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.

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

BACKGROUND: 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.

ANTECEDENTES: Muchas personas con demencia son atendidas en casa por cuidadores informales no remunerados, generalmente miembros de la familia. Los cuidadores pueden sufrir una serie de efectos perjudiciales físicos, emocionales, económicos y sociales, que a menudo se describen colectivamente como una carga para el cuidador. El grado de carga que se experimenta está asociado con las características del cuidador, como el género, y con las características de la persona con demencia, como la etapa de la demencia, y la presencia de problemas de comportamiento o trastornos neuropsiquiátricos. Es un fuerte predictor del ingreso en una residencia para personas con demencia. Las intervenciones psicoeducativas pueden prevenir o reducir la carga del cuidador. En general, tienen como objetivo mejorar los conocimientos de los cuidadores sobre la enfermedad y su cuidado; aumentar el sentido de competencia de los cuidadores y su capacidad para afrontar situaciones difíciles; aliviar los sentimientos de aislamiento y permitir que los cuidadores atiendan sus propias necesidades emocionales y físicas. Estas intervenciones son heterogéneas y varían en su marco teórico, sus componentes y sus formatos de administración. Las intervenciones que se realizan a distancia, utilizando material impreso, el teléfono o las tecnologías de vídeo, pueden ser particularmente adecuadas para los cuidadores que tienen dificultades para acceder a los servicios de forma presencial debido a sus propios problemas de salud, al escaso acceso al transporte o a la falta de un cuidado alternativo. Durante la pandemia de covid­19, las medidas de contención en muchos países exigían que las personas estuvieran aisladas en sus hogares, incluidas las personas con demencia y sus familiares cuidadores. En tales circunstancias, no hay alternativa a la realización de intervenciones a distancia. OBJETIVOS: Evaluar la eficacia y la aceptabilidad de las intervenciones realizadas a distancia con el fin de reducir la carga y mejorar el estado de ánimo y la calidad de vida de los cuidadores informales de personas con demencia. MÉTODOS DE BÚSQUEDA: El 10 de abril de 2020 se realizaron búsquedas en el Registro especializado del Grupo Cochrane de Demencia y trastornos cognitivos (Cochrane Dementia and Cognitive Improvement Group), MEDLINE, Embase y otras cuatro bases de datos, así como en dos registros internacionales de ensayos. También se examinaron las bibliografías de documentos de revisión pertinentes y de ensayos publicados. CRITERIOS DE SELECCIÓN: Sólo se incluyeron los ensayos controlados aleatorizados que evaluaron la administración a distancia de intervenciones estructuradas para los cuidadores informales que atendían a personas con demencia que vivían en el domicilio. Los cuidadores debían ser adultos no remunerados (parientes o miembros de la comunidad de la persona). Las intervenciones se podían realizar utilizando materiales impresos, el teléfono, la internet o una mezcla de estos, pero no podían implicar un contacto presencial con profesionales. Los componentes de la intervención se clasificaron como información, formación o apoyo. Las intervenciones de información incluyeron dos elementos clave: i) proporcionaron información estandarizada, y ii) el cuidador desempeñaba un papel pasivo. Las intervenciones de apoyo promovieron la interacción con otras personas (profesionales o iguales). Las intervenciones de formación entrenaron a los cuidadores en habilidades prácticas para proporcionar la atención. Se excluyeron las intervenciones que consistieron principalmente en psicoterapia individual. Los desenlaces principales fueron la carga del cuidador, el estado de ánimo, la calidad de vida relacionada con la salud y el abandono por cualquier motivo. Los desenlaces secundarios fueron los conocimientos y aptitudes de los cuidadores, la utilización de los recursos de atención sanitaria y social, el ingreso de la persona con demencia en una institución y la calidad de vida de la persona con demencia. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión realizaron de forma independiente la selección de los estudios, la extracción de los datos y la evaluación del riesgo de sesgo de los estudios incluidos. Se utilizó la Template for Intervention Description and Replication (TIDieR) para describir las intervenciones. Los metanálisis se realizaron mediante un modelo de efectos aleatorios para obtener las estimaciones del tamaño del efecto. Se utilizaron los métodos GRADE para describir el grado de certeza sobre las estimaciones del efecto. RESULTADOS PRINCIPALES: En esta revisión se incluyeron 26 estudios (2367 participantes). Se compararon (1) las intervenciones que incluyeron formación, apoyo o ambos, con o sin información (intervenciones experimentales) con el tratamiento habitual, una lista de espera o el control de la atención (12 estudios, 944 participantes); y (2) las mismas intervenciones experimentales con el suministro de información solamente (14 estudios, 1423 participantes). La calidad de la evidencia se redujo por las limitaciones de los estudios y, en el caso de algunos desenlaces, por la falta de consistencia entre los estudios. Hubo un riesgo frecuente de sesgo debido a la autocalificación de los desenlaces subjetivos por parte de participantes que no estaban cegados a la intervención. Los métodos de asignación al azar no siempre se informaron bien y hubo un posible sesgo de desgaste en algunos estudios. Por lo tanto, toda la evidencia fue de certeza moderada o baja. En la comparación de las intervenciones experimentales con el tratamiento habitual, una lista de espera o el control de la atención, se encontró que las intervenciones experimentales probablemente tienen poco o ningún efecto sobre la carga del cuidador (nueve estudios, 597 participantes; diferencia de medias estandarizada [DME] ­0,06; intervalo de confianza [IC] del 95%: ­0,35 a 0,23); los síntomas depresivos (ocho estudios, 638 participantes; DME ­0,05; IC del 95%: ­0,22 a 0,12) o la calidad de vida relacionada con la salud (dos estudios, 311 participantes; DME 0,10; IC del 95%: ­0,13 a 0,32). Las intervenciones experimentales probablemente dan lugar a poca o ninguna diferencia en el abandono por cualquier motivo (ocho estudios, 661 participantes; razón de riesgos [RR] 1,15; IC del 95%: 0,87 a 1,53). En la comparación de las intervenciones experimentales con una condición control de información sola, se encontró que las intervenciones experimentales pueden dar lugar a una leve reducción de la carga del cuidador (nueve estudios, 650 participantes; DME ­0,24; IC del 95%: ­0,51 a 0,04); probablemente dan lugar a una leve mejoría de los síntomas depresivos (11 estudios, 1100 participantes; DME ­0,25; IC del 95%: ­0,43 a ­0,06); podrían dar lugar a poca o ninguna diferencia en la calidad de vida relacionada con la salud de los cuidadores (dos estudios, 257 participantes; DME ­0,03; IC del 95%: ­0,28 a 0,21); y probablemente dé lugar a un aumento de los abandonos por cualquier motivo (12 estudios, 1266 participantes; RR 1,51; IC del 95%: 1,04 a 2,20). CONCLUSIONES DE LOS AUTORES: Las intervenciones realizadas a distancia, como el apoyo, la formación o ambas, con o sin información, podrían reducir ligeramente la carga del cuidador y mejorar los síntomas depresivos del cuidador en comparación con el suministro de información únicamente, pero no en comparación con el tratamiento habitual, una lista de espera o el control de la atención. Parecen dar lugar a poca o ninguna diferencia en la calidad de vida relacionada con la salud. Los cuidadores que recibieron formación o apoyo tuvieron más probabilidades de abandonar los estudios que los que recibieron sólo información, lo que podría limitar la aplicabilidad. La eficacia de esas intervenciones puede depender de la naturaleza y la disponibilidad de los servicios habituales en los ámbitos de estudio.

