Effectiveness of Ketamine for the Treatment of Post-Traumatic Stress Disorder - A Systematic Review and Meta-Analysis.

Objective: Post-traumatic stress disorder (PTSD) is an enduring condition characterized by a chronic course and impairments across several areas. Despite its significance, treatment options remain limited, and remission rates are often low. Ketamine has demonstrated antidepressant properties and appears to be a promising agent in the management of PTSD. Method: A systematic review was conducted in PubMed/MEDLINE, Cochrane Library, Clinicaltrials.gov, Lilacs, Scopus, and Embase, covering studies published between 2012 and December 2022 to assess the effectiveness of ketamine in the treatment of PTSD. Ten studies, consisting of five RCTs, two crossover trials, and three non-randomized trials, were included in the meta-analysis. Results: Ketamine demonstrated significant improvements in PCL-5 scores, both 24 hours after the initial infusion and at the endpoint of the treatment course, which varied between 1 to 4 weeks in each study. Notably, the significance of these differences was assessed using the Two Sample T-test with pooled variance and the Two Sample Welch's T-test, revealing a statistically significant effect for ketamine solely at the endpoint of the treatment course (standardized effect size= 0.25; test power 0.9916; 95% CI = 0.57 to 17.02, p=0.0363). It is important to note that high heterogeneity was observed across all analyses. Conclusions: Our findings suggest that ketamine holds promise as an effective treatment option for PTSD. However, further trials are imperative to establish robust data for this intervention.

Brazilian Psychiatric Association guidelines for the treatment of generalized anxiety disorder (GAD). Pharmacological and Psychotherapy approach. Perspectives.

OBJECTIVE: To combine elements of a systematic review and critical review to produce best evidence synthesis for the treatament of GAD. METHOD: There was included systematic reviews, metanalysis, and randomized controlled trials. Descriptor used was "generalized anxiety disorder", resulting in 4860 articles and 7 other studies, of which 59 were selected. RESULTS: Antidepressants and benzodiazepines are indicated, as well as pregabalin. From, atypical antipsychotics quetiapine has been studied. Cognitive behavior therapy (third wave of behavioral and cognitive therapies) as well as individual CBT proven to be effective. CONCLUSION: There is extensive literature on many effective treatments for GAD. The present work summarizes the therapeutic possibilities, emphasizing those available in the Brazil. Further studies are still needed to compare other available medications, to assess psychotherapies in more depth, new treatments and specially to assess the ideal time for maintaining therapy.

Translation and adaptation into Brazilian Portuguese and investigation of the psychometric properties of the Children's Sleep Habits Questionnaire (CSHQ-BR).

OBJECTIVES: To translate to Brazilian Portuguese, culturally adapt and confirm the psychometric parameters of validity and reliability of the Children's Sleep Habits Questionnaire (CSHQ-BR) in children. METHODS: A sample of 314 typically developing children, 51% girls, mean age 7.12 years (SD = 2.04 years) were assessed, comprising 227 from São Paulo and 87 from the Amazon region. Translation, back translation, cultural adaptation, a pilot study and item review were carried out, yielding the final version of the CSHQ. Psychometric parameters were determined based on content validity coefficient (CVC), test-retest, internal consistency, evidence of convergent validity and internal structure. RESULTS: The final CVC for the scale was 0.88. Intraclass correlation was 0.98 for the overall questionnaire and ranged from 0.88 to 0.98 for subscales. CSHQ-BR internal consistency was α = 0.81 for the CSHQ-BR total score (95% CI) and from 0.51 to 0.75 for subscales. Exploratory factor analysis suggested a novel 4-factor structure. A positive correlation was found between the CSHQ and the Questionnaire on Sleep Behavior. Mean total CSHQ score in Brazilian children was 46.85 (SD = 9.43), and boys had a higher mean total score than girls, although not statistically significant. CONCLUSION: The CSHQ-BR exhibited satisfactory equivalence for the original English abbreviated form and the Brazilian Portuguese version, proving a useful sleep screening instrument for identifying sleep problems in Brazilian children aged 4-10 years.

