Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.

BACKGROUND Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder. METHODS In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ. FINDINGS We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]). INTERPRETATION Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice. FUNDING UK National Institute for Health Research Oxford Health Biomedical Research Centre

Comparative efficacy and acceptability of psychosocial interventions for individuals with cocaine and amphetamine addiction: A systematic review and network meta-analysis.

BACKGROUND Clinical guidelines recommend psychosocial interventions for cocaine and/or amphetamine addiction as first-line treatment, but it is still unclear which intervention, if any, should be offered first. We aimed to estimate the comparative effectiveness of all available psychosocial interventions (alone or in combination) for the short- and long-term treatment of people with cocaine and/or amphetamine addiction. METHODS AND FINDINGS We searched published and unpublished randomised controlled trials (RCTs) comparing any structured psychosocial intervention against an active control or treatment as usual (TAU) for the treatment of cocaine and/or amphetamine addiction in adults. Primary outcome measures were efficacy (proportion of patients in abstinence, assessed by urinalysis) and acceptability (proportion of patients who dropped out due to any cause) at the end of treatment, but we also measured the acute (12 weeks) and long-term (longest duration of study follow-up) effects of the interventions and the longest duration of abstinence. Odds ratios (ORs) and standardised mean differences were estimated using pairwise and network meta-analysis with random effects. The risk of bias of the included studies was assessed with the Cochrane tool, and the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We followed the PRISMA for Network Meta-Analyses (PRISMA-NMA) guidelines, and the protocol was registered in PROSPERO (CRD 42017042900). We included 50 RCTs evaluating 12 psychosocial interventions or TAU in 6,942 participants. The strength of evidence ranged from high to very low. Compared to TAU, contingency management (CM) plus community reinforcement approach was the only intervention that increased the number of abstinent patients at the end of treatment (OR 2.84, 95% CI 1.24-6.51, P = 0.013), and also at 12 weeks (OR 7.60, 95% CI 2.03-28.37, P = 0.002) and at longest follow-up (OR 3.08, 95% CI 1.33-7.17, P = 0.008). At the end of treatment, CM plus community reinforcement approach had the highest number of statistically significant results in head-to-head comparisons, being more efficacious than cognitive behavioural therapy (CBT) (OR 2.44, 95% CI 1.02-5.88, P = 0.045), non-contingent rewards (OR 3.31, 95% CI 1.32-8.28, P = 0.010), and 12-step programme plus non-contingent rewards (OR 4.07, 95% CI 1.13-14.69, P = 0.031). CM plus community reinforcement approach was also associated with fewer dropouts than TAU, both at 12 weeks and the end of treatment (OR 3.92, P < 0.001, and 3.63, P < 0.001, respectively). At the longest follow-up, community reinforcement approach was more effective than non-contingent rewards, supportive-expressive psychodynamic therapy, TAU, and 12-step programme (OR ranging between 2.71, P = 0.026, and 4.58, P = 0.001), but the combination of community reinforcement approach with CM was superior also to CBT alone, CM alone, CM plus CBT, and 12-step programme plus non-contingent rewards (ORs between 2.50, P = 0.039, and 5.22, P < 0.001). The main limitations of our study were the quality of included studies and the lack of blinding, which may have increased the risk of performance bias. However, our analyses were based on objective outcomes, which are less likely to be biased. CONCLUSIONS To our knowledge, this network meta-analysis is the most comprehensive synthesis of data for psychosocial interventions in individuals with cocaine and/or amphetamine addiction. Our findings provide the best evidence base currently available to guide decision-making about psychosocial interventions for individuals with cocaine and/or amphetamine addiction and should inform patients, clinicians, and policy-makers

NERAZLIKOVNOST RAZLIKA

Analiziraju se leksikološko-leksikografska polazišta i metodološki postupci u izradi Razlikovnog rječnika srpskog i hrvatskog jezika Vladimira Brodnjaka

Real-World Use of Carvedilol in Children With Dilated Cardiomyopathy: Long-Term Effect on Survival and Ventricular Function

BackgroundCarvedilol is recommended for chronic heart failure (HF) treatment in children. However, the ideal dosage and administration are not standardized, and data on its long-term effects are lacking. This study aimed to assess the effect of a high dosage regimen of carvedilol on cardiac outcomes in children with HF.MethodsWe conducted a retrospective cohort study including all children with HF and dilated cardiomyopathy. We analyzed medical records before starting treatment, at 1 and 3 years after reaching the maximum therapeutic dosage. All data were compared with a historical control group. Kaplan–Meier analysis and Cox proportional hazard regression have been used to evaluate the effect of high dosage carvedilol therapy. The main outcome was a composite of all-cause mortality and heart transplant.ResultsOne hundred thirty-five were included in the study and 65 treated with a high dosage of carvedilol regimen (up to 1 mg/kg/day). Heart rate reduction (mean reduction 30%, p &amp;lt; 0.0001) and ejection fraction improvement (32 ± 9.4 vs. 45. ± 10.1%, p &amp;lt; 0.0001) were statistically significant in those. Long-term survival and freedom from heart transplant were significantly improved in those treated with high dosage carvedilol therapy (p = 0.00001).ConclusionsTreatment with the high dosage of carvedilol, in addition to standard HF therapy, significantly improves ventricular function and survival in children with dilated cardiomyopathy and chronic HF.</jats:sec

