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Neuropsychopharmacology Reports Mar 2024This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy,... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.
METHODS
Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.
RESULTS
A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.
CONCLUSIONS
Overall BRE showed similar utility to ARI and a good risk-benefit balance.
Topics: Humans; Aripiprazole; Depressive Disorder, Major; Japan; Psychomotor Agitation; Network Meta-Analysis; Weight Gain; Randomized Controlled Trials as Topic; Thiophenes; Quinolones
PubMed: 38219278
DOI: 10.1002/npr2.12414 -
International Journal of Molecular... Dec 2023Significant advances have been achieved in understanding the critical role of enhancer RNAs (eRNAs) in the complex field of gene regulation. However, notable uncertainty...
Significant advances have been achieved in understanding the critical role of enhancer RNAs (eRNAs) in the complex field of gene regulation. However, notable uncertainty remains concerning the biology of eRNAs, highlighting the need for continued research to uncover their exact functions in cellular processes and diseases. We present a comprehensive study to scrutinize mutation density patterns, mutation strand bias, and mutation burden in eRNAs across multiple cancer types. Our findings reveal that eRNAs exhibit mutation strand bias akin to that observed in protein-coding RNAs. We also identified a novel pattern, in which mutation density is notably diminished around the central region of the eRNA, but conspicuously elevated towards both the beginning and end. This pattern can be potentially explained by a mechanism involving heightened transcriptional activity and the activation of transcription-coupled repair. The central regions of the eRNAs appear to be more conserved, hinting at a potential mechanism preserving their structural and functional integrity, while the extremities may be more susceptible to mutations due to increased exposure. The evolutionary trajectory of this mutational pattern suggests a nuanced adaptation in eRNAs, where stability at their core coexists with flexibility at their extremities, potentially facilitating their diverse interactions with other genetic entities.
Topics: Humans; Enhancer RNAs; Biological Evolution; Excision Repair; Mutation; Neoplasms; Psychomotor Agitation
PubMed: 38203707
DOI: 10.3390/ijms25010534 -
International Journal of Molecular... Dec 2023Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases...
Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy. Thyroid nodule biopsies were subjected to a precipitation step with both the insoluble and supernatant fractions subjected to proteome and peptidome profiling. Proteomic analysis identified annexin A1 as a potential biomarker of thyroid cancer malignancy, with its levels increased in malignant samples. Also upregulated were the acetylated peptides of annexin A1, revealed by the peptidome analysis of the supernatant fraction. In addition, supernatant peptidomic analysis revealed a number of acetylated histone peptides that were significantly elevated in the malignant group, suggesting higher gene transcription activity in malignant tissue. Two of these peptides were found to be robust malignancy predictors, with an area under the receiver operating a characteristic curve (ROC AUC) above 0.95. Thus, this combination of proteomics and peptidomics analyses improved the detection of malignant lesions and also provided new evidence linking thyroid cancer development to heightened transcription activity. This study demonstrates the importance of peptidomic profiling in complementing traditional proteomics approaches.
Topics: Humans; Annexin A1; Histones; Acetylation; Proteomics; Thyroid Neoplasms; Adenocarcinoma; Biopsy, Fine-Needle; Psychomotor Agitation; Peptides
PubMed: 38203548
DOI: 10.3390/ijms25010376 -
BMC Psychiatry Jan 2024To explore the influence of CYP2D6 genetic polymorphism on risperidone metabolism, thereby affecting risperidone's effects and safeties in patients with chronic...
BACKGROUND
To explore the influence of CYP2D6 genetic polymorphism on risperidone metabolism, thereby affecting risperidone's effects and safeties in patients with chronic schizophrenia.
METHODS
Sixty-nine subjects with chronic schizophrenia treated with risperidone were recruited. CYP2D6 genotypes was determined using targeted sequencing and translated into phenotype using activity system. Risperidone plasma concentrations were measured using HPLC. Positive and Negative Symptom Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) were used to evaluate the existence and severity of psychiatric symptoms, Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS) for neurological side effects. Metabolic and endocrine status assess were also included.
RESULTS
The plasma drug concentrations varied hugely among individuals. Intermediate metabolizer (IM) group had higher plasma levels of RIP and dose corrected RIP concentration, RIP/9-OH-RIP ratio and C/D ratio than normal metabolizer (NM) group (p < 0.01). There was no statistic difference between responders and non-responders in dose-adjusted plasma concentrations and ratios of RIP/9-OH-RIP and C/D. The occurrence of EPS was related to active moiety levels in 4th week (p < 0.05). The prolactin (PRL) levels in two follow-ups were both significantly higher than baseline (p < 0.01). PRL change from baseline to week 4 and week 8 were both positively associated with active moiety concentration detected in week 4 (p < 0.05).
