Cognitive behavioural therapy plus standard care versus standard care for persistent aggressive behaviour or agitation in people with schizophrenia

Background: Schizophrenia and other psychoses are thought to be associated with a substantial increase in aggressive behaviour, violence and violent offending. However, acts of aggression or violence committed by people with severe mental illness are rare and circumscribed to a small minority of individuals. We know little about the frequency and variability of violent episodes for people with schizophrenia who present chronic or recurrent aggressive episodes, and of available interventions to reduce such problems. A psychological intervention, cognitive behavioural therapy (CBT), aims to challenge dysfunctional thoughts and has been used since the mid-1970s to improve mental health and emotional disorders. CBT includes different interventional procedures, such as cognitive therapy, elements of behavioural therapy, problem-solving interventions, and coping skills training, among others. Although CBT presents much diversity, interventions are characteristically problem-focused, goal-directed, future-oriented, time-limited (about 12 to 20 sessions over four to six months), and empirically based. CBT has shown clinically beneficial effects in persistent positive and negative symptoms of schizophrenia and its use as an add-on therapy to medication in the treatment of schizophrenia is supported by treatment guidelines. However, several Cochrane Reviews recently concluded that, due to the low quality of evidence available, no firm conclusions can currently be made regarding the effectiveness of adding CBT to standard care for people with schizophrenia, or about CBT compared to other psychosocial treatments for people with schizophrenia. Whereas CBT is not an emergency or crisis intervention that acts immediately on the known or unknown triggers underlying aggressive behaviour, might be a timely treatment used to manage persistent aggression or repeated aggressive episodes in people with schizophrenia. Objectives: To assess the efficacy and safety of cognitive behavioural therapy (CBT) plus standard care versus standard care alone for people with schizophrenia and persistent aggression. Search methods: On 18 January 2023, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed, and WHO ICTRP. We also inspected references of all identified studies for more studies. Selection criteria: All randomised controlled trials comparing CBT plus standard care with standard care alone for people with schizophrenia and persistent aggression. Data collection and analysis: We independently inspected citations, selected studies, extracted data and appraised study quality. For binary outcomes, we calculated risk ratios (RR) and their 95% confidence intervals (CIs). For continuous outcomes we calculated mean differences (MD) and their 95%CIs for outcomes reported with the same measurement scale. Post hoc, for counts over person-time outcomes, we calculated incidence rate ratios (IRRs) and their 95%CIs. If feasible, we combined study outcomes with the random-effects model. We assessed the risk of bias for included studies and created a summary of findings table using the GRADE approach. Main results: We included two studies with 184 participants with psychotic disorder (mainly schizophrenia) and violence. The studies were run in forensic units and prison. Both studies were at high risk of bias on blinding (performance and detection bias). CBT plus standard care as compared with standard care may result in little to no difference in the frequency of physical violence at end of trial (IRR 0.52; 95% CI 0.23 to 1.18) and follow-up (IRR 0.86; 95% CI 0.44 to 1.68). The confidence interval did not exclude the null effect, and the certainty of the evidence is very low due to lack of blinding and to the small sample size. One study reported no deaths in both arms and zero serious and other adverse events. The other study did not report any figure for deaths or adverse events. CBT plus standard care as compared with standard care may result in little to no difference in leaving the study early for any reason (RR 1.04; 95% CI 0.53 to 2.00). Confidence interval did not exclude the null effect and the certainty of the evidence is low due to lack of blinding and the small sample size. Authors' conclusions: Whereas the evidence from only two studies with 184 participants suggests the use of CBT plus standard care may reduce some aggressive behaviours in patients with schizophrenia, the grading of the certainty of the evidence is very low. It implies that there is not yet reliable evidence to guide clinical decisions and therefore more evidence is needed to get a more precise estimate of the effect of the intervention. Currently, we have very little confidence in the effect estimate, and the true effect could be substantially different from its estimate

Update on ocular manifestations of the main monogenic and polygenic autoinflammatory diseases

Autoinflammatory diseases include disorders with a genetic cause and also complex syndromes associated to polygenic or multifactorial factors. Eye involvement is present in many of them, with different extent and severity. The present review covers ophthalmological lesions in the most prevalent monogenic autoinflammatory diseases, including FMF (familial Mediterranean fever), TRAPS (TNF receptor-associated periodic syndrome), CAPS (cryopyrin-associated periodic syndromes), Blau syndrome, DADA2 (deficiency of adenosine deaminase 2), DITRA (deficiency of the interleukin-36 receptor antagonist), other monogenic disorders, including several ubiquitinopathies, interferonopathies, and the recently described ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome, and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Among polygenic autoinflammatory diseases, ocular manifestations have been reviewed in Behçet’s disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, Still’s disease and autoinflammatory bone diseases, which encompass CRMO (chronic recurrent multifocal osteomyelitis) and SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome

