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.

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.

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.

Reanálisis del estudio de Carlos J. Finlay acerca del mosquito como vector de la fiebre amarilla

Introducción: El primer registro de la asociación causal entre el mosquito Aedes aegypti, y la transmisión de la fiebre amarilla, lo constituyó la comunicación presentada por Carlos J. Finlay a la Academia de Ciencias de La Habana en 1881. El científico cubano mostró los resultados de la inoculación, por picadura de mosquito infectado, en cinco sujetos de un conjunto de 20 personas sanas. Objetivo: Reanalizar la evidencia mediante la aplicación de técnicas estadísticas aún no desarrolladas en tiempo del científico cubano, y evaluar la fortaleza de la evidencia causal. Métodos: Los resultados se analizaron mediante el test exacto de Fisher, el factor de Bayes y la diferencia de riesgos, el riesgo relativo y el odds ratio de la asociación. Se valoró la fortaleza de la evidencia de la asociación causal mediante criterio estadístico sin desconocer los criterios de causalidad más actualizados. Resultados: El test exacto de Fisher fue altamente significativo (p= 0,009), y el factor de Bayes (24,9) resultó compatible con una evidencia fuerte a favor de la asociación entre la inoculación y el desarrollo de la enfermedad. También apoyaron la asociación, la diferencia de riesgos (0,55; IC 95 %: 0,15-0,96), el riesgo relativo (18,7; IC 95 %: 1,12-3-10,3) y el odds ratio (43,4; IC 95 %: 1,68-11-19,7). Conclusiones: Los resultados de Finlay resultaron robustos, y se ajustaron a los criterios de causalidad para explicar la transmisión de la fiebre amarilla por el mosquito.

Introduction: The first record of the causal association between the Aedes aegypti mosquito and the transmission of yellow fever was the communication submitted by Carlos J. Finlay to the Havana Academy of Sciences in 1881. The Cuban scientist showed the results of inoculation, by infected mosquito bite, in five subjects from a group of 20 healthy people. Objective: To revise the evidence through the use of statistical techniques not yet developed at the time of the Cuban scientist and to evaluate the strength of the causal evidence. Methods: Results were analyzed using Fisher's exact test, Bayes factor, and risk difference, relative risk, and odds ratio of association. The strength of the evidence of the causal association was assessed using statistical criteria minding the most up-to-date causality criteria. Results: Fisher's exact test was highly significant (p = 0.009), and the Bayes factor (24.9) was compatible with strong evidence in favor of the association between inoculation and disease development. The association was also supported by the risk difference (0.55; 95% CI: 0.15-0.96), the relative risk (18.7; 95% CI: 1.12-310.3), and the odds ratio (43.4; 95% CI: 1.68-1119.7). Conclusions: Finlay's results were robust, and adjusted to the causality criteria to explain the transmission of yellow fever by mosquitoes.

Assessing care-related regret among nurses specialized in multiple sclerosis: A psychometric analysis of a new assessment battery.

Experiences of regret associated with caring for patients with multiple sclerosis (MS) can affect medical decisions. A non-interventional study was conducted to assess the dimensionality and item characteristics of a battery including the Regret Intensity Scale (RIS-10) and 15 items evaluating common situations experienced by nurses in MS care. A total of 97 nurses were included. The RIS-10 showed good internal reliability and a unidimensional structure according to Mokken analysis. All-item homogeneity coefficients exceeded 0.30, whereas scalability for the overall RIS-10 was 0.66, indicating a strong scale. This battery showed adequate psychometric properties to evaluate regret among MS nurses.

lncRNA deregulation in childhood acute lymphoblastic leukemia: A systematic review.

Childhood acute lymphoblastic leukemia (ALL), the most common pediatric cancer, is a heterogeneous disease comprised of multiple molecular subtypes with distinct somatic genetic alterations, which results in different outcomes for the patients. Accurate patient risk stratification through genetic markers could increase survival rates, but the identification of reliable biomarkers is needed, as 20­30% of B­ALL patients cannot be classified in the clinic with routine techniques and some patients classified as low­risk and good­responders to treatment will eventually relapse. Long non­coding RNAs (lncRNAs) can represent novel candidates with diagnostic, classification, prognosis, and treatment response potential. However, regarding childhood ALL, there is inconsistency in the data reported due to the lack of a consensus nomenclature for lncRNA naming and the methodology and designing applied for their study. Therefore, the aim of the article is to clarify the potential of lncRNAs as biomarkers in childhood ALL through a systematic review. From a revision of 23 manuscripts, it was found that AWPPH overexpression could represent a novel marker for ALL diagnosis, including both B and T immunophenotypes, and 18 lncRNAs were specifically associated with B­cell ALL (B­ALL) patients. We identified subtype­specific signatures for ETV6­RUNX1, hyperdiploidy and KMT2A subtypes. These signatures hold promise as novel diagnostic markers and could refine the classification of patients.