Apomorphine for the Treatment of Erectile Dysfunction: Systematic Review and Meta-Analysis.

Sublingual apomorphine could be an option in patients with erectile dysfunction who cannot take phosphodiesterase type 5 inhibitors (e.g., using nitrates). We have completed a systematic review to evaluate the effects of sublingual apomorphine comparing with placebo for treating erectile dysfunction. The evidence searching process finished on 9 January 2019. We included nine randomized controlled trials (RCTs). Treatment length varied from 4 to 8 weeks and doses ranged from 2 to 6 mg. The percent of successful sexual intercourse attempts per ingested dose of apomorphine was evaluated in eight studies. All the studies found that apomorphine was better than placebo (6-27% more successful intercourse attempts than with placebo), but differences were not statistically significant in one study done in patients previously treated with radical prostatectomy. Regarding erectile function scores, three studies reported higher improvement on the erectile function scores for apomorphine. Differences with placebo were not clinically relevant in another two studies, one in which only diabetic patients were included and one in which only patients with radical prostatectomy were involved. Discontinuation of treatment due to adverse events was higher for apomorphine, particularly for higher doses. Available evidence suggests that sublingual apomorphine is more effective than placebo, except for patients previously treated with radical prostatectomy, and is generally well tolerated at doses of 2 or 3 mg. Nowadays, sublingual apomorphine is the only licensed oral drug for erectile dysfunction not absolutely contraindicated with nitrates use, and more RCTs should be performed to evaluate its effects and safety for treating ED.