Remotely delivered information, training and support for informal caregivers of people with dementia

Many people with dementia are cared for at home by unpaid informal caregivers, usually family members. Caregivers may experience a range of physical, emotional, financial and social harms, which are often described collectively as caregiver burden. The degree of burden experienced is associated with characteristics of the caregiver, such as gender, and characteristics of the person with dementia, such as dementia stage, and the presence of behavioural problems or neuropsychiatric disturbances. It is a strong predictor of admission to residential care for people with dementia. Psychoeducational interventions might prevent or reduce caregiver burden. Overall, they are intended to improve caregivers' knowledge about the disease and its care; to increase caregivers' sense of competence and their ability to cope with difficult situations; to relieve feelings of isolation and allow caregivers to attend to their own emotional and physical needs. These interventions are heterogeneous, varying in their theoretical framework, components, and delivery formats. Interventions that are delivered remotely, using printed materials, telephone or video technologies, may be particularly suitable for caregivers who have difficulty accessing face-to-face services because of their own health problems, poor access to transport, or absence of substitute care. During the COVID-19 pandemic, containment measures in many countries required people to be isolated in their homes, including people with dementia and their family carers. In such circumstances, there is no alternative to remote delivery of interventions. Objectives: To assess the efficacy and acceptability of remotely delivered interventions aiming to reduce burden and improve mood and quality of life of informal caregivers of people with dementia. Search methods: We searched the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE, Embase and four other databases, as well as two international trials registries, on 10 April 2020. We also examined the bibliographies of relevant review papers and published trials. Selection criteria: We included only randomised controlled trials that assessed the remote delivery of structured interventions for informal caregivers who were providing care for people with dementia living at home. Caregivers had to be unpaid adults (relatives or members of the person's community). The interventions could be delivered using printed materials, the telephone, the Internet or a mixture of these, but could not involve any face-to-face contact with professionals. We categorised intervention components as information, training or support. Information interventions included two key elements: (i) they provided standardised information, and (ii) the caregiver played a passive role. Support interventions promoted interaction with other people (professionals or peers). Training interventions trained caregivers in practical skills to manage care. We excluded interventions that were primarily individual psychotherapy. Our primary outcomes were caregiver burden, mood, health-related quality of life and dropout for any reason. Secondary outcomes were caregiver knowledge and skills, use of health and social care resources, admission of the person with dementia to institutional care, and quality of life of the person with dementia. Data collection and analysis: Study selection, data extraction and assessment of the risk of bias in included studies were done independently by two review authors. We used the Template for Intervention Description and Replication (TIDieR) to describe the interventions. We conducted meta-analyses using a random-effects model to derive estimates of effect size. We used GRADE methods to describe our degree of certainty about effect estimates. Main results: We included 26 studies in this review (2367 participants). We compared (1) interventions involving training, support or both, with or without information (experimental interventions) with usual treatment, waiting list or attention control (12 studies, 944 participants); and (2) the same experimental interventions with provision of information alone (14 studies, 1423 participants). We downgraded evidence for study limitations and, for some outcomes, for inconsistency between studies. There was a frequent risk of bias from self-rating of subjective outcomes by participants who were not blind to the intervention. Randomisation methods were not always well-reported and there was potential for attrition bias in some studies. Therefore, all evidence was of moderate or low certainty. In the comparison of experimental interventions with usual treatment, waiting list or attention control, we found that the experimental interventions probably have little or no effect on caregiver burden (nine studies, 597 participants; standardised mean difference (SMD) -0.06, 95% confidence interval (CI) -0.35 to 0.23); depressive symptoms (eight studies, 638 participants; SMD -0.05, 95% CI -0.22 to 0.12); or health-related quality of life (two studies, 311 participants; SMD 0.10, 95% CI -0.13 to 0.32). The experimental interventions probably result in little or no difference in dropout for any reason (eight studies, 661 participants; risk ratio (RR) 1.15, 95% CI 0.87 to 1.53). In the comparison of experimental interventions with a control condition of information alone, we found that experimental interventions may result in a slight reduction in caregiver burden (nine studies, 650 participants; SMD -0.24, 95% CI -0.51 to 0.04); probably result in a slight improvement in depressive symptoms (11 studies, 1100 participants; SMD -0.25, 95% CI -0.43 to -0.06); may result in little or no difference in caregiver health-related quality of life (two studies, 257 participants; SMD -0.03, 95% CI -0.28 to 0.21); and probably result in an increase in dropouts for any reason (12 studies, 1266 participants; RR 1.51, 95% CI 1.04 to 2.20). Authors' conclusions: Remotely delivered interventions including support, training or both, with or without information, may slightly reduce caregiver burden and improve caregiver depressive symptoms when compared with provision of information alone, but not when compared with usual treatment, waiting list or attention control. They seem to make little or no difference to health-related quality of life. Caregivers receiving training or support were more likely than those receiving information alone to drop out of the studies, which might limit applicability. The efficacy of these interventions may depend on the nature and availability of usual services in the study settings