Trace elements, peripheral blood film, and gene expression status in adolescents living near an industrial area in the Colombian Caribbean Coastline.

BACKGROUND: Trace elements comprise both nutritionally essential and non-essential, and their presence in organisms plays important role in human health. OBJECTIVE: The aim of this study was to evaluate the levels of trace elements, together with cellular and molecular biomarkers, in adolescents from Tierrabomba Island, a Caribbean community located near an industrial area, comparing them with a group living in San Onofre, a reference community. METHODS: Hair and blood samples were obtained from 238 individuals aged 11-18 years old, 131 from Tierrabomba Island and 107 from San Onofre. Trace elements were quantified in hair using ICP-MS. The hematological evaluation was done by peripheral blood smears, and gene expression analysis was carried out through RT-PCR. RESULTS: Thirteen elements were analyzed; eight showed significant differences between sites. In Tierrabomba, arsenic (As) and tungsten (W) registered mean values greater than in San Onofre. In contrast, in the reference site, average values for boron (B), cobalt (Co), zinc (Zn), yttrium (Y), tin (Sn), and barium (Ba) were greater. The peripheral blood film showed differences between populations. Mean lymphocyte percentage was higher in the Island, while eosinophil and monocyte percentages displayed greater means in San Onofre. Some correlations between trace elements and hematological parameters were found, mainly with platelets in Tierrabomba. This trend remained even when partial correlation coefficients were adjusted for age. Levels of gene expression of metallothionein 1X (MT1X) and superoxide dismutase (SOD) registered significant differences between sites, being greater in Tierrabomba. Negative correlations between SOD and As were observed in both sampling sites. Discriminant analysis suggested sampling locations could be differentiated by Zn, Mo, Ba, and MT1X levels. SIGNIFICANCE: Trace elements and the relative gene expression associated with metal exposure are critical exposure biomarkers for coastal communities.

Regret and Therapeutic Decisions in Multiple Sclerosis Care: Literature Review and Research Protocol.

Background: Decisions based on erroneous assessments may result in unrealistic patient and family expectations, suboptimal advice, incorrect treatment, or costly medical errors. Regret is a common emotion in daily life that involves counterfactual thinking when considering alternative choices. Limited information is available on care-related regret affecting healthcare professionals managing patients with multiple sclerosis (MS). Methods: We reviewed identified gaps in the literature by searching for the combination of the following keywords in Pubmed: "regret and decision," "regret and physicians," and "regret and nurses." An expert panel of neurologists, a nurse, a psychiatrist, a pharmacist, and a psychometrics specialist participated in the study design. Care-related regret will be assessed by a behavioral battery including the standardized questionnaire Regret Intensity Scale (RIS-10) and 15 new specific items. Six items will evaluate regret in the most common social domains affecting individuals (financial, driving, sports-recreation, work, own health, and confidence in people). Another nine items will explore past and recent regret experiences in common situations experienced by healthcare professionals caring for patients with MS. We will also assess concomitant behavioral characteristics of healthcare professionals that could be associated with regret: coping strategies, life satisfaction, mood, positive social behaviors, occupational burnout, and tolerance to uncertainty. Planned Outcomes: This is the first comprehensive and standardized protocol to assess care-related regret and associated behavioral factors among healthcare professionals managing MS. These results will allow to understand and ameliorate regret in healthcare professionals. Spanish National Register (SL42129-20/598-E).

Quantifying the patient´s perspective in neuromyelitis optica spectrum disorder: Psychometric properties of the SymptoMScreen questionnaire.

BACKGROUND: The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. METHODS: A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. RESULTS: A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach's alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken's criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). CONCLUSIONS: The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD.

Cognitive Enhancers in Schizophrenia: A Systematic Review and Meta-Analysis of Alpha-7 Nicotinic Acetylcholine Receptor Agonists for Cognitive Deficits and Negative Symptoms.