Underlying dimensions of the EORTC QLQ-C30 in a Cuban population of patients with advanced non-small cell lung cancer.

BACKGROUND: Quality of Life Core Questionnaire of the European Organization for the Research and Treatment of Cancer (EORTC QLQ-C30) is one of the most used quality of life questionnaires in cancer studies. It provides scores for five functional scales, nine symptom scales, and two single items which assess overall health status and quality of life. However, high correlations among QLQ-C30 items suggest a reduced dimensionality for the scale. OBJECTIVE: To assess the dimensionality of the EORTC QLQ-C30 using item response theory (IRT) in a training sample and confirmatory factor analysis (CFA) in a test sample. METHODS: We analyzed responses to QLQ-C30 from 1,107 patients with advanced lung cancer who were included in five clinical trials of immunotherapy. We used non-parametric and parametric IRT models (Mokken, and Samejima's graded response) in a random training set (n = 332) for initial assessment of dimensions and item characteristics of the QLQ-C30. Finally, we used CFA in the test set (n = 775) to confirm the measurement domains. RESULTS: Mokken model showed that QLQ-C30 fits a unidimensional scale, whereas Samejima model showed that most QLQ-C30 items present adequate difficulty and discrimination. All items showed adequate scalability indexes with an overall scalability of 0.47 (medium scale). The QLQ-C30-reduced dimensionality was confirmed by CFA (comparative fit index = 0.98, root mean square error of approximation = 0.055) with all items presenting factorial loadings > 0.40. CONCLUSIONS: The EORTC QLQ-C30 fits a unidimensional latent construct identified with perceived quality of life in advanced lung cancer patients. TRIAL REGISTRATION: RPCEC00000161, RPCEC00000181 and RPCEC00000205.

Efficacy of Sertraline in Patients With Major Depressive Disorder Naive to Selective Serotonin Reuptake Inhibitors: A 10-Week Randomized, Multicenter, Placebo-Controlled, Double-Blind, Academic Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy and safety of sertraline compared with placebo in a good clinical practice trial conducted with major depressive disorder patients naive to selective serotonin reuptake inhibitors. METHODS: This was a 10-week randomized, multicenter, placebo-controlled, double blind, superiority trial. Adult patients diagnosed with major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria), total score of 19 to 36 in the 17-item Hamilton Depression Rating Scale (HAMD-17), were randomly allocated to sertraline (n = 39) or placebo (n = 38). Each patient received a fixed dose of sertraline 50 mg/d or placebo for 4 weeks. Afterward a flexible dose up to 200 mg/d was allowed if needed. The primary efficacy end point was clinical response defined as 50% score reduction in HAMD-17 at 10 weeks relative to baseline. Supplementary analysis was performed on HAMD-17 score change from baseline. FINDINGS: The clinical response favored sertraline (72% vs 32%; relative risk, 2.27; 95% confidence interval, 1.37-3.78; P = 0.0006). A linear mixed model showed arm × time interaction was significant (likelihood ratio test χ on 7 df = 48.42, P < 0.0001). The HAMD-17 change score favored sertraline from week 8 onwards. The most frequent adverse events in the sertraline arm were headache, diarrheas, and weight loss. IMPLICATIONS: In this trial, the benefit of sertraline compared with placebo appeared later than usual. The therapeutic process with a close doctor-patient relationship throughout the trial and the effect expectancy due to a new treatment might explain the response delay. TRIAL REGISTRATION: RPCEC, ID no. 00000128.

Cognitive Impairment in Patients With Neuropsychiatric and Non-neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its most prevalent manifestation is neuropsychiatric SLE (NP-SLE), which is characterized by increased involvement of the nervous system, with relevant symptoms, such as marked cognitive deficits, which are directly involved in subsequent functional disability. The objective of this study is to identify and compare the profile of cognitive deficits in patients with NP-SLE and patients with non-neuropsychiatric SLE (nonNP-SLE) by means of a systematic review and meta-analysis. METHODS: We performed a systematic literature search based on the key words "cogn* OR neurocogn* AND lupus AND neuropsychiatry*" and included articles published between April 1999 and December 2016. A total of 244 articles were retrieved. We excluded reviews and meta-analyses, experiments not performed in humans, and single case reports. We included studies that used standardized cognitive measures and had included at least the subgroups NP-SLE and non NP-SLE. RESULTS: The meta-analysis was finally based on six studies, and 10 neuropsychological variables were examined. Significant differences were observed between the groups for six variables. In the remaining four variables, we observed marked heterogeneity between the groups or a low number of studies. CONCLUSIONS: The data obtained indicate greater cognitive impairment among NP-SLE patients than among nonNP-SLE patients, at least for the cognitive domains of visuomotor coordination, attention, executive function, visual learning and memory, and phonetic fluency. The identification and definition of cognitive deficits in SLE patients is necessary to develop adequate cognitive remediation programs to improve functional outcomes. (JINS, 2018, 24, 629-639).

