Neural oscillation in bipolar disorder: a systematic review of resting-state electroencephalography studies.

Bipolar disorder (BD) is a severe psychiatric disease with high rates of misdiagnosis and underdiagnosis, resulting in a significant disease burden on both individuals and society. Abnormal neural oscillations have garnered significant attention as potential neurobiological markers of BD. However, untangling the mechanisms that subserve these baseline alternations requires measurement of their electrophysiological underpinnings. This systematic review investigates consistent abnormal resting-state EEG power of BD and conducted an initial exploration into how methodological approaches might impact the study outcomes. This review was conducted in Pubmed-Medline and Web-of-Science in March 2024 to summarize the oscillation changes in resting-state EEG (rsEEG) of BD. We focusing on rsEEG to report spectral power in different frequency bands. We identified 10 studies, in which neural oscillations was compared with healthy individuals (HCs). We found that BD patients had abnormal oscillations in delta, theta, beta, and gamma bands, predominantly characterized by increased power, indicating potential widespread neural dysfunction, involving multiple neural networks and cognitive processes. However, the outcomes regarding alpha oscillation in BD were more heterogeneous, which is thought to be potentially influenced by the disease severity and the diversity of samples. Furthermore, we conducted an initial exploration into how demographic and methodological elements might impact the study outcomes, underlining the importance of implementing standardized data collection methods. Key aspects we took into account included gender, age, medication usage, medical history, the method of frequency band segmentation, and situation of eye open/eye close during the recordings. Therefore, in the face of abnormal multiple oscillations in BD, we need to adopt a comprehensive research approach, consider the multidimensional attributes of the disease and the heterogeneity of samples, and pay attention to the standardized experimental design to improve the reliability and reproducibility of the research results.

Prediction and verification of benignancy and malignancy of pulmonary nodules based on inflammatory related biological markers.

Objective: Inflammation plays an important role in the transformation of pulmonary nodules (PNs) from benign to malignant. Prediction of benignancy and malignancy of PNs is still lacking efficacy methods. Although Mayo or Brock model have been widely applied in clinical practices, their application conditions are limited. This study aims to construct a diagnostic model of PNs by machine learning using inflammation-related biological markers (IRBMs). Methods: Inflammatory related genes (IRGs) were first extracted from GSE135304 chip data. Then, differentially expressed genes (DEGs) and infiltrating immune cells were screened between malignant pulmonary nodules (MN) and benign pulmonary nodule (BN). Correlation analysis was performed on DEGs and infiltrating immune cells. Molecular modules of IRGs were identified through Consistency cluster analysis. Subsequently, IRBMs in IRGs modules were filtered through Weighted gene co-expression network analysis (WGCNA). An optimal diagnostic model was established using machine learning methods. Finally, external dataset GSE108375 was used to verify this result. Results: 4 hub IRGs and 3 immune cells showed significantly difference between MN and BN, C1 and C2 module, namely PRTN3, ELANE, NFKB1 and CTLA4, T cells CD4 naïve, NK cells activated and Monocytes. IRBMs were screened from black module and yellowgreen module through WGCNA analysis. The Support vector machines (SVM) was identified as the optimal model with the Area Under Curve (AUC) was 0.753. A nomogram was established based on 5 hub IRBMs, namely HS.137078, KLC3, C13ORF15, STOM and KCTD13. Finally, external dataset GSE108375 verified this result, with the AUC was 0.718. Conclusion: SVM model established by 5 hub IRBMs was able to effectively identify MN or BN. Accumulating inflammation and immune dysfunction were important to the transformation from BN to MN.

Comparison of human hair cortisol concentration stability for 1-year and 2-year test-retest intervals.

Human hair cortisol concentration (HCC) has previously been found to be highly stable for a 1-year interval (r = 0.73) in terms of a product-moment correlation. The present study aimed to replicate this finding and compare HCC stability regarding 1-year and 2-year test-retest intervals. Female university students (N = 39) provided hair strands twice (t1 and t2) at intervals of 1 (n = 21) or 2 years (n = 18). Multiple regression analysis predicting HCC at t2 revealed a significant interaction term (HCC at t1 × time interval condition). It was determined that HCCs were substantially related for the 1-year interval but unrelated for the 2-year interval. The findings were not attributable to potential influences, such as hair treatment. The product-moment correlation showed nearly identical consistency with previous research regarding the 1-year test-retest interval. There was no significant product-moment correlation for the 2-year interval. Overall, these findings indicate that within a temporal framework of 1 year, HCCs may be stable predictors in correlational studies where the focus is on the rank orders of measured values.