Background: Schizophrenia is a severe and enduring disease and is one of the leading causes of disability worldwide. Cognitive impairment is a core clinical symptom that plays a crucial role in functional outcomes and prognosis, thus making it a relevant treatment target. The aim of this study was to assess the efficacy of alpha-7 nicotinic acetylcholine receptor agonists (α7 nAChR) as adjunctive treatment to enhance cognition and ameliorate negative symptoms in patients with schizophrenia. Methods: A search strategy was developed for MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to May 2019. We included randomized controlled trials (RCTs) that compared antipsychotic treatment plus α7 nAChR agonists with antipsychotic treatment plus placebo and determined their effects on the main cognitive domains proposed by the MATRICS initiative and on negative symptoms. Two authors independently reviewed study eligibility and data extraction and assessed the risk of bias of the studies included. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, we used a random-effects model and assessed the quality of the evidence. Results: Thirteen studies were included in the quantitative analysis. No differences were found in any of the cognitive domains assessed in four RCTs (n = 414). In contrast, nine RCTs (n = 978) presented a small effect in support of α7 nAChR agonists for negative symptoms [standardized mean difference -0.28, 95% CI (-0.56 to -0.00); P = 0.05], even though the confidence to support this evidence is low according to the GRADE system. Conclusions: Current evidence is too weak to consider α7 nAChR agonists as an effective add-on treatment to antipsychotics to enhance cognition and negative symptoms.

Muerte súbita relacionada con la actividad deportiva en España. Estudio poblacional multicéntrico forense de 288 casos / Sports-related sudden cardiac death in Spain. A multicenter, population-based, forensic study of 288 cases

Introducción y objetivos Conocer la incidencia, características clínico-patológicas, hábitos tóxicos y actividad deportiva relacionadas con la muerte súbita en la actividad deportiva en España.MétodosEstudio poblacional retrospectivo y multicéntrico, basado en autopsias forenses realizadas en 25 provincias durante 8 años (2010-2017).ResultadosSe investigaron 288 casos (el 98,6% varones; media de edad, 43,8±14,4 años). La incidencia fue de 0,38 casos/100.000 hab./año (0,82 entre deportistas habituales), la mayoría (54%) varones entre 35 y 54 años. Los deportes más frecuentes (el 96% recreativos) fueron ciclismo (28%), fútbol (18%) y carrera a pie (17%). La muerte fue de origen cardiovascular en el 99%: cardiopatía isquémica (63%), miocardiopatías (21%) y síndrome de muerte súbita arrítmica (6%). En los jóvenes, las miocardiopatías (38%) y la cardiopatía isquémica (30%), presente a partir de los 20 años, fueron las más prevalentes. La enfermedad se había diagnosticado en vida en 23 casos; se observaron antecedentes clínicos relevantes en 30 casos y factores de riesgo cardiovascular, principalmente obesidad, en 95. El análisis toxicológico detectó sustancias cardiotóxicas en el 7%, y destaca la relación entre cannabis y cardiopatía isquémica aguda.ConclusionesLa muerte súbita asociada a la actividad deportiva en España tiene una incidencia muy baja, afecta a varones de mediana edad que realizan deporte recreativo, principalmente ciclismo, fútbol y carrera, y es de origen cardiovascular, con aparición temprana de la cardiopatía isquémica. Los datos clínicos y los hábitos tóxicos deben tenerse en cuenta para desarrollar estrategias de prevención. (AU)

Introduction and objectives To determine the incidence of sports-related sudden cardiac death in Spain, and to identify the clinical-pathological characteristics, substance abuse, and sports activity associated with this entity.MethodsRetrospective, population-based, multicenter study of forensic autopsies conducted in 25 provinces during an 8-year period (2010-2017).ResultsWe investigated 288 cases (98.6% occurred in men with a mean age of 43.8±14.4 years). The incidence in the general population was 0.38 cases out of 100 000 inhabitants per year (0.82 among regular athletes), and most cases (54%) occurred in persons aged between 35 and 54 years. The most frequent sports (96% recreational) were cycling (28%), football (18%), and jogging (17%). Death was of cardiovascular origin in 99%. The main causes were ischemic heart disease (63%), cardiomyopathies (21%), and sudden arrhythmic death syndrome (6%). In young people, cardiomyopathies (38%) and ischemic heart disease (30%), present after the age of 20 years, were the most prevalent. The disease was diagnosed during life in 23 cases, relevant clinical antecedents were observed in 30 cases, and cardiovascular risk factors, mainly obesity, in 95 cases. Toxicological analysis detected cardiotoxic substances in 7%, highlighting the association between cannabis and acute ischemic heart disease.ConclusionsSports-related sudden cardiac death in Spain has a very low incidence and affects middle-aged men practicing recreational sports, mainly cycling, football, and jogging. This entity is of cardiovascular origin with early onset of ischemic heart disease. Clinical data and substance abuse should be taken into account to develop preventive strategies. (AU)

Quantifying Knowledge of Alzheimer's Disease: An Analysis of the Psychometric Properties of the Alzheimer's Disease Knowledge Scale.