Psychometric properties of the SDM-Q-9 questionnaire for shared decision-making in multiple sclerosis: item response theory modelling and confirmatory factor analysis.

BACKGROUND: Shared decision-making is a cornerstone of patient-centred care. The 9-item Shared Decision-Making Questionnaire (SDM-Q-9) is a brief self-assessment tool for measuring patients' perceived level of involvement in decision-making related to their own treatment and care. Information related to the psychometric properties of the SDM-Q-9 for multiple sclerosis (MS) patients is limited. The objective of this study was to assess the performance of the items composing the SDM-Q-9 and its dimensional structure in patients with relapsing-remitting MS. METHODS: A non-interventional, cross-sectional study in adult patients with relapsing-remitting MS was conducted in 17 MS units throughout Spain. A nonparametric item response theory (IRT) analysis was used to assess the latent construct and dimensional structure underlying the observed responses. A parametric IRT model, General Partial Credit Model, was fitted to obtain estimates of the relationship between the latent construct and item characteristics. The unidimensionality of the SDM-Q-9 instrument was assessed by confirmatory factor analysis. RESULTS: A total of 221 patients were studied (mean age = 42.1 ± 9.9 years, 68.3% female). Median Expanded Disability Status Scale score was 2.5 ± 1.5. Most patients reported taking part in each step of the decision-making process. Internal reliability of the instrument was high (Cronbach's α = 0.91) and the overall scale scalability score was 0.57, indicative of a strong scale. All items, except for the item 1, showed scalability indices higher than 0.30. Four items (items 6 through to 9) conveyed more than half of the SDM-Q-9 overall information (67.3%). The SDM-Q-9 was a good fit for a unidimensional latent structure (comparative fit index = 0.98, root-mean-square error of approximation = 0.07). All freely estimated parameters were statistically significant (P < 0.001). All items presented standardized parameter estimates with salient loadings (>0.40) with the exception of item 1 which presented the lowest loading (0.26). Items 6 through to 8 were the most relevant items for shared decision-making. CONCLUSIONS: The SDM-Q-9 presents appropriate psychometric properties and is therefore useful for assessing different aspects of shared decision-making in patients with multiple sclerosis.

Assessment of the consequences of caregiving in psychosis: a psychometric comparison of the Zarit Burden Interview (ZBI) and the Involvement Evaluation Questionnaire (IEQ).

BACKGROUND: The Zarit Burden Interview (ZBI) was originally developed to assess the level of subjective burden in caregivers of people with dementia. The Involvement Evaluation Questionnaire (IEQ) is amongst the leading scales to assess caregiving consequences in severe mental illness. We aimed to compare the psychometric properties of the ZBI, a generic tool, and of the IEQ, a more specific tool to assess the consequences of caregiving in schizophrenia and related disorders. METHODS: Secondary analyses of a 16-week, randomized controlled trial of a psychoeducational intervention in 223 primary caregivers of patients with schizophrenia or schizoaffective disorder. Psychometric properties (internal consistency, convergent and discriminative validity, and sensitivity to change) were evaluated for both ZBI and IEQ. RESULTS: Internal consistency was good and similar for both scales (ZBI: 0.91, 95% CI: 0.89, 0.94; IEQ: 0.86, 95% CI: 0.83, 0.89). Convergent validity was relevant for similar domains (e.g. ZBI total score vs IEQ-tension r = 0.69, 95% CI: 0.61, 0.75) and at least moderate for the rest of domains (ZBI total score, personal strain and role strain vs IEQ-urging and supervision). Discriminative validity against psychological distress and depressive symptoms was good (Area Under the Curve [AUC]: 0.77, 95% CI: 0.71, 0.83; and 0.69, 95% CI: 0.63, 0.78 - for ZBI against GHQ-28 and CES-D respectively; and AUC: 0.72, 95% CI: 0.65, 0.78; and 0.69, 95% CI: 0.62, 0.77 - for IEQ against GHQ-28 and CES-D respectively). AUCs against the reference criteria did not differ significantly between the two scales. After the intervention, both scales showed a significant decrease at endpoint (p-values < 0.001) with similar standardised effect sizes for change (-0.36, 95% CI: -0.58, -0.15 - for ZBI; -0.39, 95% CI: -0.60, -0.18 - for IEQ). CONCLUSIONS: Both ZBI and IEQ have shown satisfactory psychometric properties to assess caregiver burden in this sample. We provided further evidence on the performance of the ZBI as a general measure of subjective burden. TRIAL REGISTRATION: ( ISRCTN32545295 ).

