Risultati per: Gestione delle complicanze psichiatriche e cognitive nel Parkinson

Circulation, Volume 150, Issue Suppl_1, Page A4134619-A4134619, November 12, 2024. Background:Ebstein anomaly (EA) is a rare congenital heart defect occurring in 1.2 to 5 in 100,000 live births, characterized by a downward displacement of the tricuspid valve, thin-walled right ventricle, and tricuspid valve regurgitation. It can present variably from asymptomatic cases to severe symptoms like arrhythmias and right-sided heart failure. EA is often associated with other anomalies such as interatrial communication and mitral valve prolapse. The condition can lead to accessory atrioventricular pathways, frequently resulting in Wolff-Parkinson-White syndrome (WPW), which involves abnormal heart electrical activity and increases the risk of sudden cardiac death. While the genetic basis of EA is not fully understood, it appears to involve multiple genes like FLNA and NKX2-5, MYH6, MYH7 suggesting a complex polygenic inheritance pattern. TNNT2 is known to be associated with Cardiomyopathy but has not been previously associated with EA and WPW.Case:In this report, we present findings from a lebanese family with EA, comprising 2 affected individuals. Whole exome sequencing in the affected individuals identified a pathogenic variant in the TNNT2 gene at coding strain position 260 (a missense mutation: C to T), resulting in the substitution of Proline with Leucine at position 87 in affected individuals (Figure 1). No variants were detected in any other candidate gene examined. Individuals I:1 and II:2 were found to be normal, with no EA findings on echocardiography.Methods:Whole exome sequencing in the patients involved collecting blood samples after obtaining consent. These samples were sent to Centogene lab, where genomic DNA is enzymatically fragmented. The regions of interest are then enriched using DNA capture probes, facilitating detailed genetic analysis.Results:The whole exome sequencing identified a heterozygous missense mutation in both the father and his daughter. This nonsynonymous variant is located on chromosome 1 (GRCh37) in the TNNT2 gene region. The specific variant, NM_001276345.1:c.260C >T p.(Pro87Leu), was found in both individuals.Conclusion:In conclusion, the genetic basis of EA is rather complex and remains poorly understood. It is established that mutations in the TNNT2 gene are linked to several cardiomyopathies, none of them overlap with the described phenotype of our patients. In this report, we therefore confirm the potential role of TNNT2 gene mutation in the genetic basis of familial EA with WPW.

Circulation, Volume 150, Issue Suppl_1, Page A4146019-A4146019, November 12, 2024. Background:Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, affecting more than one million persons in the United States. Cardiovascular dysautonomia is a prominent dysfunction in PD, affecting the conduction system and causing bradyarrhythmia. However, no studies have assessed the prevalence and characteristics of bradyarrhythmia in patients with PD.Research Question:Is there an increased prevalence of bradyarrhythmia and pacemaker implantation in patients with PD?Aims:The study assessed the trends, prevalence, and risk factors of bradyarrhythmia and pacemaker implantation in PD patients.Methods:The National Inpatient Sample was utilized to identify patients’ data with primary and secondary diagnoses of Parkinson’s disease (PD) in the United States from 2016 to 2020 using the International Classification of Disease, 10th Revision codes. Outcomes of interest included the trends and prevalence of bradyarrhythmia and pacemaker implantation in PD. We assessed potential predictors of bradyarrhythmia in patients with PD using a backward selection multivariable logistic regression.Results:A total of 333,242 patients with PD diagnosis were included (76.5 ± 15.2 years, 58.7% male, 80.1% white); of these, 5,092 (20.5%) had comorbid diagnoses of bradyarrhythmia, and 328,150 (79.5%) without bradyarrhythmia. The prevalence of bradyarrhythmia in patients with PD was 351.9 per 10,000 hospitalizations (3.5%). The trends of bradyarrhythmia showed a stable increase from 291.9 to 463.8 per 10,000 (AAPC 12.5%, CI: -0.2%, 26.8%). The overall prevalence of pacemaker implantation in patients with PD was 79.9 per 10,000 hospitalizations (0.8%). The overall trends of pacemaker implantation showed a stable decrease in patients with PD during 2016-2020, with an AAPC -0.9% (CI: -4.1% to 2.3%). Age≥ 65, male sex, comorbidities (atrial fibrillation, coronary artery disease, heart failure, hypertension, liver failure, obesity, peripheral vascular disease, renal failure) were associated with a higher likelihood of bradyarrhythmia in patients with PD.Conclusions:This study’s findings revealed that the prevalence of bradyarrhythmia and subsequent pacemaker implantation in patients with PD remained relatively stable over the study period. The study provides the initial prevalence of bradyarrhythmia in patients with Parkinson’s disease. Further study is necessary to provide the characteristics and outcomes of bradyarrhythmia in PD.

