NICE diagnostic heart failure pathway: screening referrals identifies patients better served by community-based management.

AIMS: Evaluate whether UK National Institute for Health & Care Excellence (NICE) chronic heart failure (HF) guidelines can be safely and effectively refined through specialist referral management. METHODS AND RESULTS: All referrals to a UK centre 1/3/2019-30/5/2019 and 1/6/2020-31/7/2020 were reviewed by HF specialists. Patients were triaged to specialist assessment in HF clinic, according to the NICE HF diagnostic pathway [urgency based on N-terminal pro brain natriuretic peptide (NTproBNP) levels], or the referrer given remote Advice & Guidance (A&G), to aid primary care management. Standardized triage criteria for recommending primary care management were (i) presentation inconsistent with HF, (ii) competing comorbidity/frailty meant specialist assessment in clinic not in patient's best interests, (iii) recent assessment for same condition, or (iv) patient had known HF. Following triage patients managed in the primary care were categorized as low or high risk of adverse outcomes. Outcome measures were 90 day all-cause and HF hospital admission and mortality rates. Four hundred and eighty-six patients had the median age of 80 (74-86) years, and 253 (52%) were male. Two hundred and six (42%) had NTproBNP > 2000 pg/mL. Primary care management was recommended for 128 patients (26%): 105 (22%) A&G alone and 23 input from community HF nurse specialists. Primary care management was recommended due to the following: presentation inconsistent with HF 53 (42%), more important competing comorbidity/frailty 35 (27%), recent assessment 17 (13%), and known HF 23 (18%). Patients managed in primary care had higher rates of all-cause hospitalization (30% vs. 19%; P = 0.018) and death (7% vs. 2%; P = 0.0054) than those seen in HF clinic. Of those managed in primary care, 50 (39%) were determined to be at low risk and 78 (61%) at high risk. High-risk patients were older (87 vs. 80 years; P = 0.0026), had much higher NTproBNP (2666 vs. 697 pg/mL; P < 0.0001), and were managed in the primary care due to severe comorbidity (45%) or known HF (31%). They had extremely high rates of adverse outcomes: 35 all-cause hospitalization (45%), 12 HF hospitalization (15%), and 9 deaths (12%). Low-risk patients were usually felt not to have HF (86%) and confirmed to have low rates of adverse outcomes: three all-cause hospitalizations (6%; P < 0.0001 compared with high risk) and zero HF hospitalization (P = 0.0033) or death (P = <0.012). CONCLUSIONS: Incorporating specialist referral management into NICE HF diagnostic pathway reduces the demand on HF clinics and may improve the patient experience by facilitating community care. However, many of the patients identified for primary care management are at very high risk of adverse outcomes in the short term and are frequently hospitalized. Urgent implementation of alternative pathways and community-based care packages in parallel for these high-risk patients is extremely important.

Memantine: a review of possible uses in child and adolescent psychiatry.

OBJECTIVE: To provide a review of published literature regarding the pharmacology of memantine and potential benefits for use in child and adolescent psychiatry. METHOD: A LITERATURE SEARCH OF SEVERAL DATABASES (MEDLINE, PSYCHINFO, CINAHL, PSYCARTICLES) WAS CONDUCTED WITH THE SEARCH TERMS: 'memantine' with limits: English language, Human trials, all child (aged 0-18 years). The search was later expanded to include 'Adults' and relevant articles were also selected from reference lists. RESULT: The search did not find any well-controlled studies in children and adolescents except for open label trials, as monotherapy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), as well as an augmenting agent in obsessive compulsive disorder (OCD). No study was found in anxiety disorders (AD), the most common psychiatric disorder in children or in mood disorders, both major depressive disorder (MDD) and bipolar disorder (BD). Studies in adults for those disorders with onset in childhood or adolescence, were also mostly open-label and as an add-on therapy. All the studies reported that memantine is a safe drug with minimal drug interactions and a very acceptable adverse effect profile comparable to placebo. CONCLUSION: Memantine has demonstrated beneficial effects in some childhood disorders but the evidence is too limited at present and does not provide enough support of its efficacy to advocate for its regular use in those conditions. Such use remains off-label until further validation of efficacy comes from blinded, randomized, placebo controlled studies.