Cognitive, Neuropsychological and Biological Effects of Oxygen-Ozone Therapy on Frailty: A Study Protocol for a 5-Week, Randomized, Placebo-Controlled Trial.

Cognitive frailty (CF) is a heterogeneous syndrome that is becoming one of the most serious health problems as the world's population age is increasing. Elucidating its biological mechanisms as well as prevention and treatments is becoming increasingly significant, particularly in view of the associated health costs. We presented the study protocol of a research project funded by the Italian Ministry of Health (grant number RF-2016-02363298) aiming to investigate the cognitive and neuropsychological effects of a 5-week treatment with therapy based on the regenerative properties of ozone (O3) in a cohort of subjects stratified according to CF scores. We also studied the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons were recruited and randomly assigned to receive the active treatment (150 cc of oxygen-O2-O3 mixture at the concentration of 30 µg of O3 per cc of O2), O2, or the placebo (air) for 5 weeks. The main endpoints were the change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), and 15 (T15) after treatment and the change in biomarker levels resulting from transcriptomics, proteomics, and metabolomic patterns at the same times. The positive results from this study could have important clinical implications.

Risk variables of heart failure among patients in China: grey relational approach based multi-dimensional assessment study.

BACKGROUND: Understanding the potential risk factors of heart diseases is key to effectively managing cardiac diseases. The present study quantifies the association of identified risk factors. In addition, the study has compared the association of mortality with hypertension, uncontrolled diabetes, and uncontrolled hyperlipidemia using Grey Relational Approach (GRA) for stroke, lung diseases, smoking, stress, obesity, and lack of exercise. METHOD: Data on risk factors of heart failure were collected from the Global Burden of Disease (GBD) study (2001-2017). From the GBD database, variables have selected the top leading risk factors responsible for mortality from cardiac diseases. Data on risk factors was analyzed using the GRA procedure (utilizing Grey [8.0] software). In the GRA method, the correlation was categorized into three components: GRA - Deng (assesses the effect of one variable specified by data on the other variables), GRA- absolute (assesses the association between variables measured), and GRA-SS (assessed the overall association between the variables measured). Stroke, lung diseases, smoking, stress, obesity, and lack of exercise were taken as dependent variables and their impact was assessed. Hypertension (high grade) uncontrolled diabetes, and uncontrolled hyperlipidemia were considered as independent variables. The relationship between dependent and independent variables was assessed. RESULTS: Overall correlational analysis showed that type 2 diabetes (T2DM) is the risk factor that has a strong relationship with causing heart failure and thereby increases morbidity and mortality among Chinese patients. After T2DM, the second highest risk factor associated was severe dyslipidemia which is responsible for causing heart failure. High-grade hypertension is one-third most common risk factor in causing heart failure. GRA - Deng analysis showed that T2DM is the top risk factor associated with heart failure, followed by high-grade hypertension and severe dyslipidemia (uncontrolled). GRA-absolute analysis showed that severe dyslipidemia is the top risk factor associated with heart failure, followed by high-grade hypertension and T2DM (uncontrolled). GRA-SS analysis showed that high-grade hypertension is the top risk factor associated with heart failure, followed by severe dyslipidemia and T2DM (uncontrolled). CONCLUSIONS: The study reported that T2DM, severe dyslipidemia, and high-grade hypertension as strongly correlated with the development of heart failure after considering other several key risk factors (stroke, lung diseases, smoking, stress, obesity, and lack of exercise). LEVEL OF EVIDENCE: IV. TECHNICAL EFFICACY: Stage 5.

Prognostication of the development of septic complications in children with burn injuries.

