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JAMA Network Open Sep 2023Influenza-like illness (ILI) activity has been associated with increased risk of cardiopulmonary (CP) events during the influenza season. High-dose trivalent influenza... (Randomized Controlled Trial)
Randomized Controlled Trial
Temporal Association Among Influenza-Like Illness, Cardiovascular Events, and Vaccine Dose in Patients With High-Risk Cardiovascular Disease: Secondary Analysis of a Randomized Clinical Trial.
IMPORTANCE
Influenza-like illness (ILI) activity has been associated with increased risk of cardiopulmonary (CP) events during the influenza season. High-dose trivalent influenza vaccine was not superior to standard-dose quadrivalent vaccine for reducing these events in patients with high-risk cardiovascular (CV) disease in the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial.
OBJECTIVE
To evaluate whether high-dose trivalent influenza vaccination is associated with benefit over standard-dose quadrivalent vaccination in reducing CP events during periods of high, local influenza activity.
DESIGN, SETTING, AND PARTICIPANTS
This study was a prespecified secondary analysis of INVESTED, a multicenter, double-blind, active comparator randomized clinical trial conducted over 3 consecutive influenza seasons from September 2016 to July 2019. Follow-up was completed in July 2019, and data were analyzed from September 21, 2016, to July 31, 2019. Weekly Centers for Disease Control and Prevention (CDC)-reported, state-level ILI activity was ascertained to assess the weekly odds of the primary outcome. The study population included 3094 patients with high-risk CV disease from participating centers in the US.
INTERVENTION
Participants were randomized to high-dose trivalent or standard-dose quadrivalent influenza vaccine and revaccinated for up to 3 seasons.
MAIN OUTCOMES AND MEASURES
The primary outcome was the time to composite of all-cause death or CP hospitalization within each season. Additional measures included weekly CDC-reported ILI activity data by state.
RESULTS
Among 3094 participants (mean [SD] age, 65 [12] years; 2309 male [75%]), we analyzed 129 285 person-weeks of enrollment, including 1396 composite primary outcome events (1278 CP hospitalization, 118 deaths). A 1% ILI increase in the prior week was associated with an increased risk in the primary outcome (odds ratio [OR], 1.14; 95% CI, 1.07-1.21; P < .001), CP hospitalization (OR, 1.13; 95% CI, 1.06-1.21; P < .001), and CV hospitalization (OR, 1.12; 95% CI, 1.04-1.19; P = .001), after adjusting for state, demographic characteristics, enrollment strata, and CV risk factors. Increased ILI activity was not associated with all-cause death (OR, 1.00; 95% CI, 0.88-1.13; P > .99). High-dose compared with standard-dose vaccine did not significantly reduce the primary outcome, even when the analysis was restricted to weeks of high ILI activity (OR, 0.88; 95% CI, 0.65-1.20; P = .43). Traditionally warmer months in the US were associated with lower CV risk independent of local ILI activity.
CONCLUSIONS AND RELEVANCE
In this secondary analysis of a randomized clinical trial, ILI activity was temporally associated with increased CP events in patients with high-risk CV disease, and a higher influenza vaccine dose did not significantly reduce temporal CV risk. Other seasonal factors may play a role in the coincident high rates of ILI and CV events.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02787044.
Topics: United States; Humans; Male; Aged; Cardiovascular Diseases; Influenza, Human; Virus Diseases; Influenza Vaccines; Heart Failure; Psychomotor Agitation
PubMed: 37707817
DOI: 10.1001/jamanetworkopen.2023.31284 -
Life (Basel, Switzerland) Dec 2023This meta-analysis aimed to assess the association between mild traumatic brain injury (mTBI) and the risk of developing Parkinsonism. A systematic literature review was... (Review)
Review
This meta-analysis aimed to assess the association between mild traumatic brain injury (mTBI) and the risk of developing Parkinsonism. A systematic literature review was conducted using PubMed, Embase, and Cochrane Library databases. Studies were eligible if they reported on the association between MTBI and Parkinsonism. Pooled odds ratios (ORs) were calculated using a random-effects model. Publication bias was assessed using Egger's and Begg's tests. A total of 18 studies were included in this meta-analysis, with 1,484,752 participants. The overall OR for Parkinsonism in individuals with a history of mTBI was 1.637 (95% CI, 1.203-2.230; = 0.01), indicating a significant association. The OR for Parkinson's disease (PD) specifically was 1.717 (95% CI, 1.206-2.447; = 0.01). However, insufficient data on tics and akathisia limited a meta-analysis. There was no evidence of publication bias according to Egger's ( = 0.8107) and Begg's ( = 0.4717) tests. This meta-analysis provides evidence that mTBI is a significant risk factor for Parkinsonism, particularly PD. However, the findings should be interpreted with caution due to the heterogeneity among the studies included and the study's limitations. Further research is needed to confirm these findings and to investigate the underlying mechanisms of the mTBI-Parkinsonism association.