RATTLE: Train Identification Through Audio Fingerprinting

Train model identification can enhance the structural monitoring of railway infrastructures by providing contextual information about train passages. While approaches relying on timetables are impractical due to delays, camera-based solutions present challenges related to deployment costs and privacy concerns. In this paper, we propose RATTLE, a self-contained framework for train tracking and identification based on audio signal fingerprinting. We have developed a prototype IoT system tailored for train tracking and ground truth assessment, enabling the acquisition of a real-world dataset spanning four months of measurements. Then, we conducted a comparative analysis of several traditional Machine Learning (ML) and Deep Learning (DL) algorithms for audio features classification, mel spectrogram classification, and image classification (serving as baselines). Our findings highlight that mel-trained CNN algorithms achieve high accuracy (97%) comparable to the best video-based DL solution, while substantially reducing model size. Furthermore, we explored the potential for migrating the classification task to the edge through quantisation techniques

Edge human activity recognition using federated learning on constrained devices

Human Activity Recognition (HAR) using wearable Internet of Things (IoT) devices represents a well investigated researched field encompassing various application domains. Many current approaches rely on cloud-based methodologies for gathering data from diverse users, resulting in the creation of extensive training datasets. Although this strategy facilitates the application of powerful Machine Learning (ML) techniques, it raises significant privacy concerns, which can become particularly severe given the sensitivity of HAR data. Moreover, the labeling process can be extremely time-consuming and even more challenging for IoT wearable devices due to the absence of efficient input systems. In this paper, we address both aforementioned challenges by designing, implementing, and validating edge-based Human Activity Recognition (HAR) systems that operate on resource-constrained IoT devices, which relies on the utilization of Self-Organizing Maps (SOM) for activity detection. We incorporate a feature selection process before training to reduce data dimensionality and, consequently, the SOM size, aligning with the resource limitations of wearable IoT devices. Additionally, we explore the application of Federated Learning (FL) techniques for HAR tasks, enabling new users to leverage SOM models trained by others on their respective datasets. Our federated Extreme Edge (EE)-aware HAR system is implemented on a wearable IoT device and rigorously tested against state-of-the-art and experimental datasets. The results demonstrate that our C++-based SOM implementation achieves a consistent reduction in model size compared to state-of-the-art approaches. Furthermore, our findings highlight the effectiveness of the FL-based approach in overcoming personalized training challenges, particularly in onboarding scenarios

Effetto dei mass-media sull'aderenza alla vaccinazione antiinfluenzale nella stagione 2014/2015. Un’inchiesta nella regione Lazio

Introduzione. L’influenza è un’importante causa di morbosità, morbilità e mortalità. Ogni anno le istituzioni mondiali di Sanità Pubblica programmano la campagna vaccinale per prevenire l’insorgenza di complicanze anche severe, con obiettivo la copertura di almeno il 75% nella popolazione over-65. In Italia, la campagna anti-influenzale 2014/15 è stata caratterizzata da un importante caso mediatico a seguito di morti sospette collegate alla somministrazione del vaccino adiuvato con MF59. Tale sospetto non è stato confermato dalle analisi effettuate a livello nazionale ed internazionale. L’obiettivo dello studio è stato valutare le impressioni dei responsabili della campagna vaccinale anti-influenzale sull’impatto del caso mediatico sulla copertura vaccinale nella popolazione over-65 nella Regione Lazio, che assunto un atteggiamento di estrema cautela sulla pratica vaccinale. Metodi. Un questionario è stato inviato via email ai responsabili delle 12 ASL con i seguenti argomenti: tipo di vaccino distribuito; aderenza all’inizio della campagna; effetti del caso mediatico e le proiezioni sulla copertura vaccinale nella popolazione over-65. Sono stati effettuati un’analisi descrittiva delle 4 domande e il successivo confronto con i dati di copertura nella stagione precedente. Risultati. Tutti i 12 responsabili hanno risposto all’inchiesta, riferendo un impatto negativo del caso mediatico. Confrontando la loro previsione di copertura con i dati della stagione 2013/14 (54,1%) si stima un valore del 49% con una riduzione del 10% sul trend positivo delle stagioni precedenti. Discussione. La riduzione dell’aderenza alla vaccinazione negli over-65 sembra essere correlato allo scetticismo della popolazione verso la vaccinazione e ad una inadeguata gestione della Sanità Pubblica italiana e regionale del caso mediatico. In conclusione, è fondamentale migliorare la comunicazione tra sanità pubblica e la popolazione generale

The Investigational Clinical Center: a clinical-supportive and patient-centered trial unit model. Ten years of experience through normal and pandemic times of a large pediatric Trial Center in Italy.

Abstract Evidence-based medicine relies on appropriately designed, conducted and reported clinical trials (CTs) to provide the best proofs of efficacy and safety for pharmacological and non-pharmacological treatments. Modern clinical research features high complexity and requires a high workload for the management of trials-related activities, often hampering physicians’participation to clinical trials. Dealing with children in clinical research adds complexity: rare diseases, parents or legal guardian reluctance to engage and recruitment difficulties are major reasons of pediatric trials failure. However, because in paediatrics many treatments are prescribed off-label or are lacking, well-designed clinical trials are particularly needed. Clinical Trial Units (CTUs) are indeed an important asset in the implementation of clinical trials, but their support to investigators is limited to administrative and non-clinical tasks. In this paper we present the model of the Investigational Clinical Center (ICC) of the Bambino Gesù Children’s Hospital in Rome. The ICC includes clinicians supporting the Principal Investigators (PIs) for clinical management of enrolled patients in compliance of Good Clinical Practice, the legal framework of Clinical Trials. Furthermore, we present ten years’ experience in paediatric clinical trials and how it has been disrupted during the COVID-19 pandemic. The activity of the ICC has been evaluated according to six metrics of performance. The ICC model offers a complete support, helping investigators, patients and their families to overcome majority of barriers linked to clinical research, even in time of pandemic. We propose this organization as an innovative model for total-supportive and patient-centered clinical trial implementation.</jats:p