Online training and support programs designed to improve mental health and reduce burden among caregivers of people with dementia : a systematic review

Introduction -- Dementia poses a considerable socioeconomic burden to society. On a global scale, family and other unpaid care predominates. Supporting caregivers is crucial, but scalable interventions are currently lacking. Because a growing number of studies have suggested that online training and support programs hold considerable promise for scaling up, we reviewed existing literature. Methods -- We systematically searched 6 databases to identify studies of Internet-based interventions designed to train and support caregivers of people with dementia, and we formally assessed risk of bias. Our prespecified primary outcomes of interest included both mental health and caregiver burden/perceived stress. Our secondary outcomes of interest included knowledge, quality of life of caregivers, quality of care, caregiver response to challenging behaviors, coping, and self-efficacy. Results -- Eight randomized control trials met our inclusion criteria involving over 900 participants. The content and structure of Internet-based interventions, outcome measures, and duration differed markedly, and selection, performance, and reporting biases were varied and on occasion of concern. Six studies reported outcomes in caregivers' mental health outcomes, 3 studies reported burden outcomes. Three studies reported knowledge skills, quality of life and reaction to challenging behaviours, whereas 2 studies reported changes in coping outcomes and self-efficacy. No studies reported outcomes on quality of care. Discussion -- Although there is some evidence that Internet-based interventions can improve mental health outcomes for informal caregivers of people with dementia, marked methodological diversity across studies prevented the robust pooling of the results. A concerted and cohesive approach from all stakeholders is now required to help realize the full potential of this emerging field

Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and pharmacodynamic effects in their potentially additive nature

Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug-drug interactions

Antipsychotic drugs and their effects on cognitive function: protocol for a systematic review, pairwise, and network meta-analysis.

BACKGROUND There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, conventional pairwise meta-analyses will not be sufficient to inform this choice. To fill this gap, we will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomized controlled trials (RCTs) to rank antipsychotics according to their effect on cognitive functioning. METHODS In our NMA, we will include RCTs in patients with schizophrenia or schizophrenia-like psychoses comparing one antipsychotic agent with another antipsychotic agent or placebo that measures cognitive function. We will include studies on patients of every age group, in any phase of illness (e.g., acute or stable, first episode or chronic schizophrenia, in- or outpatients) with an intervention time of at least 3 weeks. The primary outcome will be the composite score of cognitive functioning, preferentially measured with the test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. The secondary outcomes include the seven cognitive domains that the composite score is composed of, as well as functioning and quality of life. Study selection and data extraction will be conducted by at least two independent reviewers. We will use the Cochrane Risk of Bias tool 2 to determine the risk of bias in studies, and we will evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). We will perform NMA using R (package netmeta). We will conduct subgroup and sensitivity analyses to explore the heterogeneity and assess the robustness of our findings. DISCUSSION This systematic review and network meta-analysis aims to inform evidence-based antipsychotic treatment choice for cognitive deficits in schizophrenia patients by analyzing existing RCTs on this subject. The results have the potential to support patients' and physicians' decision-making processes based on the latest available evidence. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42022312483

Antipsychotic Dose Mediates the Association between Polypharmacy and Corrected QT Interval

Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy

Antidepressants, benzodiazepines and azapirones for panic disorder in adults:a network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare individual active drugs (antidepressants, benzodiazepines and azapirones) and placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank treatments for panic disorder (antidepressants, benzodiazepines, azapirones and placebo) according to their effectiveness and acceptability

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550

Psychosocial interventions for post-traumatic stress disorder in refugees and asylum seekers resettled in high-income countries: Systematic review and meta-analysis

Internal funding from the University of Veron

THE VALUE OF EVIDENCE-BASED GUIDELINES IN BRIDGING THE GAP BETWEEN RESEARCH AND PRACTICE: FROM THE DEVELOPMENT OF GRADE RECOMMENDATIONS TO THE EVALUATION OF THEIR IMPLEMENTABILITY A project of knowledge translation in the Verona Department of Mental Health