Evidence for the beneficial effect of ketamine in the treatment of patients with post-traumatic stress disorder: A systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) is an anxiety disorder with manifestations somatic resulting from reliving the trauma. The therapy for the treatment of PTSD has limitations, between reduced efficacy and "PTSD pharmacotherapeutic crisis". Scientific evidence has shown that the use of ketamine has benefits for the treatment of depressive disorders and other symptoms present in PTSD compared to other conventional therapies. Therefore, this study aims to analyze the available evidence on the effect of ketamine in the treatment of post-traumatic stress. The systematic review and the meta-analysis were conducted following PRISMA guidelines and RevManager software, using randomized controlled trials and eligible studies of quality criteria for data extraction and analysis. The sample design evaluated included the last ten years, whose search resulted in 594 articles. After applying the exclusion criteria, 35 articles were selected, of which 14 articles were part of the sample, however, only six articles were selected the meta-analysis. The results showed that the ketamine is a promising drug in the management of PTSD with effect more evident performed after 24 h evaluated by MADRS scale. However, the main limitations of the present review demonstrate that more high-quality studies are needed to investigate the influence of therapy, safety, and efficacy.

Stolen innocence: Dishonor and taint in times of war.

As soon as they are taken prisoner, children and adolescents in times of war are inserted into a spiral of cruelty that progresses to rape or other countless forms of physical and psychological torture using sex as a weapon. Were these children and adolescents war sex slaves? Oral sex and other sexual barbarities are part of spaces of abuse and humiliation. The damage to the personality structure of these children and adolescents is severe. The psychological consequences are numerous. Over the years, a vicious circle has been observed around this brutality.

The impact of "the war that drags on" in Ukraine for the health of children and adolescents: Old problems in a new conflict?

The early months of 2022 have already included several distressing world events. From the ongoing COVID-19 pandemic, to protests against vaccine mandates and COVID-19 restrictions, to the Russian invasion of Ukraine. Escalating conflict in Ukraine poses an immediate and growing threat to the lives and well-being of the country's 7.5 million children. Humanitarian needs are multiplying - and spreading by the hour. Children have been killed. Children have been wounded. They are being profoundly traumatized by the violence all around them. Hundreds of thousands of people are on the move, and family members are becoming separated from their loved ones.

Ukraine: War, bullets, and bombs - millions of children and adolescents are in danger.

As the Russia-Ukraine conflict continues to unfold, the ever-evolving situation can be particularly difficult for children and teenagers. Children living in these areas face serious threats from bombing, landmines and unexploded ordnance. Their lives are also threatened by the destruction of vital infrastructure - health centers, schools and water supplies - because of the fighting. War can have a devastating effect on children's mental and physical health, with potentially lifelong consequences. Fears can generate fantasies of the end of the world, as well as the fear of losing a loved one or life itself, nightmares and regressions to previous evolutionary stages. This situation is creating dramatic scenes at train stations, where families are forced to say goodbye.

Screening for Dementia and Cognitive Decline in Adults With Down Syndrome: A Novel Approach Using the Informant Questionnaire on Cognitive Decline in the Elderly.

OBJECTIVE: The aim was to examine the psychometric properties of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a diagnostic tool to screen for dementia in aging individuals with Down syndrome (DS). METHODS: This was a cross-sectional study of 92 individuals with DS 30 y or above of age) evaluated with the IQCODE. Using the informant questionnaire of the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities, we divided the subjects into 3 diagnostic groups: stable cognition; prodromal dementia; and dementia. The ability of the IQCODE to discriminate between diagnostic groups was analyzed by calculating the areas under the receiver operator characteristic curves (AUCs). RESULTS: The optimal IQCODE cutoffs were 3.14 for dementia versus stable cognition (AUC=0.993; P<0.001) and 3.11 for prodromal dementia+dementia versus stable cognition (AUC=0.975; P<0.001), with sensitivity/specificity/accuracy of 100%/96.8%/97.3%, and 93.3%/91.9%/92.4%, respectively. The IQCODE showed a weak-to-moderate correlation with cognitive performance (P<0.05). CONCLUSION: The IQCODE is a useful tool to screen for cognitive decline in individuals with DS and is suitable for use in a primary care setting.

Inverse Association Between Hypothalamic N-Acetyl Aspartate/Creatine Ratio and Indices of Body Mass in Adolescents with Obesity.