Circulation, Volume 150, Issue Suppl_1, Page A4143917-A4143917, November 12, 2024. Background:PRKAG2 syndrome is an inherited disease caused by mutations in thePRKAG2gene, which encodes the γ2 regulatory subunit of AMP-activated protein kinase (AMPK). These mutations result in increased AMPK activity leading to aberrant myocardial glycogen deposition. Patients with PRKAG2 syndrome can develop cardiac hypertrophy, ventricular pre-excitation, supraventricular arrhythmias and conduction system disease, all of which increase the risk of sudden cardiac death. Some patients develop progressive heart failure necessitating heart transplantation. Current treatments include standard medications for heart failure and pacemaker/ICD implantation for arrhythmias. However, there is a significant need to treat the underlying causes of PRKAG2 syndrome. Small interfering RNA (siRNA) oligonucleotides present a promising therapeutic approach by reducing mutantPRKAG2mRNA levels, thereby lowering AMPK activity.Hypothesis:Antibody oligonucleotide conjugates (AOCs) can be designed to targetPRKAG2mRNA to treat PRKAG2 syndrome.Aims:To investigate the tolerability and efficacy of an AOC targetingPRKAG2mRNA in mice and non-human primates (NHPs).Methods:iPSC-derived cardiomyocytes were used to screen and identify a potent siRNA againstPRKAG2. The lead siRNA was conjugated to an anti-TfR1 monoclonal antibody to create AOC 1072 for targeted cardiac delivery and was subsequently administered to mice and NHPs.Results:In vitroscreening identified an siRNA with an EC50 90%. A single, IV injection of the mouse surrogate of AOC 1072 at 1 mg/kg (siRNA component) resulted in a potent and durable myocardialPrkag2mRNA reduction in mice, with about 75% and 50% reduction observed at 2 and 6 months, respectively. AOC treatment reduced glycogen accumulation in the skeletal muscle of mice expressing thePrkag2-R528G disease variant. A single IV administration of AOC 1072 at 3 mg/kg (siRNA component) resulted in about 85% reduction of cardiacPRKAG2mRNA in NHPs at 28 days, with no adverse effects (ECG or heart weight).Conclusions:Our data suggests AOC technology can be used efficiently to deliver siRNA to the heart. This precision cardiology treatment can significantly reducePRKAG2mRNA expression, offering a promising therapeutic approach for PRKAG2 syndrome, a currently incurable genetic condition with very limited treatment options.

Introduction
While cognitive-behavioural therapy (CBT) for obsessive-compulsive disorder (OCD) and anxiety disorders (ADs) has been proven to be effective and is commonly recommended, a considerable proportion of patients remain symptomatic, do not respond to treatment or discontinue it. Thus, augmentation strategies aimed at enhancing CBT outcomes are essential to reduce the burden of OCD and ADs on patients and society. Various augmentation strategies for CBT in OCD and ADs have been investigated, yet it remains unclear if they show robust beneficial effects beyond first-line CBT. With this systematic review and meta-analysis, we will provide an overview and critically assess the efficacy of non-pharmacological augmentation strategies in addition to first-line CBT treatment for symptom reduction, response rates and dropout rates in individuals with OCD or ADs.

Methods and analysis
We will screen PubMed, Embase, PsycArticles, PsycInfo, CINAHL, PSYNDEX and Cochrane Register of Controlled Trials without restrictions on publication dates or languages. Additionally, forward, and backward searches of included studies and systematic reviews will be conducted. Two reviewers will independently screen the studies, extract data and assess the methodological quality of the studies. We will exclusively include randomised controlled trials. The primary outcomes will be symptom severity and response rates. Dropout rates will serve as a secondary outcome. Moreover, we will provide a narrative review of the results. We will use subgroup and meta-regression analyses to identify potential moderators and sources of between-study heterogeneity. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the overall quality of evidence.