OBJECTIVE: Aim: To determine the prognostic criteria for the development of septic complications in children with thermal injury. PATIENTS AND METHODS: Materials and Methods: A single-center retrospective-prospective cohort study included a retrospective analysis of 98 medical histories of children of different ages with severe burns who were treated from 2007 to 2017. A prospective study was conducted among children (n=63) from 1 to 5 years old, who received various degrees severity burn injury, according to an open comparative method in the period from 2018 to 2021. RESULTS: Results: Indicators of a high risk of developing sepsis were burns by flames of any etiology, damage severity index ≥75 units, total burn surface ≥25 %, deep burn area ≥ 5%. The threshold value of procalcitonin (PCT) ≥ 0.86 ng/ml on the 1st-3rd day and PCT > 0.51 ng/ml on the 7th day of burn disease, had a prognostic value for assessing the probability of sepsis. On the 1st day of hospitalization, the development of sepsis was predicted if the C-reactive protein (CRP) value was higher than 6.98 ng/ml, on the 3rd - the CRP level was above 7.43 ng/ml, on the 7th day - above 7.28 ng/ml. CONCLUSION: Conclusions: Based on the obtained data, we selected the criteria with the best prognostic characteristics, which allows us to predict and prevent the development of sepsis in the early stages of burn disease in children.

Accuracy of acute hyperglycemia as a biomarker of severe brain damage in children with traumatic brain injury.

PURPOSE: Biomarkers are substances measured at the systemic level to evaluate organic responses in certain situations, establishing diagnoses, disease staging, and prognosis. Blood glucose is a biomarker recognized as a predictor of prognosis in children victims of traumatic brain injury (TBI). The scope of this study was to identify the accuracy of blood glucose as a biomarker of severe brain injury. METHODS: A retrospective analytical study was conducted through the consecutive review of medical records of children and teenage victims of TBI who underwent neurological surgery between 2016 and 2023 in a level 1 trauma center. Two groups were compared: children with Glasgow Coma Scale (GCS) score ≤ 8 and children with GCS > 8. We calculated the predictive values to define the accuracy of blood glucose as a biomarker of brain injury. RESULTS: Ninety-two medical records were included for analysis. Hyperglycemia predominated in cases with GCS ≤ 8 (48% vs 3%; p < 0.0001; OR, 30; 95% CI, 5.9902-150.2448). The glycemic measurement considering the cutoff point of 200 mg/dL or 11.1 mmol/L showed a specificity of 97%, a positive predictive value of 86%, an accuracy of 84%, and a likelihood ratio for a positive test of 16. CONCLUSION: Victims with GCS ≤ 8 are 16 times more likely to develop acute hyperglycemia after TBI when compared to those with GCS > 8. Blood glucose is a biomarker with an accuracy of 84% to predict severe brain injury, considering the cutoff point of 200 mg/dL or 11.1 mmol/L.

Ceratophyllum demersum alleviates microplastics uptake and physiological stress responses in aquatic organisms, an overlooked ability.

It has been demonstrated that microplastics (MPs) may be inadvertently ingested by aquatic animals, causing harm to their physiological functions and potentially entering the food chain, thereby posing risks to human food safety. To achieve an environmentally friendly and efficient reduction of MPs in freshwater environments, this experiment investigates the depuration effect of C. demersum on MPs using three common aquatic animals: Macrobrachium nipponense, Corbicula fluminea, and Bellamya aeruginosa as research subjects. The amounts of MPs, digestive enzyme activity, oxidative stress index, and energy metabolism enzyme activity in the digestive and non-digestive systems of three aquatic animals were measured on exposure days 1, 3, and 7 and on depuration days 1 and 3. The results indicated that the depuration effect of C. demersum and the species interaction were significant for the whole individual. Concerning digestive tissue, C. demersum was the most effective in purifying B. aeruginosa. When subjected to short-term exposure to MPs, C. demersum displayed a superior depuration effect. Among non-digestive tissues, C. demersum exhibited the earliest purifying effect on C. fluminea. Additionally, C. demersum alleviated physiological responses caused by MPs. In conclusion, this study underscores C. demersum as a promising new method for removing MPs from aquatic organisms.

Oxidative Stress Markers in Multiple Sclerosis.

