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Background: Reflex molecular testing, the process of profiling specimens at diagnosis, is emerging in oncology, allowing for prompt therapy initiation, and potentially improving outcomes. This study evaluates the impact of reflex BRAF testing on treatment timelines and outcomes in melanoma, lung and colorectal cancers at the McGill University Health Center (MUHC)., Methods: A retrospective chart review was conducted at the MUHC. The study included patients with melanoma, lung, and colorectal cancers who underwent BRAF testing from 2017 to 2022. Data on demographics, cancer type, stage, test ordering specialist, testing method, and treatment outcomes were extracted. Statistical analyses included descriptive and multivariate regression analyses., Results: 518 BRAF molecular tests were performed, with 173 patients meeting the inclusion criteria [median age 72 (IQR 60-80 years), 46.2% female]. Of these, 75.7% had melanoma, 23.7% colorectal cancer and 0.58% lung cancer. Pathologists ordered 71.1% of BRAF tests, primarily relying on immunohistochemistry. By 2022, all BRAF results were available before oncology consultations. Patients with pre-consultation BRAF results were more likely to receive targeted therapy (59.4% vs 36.4%). The availability of BRAF test results was associated with quicker treatment initiation and better alignment of therapy with mutation status., Conclusion: This study underscores the success of the pathology team at MUHC in implementing reflex BRAF mutation testing, enhancing clinical care by ensuring the timely availability of test results. Delays in testing may adversely affect clinical decision-making and therapy selection, highlighting the need for standardized reflex testing protocols across Canada to optimize patient outcomes in melanoma, lung, and colorectal cancers., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patient dignity is a core component of medicine and health care, yet maintaining patient dignity can be challenging in clinical settings in dermatology, specifically during a total body skin examinations (TBSE) for appropriate assessment and diagnosis. A recent study evaluated patient perspectives in dermatology. The purpose of this study was to investigate current draping practices and perspectives from a physicians' perspective., Methods: A cross-sectional study was performed with the use of study-specific questionnaire distributed to staff dermatologists and dermatology residents across Canada., Results: A total of 117 physicians were included (84 attending dermatologists and 33 dermatology residents). Nearly all staff and resident dermatologists (90.6%) indicated that draping was important. Specific practices differed between residents and staff ( P = .03). Only 3.1% of residents indicated that they did not receive any form of teaching on draping during their training compared to 21.4% of attending physicians ( P = .03)., Discussion: This study confirms that draping practices in dermatology are perceived as important by dermatologists, consistent with other reports emphasizing approaches to protect patient privacy and dignity. There is a shared value for draping and consistent integration of this within current practice of Canadian dermatologists. Formal and informal education incorporated in medical education and dermatology training is becoming more prominent. Major study limitations include sampling bias, convenience bias and nonresponse bias., Conclusion: This is the first study to evaluate physician perspectives on draping in dermatology or other areas in medicine. Findings from this study support a focus on draping in medical education., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We conducted a systematic review and meta-analysis of randomized control trials to formally assess the safety and efficacy of autologous whole cell vaccines as immunotherapies for solid tumors. Our primary safety outcome was number, and grade of adverse events. Our primary efficacy outcome was clinical responses. Secondary outcomes included survival metrics and correlative immune assays. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for studies published between 1946 and August 2020 using any autologous whole cell product in the treatment of any solid tumor. The Cochrane Randomized Controlled Trial risk of bias tool was used to assess risk of bias. Eighteen manuscripts were identified with a total of 714 patients enrolled in control and 808 in vaccine arms. In 698 patients receiving at least one dose of vaccine, treatment was well tolerated with a total of 5 grade III or higher adverse events. Clinical response was reported in a minority (n = 2, 14%) of studies. Autologous cell vaccines were associated with improved overall (HR 1.28, 95% CI 1.01-1.63) and disease-free survival (HR 1.33, 95% CI 1.05-1.67) over thirteen and ten trials respectively. Where reported, immune assays correlated well with clinical outcomes. Our results suggest that autologous whole cell vaccination is safe and efficacious in increasing survival in patients undergoing treatment for solid tumors.Registration: PROSPERO CRD42019140187., (© 2023. The Author(s).)

