Systematic review of drug therapy for chorea in NXK2-1-related disorders: Efficacy and safety evidence from case studies and series.

BACKGROUND: The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management. METHODS: A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO. RESULTS: Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low. CONCLUSIONS: The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.

Real-life outcomes in biotypes of psychotic disorders based on neurocognitive performance.

Aiming at discerning potential biotypes within the psychotic syndrome, we have recently reported the possible existence of two clusters or biotypes across schizophrenia and bipolar disorder characterized by their cognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) instrument and validated with independent biological and clinical indexes (Fernández-Linsenbarth et al. in Schizophr Res 229:102-111, 2021). In this previous work, the group with larger cognitive deficits (N = 93, including 69 chronic schizophrenia, 17 first episodes (FE) of schizophrenia and 7 bipolar disorder patients) showed smaller thalamus and hippocampus volume and hyper-synchronic electroencephalogram than the group with milder deficits (N = 105, including 58 chronic schizophrenia, 25 FE and 22 bipolar disorder patients). We predicted that if these biotypes indeed corresponded to different cognitive and biological substrates, their adaptation to real life would be different. To this end, in the present work we have followed up the patients' population included in that work at 1st and 3rd years after the date of inclusion in the 2021 study and we report on the statistical comparisons of each clinical and real-life outcomes between them. The first cluster, with larger cognitive deficits and more severe biological alterations, showed during that period a decreased capacity for job tenure (1st and 3rd years), more admissions to a psychiatric ward (1st year) and a higher likelihood for quitting psychiatric follow-up (3rd year). Patients in the second cluster, with moderate cognitive deficits, were less compliant with prescribed treatment at the 3rd year. The differences in real-life outcomes may give additional external validity to that yielded by biological measurements to the described biotypes based on neurocognition.

Effectiveness of psychological interventions in preventing postpartum depression in non-depressed women: a systematic review and meta-analysis of randomized controlled trials.

Postpartum depression (PPD) is one of the most common disorders following childbirth. This systematic review and meta-analysis (SR/MA) aimed to assess the effectiveness of psychological interventions in preventing PPD in non-depressed women. PRISMA guidelines were followed. MEDLINE (Ovid and PubMed), PsycINFO, Web of Science, Scopus, CINAHL, CENTRAL, OpenGrey, Australian New Zealand Clinical Trial Registry and clinicaltrial.gov were searched. Randomized controlled trials (RCTs) conducted with pregnant or postpartum (up to 12 months) women who were non-depressed at baseline were selected. The outcomes were the incidence of PPD and/or the reduction of postpartum depressive symptoms. The standardized mean difference (SMD) using random-effect models was calculated. Sensitivity, sub-group and meta-regression analyses were performed. 17 RCTs were included in the SR and 15 in the MA, representing 4958 participants from four continents. The pooled SMD was -0.175 [95% confidence interval (CI) -0.266 to -0.083; p < 0.001] and sensitivity analyses confirmed the robustness of this result. Heterogeneity was low (I2 = 21.20%) and was fully explained by a meta-regression model including one variable (previous deliveries). The meta-regression model and MA stratified by previous deliveries indicated that interventions focused on primiparous women are more effective. There was no evidence of publication bias. Few RCTs had an overall low risk of bias. According to GRADE, the quality of evidence was moderate. Psychological interventions have very little effectiveness in preventing PPD in non-depressed women, although this effectiveness is greater in interventions focused on primiparous women. Further RCTs with a low risk of bias and more effective interventions are needed.

Evaluation of the safety, efficacy, effectiveness and cost-effectiveness of implantable Holter for prolonged monitoring in patients with previous stroke: a systematic review.