OBJECTIF: Offrir une revue de la littérature publiée à propos de la pharmacologie de la mémantine et des avantages potentiels de l'utiliser en psychiatrie de l'enfant et de l'adolescent. MÉTHODE: Une recherche de la littérature dans plusieurs bases de données (Medline, Psychinfo, CINAHL, PsycARTICLES) a été menée au moyen du mot clé « mémantine ¼ avec restrictions : langue anglaise, essais sur des humains, tous les enfants (de 0 à 18 ans). La recherche a ensuite été élargie pour inclure « les adultes ¼ et des articles pertinents ont aussi été relevés dans les bibliographies. RÉSULTAT: La recherche n'a donné aucune étude bien contrôlée d'enfants et d'adolescents sauf des essais ouverts, comme une monothérapie d'un trouble du spectre de l'autisme (TSA) et du trouble de déficit de l'attention avec hyperactivité (TDAH), ainsi qu'un agent d'augmentation du trouble obsessionnel-compulsif (TOC). Aucune étude des troubles anxieux (TA), pourtant le trouble psychiatrique le plus répandu chez les enfants, n'a été trouvée, ni des troubles de l'humeur, soit le trouble dépressif majeur (TDM) et le trouble bipolaire (TB). Les études chez les adultes de ces troubles, qui sont apparus dans l'enfance ou l'adolescence, étaient également ouvertes pour la plupart, à titre de thérapie d'appoint. Toutes les études rapportaient que la mémantine est un médicament sécuritaire présentant des interactions médicamenteuses minimales et un profil très acceptable d'effets secondaires, comparables à ceux d'un placebo. CONCLUSION: La mémantine a démontré des effets bénéfiques pour certains troubles des enfants, mais les données probantes sont trop limitées à l'heure actuelle et elles ne soutiennent pas suffisamment son efficacité pour en revendiquer l'utilisation régulière dans ces troubles. Cette utilisation demeure non indiquée sur l'étiquette jusqu'à ce que des études à l'insu, randomisées, et contrôlées contre placebo en garantissent davantage l'efficacité.

Amantadine: a review of use in child and adolescent psychiatry.

OBJECTIVE: To review published literature regarding the pharmacology and use of amantadine in child and adolescent psychiatry. METHOD: A LITERATURE SEARCH OF SEVERAL DATABASES (PUBMED, PSYCHINFO, CINAHL, MEDLINE, PSYCARTICLES, BIOMEDICAL REFERENCE COLLECTION AND ACADEMIS SEARCH COMPLETE) WAS CONDUCTED WITH THE SEARCH TERMS: 'amantadine' with limits: English language, Human trials, all child (aged 0-18 years). The search was later expanded to include 'Adults' and additional relevant articles were selected from reference lists. RESULTS: The psychotropic effect of amantadine is related to its antagonism of the N-methyl-D-aspartate (NMDA) receptor. It decreases the toxic effects of the glutamatergic neurotransmitter system which plays an important role in many psychiatric disorders. Two randomized controlled trials (RCTs) of amantadine were identified in children and adolescents. One reported beneficial effects in controlling the symptoms of irritability and hyperactivity in autistic disorder and the other described a significant impact in attention deficit hyperactivity disorder (ADHD). Two open label studies also reported positive effects in ADHD. A pilot study in children with enuresis reported significant reduction in wetting frequency. Studies in adults, with relevance to children and adolescents, reported effectiveness in resistant depression, obsessive compulsive disorder and in counteracting side effects of some psychotropic medications. RCTs found in traumatic brain injury indicated a neuroprotective effect and effectiveness in controlling agitation and aggression. Amantadine is well tolerated in children and adolescents, with an acceptable side effect profile, and considered safe for long term use. CONCLUSION: Amantadine shows potential for use as a safe alternative or as an augmenting agent for treating children with neuropsychiatric and various other disorders. Available data for such use, although promising, require further confirmation.