Ethics and dissemination
Ethical approval is not required. Results will be published in a peer-reviewed journal.

PROSPERO registration number
CRD42024561027.

To the Editor We recently read with great interest the article by Ma et al, which reported that children with atopic dermatitis (AD) had significantly higher odds of difficulty with learning or memory, especially among those with comorbid neurodevelopmental conditions. However, there are some findings that conflict with previous studies, prompting the need for scrutiny into these associations.

This cohort study investigates the association between antihypertensive deprescribing and changes in cognitive function in nursing home residents.

This randomized clinical trial examines the effectiveness of a nurse-supported, self-directed behavioral insomnia intervention for decreasing insomnia severity and improving sleep outcomes among veterans.

This Viewpoint discusses the benefits of mindfulness-based cognitive therapy.

In Reply We thank Tsai and Ma for their interest in our article and appreciate the opportunity to discuss the points raised.

Introduction
Late-life depression (LLD) is a global public health issue, often accompanied by cognitive impairments that can exacerbate the severity of depression and impair social functioning. Despite being a well-established treatment for LLD, the suitability of problem-solving therapy (PST) for individuals with LLD and varying degrees of cognitive impairments warrants further investigation. This paper presents the protocol for a systematic review and meta-analysis of randomised controlled trials (RCTs) aimed at evaluating the effectiveness and acceptability of PST for this specific demographic.

Methods/analysis
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we will conduct a systematic review to synthesise existing research on PST for individuals in this demographic. We will comprehensively search multiple databases and sources, including PubMed, EMBASE, the Cochrane Database and APA PsycNET from inception to October 2023, without language, publication year or type restrictions. Relevant studies will be manually screened from the references. Only RCTs involving PST for LLD will be included. The primary efficacy outcome will be the standardised mean difference in total scores on continuous depression severity scales across different comparison arms. Data extraction will be conducted independently by two reviewers (CH and J-JW), and methodological rigour will be assessed using the Cochrane Risk of Bias assessment tool. Subgroup and sensitivity analyses will be performed to investigate the impact of concomitant cognitive impairments and to evaluate the robustness of the findings.

Ethics and dissemination
The meta-analysis project is expected to be ethically unproblematic and does not require approval from a research ethics committee. The results of this study will be shared through articles in scholarly peer-reviewed journals and presentations in various formats, both print and digital.

PROSPERO registration number
CRD42023473782

Introduction
Insomnia is the most common sleep disorder, and it adversely impacts daily living and increases the risk of chronic and acute health problems. Of the few individuals who seek treatment for insomnia, most pursue help in primary care settings. The management of insomnia most commonly focuses on the prescription of hypnotics and sleep hygiene recommendations, although these are not the most effective treatments. Conversely, cognitive–behavioural therapy for insomnia (CBT-i), which is considered to be the first-line treatment for persistent insomnia, is seldom prescribed by primary care physicians (PCPs) or primary care nurses (PCNs). The hesitancy of these professionals to provide CBT-i is mainly attributed to their heavy workloads and the difficulties in acquiring the skills needed to administer this intervention.

Methods and analysis
A two-arm cluster-randomised study (in which patients are assigned to a PCP or PCN) will be conducted in primary health centres of Majorca Island (Spain). A total of 206 patients will be recruited. Healthcare professionals will be allocated to the intervention or control group in a 1:1 ratio. The intervention group will receive CBT-i and the control group will receive usual care. We will include patients with Insomnia Severity Index scores of 8 or more who also report that insomnia interferes with daily functioning or is noticeable to others. The CBT-i will consist of four individual structured sessions, three in person (20 min each) and one by telephone (10 min) that are administered at intervals of 2–3 weeks. An additional session will be provided for patients taking hypnotic medications. The primary outcome measure is the decrease in sleep latency, which will be measured with the Pittsburg Sleep Quality index at 6 months and 12 months.

Ethics and dissemination
This project was approved by the Ethical Committee of the Balearic Islands (IB 4604/21 PI) and the Primary Care Research Committee of the Department of Majorca Primary Care (PI19/24). All participants are required to provide written informed consent and no study-related procedures will be performed until consent is obtained. The trial results will be published in peer-reviewed journals and presented at conferences.

Trial registration number
ISRCTN10144646.

New England Journal of Medicine, Volume 391, Issue 16, Page 1558-1559, October 24, 2024.