Background: Atrial fibrillation (AF), which is associated with cryptogenic stroke, is the most common sustained arrhythmia in the general population. Because AF is asymptomatic and intermittent, its detection rate increases with the duration of monitoring. The objective of this study is to review the available evidence on the safety, efficacy, effectiveness and cost-effectiveness of AF diagnosis by prolonged monitoring with an implantable Holter monitor in adult patients with idiopathic or cryptogenic stroke of suspected cardioembolic origin, compared to conventional monitoring. Methods: Two independent reviewers performed a systematic review of the literature, identifying relevant studies through a structured search of Medline (Ovid), EMBASE, Web of Science and Cochrane Library and the databases of national and international health technology assessment agencies. The quality of the included studies was assessed with AGREE-II, AMSTAR-2 and CHEC. GRADE criteria were used to summarise the evidence. Results: Four of the 211 papers identified were included: 1 clinical practice guideline, 2 systematic reviews, and 1 economic evaluation. The quality of the evidence reviewed was low. An implantable Holter monitor might be more effective in detecting AF than conventional monitoring. Serious adverse events were similar in both groups. The economic evaluation suggests that the technology is cost-effective. Conclusions: The available evidence suggests the diagnostic superiority of the implantable Holter monitor over the traditional Holter monitor. Due to the low quality of the evidence, further and higher quality studies on these technologies are needed before solid conclusions can be drawn.

Exploring the values, preferences, and information needs of patients with NKX2-1-related disorders: A qualitative study protocol.

BACKGROUND: NKX2-1-related disorders have a prevalence of 1:500,000 and are therefore considered a rare condition according to the European Commission's definition. The European Reference Network of Rare Neurological Disorders is developing the first clinical practice guideline on the management of this condition, with the support of the Andalusian Health Technology Assessment Area, Endo-ERN, ERN-Lung and Imegen, within the framework of the ERNs Guidelines programme (DG SANTE/2018/B3/030). Within the scope of this programme, it becomes necessary to explore the patient perspective in order to include it in the ongoing clinical practice guideline and accompanying patient information booklet. METHODS AND ANALYSIS: This study will use qualitative methods to explore the values, preferences and information needs of patient with NKX2-1-related disorders and their caregivers. Participants will come from a variety of countries throughout Europe. One focus group and four semi-structured interviews will be conducted. Pairs will analyse the data using Grounded Theory. The Andalusian Regional Ministry of Health's Ethics Coordinating Committee for Biomedical Research (Sevilla, Andalucía, Spain) has approved this study protocol (29/03/2022). DISCUSSION: This is the first study to explore the values, preferences, and information needs of patients with NKX2-1-related disorders. The proposed study's findings will contribute to the generation of useful knowledge that will provide guidance to improve the care given to patients with the studied condition. While this study will provide valuable insights into the perspectives of patients with NKX2-1-related disorders, the findings are unlikely to be generalizable to patients with other conditions.

Effectiveness of web-based and mobile-based psychological interventions to prevent perinatal depression: Study protocol for a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Perinatal depression is one of the most common complications during pregnancy and one year following childbirth. A negative impact on the mental and physical health of women, their children, partners, or significant others has been associated with this disease. Web-based and Mobile-based psychological interventions can reduce the burden of the disease through prevention of new cases of depression. It is crucial to know the effectiveness of these interventions to implement them around the globe. This systematic review and meta-analysis aims to assess the effectiveness of Web-based and Mobile-based psychological interventions to prevent depression during the perinatal period. METHOD AND ANALYSIS: A systematic review and meta-analysis will adhere to the PRISMA guidelines. Studies will be identified through MEDLINE, PsycINFO, Web of Science, Scopus, CINAHL, CENTRAL, Opengrey, Australian New Zealand Clinical Trial Registry, National Institute for Mental Health Research at the Australian National University, clinicaltrial.gov, beacon.anu.edu.au, and evidencebasedpsychotherapies.org from inception until 31 March 2021. We will also search the reference lists provided in relevant studies and reviews. The selection criteria will be as follows: 1) pregnant women or women who have given birth in the last 12 months and who were non-depressive at baseline; 2) Web-based and Mobile-Based psychological interventions; 3) comparators will be usual care, attention control, waiting list or no intervention; 4) outcomes will be the incidence of new cases of perinatal depression and/or the reduction of depressive symptoms as measured by validated instruments; and 5) the design of the studies will be randomized controlled trials. No restrictions regarding the year or language of publication will be considered. Pooled standardized mean differences and 95% confidence intervals will be calculated. The risk of bias of the studies will be assessed through the Cochrane Collaboration risk of bias 2.0 tool. Heterogeneity and publication bias will be estimated. Sensitivity and sub-group analyses will also be conducted. Random effects meta-regression will be performed. ETHICS AND DISSEMINATION: As a systematic review, ethical approval is not required. The results from this study will be presented at international conferences and disseminated through peer-reviewed publications. Patients and the public will be involved in the dissemination plans. PROSPERO REGISTRATION NUMBER: 230,089 (submitted).