BACKGROUND: Approximately 10% of adolescents worldwide are overweight or obese, hence the urgent and universal need to elucidate possible mechanisms that lead to obesity in the adolescent population. OBJECTIVES: We examined the hypothalamic metabolism and its relationship with physical development in obese and eutrophic adolescents. METHODS: We performed a case-control study with 115 adolescents between 11 and 18 years of age, to compare obese (BMI z-score ≥ 2) and nonobese individuals (eutrophic controls; BMI z-score ≤ 1). The following hypothalamic metabolite ratios were examined as primary outcomes: glutamate/creatine (Cr), the sum of glutamate and glutamine/Cr, N-acetylaspartate (NAA)/Cr, myoinositol/Cr, and total choline/Cr (glycerophosphocholine +  phosphocholine/Cr), quantified by magnetic resonance spectroscopy. BMI z-scores, pubertal status, and scores on the Yale Food Addiction Scale, the Binge Eating Scale, and the Child Depression Inventory were assessed as secondary outcomes. Pearson coefficients (r) or nonparametric Spearman correlation (rho) analyses were performed between hypothalamic metabolite ratios and other parameters, such as BMI z-scores, physical development, food habits, depression symptoms, and serum protein concentrations (cytokines, hormones, and neuropeptides). RESULTS: Adolescents with obesity showed a lower hypothalamic NAA/Cr ratio (0.70 ± 0.19) compared to their eutrophic counterparts (0.84 ± 0.20; P = 0.004). The NAA/Cr ratio was negatively correlated with BMI z-scores (r = -0.25; P = 0.03) and serum insulin (rho = -0.27; P = 0.04), C-peptide (rho = -0.26; P = 0.04), amylin (r = -0.27; P = 0.04), ghrelin (rho = -0.30; P = 0.02), and neuropeptide Y (r = -0.27; P = 0.04). Also, the NAA/Cr ratio was positively correlated with circulating IL-8 levels (rho = 0.26; P = 0.04). CONCLUSIONS: High BMI z-scores are associated with lower hypothalamic NAA/Cr ratios. The negative correlations found between the NAA/Cr ratio and serum cytokines, hormones, and neuropeptides suggest a broad cross-talk linking hormonal imbalances, neurohumoral alterations, and hypothalamic functions in adolescents with obesity.

Costs associated with depression and obesity among cardiovascular patients: medical expenditure panel survey analysis.

BACKGROUND: There is a lack of information on the cost of depression associated with metabolic syndrome and cardiovascular diseases in the literature. METHODS: We evaluated the synergistic effects of depression and obesity on total expenditures for cardiovascular conditions using data from the Medical Expenditure Panel Survey (MEPS) database. We analyzed MEPS data from 1996 to 2017 comprising adult cardiovascular subjects. We categorized individuals following a combination of International Classification of Diseases ICD-9-CM and ICD-10 codes, and depression symptoms as evaluated using the Patient Health Questionnaire-2 (PHQ-2) depression screening tool. Our sample comprised cardiovascular patients aged 18 years and older, with a body mass index (BMI) between 18.5 and 60. Our study comprised unweighted sample of 96,697 (weighted sample of 938,835,031) adults, a US-nationwide representative sample of cardiovascular disease patients. The four response categories were: no depression; unrecognized depression; asymptomatic depression; and symptomatic depression. Our evaluated outcomes were total annual healthcare expenditures, including dental, emergency room, hospital outpatient, hospital inpatient, office-based, prescription, and home health care expenses. RESULTS: Asymptomatic and symptomatic depression was more frequent among obese individuals than in individuals with a normal BMI (p <  0.001). Total expenditure was highest among symptomatic depression individuals (17,536) and obese (9871) with cardiovascular disease. All the expenditure outcomes were significantly higher among symptomatic depression individuals than those without depression (p <  0.001), except for dental costs. All healthcare expenditures associated with obesity were higher compared to individuals with normal BMI with p <  0.001, except for emergency and home healthcare costs. Most importantly, among obese individuals, all healthcare expenditures were significantly higher (p <  0.001) in those with symptomatic depression than those without depression, except for dental costs, where the difference was not significant (0.899). Therefore, obesity and depression entail increased expenses in patients with cardiovascular disease. CONCLUSIONS: We found incremental expenditures among unrecognized, asymptomatic, and symptomatic depressed individuals with obesity compared to non-depressed, non-obese subjects. However, these are preliminary results that should be further validated using different methodologies.

Sex dimorphism in inflammatory response to obesity in childhood.

