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Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13–83.76) when compared to placebo groups (71.21%, 67.00–75.09). Nausea was the most common adverse event (25.71%, CI 23.96–27.54), while weight change was the least common (3.56%, 1.68–7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.
Background: ALS is a progressive neurodegenerative disease without a cure and limited treatment options. Edaravone, a free radical scavenger, was shown to slow disease progression in a select group of patients with ALS over 6 months; however, the effect on survival was not investigated in randomized trials. The objective of this study is to describe real-world survival effectiveness over a longer timeframe. Methods: This retrospective cohort study included patients with ALS across Canada with symptom onset up to three years. Those with a minimum 6-month edaravone exposure between 2017 and 2022 were enrolled in the interventional arm, and those without formed the control arm. The primary outcome of tracheostomy-free survival was compared between the two groups, accounting for age, sex, ALS-disease progression rate, disease duration, pulmonary vital capacity, bulbar ALS-onset, and presence of frontotemporal dementia or C9ORF72 mutation using inverse propensity treatment weights. Results: 182 patients with mean ± SD age 60±11 years were enrolled in the edaravone arm and 860 in the control arm (mean ± SD age 63±12 years). Mean ± SD time from onset to edaravone initiation was 18±10 months. Tracheostomy-free survival will be calculated. Conclusions: This study will provide evidence for edaravone effectiveness on tracheostomy-free survival in patients with ALS.
Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.
Background: What is the number and size of motor units, and axonal excitability profile in the early stages of muscle weakness in ALS compared to controls? Methods: We enrolled ALS patients with APB manual strength testing rated four or four-minus (ALS:4-arm) and four-plus (ALS:4+ arm) and control participants >35 years-old from the University of Toronto, University of Alberta and Universidade Federal de Sao Paulo. Mean±SD, one-way ANOVA and ANCOVA of ALSFRS-R, PUMN Score, MUNIX, MUSIX, and nerve-excitability testing using QTRAC TROND protocol were reported. Results: Twenty-five ALS patients and 63 controls were included. Mean MUNIX was significantly lower (p<0.0001) and MUSIX was significantly higher (p<0.001) in both ALS groups compared to controls. Mean strength-duration time constant in the ALS:4- arm (0.50ms±0.11; p<0.05) and superexcitability in both ALS groups (ALS:4- -29.05%±9.24, ALS:4+ -27.67%±8.03; p<0.05) were relatively increased, supporting axonal hyperexcitability. Conclusions: Significant motor unit loss measured by MUNIX is already present at the earliest detection of muscle weakness in ALS. Increased MUSIX and altered axonal physiology are associated with axonal sprouting and geometry change(1), along with ion channel dysfunction(2). Future trials targeting muscle weakness in ALS should consider the altered neuronal physiology during early disease stages and utilize neurophysiological biomarkers only in normal-to-mildly weak muscles.
Gene-environment interactions (GxE) have been increasingly explored in psychiatry but with low replication rates. Attention-deficit/hyperactivity disorder (ADHD) is a suitable candidate for studying GxE due to its high heritability and well-defined environmental risk factors. Here, we explored GxE using polygenic risk score (PRS) to represent the genetic liability to ADHD (ADHD-PRS) and environmental risk score (ERS) to represent the combined effects of environmental risk factors. We analyzed longitudinal data of 2,046 individuals (6-14 years of age at baseline and 14-23 at the last follow-up) from the Brazilian High-Risk Cohort Study for Psychiatric Disorders. Psychiatric evaluation included the Child Behavior Checklist and the Strength and Difficulties Questionnaire. Statistical analyses were performed using mixed-effects models. We observed statistically significant interactions between ADHD-PRS and ERS, suggesting that environmental and genetic factors act synergistically in the development of ADHD symptoms. These effects were not present for depression or anxiety symptoms. No evidence of GxE correlation was detected. Mechanistically, our findings suggest that environmental stressors modulate the genetic risk for ADHD. Future studies should investigate whether the reduction of environmental risks can prevent the development of symptoms of ADHD, especially in children with a family history of the disorder.