Effectiveness of psychological, psychoeducational and psychosocial interventions to prevent postpartum depression in adolescent and adult mothers: study protocol for a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: The prevalence of postpartum depression (PPD) is 17%, and the incidence is 12% worldwide. Adverse consequences for mothers and babies have been associated with this disease. To assess the effectiveness of psychological, psychoeducational and psychosocial interventions in preventing PPD, a systematic review and meta-analysis (SR/MA) will be conducted. METHODS AND ANALYSIS: A SR/MA will be performed following the indications of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies will be identified through MEDLINE (Ovid and PubMed), PsycINFO, Web of Science, Scopus, CINAHL, Cochrane Central Register of Controlled Trials, OpenGrey, Australian New Zealand Clinical Trial Registry, ClinicalTrials.gov and evidencebasedtherapy.org from inception until 31 January 2020. Bridging searches will be also conducted until the review is completed. The selection criteria will be as follows: (1) subjects will be pregnant females or females who have given birth in the last 12 months and who were non-depressive at baseline; (2) psychological, psychoeducational and psychosocial interventions; (3) comparator will be usual care, attention control, waiting list or no intervention; (4) outcomes will be specific results on PPD; and (5) the design of the studies will be randomised controlled trials. No restrictions regarding the year of publication, the setting of the intervention or the language of publication will be considered. Pooled standardised mean differences and 95% CIs will be calculated. The risk of bias of the studies will be assessed through the Cochrane Collaboration risk of bias tool. Heterogeneity between the studies will be determined by the I2 and Cochran's Q statistics. Sensitivity and subgroup analyses will also be performed. Publication bias will be checked with funnel plots and Egger's test. Heterogeneity will be explored by random-effects meta-regression analysis. ETHICS AND DISSEMINATION: The ethical assessment was not required. The results will be presented at conferences and disseminated through publications. PROSPERO REGISTRATION NUMBER: CRD42018109981.

Effectiveness of online psychological and psychoeducational interventions to prevent depression: Systematic review and meta-analysis of randomized controlled trials.

Although evidence exists for the efficacy of interventions to prevent depression, little is known about its prevention through online interventions. We aim to assess the effectiveness of online psychological and psychoeducational interventions to prevent depression in heterogeneous populations. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted based on literature searches in eight electronic data bases and other sources from inception to 22 July 2019. Of the 4181 abstracts reviewed, 501 were selected for full-text review, and 21 RCTs met the inclusion criteria, representing 10,134 participants from 11 countries and four continents. The pooled SMD was -0·26 (95%CI: -0·36 to -0·16; p < 0.001) and sensitivity analyses confirmed the robustness of this result. We did not find publication bias but there was substantial heterogeneity (I2 = 72%; 95%CI, 57% to 82%). A meta-regression including three variables explained 81% of the heterogeneity. Indicated prevention and interactive website delivery were statistically associated with higher effectiveness, and no association was observed with risk of bias. Online psychological and psychoeducational interventions have a small effect in reducing depressive symptoms in non-depressed and varied populations, and the quality of evidence is moderate. Given that these types of interventions are very accessible and can be applied on a wide scale, they should be further developed and implemented. Registration details: Registration number (PROSPERO): CRD42014014804.