PubMed: 38255648
DOI: 10.3390/life14010032 -
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 -
The Annals of Pharmacotherapy Feb 2024Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical...
BACKGROUND
Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo.
OBJECTIVE
Our study's aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19.
METHOD
We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with "Covid-19" excluded.
RESULTS
A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively.
CONCLUSIONS AND RELEVANCE
This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.
Topics: Humans; SARS-CoV-2; COVID-19; Retrospective Studies; Ritonavir; Dysgeusia; Pharmacovigilance; Antiviral Agents
PubMed: 37144730
DOI: 10.1177/10600280231169256 -
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 -
Frontiers in Psychiatry 2024Cariprazine, a third-generation antipsychotic (TGAs), has demonstrated efficacy in the treatment of schizophrenia with good tolerability profile. Actual real-world...
BACKGROUND
Cariprazine, a third-generation antipsychotic (TGAs), has demonstrated efficacy in the treatment of schizophrenia with good tolerability profile. Actual real-world literature data are lacking, particularly when exploring its efficacy in the long term. The present study examined the effects of cariprazine treatment on specific psychopathological domains with a particular focus on outcomes and side effects in real-life experience, after a long-term treatment.
METHODS
The present 12-month longitudinal naturalistic study included a sample of subjects with a DSM-5-TR diagnosis of schizophrenia, recruited in the outpatients' psychiatric services of university and community hospitals in Italy, naturally treated with cariprazine. The assessments included: a sociodemographic data sheet, the Structured Clinical Interview for the DSM-5 (SCID-5), the Positive and Negative Symptom Scale (PANSS) and the St. Hans Rating Scale (SHRS). The PANSS was also administered after 6 (T1) and 12 (T2) months of treatment with cariprazine while the SHRS at T1.
RESULTS
The total sample consisted of 31 patients, 15 males and 16 females. A significant decrease of the PANSS' subscales, Marder factors and total mean scores emerged at both T1 and T2 with respect to T0. Extrapyramidal symptoms occurred in a minority of patients and in mild or mild/moderate forms: no patient showed moderate forms of psychic/motor akathisia or dystonia, three subjects showed moderate parkinsonism.
CONCLUSIONS
This study confirms a good efficacy profile of cariprazine in both positive and negative symptoms in patients with Schizophrenia, combined with a good tolerability profile in extrapyramidal symptoms.
PubMed: 38835554
DOI: 10.3389/fpsyt.2024.1382013 -
BMC Public Health Dec 2023There is conclusive evidence of a multifaceted and bidirectional relationship between loneliness and depression and anxiety. Nonetheless, more extensive research is...
BACKGROUND
There is conclusive evidence of a multifaceted and bidirectional relationship between loneliness and depression and anxiety. Nonetheless, more extensive research is needed to examine their relationships at a more granular level. This study employed a network analysis approach to identify the pathological mechanisms underpinning those relationships and to identify important bridge nodes as potential targets for intervention.
METHODS
941 University students were included in this study. The ULS-6 (the short-form UCLA Loneliness Scale) was used to assess loneliness, the PHQ-9 (Patient Health questionnaire-9) and GAD-7 (Generalized anxiety disorder 7-item) scales were used to assess the symptoms of depression and anxiety. We constructed two network structures of loneliness-anxiety and loneliness-depression and computed bridge expected influence for each symptom. In addition, we showed a flow network of "Suicide" containing symptoms of depression and loneliness.
RESULTS
All edges were positive in both networks constructed and the strongest edges were present within disorder communities. The overall connection between loneliness and depression was stronger compared to anxiety. The results demonstrated that the loneliness item "People are around me but not with me" was identified as bridge symptom in both networks. Furthermore, "Suicide" was directly connected to five symptoms of depression and four items of loneliness, with the strongest connections being between it and "Feeling of worthlessness" and "Psychomotor agitation/retardation".
CONCLUSIONS
Our findings provide a more nuanced explanation of the link between loneliness and depression and anxiety. The results identified the bridge symptom "People are around me but not with me", which had the strongest effect on enhancing symptoms of depression and anxiety. Clinical improvements based on the findings of this study and the impact of the intervention are discussed.
Topics: Humans; Loneliness; Depression; Universities; Anxiety; Anxiety Disorders; Students
PubMed: 38093295
DOI: 10.1186/s12889-023-17435-4 -
Molecular Psychiatry Feb 2024Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited....
Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited. In this study, we capitalized on a large sample of patients to examine the neural correlates of PmD in depression. This study included 820 healthy participants and 699 patients with remitted (n = 402) or current (n = 297) depression. Patients were further categorized as having psychomotor retardation, agitation, or no PmD. We compared resting-state functional connectivity (ROI-to-ROI) between nodes of the cerebral motor network between the groups, including primary motor cortex, supplementary motor area, sensory cortex, superior parietal lobe, caudate, putamen, pallidum, thalamus, and cerebellum. Additionally, we examined network topology of the motor network using graph theory. Among the currently depressed 55% had PmD (15% agitation, 29% retardation, and 11% concurrent agitation and retardation), while 16% of the remitted patients had PmD (8% retardation and 8% agitation). When compared with controls, currently depressed patients with PmD showed higher thalamo-cortical and pallido-cortical connectivity, but no network topology alterations. Currently depressed patients with retardation only had higher thalamo-cortical connectivity, while those with agitation had predominant higher pallido-cortical connectivity. Currently depressed patients without PmD showed higher thalamo-cortical, pallido-cortical, and cortico-cortical connectivity, as well as altered network topology compared to healthy controls. Remitted patients with PmD showed no differences in single connections but altered network topology, while remitted patients without PmD did not differ from healthy controls in any measure. We found evidence for compensatory increased cortico-cortical resting-state functional connectivity that may prevent psychomotor disturbance in current depression, but may perturb network topology. Agitation and retardation show specific connectivity signatures. Motor network topology is slightly altered in remitted patients arguing for persistent changes in depression. These alterations in functional connectivity may be addressed with non-invasive brain stimulation.
Topics: Humans; Female; Male; Adult; Depressive Disorder, Major; Magnetic Resonance Imaging; Middle Aged; Psychomotor Disorders; Psychomotor Agitation; Brain; Depression; Neural Pathways; Motor Cortex; Brain Mapping; Nerve Net
PubMed: 38036604
DOI: 10.1038/s41380-023-02327-1 -
JMIR Mental Health Oct 2023Anhedonia and depressed mood are considered the cardinal symptoms of major depressive disorder. These are the first 2 items of the Patient Health Questionnaire (PHQ)-9...
BACKGROUND
Anhedonia and depressed mood are considered the cardinal symptoms of major depressive disorder. These are the first 2 items of the Patient Health Questionnaire (PHQ)-9 and comprise the ultrabrief PHQ-2 used for prescreening depressive symptomatology. The prescreening performance of alternative PHQ-9 item pairings is rarely compared with that of the PHQ-2.
OBJECTIVE
This study aims to use machine learning (ML) with the PHQ-9 items to identify and validate the most predictive 2-item depressive symptomatology ultrabrief questionnaire and to test the generalizability of the best pairings found on the primary data set, with 6 external data sets from different populations to validate their use as prescreening instruments.
METHODS
All 36 possible PHQ-9 item pairings (each yielding scores of 0-6) were investigated using ML-based methods with logistic regression models. Their performances were evaluated based on the classification of depressive symptomatology, defined as PHQ-9 scores ≥10. This gave each pairing an equal opportunity and avoided any bias in item pairing selection.
RESULTS
The ML-based PHQ-9 items 2 and 4 (phq2&4), the depressed mood and low-energy item pairing, and PHQ-9 items 2 and 8 (phq2&8), the depressed mood and psychomotor retardation or agitation item pairing, were found to be the best on the primary data set training split. They generalized well on the primary data set test split with area under the curves (AUCs) of 0.954 and 0.946, respectively, compared with an AUC of 0.942 for the PHQ-2. The phq2&4 had a higher AUC than the PHQ-2 on all 6 external data sets, and the phq2&8 had a higher AUC than the PHQ-2 on 3 data sets. The phq2&4 had the highest Youden index (an unweighted average of sensitivity and specificity) on 2 external data sets, and the phq2&8 had the highest Youden index on another 2. The PHQ-2≥2 cutoff also had the highest Youden index on 2 external data sets, joint highest with the phq2&4 on 1, but its performance fluctuated the most. The PHQ-2≥3 cutoff had the highest Youden index on 1 external data set. The sensitivity and specificity achieved by the phq2&4 and phq2&8 were more evenly balanced than the PHQ-2≥2 and ≥3 cutoffs.
CONCLUSIONS
The PHQ-2 did not prove to be a more effective prescreening instrument when compared with other PHQ-9 item pairings. Evaluating all item pairings showed that, compared with alternative partner items, the anhedonia item underperformed alongside the depressed mood item. This suggests that the inclusion of anhedonia as a core symptom of depression and its presence in ultrabrief questionnaires may be incompatible with the empirical evidence. The use of the PHQ-2 to prescreen for depressive symptomatology could result in a greater number of misclassifications than alternative item pairings.
PubMed: 37856186
DOI: 10.2196/48444