The global and uneven spread of COVID-19, mirrored at the local scale, reveals stark differences along racial and ethnic lines. We respond to the pressing need to understand these divergent outcomes via neighborhood level analysis of mobility and case count information. Using data from Chicago over 2020, we leverage a metapopulation Susceptible-Exposed-Infectious-Removed model to reconstruct and simulate the spread of SARS-CoV-2 at the ZIP Code level. We demonstrate that exposures are mostly contained within one’s own ZIP Code and demographic group. Building on this observation, we illustrate that we can understand epidemic progression using a composite metric combining the volume of mobility and the risk that each trip represents, while separately these factors fail to explain the observed heterogeneity in neighborhood level outcomes. Having established this result, we next uncover how group level differences in these factors give rise to disparities in case rates along racial and ethnic lines. Following this, we ask what-if questions to quantify how segregation impacts COVID-19 case rates via altering mobility patterns. We find that segregation in the mobility network has contributed to inequality in case rates across demographic groups.
Motor unit number index of the upper trapezius (MUNIX-Trapezius) is a candidate biomarker for bulbar lower motor neuron function; however, reliability data is incomplete. To assess MUNIX-Trapezius reliability in controls, we conducted a systematic review, a cross-sectional study (n = 20), and a meta-analysis. We demonstrated a high inter- and intra-rater intraclass correlation (0.86 and 0.94, respectively), indicating that MUNIX-Trapezius is reliable with between-study variability moderated by age and MUNIX technique. With further validation, this measure can serve as a disease monitoring and response biomarker of bulbar function in the therapeutic development for amyotrophic lateral sclerosis.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, first notified in China, has spread around the world causing high morbidity and mortality, which is due to factors such as the subversion of the immune response. The aims of the study are to summarise and present the immunopathological relationship of COVID-19 with innate immunity. This is a systematic review conducted by the National Library of Medicine – National Institutes of Health, USA (PUBMED), Latin American and Caribbean Literature on Health Sciences (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Scientific Electronic Library Online (SCIELO) databases with clinical trials, in vitro assays, case-controls, cohort studies, systematic reviews and meta-analyses between February 2020 and July 2021. The version 2 of the Cochrane risk-of-bias tool for RCTs (RoB 2), Joana Briggs Institute (JBI) Critical Appraisal (for the review articles) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tools were used to evaluate the quality and the risk of bias of the studies included in this review. The innate immune response through the generation of interferons, alternative pathways and complement system lectins and the joint action of innate immune cells and cytokines and chemokines lead to different clinical outcomes, taking into account the exacerbated inflammatory response and pathogenesis. Then, in addition to interacting as a bridge for adaptive immunity, the innate immune response plays an essential role in primary defense and is one of the starting points for immune evasion by SARS-CoV-2.
Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.
The objective was to use bibliometric analysis to create an infographic of motor unit number estimation methods over the past 50 years. The original method was published in 1971, but secondary and tertiary waves of research using alternative methods occurred in the early 2000s and a decade later. A metric of influence was used to determine if different methods had clear peaks of use over the past 50 years. While the original method continues to register influence, the MUNIX method introduced in 2004 stands out as the most influential method to estimate the innervation status of skeletal muscles.
Mental health problems early in life can negatively impact educational attainment, which in turn have negative long-term effects on health, social and economic opportunities. Our aims were to: (i) estimate the impacts of different types of psychiatric conditions on educational outcomes and (ii) to estimate the proportion of adverse educational outcomes which can be attributed to psychiatric conditions.
Participants (N = 2511) were from a school-based community cohort of Brazilian children and adolescents aged 6–14 years enriched for high family risk of psychiatric conditions. We examined the impact of fear- (panic, separation and social anxiety disorder, specific phobia, agoraphobia and anxiety conditions not otherwise specified), distress- (generalised anxiety disorder, major depressive disorder and depressive disorder not otherwise specified, bipolar, obsessive-compulsive, tic, eating and post-traumatic stress disorder) and externalising-related conditions (attention deficit and hyperactivity disorder, conduct and oppositional-defiant conditions) on grade repetition, dropout, age-grade distortion, literacy performance and bullying perpetration, 3 years later. Psychiatric conditions were ascertained by psychiatrists, using the Development and Well-Being Behaviour Assessment. Propensity score and inverse probability weighting were used to adjust for potential confounders, including comorbidity, and sample attrition. We calculated the population attributable risk percentages to estimate the proportion of adverse educational outcomes in the population which could be attributed to psychiatric conditions. Analyses were conducted separately for males and females.