The pathogenesis of multiple sclerosis (MS) is not completely understood, but genetic factors, autoimmunity, inflammation, demyelination, and neurodegeneration seem to play a significant role. Data from analyses of central nervous system autopsy material from patients diagnosed with multiple sclerosis, as well as from studies in the main experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), suggest the possibility of a role of oxidative stress as well. In this narrative review, we summarize the main data from studies reported on oxidative stress markers in patients diagnosed with MS and in experimental models of MS (mainly EAE), and case-control association studies on the possible association of candidate genes related to oxidative stress with risk for MS. Most studies have shown an increase in markers of oxidative stress, a decrease in antioxidant substances, or both, with cerebrospinal fluid and serum/plasma malonyl-dialdehyde being the most reliable markers. This topic requires further prospective, multicenter studies with a long-term follow-up period involving a large number of patients with MS and controls.

Evaluation of biological markers for the risk assessment of carbon black in epidemiological studies.

Background/objectives: Engineered nanomaterials (ENMs) have been suggested as being capable of promoting inflammation, a key component in the pathways associated with carcinogenesis, cardiovascular disease, and other conditions. As a result, the risk assessment of biological markers as early-stage indicators has the potential to improve translation from experimental toxicologic findings to identifying evidence in human studies. The study aims to review the possible early biological changes in workers exposed to carbon black (CB), followed by an evidentiary quality evaluation to determine the predictive value of the biological markers. Methods: We conducted a literature search to identify epidemiological studies that assessed biological markers that were involved in the inflammatory process at early stages among workers with exposure to CB. We reviewed the studies with specific reference to the study design, statistical analyses, findings, and limitations. Results: We identified five Chinese studies that investigated the potential impact of exposure to CB on inflammatory markers, bronchial wall thickening, genomic instability, and lung function impairment in CB production workers. Of the five Chinese studies, four were cross-sectional; another study reported results at two-time points over six years of follow-up. The authors of all five studies concluded positive relationships between exposure and the inflammatory cytokine profiles. The weak to very weak correlations between biomarkers and early-stage endpoints were reported. Conclusion: Most inflammatory markers failed to satisfy the proposed evidentiary quality criteria. The significance of the results of the reviewed studies is limited by the cross-sectional study design, inconsistency in results, uncertain clinical relevance, and high occupational exposures. Based on this review, the risk assessment relying on inflammatory markers does not seem appropriate at this time. Nevertheless, the novel research warrants further exploration in assessing exposure to ENMs and corresponding potential health risks in occupational settings.

Building diagnostic neuroimaging biomarkers for psychiatric disorders using reverse inference approaches: A viable route?

The advent of structural magnetic resonance imaging (sMRI) at the end of the 20th century opened the way toward a deeper understanding of the neurophysiology of psychiatric disorders, substantiating regional structural abnormalities underlying this group of clinical conditions. However, despite abundant and flourishing scientific research, sMRI methodologies are not currently integrated into daily diagnostic practice. One reason behind this failed translation may be the prevailing approach to logical reasoning in neuroimaging: The forward inference via frequentist-based statistics. This reasoning prevents clinicians from obtaining information about the selectivity of results, which are therefore of limited use regarding the definition of biomarkers and refinement of diagnostic processes. Recently, another type of inferential approach has started to emerge in the neuroimaging field: The reverse inference via Bayesian statistics. Here, we introduce the key concepts of this approach, with a particular emphasis on the clinical sMRI environment. We survey recent findings showing significant potential for clinical translation. Clinical opportunities and challenges for developing reverse inference-based neural markers for psychiatry are also discussed. We propose that a systematic sharing of imaging data across the human brain mapping community is an essential first step toward a paradigmatic clinical shift. We conclude that a defined synergy between forward-based and reverse-based sMRI research can illuminate current discussions on diagnostic brain markers, offering clarity on key issues and fostering new tailored diagnostic avenues.

Unveiling ecological/evolutionary insights in HIV viral load dynamics: Allowing random slopes to observe correlational changes to CpG-contents and other molecular and clinical predictors.