MS/MS networking guided analysis of molecule and gene cluster families.

The ability to correlate the production of specialized metabolites to the genetic capacity of the organism that produces such molecules has become an invaluable tool in aiding the discovery of biotechnologically applicable molecules. Here, we accomplish this task by matching molecular families with gene cluster families, making these correlations to 60 microbes at one time instead of connecting one molecule to one organism at a time, such as how it is traditionally done. We can correlate these families through the use of nanospray desorption electrospray ionization MS/MS, an ambient pressure MS technique, in conjunction with MS/MS networking and peptidogenomics. We matched the molecular families of peptide natural products produced by 42 bacilli and 18 pseudomonads through the generation of amino acid sequence tags from MS/MS data of specific clusters found in the MS/MS network. These sequence tags were then linked to biosynthetic gene clusters in publicly accessible genomes, providing us with the ability to link particular molecules with the genes that produced them. As an example of its use, this approach was applied to two unsequenced Pseudoalteromonas species, leading to the discovery of the gene cluster for a molecular family, the bromoalterochromides, in the previously sequenced strain P. piscicida JCM 20779(T). The approach itself is not limited to 60 related strains, because spectral networking can be readily adopted to look at molecular family-gene cluster families of hundreds or more diverse organisms in one single MS/MS network.

Efficacy of MLC601 on functional recovery after stroke: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Traditional Chinese medicine (TCM) MLC601 has shown promising results on functional recovery of patients after stroke. This study aimed to evaluate the pooled effect of its efficacy. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) assessing efficacy of MLC601 vs other TCM compounds or placebo. The pooled effect was the relative risk (RR) combined by random effects model. A prediction effect interval was estimated for new studies and a cumulative meta-analysis was performed. RESULTS: Four studies comprising five RCTs were included. The pooled RR was 1.64 (95% CI = 1.05-2.57; p-value = 0.031) favouring MLC601, but heterogeneity was large (I(2) = 80%; Q-test p-value = 0.0005). Therefore, the prediction interval was wide and consistent with a null effect (RR range = 0.36-7.45). The cumulative meta-analysis showed a decreasing pattern of effect size through time, with higher effects for trials comparing MLC601 vs other TCM and a systematic decrease of the pooled effect when including later trials comparing MLC601 vs placebo. CONCLUSIONS: Evidence on the efficacy of MLC601 has decreased over time and when the comparison arm is placebo instead of other TCM compound. Current evidence suggests MLC601 does not outperform placebo on functional recovery after stroke.

L-acetylcarnitine for treating fragile X syndrome.