Fear and distress conditions in males were associated with school dropout (odds ratio (OR) = 2.76; 95% confidence interval (CI) = 1.06, 7.22; p < 0.05) and grade repetition (OR = 2.76; 95% CI = 1.32, 5.78; p < 0.01), respectively. Externalising conditions were associated with grade repetition in males (OR = 1.66; 95% CI = 1.05, 2.64; p < 0.05) and females (OR = 2.03; 95% CI = 1.15, 3.58; p < 0.05), as well as age-grade distortion in males (OR = 1.66; 95% CI = 1.05, 2.62; p < 0.05) and females (OR = 2.88; 95% CI = 1.61, 5.14; p < 0.001). Externalising conditions were also associated with lower literacy levels (β = −0.23; 95% CI = −0.34, −0.12; p < 0.001) and bullying perpetration (OR = 3.12; 95% CI = 1.50, 6.51; p < 0.001) in females. If all externalising conditions were prevented or treated, we estimate that 5.0 and 4.8% of grade repetition would not have occurred in females and males, respectively, as well as 10.2 (females) and 5.3% (males) of age-grade distortion cases and 11.4% of female bullying perpetration.
The study provides evidence of the negative impact of psychiatric conditions on educational outcomes in a large Brazilian cohort. Externalising conditions had the broadest and most robust negative impacts on education and these were particularly harmful to females which are likely to limit future socio-economic opportunities.
There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) São Paulo Research Center.
Between pre-pandemic ELSA-Brasil assessments in 2008–2010 (wave-1), 2012–2014 (wave-2), 2016–2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May–July, July–September, and October–December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders.
In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008–2010: 13.8%; 2016–2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [β = −0.37, 99.5% confidence interval (CI) −0.50 to −0.23], anxiety (β = −0.37, 99.5% CI −0.48 to −0.26), and stress (β = −0.48, 99.5% CI −0.64 to −0.33) symptoms (all ps < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk.
No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.
External causes have been responsible for increased morbidity and mortality rates in Brazil. The most affected age range includes adolescent and young people, indicating the need for investments in public policies with a focus on health promotion. Violence, as one of these causes, has become treated as a public health problem, influenced by social determinants of health.
Describe health promotion practices involving adolescent participants in a health promotion and education group.
Enhance the understanding of adolescent's health promotion.
A qualitative and descriptive experience report was carried out at the Child and Adolescent Care Center in the interior of São Paulo State - Brazil. The programmed activities involved 15 adolescents and took place on sports courts, streets and sidewalks near the Center and in a room for group discussions.
The themes drugs, sexual and reproductive health, interpersonal violence at school and in the neighborhood emerged from the adolescents’ inquiries while accomplishing the proposed tasks in the different study environments. Group discussions were perceived as spaces for reflection and relaxation, and also as facilitators of bonding and, at the same time, of group adherence.
For the study subjects, making good friends, participating in sports and leisure, and talking about themes that are in line with their needs represented an important facilitator for health promotion and social inclusion.
Both psychodynamic group therapy (PGT) and clonazepam are used as treatment strategies in reducing symptoms of generalized social anxiety disorder (GSAD). However, many individuals remain symptomatic after treatment with PGT or clonazepam.
Fifty-eight adult outpatients with a diagnosis of GSAD according to DSM-IV were randomized to 12 weeks PGT plus clonazepam or clonazepam. The Clinical Global Impression-Improvement (CGI-I) Scale was the primary efficacy measure. Secondary efficacy measures included the Liebowitz Social Anxiety Scale (LSAS) total score, the World Health Organization Instrument to Assess Quality of Life—Brief (WHOQOL-Bref) Scale and the Beck Depression Inventory (BDI).
CGI-I data from 57 patients (intent-to-treat population) showed that patients who received PGT plus clonazepam presented significantly greater improvement than those who received clonazepam (P = 0.033). There were no significant differences between the two groups in the secondary efficacy measures.
Our study suggests that the combination of PGT with clonazepam may be a promising strategy for the treatment of GSAD, regarding gains in the global functioning. However the present study failed to detect more specific changes in social anxiety symptomatology between the two groups.