Résumé OBJECTIF: Passer en revue, résumer et discuter la littérature publiée sur la pharmacologie et l'utilisation de l'amantadine en pédopsychiatrie. MÉTHODE: Une recherche de la littérature dans plusieurs bases de données (PubMed, Psychinfo, CINAHL, Medline, PsycARTICLES, Biomedical Reference Collection et Academis Search Complete) a été menée avec le mot clé « amantadine ¼ avec des limites: langue anglaise, essais sur des humains, tous les enfants (de 0 à 18 ans). Des articles additionnels pertinents ont été relevés dans les bibliographies. Étant donné la quantité limitée d'information obtenue, la recherche s'est élargie et a inclus « tous les enfants et les adultes ¼, et l'information pertinente a été saisie. RÉSULTATS: L'utilisation de l'amantadine pour traiter les troubles neuro-développementaux chez les enfants est due à son effet antagoniste au recepteur N-methyl-D-aspartate (NMDA). L'effet de l'amantadine sur le système glutamatergique des neurotransmetteurs, jouer un rôle important dans de nombreux troubles psychiatriques. La majorité des études relevées étaient des études ouvertes et seulement deux étaient des études contrôlées d'enfants et d'adolescents. Un essai randomisé contrôlé rendait compte des effets bénéfiques du contrôle des symptômes d'irritabilité et d'hyperactivité chez les enfants souffrant d'un trouble autiste. Un autre essai randomisé contrôlé, une étude de comparaison directe avec le méthylphénidate, a constaté un effet statistiquement significatif sur le trouble de déficit de l'attention avec hyperactivité (TDAH). Deux autres études ouvertes constataient aussi des effets positifs sur le TDAH. Une étude pilote sur des enfants souffrant d'énurésie constatait une réduction significative de la fréquence de l'incontinence. Ouvertes pour la plupart, les études sur les adultes, relativement aux enfants et aux adolescents, rapportaient une efficacité dans la dépression résistante, le trouble obsessionnel compulsif et pour compenser certains effets secondaires des psychotropes. Des essais contrôlés sur les traumatismes cérébraux indiquaient un effet neuroprotecteur et une efficacité pour contrôler les comportements aberrants comme l'agitation et l'agressivité. L'amantadine était constamment désignée comme étant bien tolérée, ayant un profil acceptable d'effets secondaires et étant sécuritaire pour une utilisation à long terme. Son congénère analogue mais plus puissant, la mémantine, a également démontré des effets bénéfiques potentiels pour des troubles semblables, mais aucune étude bien contrôlée n'a été trouvée chez les enfants et les adolescents. CONCLUSION: L'amantadine pourrait être utilisée comme agent de rechange sécuritaire ou agent d'augmentation dans le traitement des enfants souffrant de troubles neuropsychiatriques développementaux ou d'autres troubles qui ont démontré une résistance aux agents psychopharmacologiques d'usage courant. Cependant, les données disponibles pour un tel usage, bien que prometteuses, sont limitées et proviennent surtout d'études ouvertes. Il faut que cette efficacité soit confirmée par des études bien contrôlées.

A review of executive function deficits and pharmacological management in children and adolescents.

OBJECTIVE: To review both the functions and dysfunction of the executive system (ES) focusing on the extent of executive function (EF) deficits in most psychiatric disorders in children and adolescents and the possibility of such deficits acting as markers for pharmacological management. METHOD: A LITERATURE REVIEW WAS CONDUCTED USING MEDLINE, PSYCHINFO, CINAHL, PSYCHARTICLES AND PUBMED WITH THE FOLLOWING KEYWORDS: executive function or dysfunction, pediatric or children or adolescents, psychopharmacology, psychotropic medications, attention deficit hyperactivity disorder (ADHD), depression, obsessive compulsive disorder, anxiety disorders, bipolar disorder, schizophrenia, autism spectrum disorders (ASD), fetal alcohol spectrum disorders (FASD). Due to the limited amount of specific information obtained for some childhood disorders, the search was broadened to include relevant adult literature where information was extrapolated. RESULTS: Abundant literature was found on the nature of the ES and the executive dysfunctions in most psychiatric disorders in children and adolescents, but not so much on the use of medication. EF deficits were found to be more consistent in disorders such as ADHD, ASD and FASD than in the other disorders but were not specific enough for use as clinical markers for those disorders. For children with ADHD and ASD there was adequate information on the use of psychotropic medications and impact on some EF domains but information on the impact of medication on EF in the other disorders in children and adolescents was fairly limited. Medications acting on the dopaminergic system also showed positive effects on EF deficits and are commonly used in the treatment of EF disorders such as ADHD, ASD and FASD. CONCLUSION: Existing literature indicates that EF deficits underlie most psychiatric disorders in children and adolescents. However, there are so many executive functions linked to so many activities and circuits in the brain that it is hard to quantify them in a particular disorder for use as specific markers for that disorder. The ES uses dopamine as its main neurotransmitter and this has implications for clinical management. Dopamine agonists (e.g. stimulants) and antagonists (e.g. neuroleptics) are medications that have direct impact on the ES and are commonly used to treat EF disorders in children and adolescents while serotonergic medications e.g. selective serotonin reuptake inhibitors (SSRIs) have not been very successful in treating such disorders. Identifying EF deficits early could be useful in guiding management including the use of medication in those disorders.