Systematic Review of the Potential of MicroRNAs in Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of invasive non-Hodgkin’s lymphoma (NHL). DLBCL presents with variable backgrounds, which results in heterogeneous outcomes among patients. Although new tools have been developed for the classification and management of patients, 40% of them still have primary refractory disease or relapse. In addition, multiple factors regarding the pathogenesis of this disease remain unclear and identification of novel biomarkers is needed. In this context, recent investigations point to microRNAs as useful biomarkers in cancer. The aim of this systematic review was to provide new insight into the role of miRNAs in the diagnosis, classification, treatment response and prognosis of DLBCL patients. We used the following terms in PubMed„ ((‘Non-coding RNA’) OR (‘microRNA’ OR ‘miRNA’ OR ‘miR’) OR (‘exosome’) OR (‘extracellular vesicle’) OR (‘secretome’)) AND (‘Diffuse large B cell lymphoma’ OR ‘DLBCL’)„ to search for studies evaluating miRNAs as a diagnosis, subtype, treatment response or prognosis biomarkers in primary DLBCL in human patient populations. As a result, the analysis was restricted to the role of miRNAs in tumor tissue and we did not consider circulating miRNAs. A total of thirty-six studies met the inclusion criteria. Among them, twenty-one were classified in the diagnosis category, twenty in classification, five in treatment response and nineteen in prognosis. In this review, we have identified miR-155-5p and miR-21-5p as miRNAs of potential utility for diagnosis, while miR-155-5p and miR-221-3p could be useful for classification. Further studies are needed to exploit the potential of this field

Agreement between clinician-centred and patient-centred depressive symptoms scales

Ponencia en el congreso "31st Congress of the European-College-of-Neuropsychopharmacology (ECNP)

Cognitive improvement of acetylcholinesterase inhibitors in schizophrenia

Background: Schizophrenia is a severe, persistent mental disorder, and a leading cause of disability worldwide. Cognitive impairments presented in schizophrenia lead to a worse prognostic, thus treatments targeted to enhance cognition in schizophrenia may be clinically relevant. Aims: The purpose of this study was to assess the efficacy of acetylcholinesterase inhibitors as add-on medication to antipsychotics on cognition in patients with schizophrenia. Methods: Search strategies were developed for Medline, Embase and Cochrane Central Register of Controlled Trials, and are current to March 2018. We included randomised controlled trials that compared antipsychotics plus acetylcholinesterase inhibitors versus antipsychotics plus placebo on prespecified cognitive domains (speed of processing, attention and working memory). Two review authors independently evaluated study eligibility, extracted data and assessed the risk of bias of included studies. We used random-effects model for meta-analyses and assessed the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We included nine randomised controlled trials. Six randomised controlled trials (n=219) presented evidence that acetylcholinesterase inhibitors improve speed of processing (standardised mean difference -0.52, 95% confidence interval (-0.79 to -0.25); p value=0.0002). However, eight randomised controlled trials (n=252) did find placebo was better than acetylcholinesterase inhibitors in the attention domain (-0.43, (-0.72 to -0.13); p value=0.005) and eight randomised controlled trials (n=273) did not find differences in the working memory (-0.14, (-0.51 to 0.24), p value=0.47). Conclusions: The current evidence is too weak to base recommendations on the use of acetylcholinesterase inhibitors as adjunctive treatments to antipsychotics to improve basic cognitive functions. We have limited confidence in the effect estimates

Which are the risk factors of violence in mental illness? A scoping review

Documento de trabajo sobre psiquiatrí

Variants in the 14q32 miRNA cluster are associated with osteosarcoma risk in the Spanish population

Abstract Association studies in osteosarcoma risk found significant results in intergenic regions, suggesting that regions which do not codify for proteins could play an important role. The deregulation of microRNAs (miRNAs) has been already associated with osteosarcoma. Consequently, genetic variants affecting miRNA function could be associated with risk. This study aimed to evaluate the involvement of all genetic variants in pre-miRNAs described so far in relationship to the risk of osteosarcoma. We analyzed a total of 213 genetic variants in 206 pre-miRNAs in two cohorts of osteosarcoma patients (n = 100) and their corresponding controls (n = 256) from Spanish and Slovenian populations, using Goldengate Veracode technology (Illumina). Four polymorphisms in pre-miRNAs at 14q32 miRNA cluster were associated with osteosarcoma risk in the Spanish population (rs12894467, rs61992671, rs58834075 and rs12879262). Pathway enrichment analysis including target genes of these miRNAs pointed out the WNT signaling pathways overrepresented. Moreover, different single nucleotide polymorphism (SNP) effects between the two populations included were observed, suggesting the existence of population differences. In conclusion, 14q32 miRNA cluster seems to be a hotspot for osteosarcoma susceptibility in the Spanish population, but not in the Slovenian, which supports the idea of the existence of population differences in developing this disease