In the context of infectious diseases, the dynamic interplay between ever-changing host populations and viral biology demands a more flexible modeling approach than common fixed correlations. Embracing random-effects regression models allows for a nuanced understanding of the intricate ecological and evolutionary dynamics underlying complex phenomena, offering valuable insights into disease progression and transmission patterns. In this article, we employed a random-effects regression to model an observed decreasing median plasma viral load (pVL) among individuals with HIV in Mexico City during 2019-2021. We identified how these functional slope changes (i.e. random slopes by year) improved predictions of the observed pVL median changes between 2019 and 2021, leading us to hypothesize underlying ecological and evolutionary factors. Our analysis involved a dataset of pVL values from 7325 ART-naïve individuals living with HIV, accompanied by their associated clinical and viral molecular predictors. A conventional fixed-effects linear model revealed significant correlations between pVL and predictors that evolved over time. However, this fixed-effects model could not fully explain the reduction in median pVL; thus, prompting us to adopt random-effects models. After applying a random effects regression model-with random slopes and intercepts by year-, we observed potential "functional changes" within the local HIV viral population, highlighting the importance of ecological and evolutionary considerations in HIV dynamics: A notably stronger negative correlation emerged between HIV pVL and the CpG content in the pol gene, suggesting a changing immune landscape influenced by CpG-induced innate immune responses that could impact viral load dynamics. Our study underscores the significance of random effects models in capturing dynamic correlations and the crucial role of molecular characteristics like CpG content. By enriching our understanding of changing host-virus interactions and HIV progression, our findings contribute to the broader relevance of such models in infectious disease research. They shed light on the changing interplay between host and pathogen, driving us closer to more effective strategies for managing infectious diseases. SIGNIFICANCE OF THE STUDY: This study highlights a decreasing trend in median plasma viral loads among ART-naïve individuals living with HIV in Mexico City between 2019 and 2021. It uncovers various predictors significantly correlated with pVL, shedding light on the complex interplay between host-virus interactions and disease progression. By employing a random-slopes model, the researchers move beyond traditional fixed-effects models to better capture dynamic correlations and evolutionary changes in HIV dynamics. The discovery of a stronger negative correlation between pVL and CpG content in HIV-pol sequences suggests potential changes in the immune landscape and innate immune responses, opening avenues for further research into adaptive changes and responses to environmental shifts in the context of HIV infection. The study's emphasis on molecular characteristics as predictors of pVL adds valuable insights to epidemiological and evolutionary studies of viruses, providing new avenues for understanding and managing HIV infection at the population level.

Diagnostic value of procalcitonin in patients with periprosthetic joint infection: a diagnostic meta-analysis.

Background: The success rate of periprosthetic joint infection (PJI) treatment is still low. Early diagnosis is the key to successful treatment. Therefore, it is necessary to find a biomarker with high sensitivity and specificity. The diagnostic value of serum procalcitonin (PCT) for PJI was systematically evaluated to provide the theoretical basis for clinical diagnosis and treatment in this study. Methods: We searched the Web of Science, Embase, Cochrane Library, and PubMed for studies that evaluated the diagnostic value of serum PCT for PJI (from the inception of each database until September 2020). Two authors independently screened the literature according to the inclusion and exclusion criteria. The quality of each selected literature was evaluated by using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) tool. RevMan 5.3 software was used for the quality evaluation. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were merged by using Meta-DiSc 1.4 software. The area under the curve (AUC) and Q index were calculated after the summary receiver operating characteristic (SROC) was generated. We also performed subgroup analysis. Results: A total of 621 patients were enrolled in the nine studies. The pooled sensitivity of serum PCT for PJI diagnosis was 0.441 [95% confidence interval (CI), 0.384-0.500], the pooled specificity was 0.852 (95% CI, 0.811-0.888), the pooled PLR was 2.271 (95% CI, 1.808-2.853), the pooled NLR was 0.713 (95% CI, 0.646-0.786), and the pooled DOR was 5.756 (95% CI, 3.673-9.026). The area under SROC (the pooled AUC) was 0.76 (0.72-0.79). Q index was 0.6948. Conclusion: This study showed that PCT detection of PJI had poor diagnostic accuracy. Hence, the serum PCT is not suitable as a serum marker for PJI diagnosis.