BACKGROUND: Childhood overweight and obesity are a global concern, with prevalence rising dramatically over the last decades. The condition is caused by an increase in energy intake and reduction of physical activity, leading to excessive fat accumulation, followed by systemic chronic inflammation and altered function of immune cell responses. This study aimed at providing new insights regarding sex-specificity on the inflammatory response to obesity in the young patient. DESIGN: Forty-three Brazilian obese adolescents (Female = 22 and Male=21, BMI (body mass index) Z-score average = 2.78 ± 0.51) and forty-nine eutrophic adolescents (Female = 24 and Male = 25, BMI Z-score average = -0.35 ± 0.88) were enrolled in the study. Anthropometrical analyses and blood cell counts were carried out. Using Luminex®xMAP™ technology, circulating serum cytokines, chemokines, and inflammatory biomarkers were analyzed. Two-way ANOVA test, Tukey's test, and Spearman's correlation coefficient were employed, with a significance threshold set at p < 0.05. RESULTS: We identified increased levels of serum amyloid A (SAA), platelets, and leukocytes solely in male obese patients. We found a noteworthy sex-dependent pattern in regard to inflammatory response: obese boys showed higher TNFß, IL15, and IL2 and lower IL10 and IL13, while obese girls showed increased TNFα, CCL3, CCL4, and IP10 content in the circulation. BMI Z-score was significantly linearly correlated with neutrophils, leukocytes, platelets, SAA, TNFα, CCL3, CCL4, IP10, and IL13 levels within the entire cohort (non-sex-dependent). CONCLUSIONS: Our data support a complex relationship between adiposity, blood cell count, and circulating inflammatory cytokine content. High SAA levels suggest that this factor may play a critical role in local and systemic inflammation. In the eutrophic group, females presented a lower status of inflammation, as compared to males. Both obese boys and girls showed an increased inflammatory response in relation to eutrophic counterparts. Taken together, results point out to clear sex dimorphism in the inflammatory profile of obese adolescents.

Sex-Dependent Dyslipidemia and Neuro-Humoral Alterations Leading to Further Cardiovascular Risk in Juvenile Obesity.

Objective: Childhood obesity is a growing concern as the World Health Organization (WHO) states that ~10% of adolescents worldwide are overweight or obese. This condition is the reflex of energy imbalance between the calories consumed and those expended. Sex-related responses associated with dyslipidemia, hormonal alterations, and neuro-humoral disruptions in childhood obesity are the focus of the present investigation. Methods: Ninety-two Brazilian adolescents were enrolled and divided between obese and eutrophic groups. Obesity was assessed using body mass index Z-score according to age and weight. Anthropometrical analyses, blood pressure, blood lipids, metabolism-regulating hormones, and neuropeptides were carried out. Results: Systolic blood pressure was higher in female and male patients with obesity. Obese females presented alterations in lipid profile and an augment of cardiovascular disease prediction ratios TC/HDL, TG/HDL, LDL/HDL, and VLDL/HDL. The levels of leptin, GIP, and neuropeptide showed sex-dimorphism in obesity. The obese adolescents presented increased levels of circulating insulin, c-peptide, amylin, glucagon, and GLP-1. Correlation analysis showed significant linearity between body mass index, blood pressure, lipids, lipoproteins, hormones, and neuropeptides content. Conclusions: Our data support an existing link associating hypertension, dyslipidemia, and neuro-hormonal imbalance in childhood obesity. We also described a sex-dependent pattern in childhood obesity-associated dyslipidemia and blood pressure in female patients with obesity solely.

Predictors of Disagreement Between Diagnoses From Consult Requesters and Consultation-Liaison Psychiatry.

We evaluated disagreement between reported symptoms and a final diagnosis of depression, anxiety, withdrawal, psychosis, or delirium through regression models assessing individual and combined diagnoses. Highest disagreement rates were reported for services classified as others (88.2%), general surgery (78.5%), and bone marrow transplant (77.7%). Disagreement rates varied widely across different diagnoses, with anxiety having the highest disagreement rate (63.3%), whereas psychosis had the lowest disagreement rate (10.6%). When evaluating kappa coefficients, the highest agreement occurred with diagnoses of withdrawal and psychosis (0.66% and 0.51%, respectively), whereas anxiety and depression presented the lowest values (0.31% and 0.11%, respectively). The best-performing predictive model for most outcomes was random forest, with the most important predictors being specialties other than the ones focused on single systems, older age, lack of social support, and the requester being a resident. Monitoring disagreement rates and their predictors provides information that could lead to quality improvement and safety programs.