Individualisation of radiation protection recommendations for patients treated with [177Lu]Lu-DOTA-TATE

Abstract Background As for any other nuclear medicine treatment, patients treated with [177Lu]Lu-DOTA-TATE should be given some radiation protection recommendations after being discharged to limit the dose received by family members and public. The restriction periods will depend on the remaining activity at the time of discharge, the washout rate and patients’ personal conditions. The activity in patients’ whole-body follows a bi-exponential behaviour. At the time of discharge only the first part of the time-activity curve is known. However, the second phase of the bi-exponential curve should be known to individualize the time of restrictions. The main purpose of this prospective study was to establish a simple method for calculating the restriction periods based on measurements taken before discharge. Methods The whole-body time-activity curve was calculated for 20 patients from dose-rate measurements performed during the first week post-administration. An effective decay time $$T_{{{\text{eff}}}}^{6,24}$$ T eff 6 , 24 was calculated from a mono-exponential fit performed with the 6 h and 24 h measurements and compared with the effective decay time $$T_{{{\text{eff}}}}^{24,48,168}$$ T eff 24 , 48 , 168 obtained from the mono-exponential fit performed with the 24 h, 48 h and 168 h measurements. The differences between them were calculated and the 95th percentile of these differences was used as a correction factor for $$T_{{{\text{eff}}}}^{6,24}$$ T eff 6 , 24 . A modified effective decay $$T_{{{\text{eff}},{\text{ mod}}}}^{6,24}$$ T eff , mod 6 , 24 was obtained by adding the correction factor to $$T_{{{\text{eff}}}}^{6,24}$$ T eff 6 , 24 and the restriction periods for each patient was calculated. The whole body activity washout between the first and the fourth treatment cycles of 16 patients was also compared. Results The comparison of the whole-body activity curves between the first and the fourth cycle of the treatment for 16 patients would indicate that the recommendations on radiation protection determined from the first cycle could reasonably be used for the remaining cycles in most patients. The values of $$T_{{{\text{eff}}}}^{6,24}$$ T eff 6 , 24 and $$T_{{{\text{eff}}}}^{24,48,168}$$ T eff 24 , 48 , 168 obtained for the 20 patients were significantly different. The 95th percentile of the differences between $$T_{{{\text{eff}}}}^{6,24}$$ T eff 6 , 24 and $$T_{{{\text{eff}}}}^{24,48,168}$$ T eff 24 , 48 , 168 was 46 h, which is thus the time to be added to $$T_{{{\text{eff}}}}^{6,24}$$ T eff 6 , 24 so as to determine the restriction periods. Conclusions The proposed method makes it possible to calculate the restriction periods for patients treated with [177Lu]Lu-DOTA-TATE before they leave the hospital in a conservative and individualized way

Variants in the 14q32 miRNA cluster are associated with osteosarcoma risk in the Spanish population.

Association studies in osteosarcoma risk found significant results in intergenic regions, suggesting that regions which do not codify for proteins could play an important role. The deregulation of microRNAs (miRNAs) has been already associated with osteosarcoma. Consequently, genetic variants affecting miRNA function could be associated with risk. This study aimed to evaluate the involvement of all genetic variants in pre-miRNAs described so far in relationship to the risk of osteosarcoma. We analyzed a total of 213 genetic variants in 206 pre-miRNAs in two cohorts of osteosarcoma patients (n = 100) and their corresponding controls (n = 256) from Spanish and Slovenian populations, using Goldengate Veracode technology (Illumina). Four polymorphisms in pre-miRNAs at 14q32 miRNA cluster were associated with osteosarcoma risk in the Spanish population (rs12894467, rs61992671, rs58834075 and rs12879262). Pathway enrichment analysis including target genes of these miRNAs pointed out the WNT signaling pathways overrepresented. Moreover, different single nucleotide polymorphism (SNP) effects between the two populations included were observed, suggesting the existence of population differences. In conclusion, 14q32 miRNA cluster seems to be a hotspot for osteosarcoma susceptibility in the Spanish population, but not in the Slovenian, which supports the idea of the existence of population differences in developing this disease