Background: Antimicrobial resistance (AMR) in Gram-negative bacteria-causing bloodstream infections (BSIs), such as Klebsiella pneumoniae and non-typhoidal Salmonella (NTS), is a major public health concern. Nonetheless, AMR surveillance remains scarce in sub-Saharan Africa, where BSI treatment is largely empirical. The aim of the study was to determine the distribution and AMR patterns of BSI-causing NTS, K. pneumoniae , and other Gram-negative bacteria in Ghana., Methods: A cross-sectional study was conducted between April and December 2021 at eleven sentinel health facilities across Ghana as part of a pilot study on the feasibility and implementation of the human sector AMR surveillance harmonized protocol in sub-Saharan Africa. Gram-negative bacteria recovered from blood specimens of febrile patients were identified using MALDI-TOF and evaluated for antimicrobial resistance using the BD Phoenix M50 analyzer and Kirby-Bauer disc diffusion. The Department of Medical Microbiology at the University of Ghana served as the reference laboratory., Results: Out of 334 Gram-negative blood isolates, there were 18 (5.4%) NTS, 85 (25.5%) K. pneumoniae , 88 (26.4%) Escherichia coli , 40 (12.0%) Acinetobacter baumannii , 25 (7.5%) Pseudomonas aeruginosa , and 77 (23.1%) other Gram-negative bacteria. As a composite, the isolates displayed high resistance to the antibiotics tested-amoxicillin (89.3%), tetracycline (76.1%), trimethoprim-sulfamethoxazole (71.5%), and chloramphenicol (59.7%). Resistance to third-generation cephalosporins [ceftriaxone (73.7%), cefotaxime (77.8%), and ceftazidime (56.3%)] and fluoroquinolones [ciprofloxacin (55.3%)] was also high; 88% of the isolates were multidrug resistant, and the rate of extended-spectrum beta-lactamase (ESBL) production was 44.6%. Antibiotic resistance in K. pneumoniae followed the pattern of all Gram-negative isolates. Antibiotic resistance was lower in NTS blood isolates, ranging between 16.7-38.9% resistance to the tested antibiotics. Resistance rates of 38.9%, 22.2%, and 27.8% were found for cefotaxime, ceftriaxone, and ceftazidime, respectively, and 27.8% and 23.8% for ciprofloxacin and azithromycin, respectively, which are used in the treatment of invasive NTS. The prevalence of multidrug resistance in NTS isolates was 38.9%., Conclusions: Multicenter AMR surveillance of Gram-negative blood isolates from febrile patients was well-received in Ghana, and the implementation of a harmonized protocol was feasible. High resistance and multidrug resistance to first- or second-choice antibiotics, including penicillins, third-generation cephalosporins, and fluoroquinolones, were found, implying that these antibiotics might have limited effectiveness in BSI treatment in the country. Continuation of AMR surveillance in Gram-negative blood isolates is essential for a better understanding of the extent of AMR in these pathogens and to guide clinical practice and policymaking.

Competing Interests: None disclosed.

Background/objectives: Patient dignity is a core component of the Canadian health care system; however, there may be challenges to maintaining patient dignity in clinical settings requiring total body skin examination (TBSE) for adequate assessment and diagnosis. As standardized TBSE draping practices have not been investigated in a dermatology setting, we sought out to investigate subjective patient experiences of draping practices., Methods: A cross-sectional study was performed using a paper survey in dermatology hospital clinics over a 6-month period to 150 patients., Results: Draping was considered important by over 50% of patients surveyed (54.7%). Respondents who indicated that draping impacted their comfort level "a lot" or "very much" had a mean age of 52 and were more likely to be females ( P < .05). Females were also more likely to answer that their body weight/shape ( P < .05), physician of same ( P < .01) or opposite sex ( P < .001), and the degree of privacy offered by drapes ( P < .001) impacted their comfort level when undressing for a TBSE. Respondents who reported that any assessed factor impacted their comfort during a TBSE were also younger ( P < .05), suggesting that younger and female patients were more likely to have comfort concerns than males., Conclusions: Our study confirmed that most patients surveyed considered draping to be important. Our findings highlight the importance of adequate draping practices to maintain patient privacy and dignity for all patients, with special attention to younger female patients to ensure they feel as comfortable as possible. Future research should focus on how these identified patient comfort factors can be implemented into medical education.