Obsessive-Compulsive Disorder as an Epiphenomenon of Comorbid Bipolar Disorder? An Updated Systematic Review.

BACKGROUND: Bipolar disorder (BD) and obsessive-compulsive disorder (OCD) comorbidity is an emerging condition in psychiatry, with relevant nosological, clinical, and therapeutic implications. METHODS: We updated our previous systematic review on epidemiology and standard diagnostic validators (including phenomenology, course of illness, heredity, biological markers, and treatment response) of BD-OCD. Relevant papers published until (and including) 15 October 2023 were identified by searching the electronic databases MEDLINE, Embase, PsychINFO, and Cochrane Library, according to the PRISMA statement (PROSPERO registration number, CRD42021267685). RESULTS: We identified 38 new articles, which added to the previous 64 and raised the total to 102. The lifetime comorbidity prevalence ranged from 0.26 to 27.8% for BD and from 0.3 to 53.3% for OCD. The onset of the two disorders appears to be often overlapping, although the appearance of the primary disorder may influence the outcome. Compared to a single diagnosis, BD-OCD exhibited a distinct pattern of OC symptoms typically following an episodic course, occurring in up to 75% of cases (vs. 3%). Notably, these OC symptoms tended to worsen during depressive episodes (78%) and improve during manic or hypomanic episodes (64%). Similarly, a BD course appears to be chronic in individuals with BD-OCD in comparison to patients without. Additionally, individuals with BD-OCD comorbidity experienced more depressive episodes (mean of 8.9 ± 4.2) compared to those without comorbidity (mean of 4.1 ± 2.7). CONCLUSIONS: We found a greater likelihood of antidepressant-induced manic/hypomanic episodes (60% vs. 4.1%), and mood stabilizers with antipsychotic add-ons emerging as a preferred treatment. In line with our previous work, BD-OCD comorbidity encompasses a condition of greater nosological and clinical complexity than individual disorders.

Narrative Review of Biological Markers in Chronic Limb-Threatening Ischemia.

BACKGROUND: Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. METHODS: A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it. RESULTS: We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. CONCLUSIONS: All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

Biological markers of adipose tissue: Adipokines.

We currently have a large sum of clinical and experimental data documenting the involvement of numerous adipokines in the maintenance of energy homeostasis in healthy individuals and their dysregulation in diseases such as obesity, metabolic syndrome or type 2 diabetes. Despite the impressive discoveries made in this field over many years, much remains to be done before understanding all the physiological and pathological implications, and hoping for the development of other effective and safe therapeutic strategies. Two original adipokines will be taken as examples to illustrate these remarks, chemerin and neuregulin 4.

Pharmacogenomic Clinical Support Tools for the Treatment of Depression.

OBJECTIVE: In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression. METHODS: The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized. RESULTS: Eleven new clinical trials and five meta-analyses were identified; all studies had primary outcome measures related to speed or efficacy of treatment response. Three trials (27%) demonstrated efficacy on the primary outcome measure with statistical significance; the three studies used different PGx tools; one study was open-label and the other two were small single-blind trials. Five trials (45%) did not detect efficacy with statistical significance on either primary or secondary outcome measures. Only one trial (9%) used adverse events as a primary outcome measure. All studies had significant limitations; for example, none adopted a fully blinded study design, only two studies attempted to blind the treating clinician, and none incorporated measures to estimate the effectiveness of the blinds or the influence of lack of blinding on the study results. CONCLUSIONS: The addition of these new data do not alter the recommendations of the 2018 report, or the advice of the U.S. Food and Drug Administration, that the evidence does not support the use of currently available combinatorial PGx tools for treatment selection in major depressive disorder. Priority efforts for future studies and the development and testing of effective tools include fully blinded study designs, inclusion of promising genetic variants not currently included in any commercially available tests, and investigation of other uses of pharmacogenomics, such as estimating the likelihood of rare adverse drug effects, rather than increasing the speed or magnitude of drug response.

