Circulating proteins to predict COVID-19 severity.

Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.

The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals.

INTRODUCTION: Severe COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions. METHODS: We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada and the United States. We fit generalized additive models with cubic splines from the start of symptom onset to identify protein levels over the first 14 days of infection which were different between severe cases and controls, adjusting for age and sex. Severe cases were defined as individuals with COVID-19 requiring invasive or non-invasive mechanical respiratory support. RESULTS: 580 individuals were included in the analysis. Mean subject age was 64.3 (sd 18.1), and 47% were male. Of the 147 proteins, 69 showed a significant difference between cases and controls (p < 3.4 × 10-4). Three clusters were formed by 108 highly correlated proteins that replicated in both cohorts, making it difficult to determine which proteins have a true causal effect on severe COVID-19. Six proteins showed sex differences in levels over time, of which 3 were also associated with severe COVID-19: CCL26, IL1RL2, and IL3RA, providing insights to better understand the marked differences in outcomes by sex. CONCLUSIONS: Severe COVID-19 is associated with large changes in 69 immune-related proteins. Further, five proteins were associated with sex differences in outcomes. These results provide direct insights into immune-related proteins that are strongly influenced by severe COVID-19 infection.

Early Clinical Exposure to Geriatric Psychiatry and Medical Students' Interest in Caring for Older Adults: A Randomized Controlled Trial.

OBJECTIVE: In the next 25 years, the population aged 65 and older will nearly double in many countries, with few new doctors wishing to care for older adults. The authors hypothesize that early clinical exposure to elderly patient care could increase student interest in caring for older adults during their future career. METHODS: The authors conducted a pragmatic medical education randomized controlled trial (RCT) at the Jewish General Hospital and the Douglas Mental Health Institute, McGill University, in Montreal, Canada. Third-year medical students undergoing their mandatory 16-week half-time clerkship rotation in psychiatry were randomly assigned to the equivalent of 2-4 weeks of full-time exposure to clinical geriatric psychiatry (n = 84). RESULTS: Being randomly assigned to geriatric psychiatry exposure (n = 44 of 84) was associated with increased "comfort in working with geriatric patients and their families" at 16-week follow-up (59.1% versus 37.5%, χ2 (1) = 3.9; p = 0.05). However, there was no significant association found between geriatric psychiatry exposure and change "in interest in caring for older adults," or change in "interest in becoming a geriatric psychiatrist." CONCLUSION: The results of this pragmatic education RCT suggest that exposing third-year medical students to 2-4 weeks of geriatric psychiatry did not increase their interest to care for older adults or become a geriatric psychiatrist. However, it did increase their comfort level in working with older adults and their families. However, more research is necessary to identify potential interventions that could inspire and increase medical student interest in caring for older adults as part of their future careers.

De-labeling of ß-lactam allergy reduces intraoperative time and optimizes choice in antibiotic prophylaxis.

BACKGROUND: Suspected penicillin allergic individuals receive suboptimal non-ß-lactams for intraoperative prophylaxis which may prolong operations and have negative clinical outcomes. We therefore studied if ß-lactam de-labeling optimized choice of prophylactic antibiotics and improved intraoperative time efficiency. METHODS: A multistep approach was used. It included a risk assessment tool by an allergist, ß-lactam skin testing and oral provocation. To determine the value of de-labeling, we appraised intraoperative antibiotic choices and correlated them with time to first incision. RESULTS: A total of 194 patients were evaluated preoperatively. Four patients were diagnosed ß-lactam allergic on skin testing. Of the remaining 190 skin test negative patients, 146 were ß-lactam challenged. Only 5% reacted and were considered ß-lactam allergic. Cefazolin became the perioperative antibiotic of choice for 77% of patients requiring antibiotic prophylaxis. Only 5 confirmed ß-lactam allergic patients received intraoperative vancomycin. Patients avoiding use of vancomycin saved an average of 22 minutes in operative time. Of the 44 patients not having a ß-lactam challenge, 36 received antibiotics and 18 (50%) of these were prescribed intraoperative cefazolin. CONCLUSION: Using this three step process, almost all of those claiming penicillin allergy were de-labeled. In most patients that were drug challenged, ß-lactam antibiotics became the perioperative drug of choice. In cases where oral challenge was not used in the assessment only 50% were given a ß-lactam. The reduced use of vancomycin minimized delays in initiation of incision time, thus improving operative efficiency. Ultimately, randomized controlled studies are required to objectively determine the effectiveness of this approach.

Mindfulness in severe and persistent mental illness: a systematic review.

OBJECTIVE: This systematic review summarises the current state of research on mindfulness in SPMI, given the pressing need to provide alternative, scalable and cost-effective treatment modalities for patients with severe and persistent mental illness (SPMI). METHODS: Articles included mindfulness-based interventions for SPMI. Excluded articles included qualitative studies, acceptance and compassion therapies, case reports and reviews. Studies were identified by searching the databases Medline, Embase and PsycINFO. RESULTS: Six randomised controlled trials, seven prospective studies and one retrospective study were identified. Clinical improvements were observed on psychotic symptoms, and on improvements of depression symptoms, cognition, mindfulness, psycho-social and vocational factors. CONCLUSIONS: Findings suggest that mindfulness is feasible for individuals with SPMI, and displays potential benefits in outcomes aside from psychotic symptoms. The effects of mindfulness in psychotic symptoms needs further investigation in larger definitive studies using methodological rigor and thorough assessments of other psychiatric populations who are also representative of SPMI.

Mobile Health Technology in Late-Life Mental Illness: A Focused Literature Review.

OBJECTIVE: In an era of rising geriatric mental health care needs worldwide, technological advances can help address care needs in a cost-effective fashion. Our objective in this review was to assess whether mobile health technology, such as tablets and smartphones, are feasible to use in patients with late-life mental and cognitive disorders, as well as whether they were generally reliable modes of mental health/cognitive assessment. METHODS: We performed a focused literature review of MEDLINE, PsychInfo, and Embase databases, including papers specifically assessing the implementation of mobile health technologies: electronic tablets (e.g., iPad), smartphones, and other mobile computerized equipment in older adults (age ≥65 years) diagnosed with or at risk of a mental and/or cognitive disorder. RESULTS: A total of 2,079 records were assessed, of which 7 papers were of direct relevance. Studies investigated a broad variety of mobile health technologies. Almost all examined samples with dementia/cognitive dysfunction or at risk for those disorders. All studies exclusively examined the use of mobile health technologies for the assessment of cognitive and or mental illness symptoms or disorders. None of the studies reported participants having any difficulties using the mobile health technology assessments and overall reliability was similar to paper-and-pencil modes of assessment. CONCLUSION: Overall, mobile health technologies were found to be feasible by patients and had promising reliability for the assessment of cognitive and mental illness domains in older adults. Future clinical trials will be necessary to assess whether portable communication interventions (e.g., symptom tracking) can improve geriatric mental health outcomes.