INTRODUCTION: The Alzheimer's Disease Knowledge Scale (ADKS) is one of the most popular instruments for assessing a person's knowledge regarding Alzheimer's disease (AD). The objective of this study was to explore ADKS item characteristics with item response theory (IRT) procedures. METHODS: A noninterventional web-based study was conducted. A nonparametric IRT procedure, Mokken analysis, was used to explore the underlying latent structure of the ADKS and ADKS item characteristics regarding scalability and violations of the monotone homogeneity (MH) model. A random-effects meta-analysis was implemented that combined ADKS scores from independent studies. RESULTS: A total of 447 employees of a pharmaceutical company participated in the study. The mean ADKS score was 21.2 (SD 2.8). Mokken analysis showed that most ADKS items (22 of 30) do not fit to any scale and can be considered to be scale independent. Two items (#1: particularly prone to depression; #20: depression can be mistaken for AD) fit to a domain relating to depression, another two items (#2: mental exercise can prevent AD development; #8: benefit of psychotherapy) can be related to potential prevention and improvement, and four items (#12: poor nutrition can make the symptoms worse; #18: high cholesterol may increase the risk of AD; #26: high blood pressure may increase the risk of AD; #27: genes can only partially account for AD development) fit to a risk factor domain. As expected from those results, neither the overall scale (H = 0.033) nor its items showed appropriate scalability index values, suggesting that ADKS does not fit to a MH model. Eleven items showed violations of the assumptions of the MH model. The meta-analytical average score was 21.78 (95% CI 20.67-22.90), with healthcare professionals and caregivers showing the highest levels of AD knowledge. CONCLUSION: Although the ADKS does not present a unidimensional structure, its independent items together provide a comprehensive spectrum of information regarding AD knowledge.

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.

Sports-related sudden cardiac death in Spain. A multicenter, population-based, forensic study of 288 cases.

INTRODUCTION AND OBJECTIVES: To determine the incidence of sports-related sudden cardiac death in Spain, and to identify the clinical-pathological characteristics, substance abuse, and sports activity associated with this entity. METHODS: Retrospective, population-based, multicenter study of forensic autopsies conducted in 25 provinces during an 8-year period (2010-2017). RESULTS: We investigated 288 cases (98.6% occurred in men with a mean age of 43.8±14.4 years). The incidence in the general population was 0.38 cases out of 100 000 inhabitants per year (0.82 among regular athletes), and most cases (54%) occurred in persons aged between 35 and 54 years. The most frequent sports (96% recreational) were cycling (28%), football (18%), and jogging (17%). Death was of cardiovascular origin in 99%. The main causes were ischemic heart disease (63%), cardiomyopathies (21%), and sudden arrhythmic death syndrome (6%). In young people, cardiomyopathies (38%) and ischemic heart disease (30%), present after the age of 20 years, were the most prevalent. The disease was diagnosed during life in 23 cases, relevant clinical antecedents were observed in 30 cases, and cardiovascular risk factors, mainly obesity, in 95 cases. Toxicological analysis detected cardiotoxic substances in 7%, highlighting the association between cannabis and acute ischemic heart disease. CONCLUSIONS: Sports-related sudden cardiac death in Spain has a very low incidence and affects middle-aged men practicing recreational sports, mainly cycling, football, and jogging. This entity is of cardiovascular origin with early onset of ischemic heart disease. Clinical data and substance abuse should be taken into account to develop preventive strategies.

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.

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.

Assessment of Psychiatric Symptomatology in Bilingual Psychotic Patients: A Systematic Review and Meta-Analysis.

Language plays an important role in psychiatric conditions. Language disturbances are core symptoms of psychiatric ailments, and language is the main diagnostic tool to assess psychopathological severity. Although the importance of language in psychiatry, the effect of bilingualism, and more specifically of using the mother language or a later acquired language at the time of assessing psychotic symptoms, has been scarcely studied and, thus, remains unclear. We conducted a systematic review and meta-analysis to ascertain whether differences exist in the severity of psychopathology in psychotic patients when assessed either in the mother language or in an acquired language. Of 3121 retrieved references from three databases (PsycINFO, MEDLINE, Embase) and complementary searches, four studies-including 283 psychotic patients-were included in the review. The meta-analytical combined effect suggested that more overall symptomatology is detected when clinical assessment is conducted in the mother language rather than in the acquired language (very low quality evidence, random effects model standardized mean difference (SMD) 0.44, 95% CI = 0.19 to 0.69, p value = 0.0006, I2 = 90%). Considering the growing migration flows and the increasing number of bilingual people in the world population, the effect of the chosen language to conduct at the time of conducting psychopathological assessments of psychotic patients is a clinically relevant issue. Based on our findings, we recommend that clinical interviews with bilingual psychotic patients should be conducted, when feasible, in the patient's mother language.