Moderators of psychological and psychoeducational interventions for the prevention of anxiety: A systematic review.

The aim of this study was to assess the available evidence on potential moderators of psychological and psychoeducational interventions for the prevention of anxiety. A systematic review using PubMed, PsycINFO, Web of Science, Embase, OpenGrey, and CENTRAL was performed up to October 2019. Two independent researchers assessed the fulfillment of eligibility criteria, extracted the data and performed a quality assessment of the included studies. Outcomes were moderators of the reduction of anxious symptoms or the incidence of anxiety disorders. Fourteen studies reporting results on moderator analyses performed in 13 randomized controlled trials were included. Twenty-seven potential moderators were organized into six categories: sociodemographic, clinical characteristics, cognitive variables, life events, interpersonal functioning and intervention characteristics. The most frequently examined variables were gender, age and baseline anxiety. We found insufficient evidence for all moderator categories studied. In children and adolescents, we found some studies with significant results for the low family support variable and higher levels of anxiety symptoms at baseline, which were both associated with higher effectiveness. Limited conclusions can be drawn about for whom and under what conditions interventions work in the prevention of anxiety. A strong need to improve the methodological quality and the number of moderator studies was identified.

Moderators of psychological and psychoeducational interventions for the prevention of depression: A systematic review.

Psychological and psychoeducational interventions have proven to be effective in preventing depression. However, the identification of the patients that benefit the most from each type of intervention has not yet been established. A systematic review was performed of the literature on moderators of preventive psychological and psychoeducational interventions for depression in all types of population. A search was performed on PubMed, PsycINFO, Web of Science, Embase, Cochrane Central Register of Controlled Trials and OpenGrey up to July 2019. Fulfillment of eligibility criteria, data collection, and study quality assessment were assessed by two independent researchers. Outcomes were moderators of the reduction of depressive symptoms or the incidence of depression. Twenty-seven moderator effect studies performed in 19 randomized controlled trials were included. Thirty-four potential sociodemographic, clinical, interpersonal, personality and life-event moderators were evaluated. Baseline depressive symptoms, gender, age, baseline parental depression and social support were the most frequently studied potential moderators. In interventions for children and adolescents, the moderator for which evidence was strongest was having parents free of depression at baseline. Psychological and psychoeducational interventions seem to be more effective in children and adolescents who exhibit a lower use of substances and whose parents do not have symptoms of depression at baseline. In adults, a lower age was associated with greater effects of preventive interventions. ETHICS: As this systematic review is based on published data, approval from the local ethics committee was not required.

Motor control using cranio-cervical flexion exercises versus other treatments for non-specific chronic neck pain: A systematic review and meta-analysis.

BACKGROUND: Chronic neck pain affects a significant percentage of the adult population. Commonly, the pain is of unknown origin. In those cases, some alterations in motor control (MC) can appear in the deep cervical muscles. The specific training of these muscles could improve muscular function and reduce pain and disability. OBJECTIVE: To determine whether MC, using cranio-cervical flexion (CCF), is more effective than other treatments for non-specific chronic neck pain (NSCNP). DESIGN: Systematic review with meta-analysis. METHODS: A search was done in journals and in a variety of databases, between December 2017 and March 2018. Randomized clinical trials (RCTs) and systematic reviews of RCTs comparing MC with other treatments in adults with NSCNP, regarding pain and disability, were included. Risk of bias was analysed using the Cochrane risk of bias tool. Data was analysed using a random effects model. Heterogeneity was evaluated using the I2statistic. The quality of the evidence was measured using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Ten articles were included for qualitative review; nine were used for a quantitative analysis about the effect of MC on pain and eight for the analysis regarding disability. The meta-analysis comparing MC versus other treatments showed significant differences regarding pain and disability. CONCLUSIONS: MC interventions for NSCNP patients reduces pain and disability. MC seems to be more effective to reduce pain and disability than other treatments.