BACKGROUND: People with fragile X syndrome (FXS) have an intellectual dysfunction that can range from very mild to severe. Symptoms can include speech and language delays and behavioural difficulties such as aggression or self injurious behaviours, emotional lability, and anxiety-related problems (for example obsessive-compulsive symptoms and perseverative behaviours). In some cases, affected people may have an additional diagnosis of attention deficit hyperactivity disorder or an autism spectrum disorder. OBJECTIVES: To review the efficacy and safety of L-acetylcarnitine in improving the psychological, intellectual, and social performance of people with FXS. SEARCH METHODS: In May 2015 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, Web of Science, and two other databases. We also searched three trials registers, four theses databases, and the reference lists of relevant studies and reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed the efficacy of L-acetylcarnitine, at any dose, in people of any age diagnosed with FXS compared with placebo. DATA COLLECTION AND ANALYSIS: For each trial, two review authors independently extracted data on the children included and interventions compared, and assessed the risk of bias of the studies across the following domains: randomisation sequence generation, allocation concealment, blinding (of participants, personnel, and outcome assessors), incomplete outcome data, selective outcome reporting, and other potential sources of bias. MAIN RESULTS: We found only two RCTs that compared oral L-acetylcarnitine (LAC) with oral placebo in children with FXS. The studies included a total of 83 participants, all of them male, who were treated and followed for one year. The age of participants at the start of treatment ranged from 6 to 13 years, with a mean age of 9 years. Neither study provided information on randomisation, allocation concealment procedures, or blinding of outcome assessment, and we received no responses from the authors we emailed for clarification. We therefore rated studies as being at unclear risk of bias on these domains. We judged both studies to be at low risk of bias for blinding of participants and personnel, incomplete outcome data, and selective reporting, but to be at high risk of other bias, as at least one study was funded by a drug company, and in both studies people working for the company were part of the research team.We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of the available evidence. Overall, the quality of the evidence was low due to the imprecision of results and high risk of other bias.Regarding the primary outcome of psychological and learning capabilities, both studies assessed the effect of interventions on children's verbal and non-verbal intellectual functioning using the Wechsler Intelligence Scale for Children - Revised. The authors did not provide detailed data on those results but said that they found no important differences between treatment and placebo.Both studies evaluated the impact of the treatment on hyperactive behaviour using the Conners' Abbreviated Parent-Teacher Questionnaire. In one study, teachers' assessments of the children found no clear evidence of a difference (mean difference (MD) 0.50, 95% confidence interval (CI) -5.08 to 6.08, n = 51; low-quality evidence). The other study stated that there were no differences between treated and untreated participants, but did not provide detailed data for inclusion in the meta-analysis.Parents' assessments favoured LAC in one study (MD -0.57, 95% CI -0.94 to -0.19, n = 17; low-quality evidence), but not in the other (MD -2.80, 95% CI -7.61 to 2.01, n = 51; low-quality evidence), though changes were not large enough to be considered clinically relevant.Regarding social skills, one study reported no clear evidence of a difference in Vineland Adaptive Behavior composite scores (MD 8.20, 95% CI -0.02 to 16.42, n = 51; low-quality evidence), yet results in the socialisation domain favoured LAC (MD 11.30, 95% CI 2.52 to 20.08, n = 51; low-quality evidence).Both studies assessed the safety of the active treatment and recorded no side effects. Neither of the included studies assessed the secondary outcome of caregiver burden. AUTHORS' CONCLUSIONS: Low-quality evidence from two small trials showed that when compared to placebo, LAC may not improve intellectual functioning or hyperactive behaviour in children with FXS.

Suicidal ideation in patients with fibromyalgia: a cross-sectional study.

Chronic pain, sleep disturbances, and depression, which are relevant symptoms of fibromyalgia syndrome, have been demonstrated to be associated with an increased likelihood of suicidal behaviors. Mortality from suicide has been shown to be greater among patients with fibromyalgia. This study aimed to assess the prevalence of suicidal ideation among a sample of patients with fibromyalgia and to evaluate its relationship with the clinical symptomatology of fibromyalgia. Baseline data from fibromyalgia patients willing to participate in different clinical studies were collected. Outcome measures included the Fibromyalgia Impact Questionnaire, the Beck Depression Inventory, the Pittsburgh Sleep Quality Index, the Brief Pain Inventory, and the SF-12 Health Survey. The scores for these scales were compared between patients with and without suicidal ideation. The presence of suicidal ideation was assessed using the answer provided to item 9 of the Beck Depression Inventory. The results were adjusted by age, sex, total comorbidity, and time since diagnosis with multiple linear regression. The sample comprised 373 patients of whom one hundred and seventy-nine (48%) reported suicidal ideation: 148 (39.7%) reported passive suicidal ideation and 31 (8.3%) active suicidal ideation. Suicidal ideation was markedly associated with depression, anxiety, sleep quality, and global mental health, whereas only weak relationships were observed between suicidal ideation and both pain and general physical health.

Is there a subgroup of long-term evolution among patients with advanced lung cancer?: hints from the analysis of survival curves from cancer registry data.

BACKGROUND: Recently, with the access of low toxicity biological and targeted therapies, evidence of the existence of a long-term survival subpopulation of cancer patients is appearing. We have studied an unselected population with advanced lung cancer to look for evidence of multimodality in survival distribution, and estimate the proportion of long-term survivors. METHODS: We used survival data of 4944 patients with non-small-cell lung cancer (NSCLC) stages IIIb-IV at diagnostic, registered in the National Cancer Registry of Cuba (NCRC) between January 1998 and December 2006. We fitted one-component survival model and two-component mixture models to identify short- and long- term survivors. Bayesian information criterion was used for model selection. RESULTS: For all of the selected parametric distributions the two components model presented the best fit. The population with short-term survival (almost 4 months median survival) represented 64% of patients. The population of long-term survival included 35% of patients, and showed a median survival around 12 months. None of the patients of short-term survival was still alive at month 24, while 10% of the patients of long-term survival died afterwards. CONCLUSIONS: There is a subgroup showing long-term evolution among patients with advanced lung cancer. As survival rates continue to improve with the new generation of therapies, prognostic models considering short- and long-term survival subpopulations should be considered in clinical research.