CONCLUSIONS
The risperidone plasma levels have great inter- and intraindividual variations, and are associated with the CYP2D6 phenotypes, as well as the changes in serum prolactin in patients diagnosed with chronic schizophrenia.
Topics: Humans; Risperidone; Schizophrenia; Cytochrome P-450 CYP2D6; Prolactin; Polymorphism, Genetic
PubMed: 38200532
DOI: 10.1186/s12888-023-05488-z -
Journal of Autoimmunity Feb 2024The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by... (Review)
Review
The term Hoigné's syndrome denotes a mimicker of anaphylaxis, which occurs immediately after the parenteral administration of a drug and is likely caused by non-thrombotic pulmonary and systemic drug micro-embolization. It has so far been documented uniquely in case reports and small case series. Because this condition has never been systematically evaluated, we performed a structured literature review (pre-registered as CRD42023392962). The search was carried out in Excerpta Medica, National Library of Medicine, and Google Scholar. Cases with features consistent with anaphylaxis, urticaria, angioedema, asthma, syncope, anxiety, or panic attack triggered by needle phobia, and local anesthetic systemic toxicity were excluded. For the final analysis, we retained reports published between 1951 and 2021, which presented 247 patients with Hoigné's syndrome: 37 children and 211 adults with a male: female ratio of 2.1 : 1.0. The patients presented within 1 min after parenteral administration of a drug (intramuscular penicillin in 90 % of the cases) with chest discomfort, shortness of breath, fear of death, psychomotor agitation, and auditory or visual hallucinations and impairment. Recovery occurred within 30 min. The diagnosis of Hoigné's syndrome was also established in five patients 66-91 years of age with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the aforementioned symptoms. It was therefore speculated that pulmonary drug micro-embolization induced a lethal cardiovascular compromise in these individuals. Histologic investigations supporting this hypothesis were performed in only one case. The diagnosis of Hoigné's pulmonary drug micro-embolization was established also in five patients with pre-existing cardiovascular or pulmonary diseases, who suddenly died after the administration of penicillin despite not exhibiting the afore mentioned symptoms. Histologic investigations supporting this hypothesis were performed in only one case. In conclusion, Hoigné's syndrome is an uncommon non-immune-mediated reaction. This report seeks to promote broader awareness and knowledge regarding this alarming mimicker of anaphylaxis. Diagnosis relies solely on clinical evaluation.
Topics: United States; Adult; Child; Humans; Male; Female; Penicillin G Procaine; Anaphylaxis; Penicillins; Hallucinations; Syndrome; Lung Diseases
PubMed: 38194789
DOI: 10.1016/j.jaut.2023.103164 -
Sleep Mar 2024
Topics: Humans; Psychomotor Agitation; Restless Legs Syndrome; Dopamine; Iron; Antipsychotic Agents; Analgesics, Opioid
PubMed: 38190342
DOI: 10.1093/sleep/zsae008 -
Cureus Dec 2023Antipsychotics are the mainstay for the treatment of schizophrenia and other psychotic disorders; however, these agents are associated with an extensive side effect...
Antipsychotics are the mainstay for the treatment of schizophrenia and other psychotic disorders; however, these agents are associated with an extensive side effect profile that may complicate treatment outcomes. We present the case of a 35-year-old woman with a history of schizoaffective disorder and five prior psychiatric hospitalizations. The patient first presented to the hospital for disorganized behavior, in addition to poor sleep, auditory hallucinations, and racing thoughts in the context of medication nonadherence. She received two loading doses of intra-muscular paliperidone with fair symptomatic improvement. After discharge, she was scheduled to receive a monthly dose of paliperidone, which she missed, resulting in decompensation, re-emergence of psychosis, and another hospitalization two months later. She was given the missed dose with no improvement and progressive deterioration, for which alternative agents were tried. She received olanzapine and was tried briefly on quetiapine and haloperidol as well, with no benefit, and she also developed abnormal perioral movements. She was reloaded with paliperidone, and her psychotic symptoms improved, although she developed akathisia and hyperprolactinemia. The patient returned to the hospital two days later after being discharged, due to disorganized behavior and multiple delusions. Clozapine was started and titrated to 100 mg qam and 200 mg qhs. While on clozapine, she developed profuse sialorrhea that was treated with sublingual atropine drops, and by the time of discharge psychotic symptoms had markedly improved, perioral movements diminished, and prolactin level trended down. The patient maintained stability for over a year after the last admission. Identifying antipsychotics to successfully treat refractory psychosis and managing their multiple potential side effects is challenging but can result in better quality of life for patients as well as improved treatment adherence. This case report is unique in the way it illustrates this point, while discussing different approaches to managing multiple side effects that can happen simultaneously.
PubMed: 38186486
DOI: 10.7759/cureus.50063 -
BMC Psychiatry Jan 2024Dizziness is a common symptom in adults, and chronic dizziness, such as persistent postural-perceptual dizziness, is also frequently reported and affects the quality of...
