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Over the past 30 years there have been numerous large-scale and longitudinal psychiatric research efforts to improve our understanding and treatment of mental health conditions. However, despite the huge effort by the research community and considerable funding, we still lack a causal understanding of most mental health disorders. Consequently, the majority of psychiatric diagnosis and treatment still operates at the level of symptomatic experience, rather than measuring or addressing root causes. This results in a trial-and-error approach that is a poor fit to underlying causality with poor clinical outcomes. Here we discuss how a research framework that originates from exploration of causal factors, rather than symptom groupings, applied to large scale multi-dimensional data can help address some of the current challenges facing mental health research and, in turn, clinical outcomes. Firstly, we describe some of the challenges and complexities underpinning the search for causal drivers of mental health conditions, focusing on current approaches to the assessment and diagnosis of psychiatric disorders, the many-to-many mappings between symptoms and causes, the search for biomarkers of heterogeneous symptom groups, and the multiple, dynamically interacting variables that influence our psychology. Secondly, we put forward a causal-orientated framework in the context of two large-scale datasets arising from the Adolescent Brain Cognitive Development (ABCD) study, the largest long-term study of brain development and child health in the United States, and the Global Mind Project which is the largest database in the world of mental health profiles along with life context information from 1.4 million people across the globe. Finally, we describe how analytical and machine learning approaches such as clustering and causal inference can be used on datasets such as these to help elucidate a more causal understanding of mental health conditions to enable diagnostic approaches and preventative solutions that tackle mental health challenges at their root cause.
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Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinical condition with abrupt onset of obsessive-compulsive symptoms and/or severe eating restrictions and at least two concomitant cognitive, behavioral, or neurological symptoms. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is a subtype of PANS with a controversial diagnosis. A case of a 12-year-old girl with severe eating restriction, obsessive-compulsive symptoms, anxiety, and neurological symptoms who initially was diagnosed with obsessive-compulsive disorder is presented. Published reports were reviewed for the evidence of diagnosis and treatment options of PANS/PANDAS. Studies show controversy regarding diagnosis. Moreover, study reports showed limited evidence for the treatment options. Selective serotonin reuptake inhibitors and psychotherapy are considered the main treatment with prompt infection treatment in the case of PANDAS.
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Immune checkpoint inhibitors have revolutionized cancer treatment. They can induce cutaneous immune-related adverse events. One patient with immune-related eczema and two with immune-related bullous pemphigoid were successfully treated with dupilumab. Guidelines recommend the use of systemic steroids to manage moderate-to-severe cutaneous immune-related adverse events. They could potentially interfere with immunotherapy. There is a need to find alternative treatments that are safe in a cancer setting.
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The electrochemical CO2 reduction reaction (CO2 RR) to fuels and feedstocks presents an opportunity to decarbonize the chemical industry, and current electrolyzer performance levels approach commercial viability. However, stability remains below that required, in part because of the challenge of probing these electrolyzer systems in real time and the challenge of determining the root cause of failure. Failure can result from initial conditions (e. g., the over- or under-compression of the electrolyzer), gradual degradation of components (e. g., cathode or anode catalysts), the accumulation of products or by-products, or immediate changes such as the development of a hole in the membrane or a short circuit. Identifying and mitigating these assembly-related, gradual, and immediate failure modes would increase both electrolyzer lifetime and economic viability of CO2 RR. We demonstrate the continuous monitoring of CO2 RR electrolyzers during operation via non-disruptive, real-time electrochemical impedance spectroscopy (EIS) analysis. Using this technique, we characterise common failure modes - compression, salt formation, and membrane short circuits - and identify electrochemical parameter signatures for each. We further propose a framework to identify, predict, and prevent failures in CO2 RR electrolyzers. This framework allowed for the prediction of anode degradation ~11â hours before other indicators such as selectivity or voltage.
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Immune checkpoint inhibitors have revolutionized cancer treatment but can induce immune-related adverse events including psoriasis. Managing immune-related psoriasis or psoriasis in a cancer setting is challenging with a lack of safety data. We describe three patients receiving interleukin-23 inhibitors to manage psoriasis in an active cancer setting, including one with immune-related psoriasis. Interleukin-23 inhibitors were effective for all patients. While being on interleukin-23 inhibitors, one patient had cancer partial response, one had deep partial response but then progressed and died from her melanoma, and one suffered melanoma progression.
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OBJECTIVES/HYPOTHESIS: For most pediatric specialty clinics, mental health is not the primary presenting complaint, yet can portend unrecognized morbidity. We describe rates and risk factors of depression and suicidal ideation in adolescents seen at a pediatric specialty clinic and examine changes during COVID-19. STUDY DESIGN: Retrospective database review. METHODS: Outpatient pediatric otolaryngology clinic encounters of patients aged 12-19 years at a tertiary academic medical center were identified from October 2018 to July 2020. Demographic characteristics, ICD-10 primary diagnosis, Patient Health Questionnaire (PHQ)-2 score, and PHQ-9 score (if administered) were obtained. Multivariable regression examined risk factors for PHQ-9 administration, PHQ-9 scores ≥10, and suicidal ideation. Patient characteristics and PHQ scores were compared before and after March 23, 2020 (California COVID-19 Stay-at-Home order). RESULTS: Three thousand six hundred nine encounters with PHQ-2 data were identified. Of these, 223 (6.2%) scored ≥3 and underwent PHQ-9 assessment, of which 121 (3.4% of 3,609) scored ≥10 on the PHQ-9 and 53 (1.5%) endorsed suicidal ideation. Factors associated with PHQ-9 administration were female gender (odds ratio [OR] 1.58, P = .001), obesity (OR 1.48, P = .043), and neck mass/neoplasm/cancer diagnosis (OR 1.99, P = .013). Female gender was also associated with suicidality (OR 2.47, P = .008). Comparison of pre-COVID-19 versus during COVID-19 showed no differences in depression or suicidality. However, subgroup analysis revealed some significant findings. CONCLUSIONS: We demonstrate substantial prevalence of positive depression screening and suicidal ideation among adolescent pediatric otolaryngology clinic encounters. Depression rates were similar to pre-COVID-19 and during COVID-19, yet barriers to screening during this time were substantial. Pediatric specialty providers must remain vigilant for mental health issues in their patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1104-1111, 2022.