Effectiveness of a psychoeducational intervention group program in the reduction of the burden experienced by caregivers of patients with dementia: the EDUCA-II randomized trial.

We conducted a multicenter, prospective, evaluator-blinded, 2-arm parallel randomized trial to compare the effectiveness of a group psychoeducational intervention (PIP) with that of standard care in dementia caregivers. The primary outcome was the burden experience evaluated by the Zarit Burden Interview. Secondary outcomes were psychological distress evaluated with the scaled General Health Questionnaire-28 items, and quality of life evaluated with the Short-Form Health Survey 12. Effectiveness endpoint was at 4 months since inception. Statistical analyses used complete case and intention-to-treat analysis (ITT). The trial recruited 238 caregivers from 22 research sites (115 randomized to PIP, 123 randomized to standard care). No differences were found in the Zarit Burden Interview scores (complete case analysis: mean difference=-1.02, 95% confidence interval=-4.41 to 2.37; ITT analysis: MD=-0.55, 95% confidence interval=-3.64 to 2.55), the Short-Form Health Survey 12 domain scores (all P>0.05), and total General Health Questionnaire-28 items scores and some of its subscales (all P>0.05) except the anxiety and insomnia subscale for the ITT analysis (P=0.03). In summary, PIP in modality of group intervention was not better than standard care to reduce caregiver burden and overall psychological distress or to improve quality-of-life domains. EDUCA-II trial registry: ISRCTN14411440.

Common errors in statistics and methods.

As statistical reviewers and editors for BMJ Paediatrics Open (BMJPO), we frequently see methodological and statistical errors in articles submitted to our journal. To make a list of these common errors and propose suitable corrections, and inspired by similar efforts at other leading journals, we surveyed the statistical reviewers and editors at BMJPO to collect their 'pet peeves' and examples of best practices.(1, 2) We have divided these into seven sections: graphics; statistical significance and related issues; presentation, vocabulary, textual and tabular presentation; causality; model building, regression and choice of methods; meta-analysis; and miscellaneous. Here, we present the common errors, with brief explanations. We hope that the guidance provided here will help guide authors as they prepare their submissions to the journal, leading to higher quality and more robust research reporting.

Effectiveness of neural mobilisation for the treatment of nerve-related cervicobrachial pain: a systematic review with subgroup meta-analysis.

ABSTRACT: Neural mobilisations (NM) have been advocated for the treatment of nerve-related cervicobrachial pain; however, it is unclear what types of patients with nerve-related cervicobrachial pain (if any) may benefit. Medline, Web of Science, Scopus, PeDro, Cinahl, and Cochrane databases were searched from inception until December 2022. Randomised controlled trials were included if they assessed the effectiveness of NM in nerve-related cervicobrachial pain, and outcome measures were pain intensity and/or disability. Studies were classified according to their inclusion/exclusion criteria as radiculopathy , Wainner cluster , Hall , and Elvey cluster or other . Meta-analyses with subgroup analyses were performed. Risk of bias was assessed using Cochrane Rob2 tool. Twenty-seven studies were included. For pain and disability reduction, NM was found to be more effective than no treatment (pooled pain mean difference [MD] = -2.81, 95% confidence interval [CI] = -3.81 to -1.81; pooled disability standardized mean difference = -1.55, 95% CI = -2.72 to -0.37), increased the effectiveness of standard physiotherapy as an adjuvant when compared with standard physiotherapy alone (pooled pain MD = -1.44, 95% CI = -1.98 to -0.89; pooled disability MD = -11.07, 95% CI = -16.38 to -5.75) but was no more effective than cervical traction (pooled pain MD = -0.33, 95% CI = -1.35 to 0.68; pooled disability MD = -10.09, 95% CI = -21.89 to 1.81). For disability reduction, NM was found to be more effective than exercise (pooled MD = -18.27, 95% CI = -20.29 to -17.44). In most comparisons, there were significant differences in the effectiveness of NM between the subgroups. Neural mobilisations was consistently more effective than all alternative interventions (no treatment, traction, exercise, and standard physiotherapy alone) in 13 studies classified as Wainner cluster . PROSPERO registration: CRD42022376087.

Assessing illness-related uncertainty in relapsing-remitting multiple sclerosis: A psychometric analysis of the Mishel Uncertainty of Illness Scale.