Capacidad del biomarcador suPAR para estratificar el pronóstico en pacientes atendidos en servicios de urgencias hospitalarios / Value of the soluble urokinase-type plasminogen activator receptor as a predictor of prognosis in patients attended in hospital emergency departments

Objetivos. Determinar la capacidad del receptor soluble del activador del plasminógeno tipo uroquinasa (suPAR) para la estratificación pronóstica en pacientes atendidos en servicios de urgencias hospitalarios (SUH). Los objetivos secundarios son: 1)medir la capacidad de los puntos de decisión habituales, 2)identificar una población de bajo riesgo de mortalidad que puede darse de alta de forma segura desde el SUH, y 3)medir la correlación entre suPAR y otros biomarcadores. Métodos. Estudio observacional de cohortes prospectivo de pacientes atendidos en SUH. Se registraron variables sociodemográficas, de comorbilidad, datos del episodio agudo, biomarcadores de uso común en urgencias y suPAR. Las variables de resultado fueron la necesidad de ingreso en el episodio índice, reconsulta al SUH y mortalidad a los 90 días. Resultados. Se incluyeron 990 pacientes, la edad fue de 68 (53-81) años, 50,8% eran hombres, la mediana de suPAR fue de 3,8 (2,8-6,0) ng/ml, 112 pacientes (11,31%) requirieron ingreso. En el seguimiento a 90 días hubo 276 reconsultas (27,9%) y 47 pacientes (4,74%) fallecieron. Los pacientes con suPAR<4 ng/ml (52,5%) tenían menor mortalidad (1%), menor reconsulta (24,4%) y menor necesidad de ingreso hospitalario (20,6%), que pacientes con suPAR>6 ng/ml (mortalidad 13,5%, reconsulta 39,6% e ingreso 56,3%). Un suPAR>6 ng/ml mostró una hazard ratio (IC 95%) ajustada de 4,61 (1,68-12,67) para predecir mortalidad a 90 días y de 1,59 (1,13-2,10) para la reconsulta, y una odds ratio de 1,62 (0,99-2,62) para la necesidad de ingreso hospitalario. Conclusiones. Un valor de suPAR < 4 ng/ml identifica pacientes con riesgo bajo de mortalidad a 90 días, de reconsulta y de necesidad de ingreso, mientras que los pacientes con suPAR>6 ng/ml tienen mayor mortalidad, reconsulta y necesidad de ingreso. (AU)

Objectives. To determine the value of the soluble urokinase-type plasminogen activator receptor (suPAR) for predicting outcomes in emergency department (ED) patients. Secondary objectives were 1)to measure the predictive value of the usual decision points, 2)to identify patients at low risk for mortality who could be safely discharged from the ED, and 3)to measure the correlation between suPAR and other biomarkers. Methods. Prospective observational cohort study of patients attended in the EDs of participating hospitals. We recorded sociodemographic variables, comorbidity, variables related to the acute episode, prognostic markers commonly used in EDs, and suPAR concentration. Outcome variables were the need for hospital admission during the index episode, ED revisits within 90 days, and 90-day mortality. Results. A total of 990 patients with a median (interquartile range) age of 68 (53-81 years) were studied; 50.8% were men. The median suPAR concentration was 3.8 (2.8-6.0) ng/mL, and 112 patients (11.31%) required admission. At 90 days there were 276 revisits (27.9% of the cohort), and 47 patients (4.74%) had died. Mortality was lower (1%) in patients with suPAR concentrations less than 4 ng/mL (52.5%), and fewer of these patients revisited (24.4%) or required hospitalization (20.6%) than patients with suPAR concentrations higher than 6 ng/mL (mortality, 13.5%; revisits, 39.6%; admissions, 56.3%). A suPAR concentration over 6 ng/mL was associated with 90-day mortality and revisits (adjusted hazard ratios and 95% CIs of 4.61 [1.68-12.67] and 1.59 [1.13-2.10]), respectively. The high suPAR concentration was also associated with hospital admission (odds ratio, 1.62 [0.99-2.62]). Conclusions. A suPAR concentration of less than 4 ng/mL identifies patients at low risk of 90-day mortality and revisits or need for hospitalization, whereas a suPAR concentration higher than 6 ng/mL is associated with higher risk for these outcomes. (AU)