Effect of a 10-day transcutaneous trigeminal nerve stimulation (TNS) protocol for depression amelioration: A randomized, double blind, and sham-controlled phase II clinical trial.

BACKGROUND: Major depressive disorder (MDD) is one of the leading causes of disability in the world. However, treatment options are still limited, and marked by high refractoriness rates, new approaches are needed to optimize clinical improvement. Trigeminal nerve stimulation (TNS) is an innovative neuromodulation strategy consisting on the application of an electric current over the trigeminal nerve that propagates stimuli towards brain areas involved in mood control. OBJECTIVE: We examined the effects of TNS in MDD after a 10-day experimental protocol. METHODS: This was a randomized, double blind, and sham-controlled phase II study with 24 patients with severe MDD. Patients underwent a 10-day intervention protocol and were assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) at following three observation points: baseline (T1), after 10 days (T2), and after one month of the last stimulation session (T3). Main clinical outcome analysis of variance (ANOVA) was performed. RESULTS: Patients in the active group presented a mean reduction of 36.15% in depressive symptoms after the stimulation protocol. There was a significant interaction between group and time regarding HDRS-17 scores (F = 3.18; df = 2; p = 0.0456). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms at T2 (p = 0.040) and T3 (p = 0.026), which highlights the sustained amelioration of depressive symptoms. CONCLUSION: The present study found amelioration of depressive symptoms for patients undergoing a 10-day stimulation protocol of TNS, and this was sustained after one month of follow-up.

Misidentification of mental health symptoms in presence of organic diseases and delirium during psychiatric liaison consulting.

OBJECTIVE: To identify predictors of misidentification of organic mental disorders and delirium in patients undergoing psychiatric liaison consultation. METHODS: Data were collected at Santa Casa de São Paulo between July of 2009 and March of 2013. We included in our analysis all inpatients for whom the requesting service judged that a psychiatric consultation was required for a possible mental health condition. Outcomes of interest were the instances of misidentification where a condition was initially deemed to be of a psychiatric nature, whereas the final diagnosis by the liaison psychiatric team was of an organic disease or delirium. Our predictors were the clinical specialty of the requesting service, requester and patient characteristics. A series of generalised linear models were used to evaluate misidentification risks. RESULTS: A total of 947 subjects met our inclusion criteria, 14.6% having a final liaison diagnosis of organic mental disorder and 8.1% of delirium. Older patients were significantly associated with increased risk of misidentification for both organic conditions (OR 3.01 - 95% CI 2.01, 4.5) and delirium (OR 3.92 - 2.4, 6.39). CONCLUSIONS: Educational interventions in general hospitals focused on preventing psychiatric misdiagnosis should target in-hospital services where patients tend to be older.

Effect of transcranial direct current stimulation (tDCS) over the prefrontal cortex combined with cognitive training for treating schizophrenia: a sham-controlled randomized clinical trial.

INTRODUCTION:: We report a transcranial direct current stimulation (tDCS) protocol over the dorsolateral prefrontal cortex (DLPFC) combined with cognitive training in schizophrenia. METHOD:: We assessed psychotic symptoms in nine patients using the Positive and Negative Syndrome Scale (PANSS). All evaluations were scored at baseline, at the end of the intervention protocol, and during a 4-week follow-up. The tDCS protocol consisted of 10 consecutive sessions over 5-day periods. We placed the cathode over the right and the anode over the left DLPFC. For sham stimulation, we turned the device off after 60 seconds. Cognitive training consisted of the administration of N-back and sequence learning tasks. RESULTS:: We performed an analysis of covariance (ANCOVA) to adjust for the dependent variable PANSS, considering the interaction with baseline severity scores (p = 0.619). Mixed analysis of variance (ANOVA) showed no statistical significance between the groups regarding final PANSS scores. CONCLUSION:: The results failed to demonstrate that the concomitant use of tDCS and cognitive training is effective to improve clinical outcomes in patients with schizophrenia. The present findings should be analyzed with care, considering the small sample size. Larger controlled trials on electric/cognitive stimulation should be produced in order to enhance therapeutic strategies in schizophrenia.