

IntroductionMedication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1-2%, with higher rates among women aged 30-50 years and with comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a consensus document addressing this disorder.DevelopmentThese guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important.ConclusionsWe hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management.     

Consensus-recommended diagnostic and therapeutic guidelines for drug-resistant epilepsy in Spain (Consenso RATE-España)

OBJECTIVE: To ascertain the opinions of an Epilepsy Expert Group and prepare a consensus document on the definition of drug-resistant epilepsy (DRE) according to the International League Against Epilepsy (ILAE) and the different healthcare levels for the patient with epilepsy in Spain. MATERIAL Y METHODS: The study was conducted using the Delphi method, by means of successive rounds of questionnaires. A scientific committee prepared a preliminary document and fourteen associated questions, which were sent by e-mail to the panel of experts. They included items related to the concept of DRE, health care levels and the route between these levels for patients with DRE. RESULTS: A total of 41 experts answered the questionnaire. They agreed regarding the necessity and applicability of the DRE definition according to the ILAE, the need for an expert panel on epilepsy, specialist epilepsy clinics, and clinical epilepsy units stratified depending on the level of activities they carried out. There was moderate consensus on the resources and activity of the clinical units of reference and there was no consensus on the referral of patients who have suffered an epileptic seizure to an epilepsy clinic. CONCLUSIONS: The expert panel agreed with the definition of DRE according to the ILAE and on referring patients with DRE for a detailed study in an epilepsy clinic or epilepsy clinical unit. They highlighted the need for video-EEG monitoring in the study of patients with DRE and the need to propose other forms of treatment in selected patients.