A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.

Impact on the time elapsed since SARS-CoV-2 infection, vaccination history, and number of doses, on protection against reinfection.

SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection + vaccination) is affected by the moment of vaccination and number of doses received. We conducted a retrospective study in 746 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(tRI) between unvaccinated, vaccinated before 6 months, and later; and comparing one, two or three doses (incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan-Meier estimator. Also, an adjusted Cox-regression was performed to evaluate the risk of reinfection in all groups. The tRI was significantly higher in those vaccinated vs. non-vaccinated (p < 0.001). However, an early incomplete regime protects similar time than not receiving a vaccine. Vaccination before 6 months after infection showed a lower tRI compared to those vaccinated later with the same regime (adj-p < 0.001). Actually, early vaccination with complete and booster regimes provided lower length of protection compared to vaccinating later with incomplete and complete regime, respectively. Vaccination with complete and booster regimes significantly increases the tRI (adj-p < 0.001). Vaccination increases the time it takes for a person to become reinfected with SARS-CoV-2. Increasing the time from infection to vaccination increases the time in which a person could be reinfected and reduces the risk of reinfection, especially in complete and booster regimes. Those results emphasize the role of vaccines and boosters during the pandemic and can guide strategies on future vaccination policy.

Polymorphisms in the methotrexate transport pathway: a new tool for MTX plasma level prediction in pediatric acute lymphoblastic leukemia.

OBJECTIVES: Methotrexate (MTX) is an important component of therapy for pediatric acute lymphoblastic leukemia (ALL). Treatment with MTX often causes toxicity, which can necessitate dose reduction or treatment cessation. Interindividual differences in adverse reactions can be due to different factors, including polymorphisms in key genes. Recently, we confirmed the association between SLCO1B1 rs11045879 polymorphism and toxicity previously proposed by Treviño and colleagues. As SLCO1B1 is a transporter involved in MTX elimination, other polymorphisms in genes from this pathway could also have a role in MTX toxicity. The aim of the present study was to analyze in depth the role of polymorphisms in the genes of the MTX transport pathway as putative toxicity predictors in pediatric ALL. METHODS: We analyzed 384 single nucleotide polymorphisms in 12 transporter genes (SLCO1B1, SLCO1B3, SLCO1A2, ABCB1, ABCG2, ABCC1, ABCC2, ABCC3, ABCC4, SLC19A1, SLC22A6 and SLC22A8) and their correlation with different toxicity parameters in 151 pediatric ALL patients treated using the LAL/SHOP protocol. RESULTS: A significant association with MTX plasma levels was found for 21 polymorphisms from seven genes and 15 haplotypes. After correction, rs9516519 in ABCC4, rs3740065 in ABCC2, and haplotype GCGGG in ABCC2 remained significantly associated. CONCLUSION: Our results suggest that polymorphisms in ABCC4 and ABCC2 could be novel markers for MTX toxicity in pediatric ALL.

Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial.

BACKGROUND: The prognosis of patients bearing high grade glioma remains dismal. Epidermal Growth Factor Receptor (EGFR) is well validated as a primary contributor of glioma initiation and progression. Nimotuzumab is a humanized monoclonal antibody that recognizes the EGFR extracellular domain and reaches Central Nervous System tumors, in nonclinical and clinical setting. While it has similar activity when compared to other anti-EGFR antibodies, it does not induce skin toxicity or hypomagnesemia. METHODS: A randomized, double blind, multicentric clinical trial was conducted in high grade glioma patients (41 anaplastic astrocytoma and 29 glioblastoma multiforme) that received radiotherapy plus nimotuzumab or placebo. Treatment and placebo groups were well-balanced for the most important prognostic variables. Patients received 6 weekly doses of 200 mg nimotuzumab or placebo together with irradiation as induction therapy. Maintenance treatment was given for 1 year with subsequent doses administered every 3 weeks. The objectives of this study were to assess the comparative overall survival, progression free survival, response rate, immunogenicity and safety. RESULTS: The median cumulative dose was 3200 mg of nimotuzumab given over a median number of 16 doses. The combination of nimotuzumab and RT was well-tolerated. The most prevalent related adverse reactions included nausea, fever, tremors, anorexia and hepatic test alteration. No anti-idiotypic response was detected, confirming the antibody low immunogenicity. The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group. CONCLUSIONS: In this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation. TRIAL REGISTRATION: Cuban National Register for clinical trials (No. 1745) (http://registroclinico.sld.cu/ensayos).