Titolo Il valore delle linee guida basate sulle evidenze nel superare il gap tra ricerca e pratica: dallo sviluppo di raccomandazioni GRADE alla valutazione della loro implementabilit\ue0. Un progetto di traduzione delle conoscenze all\u2019interno del Dipartimento di Salute Mentale di Verona Background Le evidenze provenienti dalla ricerca non possono da sole determinare le strategie cliniche, ma quando vengono integrate con i bisogni del paziente e le sue preferenze costituiscono un contributo fondamentale per prendere decisioni riguardo la gestione del trattamento ed il miglioramento della qualit\ue0 delle cure fornite. Questo \ue8 in linea con i principi della medicina basata su evidenze. Tuttavia l\u2019accesso e l\u2019utilizzo dei dati provenienti dalla ricerca non \ue8 sempre immediato per la maggior parte dei clinici, e questo pu\uf2 determinare un fallimento nel processo della traduzione dei risultati di ricerca nella pratica clinica; questo \ue8 stato descritto come un gap tra ricerca e pratica, e pu\uf2 avere conseguenze negative per i pazienti, che potrebbero non beneficiare delle pi\uf9 recenti conoscenze mediche. Un valido metodo per colmare questa distanza \ue8 lo sviluppo di linee guida basate su evidenze. Uno degli approcci pi\uf9 utilizzati per aggregare, sintetizzare e valutare la qualit\ue0 delle evidenze provenienti da revisioni sistematiche \ue8 il metodo GRADE (Grading of Recommendations Assessment, Development and Evaluation). Obiettivi I) Sviluppare linee guida basate sulle evidenze che possano costituire un ponte tra risultati della ricerca e la pratica clinica; II) Costruire una metodologia condivisa per la scelta e la gestione dei trattamenti farmacologici nel contesto del Dipartimento di Salute Mentale di Verona (DISM); III) Valutare l\u2019impatto delle linee guida sulla pratica clinica. Metodi \uc8 stato composto un gruppo di lavoro (GDG) formato da psichiatri appartenenti ai quattro servizi del DISM. Il GDG ha prodotto le raccomandazioni con il supporto metodologico e scientifico della Unit\ue0 di Psicofarmacologia Clinica dell\u2019Universit\ue0 di Verona (segreteria scientifica). Dopo aver identificato le situazioni cliniche complesse, in cui fosse avvertito dai clinici il bisogno di linee guida per l\u2019utilizzo dei farmaci, il GDG ha effettuato una revisione della letteratura per ciascun argomento, e la segreteria scientifica ha riassunto le evidenze utilizzando la metodologia GRADE per la produzione di linee guida basate su evidenze di efficacia. Per ogni argomento sono stati inoltre considerati valori, preferenze ed aspetti di fattibilit\ue0 legati al contesto. Le raccomandazioni cos\uec preparate sono state presentate e discusse in due sessioni plenarie con tutto lo staff medico del DISM per raggiungere un consenso ed un accordo sulla versione finale. Successivamente le raccomandazioni sono state distribuite a tutti i clinici del DISM, con la richiesta di tenerne in considerazione i contenuti nella loro pratica clinica di routine. Infine sono stati identificati alcuni indicatori per monitorare il grado di coerenza tra i contenuti delle linee guida e le reali pratiche prescrittive. Risultati Sono state formulate raccomandazioni su 12 argomenti. I risultati della fase di valutazione hanno mostrato che dopo la disseminazione delle linee guida, per alcune di esse l\u2019uso dei farmaci nel DISM segue dei trend che sono coerenti con il contenuto delle stesse, mentre per altre questo non si verifica. Conclusioni Questo progetto di produzione di linee guida include molti aspetti peculiari, tra cui un approccio bottom-up; ci\uf2 significa che i medici sono stati coinvolti fin dalle prime fasi dello sviluppo delle linee guida, a partire dalla scelta degli argomenti sui quali formulare le raccomandazioni. Il progetto \ue8 stato strutturato e condotto con criteri metodologici rigorosi, dalle fasi di scelta degli argomenti e produzione delle raccomandazioni fino alla loro disseminazione e valutazione.Title The value of evidence-based guidelines in bridging the gap between research and practice: from the development of GRADE recommendations to the evaluation of their implementability. A project of knowledge translation in the Verona Department of Mental Health. Background Research evidence alone cannot determine clinical strategies, but when integrated with patients\u2019 clinical needs and wishes, it provides a fundamental input for producing meaningful decisions about treatment management and quality improvement. This is in line with the principles of evidence-based medicine. However, access and use of research findings may not be straightforward for most doctors, and this may determine a failure in the process of translating research findings into practice. This failure has often been described as a gap between evidence and practice, with negative consequences for patients who may not benefit optimally from advances in healthcare. In order to fill this gap, the development of evidence-based treatment guidelines has been suggested as a valuable link between primary research and daily clinical practice. One of the best developed approaches for aggregating, synthesizing and grading the quality of evidence extracted from systematic reviews is the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Objectives I) To develop a set of evidence-based guidelines which may bring research findings into clinical practice; II) To build up a shared strong methodology for choosing and managing pharmacological treatments in the context of the Verona Department of Mental Health; III) To assess guideline impact on clinical practice. Methods A Guideline Development Group (GDG), including representatives of the four Mental Health Services of the Verona Department of Mental Health (DMH), was created. The GDG developed recommendations supported by the Unit of Clinical Psychopharmacology of the University of Verona. After identification of the most problematic clinical situations where recommendations in the field of psychotropic drugs were thought to be needed, the GDG reviewed all available evidence for each topic, and the Scientific Committee summarized the evidence base using the GRADE methodology for the production of recommendations sustained by evidence of efficacy. For each question, values, preferences, and feasibility considerations relating to the local context were also taken into account. Draft recommendations were presented and discussed in two plenary sessions with all medical staff of the DMH in order to reach a consensus and a formal agreement. After that, recommendations were distributed to all clinicians of the DMH, with the request of taking them into consideration in their routine clinical practice. As final step, some indicators were identified to monitor the degree of coherence between what the guidelines report and what is actually done. Results Recommendations were formulated on 12 topics. The results of the evaluation phase showed that after the dissemination of guidelines the use of medicines in the DMH follows a trend that is consistent with the content of their content for some recommendations, but not for others. Conclusions This project of guidelines development included several peculiar aspects, such as a bottom-up approach; this means that physicians were involved since the very initial steps of guideline production, starting from the choice of topics on which formulate recommendations. A methodologically sound procedure, from the phases of guidelines choice and production, to the one of their dissemination and evaluation, was conceptualized and structured. To our knowledge, not many examples of such a methodology are available in the literature