BACKGROUND
Dizziness is a common symptom in adults, and chronic dizziness, such as persistent postural-perceptual dizziness, is also frequently reported and affects the quality of life of patients. This study aimed to identify psychosocial factors related to dizziness and chronic dizziness in a large-scale nationwide cohort.
METHODS
This population-based cross-sectional study used the database of the Eighth Korea National Health and Nutrition Examination Survey in 2020. Data from 4,147 adults over 40 years old were analyzed, and 1,102 adults who experienced dizziness were included in the dizziness cohort. Demographic data, medical conditions, comorbidities, functional status variables, nutritional variables and psychological variables were collected. The pattern of depressive symptoms according to the severity of dizziness was analyzed by network analysis.
RESULTS
The prevalence rate of dizziness was 24.6% in the general population, and chronic dizziness (≥ 3 months) developed in 210 of 1,102 (17.1%) individuals who experienced dizziness. Multiple logistic regression analysis revealed that female sex, stress, and depression were associated with dizziness. Chronic dizziness was related to tympanic abnormalities, diabetes, short sleep duration, and higher levels of stress and depression. Psychomotor retardation/agitation was a central symptom of depression in patients with chronic dizziness.
CONCLUSIONS
This study found sex differences in factors associated with dizziness and identified psychosocial factors linked to chronic dizziness. Focusing on somatic factors rather than depressive symptoms may benefit patients with chronic dizziness.
Topics: Adult; Humans; Male; Female; Dizziness; Cross-Sectional Studies; Nutrition Surveys; Quality of Life; Comorbidity
PubMed: 38166799
DOI: 10.1186/s12888-023-05464-7 -
Neuropsychiatric Disease and Treatment 2023Major depressive disorder (MDD) often co-occurs with dementia and other neurological disorders, and treatment with antidepressants can improve symptoms, quality of life,...
OBJECTIVE
Major depressive disorder (MDD) often co-occurs with dementia and other neurological disorders, and treatment with antidepressants can improve symptoms, quality of life, and survival in these patients. This narrative review provides an expert opinion about the role and effectiveness of trazodone in the treatment of older adults with MDD and cognitive impairment due to physical illnesses, such as dementia.
RESULTS
Because of its mechanism of action, trazodone can treat several depression symptoms often seen in people with dementia, including insomnia, agitation, anxiety, cognitive impairment, and irritability.
CONCLUSION
Trazodone may be beneficial for patients with dementia or other neurological disorders comorbid with MDD, especially when the clinical picture of depression includes or is comorbid to symptoms of insomnia, irritability, inner tension, anxiety, or psychomotor agitation.
PubMed: 38155994
DOI: 10.2147/NDT.S434130 -
Alzheimer's & Dementia : the Journal of... Mar 2024iWHELD is a digital person-centered care program for people with dementia in nursing homes adapted for remote delivery during the COVID-19 pandemic. (Randomized Controlled Trial)
Randomized Controlled Trial
Impact of the iWHELD digital person-centered care program on quality of life, agitation and psychotropic medications in people with dementia living in nursing homes during the COVID-19 pandemic: A randomized controlled trial.
INTRODUCTION
iWHELD is a digital person-centered care program for people with dementia in nursing homes adapted for remote delivery during the COVID-19 pandemic.
METHODS
A 16-week two-arm cluster-randomized controlled trial in 149 UK nursing homes compared iWHELD with treatment as usual (TAU). Primary outcome was the overall quality of life with secondary outcomes of agitation and psychotropic use.
RESULTS
iWHELD conferred benefit to quality of life on the primary (F = 4.3, p = 0.04) and secondary measures of quality of life (F = 6.45, p = 0.01) and reduced psychotropic medication use (χ = 4.08, p = 0.04) with no worsening of agitation. Benefit was seen in participants who contracted COVID-19, those with agitation at baseline, and those taking psychotropic medications.
DISCUSSION
iWHELD confers benefits to quality of life and key measures of well-being, can be delivered during the challenging conditions of a pandemic, and should be considered for use alongside any emerging pharmacological treatment for neuropsychiatric symptoms.
HIGHLIGHTS
iWHELD is the only remote, digital delivery nursing home training programme for dementia care iWHELD improved quality of life in people with dementia and reduced antipsychotic use without worsening of agitation Residents who contracted Covid-19 during the study also experienced benefits from iWHELD iWHELD offers a valuable, pandemic-safe tool for improving dementia care.
Topics: Humans; Aged; Pandemics; Homes for the Aged; Quality of Life; Dementia; COVID-19; Nursing Homes; Patient-Centered Care; Psychomotor Agitation
PubMed: 38116916
DOI: 10.1002/alz.13582