SSRIs and SNRIs: A review of the Discontinuation Syndrome in Children and Adolescents.

OBJECTIVE: To review the occurrence, clinical relevance and characteristics of the discontinuation syndrome in children and adolescents who have been on a selective serotonin reuptake inhibitor (SSRI) or a serotonin/norepinephrine re-uptake inhibitor (SNRI) for various conditions as an update for physicians prescribing these medications in this population. METHOD: An on-line literature search was done using MEDLINE, PubMed, CINAHL, PsychARTICLES, and PsychINFO with the following key words: selective serotonin reuptake inhibitors or SSRIs, serotonin/norepinephrine re-uptake inhibitors or SNRIs, discontinuation syndrome, pediatric or children or adolescents, occurrences and characteristics. RESULTS: Not a single randomized placebo-controlled trial was found that addresses this condition solely in the child and adolescent population. A couple of papers written by the same authors indicate that children and adolescents taking an SSRI definitely experience discontinuation reactions that can be mild, moderate or severe when the medication is stopped suddenly or high doses are reduced substantially. Among the SSRIs paroxetine seems to be the worst offender and fluoxetine the least while sertraline and fluvoxamine tend to be intermediate. However, the most serious discontinuation reactions came from the SNRI venlafaxine. There was no study or reports found on citalopram, another SSRI that is commonly prescribed in children and youth. While the adult literature abounds with papers describing the different aspects of this condition including clinical features, diagnostic criteria, management and prevention, the limited information available to-date in children and adolescents indicate that the essential features of the discontinuation syndrome may not be significantly different than in adults. There were no specific characteristics identified relating to the child population. CONCLUSION: In considering the use of an SSRI in children, physicians must seriously weigh the not so clear benefits against the risks of adverse reactions including the discontinuation syndrome. The frequency and severity of this reaction seem dependent on the SSRI half-life and although children metabolize drugs much faster than adults the reactions to-date have been reported as similar. The use of fluoxetine with its long half-life appears safer in this respect with paroxetine and venlafaxine causing the most concerns. Patients and their families should be well informed of the risks of stopping the medication abruptly and instructed not to do so without consulting their physician. Physicians in Canada who are using these medications off-label in children need to be knowledgeable and vigilant about such adverse reactions. These could be avoided through adequate follow ups which will also ensure better adherence. They may benefit from this review even though the information comes mostly form the adult literature. More prospective studies are needed to clarify this issue and identify any specific features relating to the pediatric population.

A review of long-acting medications for ADHD in Canada.

OBJECTIVE: To review and comment on the long-acting medications presently marketed in Canada for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in terms of design, composition, mode of action and efficacy including other long-acting products that are not yet available in Canada. METHOD: A literature review was conducted using MEDLINE, PsycInfo, CINAHL, and PubMed with additional information gathered from other sources. RESULTS: The American Academy of Pediatrics (AAP), the American Academy of Child and Adolescent Psychiatry (AACAP) and the Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA) while endorsing the stimulants as first line medications to treat ADHD also recommended the use of long-acting once-a-day medication for better efficacy, convenience and adherence. Most studies rated the controlled release and the immediate release medications as similar in efficacy. However, long-acting medication was shown to be superior in terms of remission rates. CONCLUSION: When a child is receiving a long-acting medication for treatment of ADHD, he may feel less stigmatized, is more likely to be adherent and achieve remission. A child in remission can benefit from other treatment modalities thus improving long-term prognosis.