As panic disorder (PD) has a chronic course, it is important to identify predictors that might be related to non-remission. The aim of this study is to verify whether history of trauma and defense style are predictors to pharmacological treatment response in PD patients.
The sample was composed by 47 PD patients according to DSM-IV who were treated with sertraline for 16 weeks. Evaluations were assessed by the C.G.I. (Clinical Global Impression), the Hamilton-Anxiety Scale, the Hamilton-Depression Scale, the Panic Inventory and the DSQ-40 (Defense Style Questionnaire) at baseline and after treatment.
Full remission was observed in 61.7% of the sample. The predictors significantly associated with non-remission were: severity of PD (p = 0.012), age of onset (p = 0.02) and immature defenses (p = 0.032). In addition, the history of trauma was associated with early onset of PD (p = 0.043).
Panic patients had as predictors of worse response to pharmacological treatment the early onset and the severity of PD symptoms as well as the use of immature defenses at baseline. This finding corroborates the relevance of the evaluation of factors that might affect the response so as to enable the development of appropriate treatment for each patient.
Adolescent violence represents a severe public health problem. Adolescents between 10 and 19 years old can get involved in violent acts as victims as well as perpetrators.
Get to know the senses and meanings attributed to violence from the perspective of adolescent participants in a health promotion and education group.
Enhance the understanding of the adolescent violence phenomenon.
A qualitative and descriptive experience report was carried out at the Child and Adolescent Care Center in the interior of São Paulo State – Brazil. The 15 study subjects participated in weekly group meetings taking between one and two hours, during which the brainstorming creativity technique was used.
According to the adolescent participants, violence means everything that causes pain, suffering and is related with physical aggressions, discussions, rape, scolding and humiliation, pedophilia and violent movies on television. They denoted special concern with physical violence between couples and siblings and with songs that defile mainly the feminine image.
Group activities that allow adolescents to reflect can enhance a more critical awareness of themes like violence. They can also stimulate the search for actions to improve the reality these subjects are inserted in.
Previous work showed traumatic life events (TLE) with intention to harm, like bullying and abuse, to be more strongly associated with psychotic experiences (PE) than other types of trauma, like accidents. However, this association is subject to reporting bias and can be confounded by demographic characteristics and by differences in dose of exposure across different trauma categories. We studied the association between TLE with and without intention to harm and PE, taking into account potential confounders and biases.
A total of 2245 children and adolescents aged 6–14 years were interviewed by psychologists. The interview included the presence of 20 PE (both self-report and psychologist evaluation). In addition, parents provided information on child exposure to trauma, mental health and PE.
Results showed no significant association between TLE without intention to harm only and PE for the three methods of assessment of PE (self-report, parent report and psychologist rating). On the other hand, there was a positive association between PE and TLE in groups exposed to traumatic experiences with intention to harm (with intention to harm only and with and without intention to harm). Results remained significant after controlling for demographic and clinical confounders, but this positive association was no longer significant after adjusting for the number of TLE.
TLE with intention to harm display a stronger association with PE than TLE without intention to harm, and this difference is likely reducible to a greater level of traumatic exposure associated with TLE with intention to harm.
This in vitro study evaluated the effect of light curing unit (LCU) type, mouthwashes, and soft drink on chemical degradation of a nanofilled resin composite. Samples (80) were divided into eight groups: halogen LCU, HS—saliva (control); HPT—Pepsi Twist®; HLC—Listerine®; HCP—Colgate Plax®; LED LCU, LS—saliva (control); LPT—Pepsi Twist®; LLC—Listerine®; LCP—Colgate Plax®. The degree of conversion analysis and the measure of the peak area at 2,930 cm−1 (organic matrix) of resin composite were done by Fourier-transform Raman spectroscopy (baseline, after 7 and 14 days). The data were subjected to multifactor analysis of variance (ANOVA) at a 95% confidence followed by Tukey's HSD post-hoc test. The DC ranged from 58.0% (Halogen) to 59.3% (LED) without significance. Differences in the peak area between LCUs were found after 7 days of storage in S and PT. A marked increase in the peak intensity of HLC and LLC groups was found. The soft-start light-activation may influence the chemical degradation of organic matrix in resin composite. Ethanol contained in Listerine® Cool Mint mouthwash had the most significant degradation effect. Raman spectroscopy is shown to be a useful tool to investigate resin composite degradation.