Background: Individual differences in stress appraisals influence trajectories of risk and resilience following exposure to chronic and acute stressors. Smaller hippocampal volume may contribute to elevated stress appraisals via deficient pattern separation, a process depending on dentate gyrus (DG)/CA3 hippocampal subfields. Here, we investigated links between perceived stress, DG/CA3 volume, and behavioral pattern separation to test hypothesized mechanisms underlying stress-related psychopathology., Methods: We collected the Perceived Stress Scale (PSS) and ratings of subjective stress reactivity during the Trier Social Stress Test (TSST) from 71 adult community participants. We obtained high-resolution T2 MRI scans and used Automatic Segmentation of Hippocampal Subfields to estimate DG/CA3 volume in 56 of these participants. Participants completed the mnemonic similarity task, which provides a behavioral index of pattern separation. Analyses investigated associations between perceived stress, DG/CA3 volume, and behavioral pattern separation, controlling for age, gender, hemisphere, and intracranial volume., Results: Greater PSS scores and TSST subjective stress reactivity were each independently related to poorer behavioral pattern separation, together accounting for 15% of variance in behavioral performance in a simultaneous regression. Contrary to hypotheses, DG/CA3 volume was not associated with either stress measure, although exploratory analyses suggested a link between hippocampal volume asymmetry and PSS scores., Conclusions: We observed novel associations between laboratory and questionnaire measures of perceived stress and a behavioral assay of pattern separation. Additional work is needed to clarify the involvement of the hippocampus in this stress-behavior relationship and determine the relevance of behavioral pattern separation for stress-related disorders., Competing Interests: Dr. Richard Davidson is the founder and president, and sits on the board of, the non-profit organization Healthy Minds Innovations, Inc. The other authors have no disclosures to report., (© 2022 The Authors.)

Greater engagement in a range of daily activities is associated with better cognitive functioning (Lee et al., Lee et al., 2020). The hippocampus, a subcortical brain structure implicated in learning, memory, spatial navigation and other aspects of cognitive functioning, may be structurally sensitive to exposure to and engagement with novel experiences and environments. The present study tested whether greater activity diversity, defined as the range of common daily activities engaged in and the proportion of time spent in each, is associated with larger hippocampal volume. Greater diversity of activities, as measured using daily diaries across an 8-day period, was related to greater hippocampal volume averaged across the left and right hemispheres, even when adjusting for estimated intracranial volume, total activity time, sociodemographic factors, and self-reported physical health. These findings are broadly consistent with nonhuman animal studies, demonstrating a link between enriched environments and structural changes to the hippocampus. Future longitudinal and experimental work can elucidate causal and directional relationships between diversity of daily activities and hippocampal volume., (© 2021. The Psychonomic Society, Inc.)

Psychological stress, an important contributor to asthma morbidity, potentiates the immune response to allergen, but the brain mechanisms mediating this response are not fully understood. The amygdala is likely to play an important role, given its sensitivity to threat and connectivity with descending immune modulatory pathways. In this study, we recruited thirty asthmatic participants and examined glucose metabolism in the amygdala, using [F-18]fluorodeoxyglucose positron emission tomography, during a laboratory stressor. Stress hormone and airway inflammatory measurements were also acquired. Results showed that activity in the amygdala was significantly increased during the stressor, compared to a matched control task (p < .05 corrected). Moreover, the increase in amygdala activity was associated with a greater increase in sputum IL-1R1 mRNA and alpha amylase response (p < .05 corrected), which were also positively correlated (p = .01). These findings suggest that heightened amygdala reactivity may contribute to asthma morbidity via descending proinflammatory sympathetic signaling pathways., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Autologous cell vaccines use a patient's tumor cells to stimulate a broad antitumor response in vivo. This approach shows promise for treating hematologic cancers in early phase clinical trials, but overall safety and efficacy remain poorly described. We conducted a systematic review assessing the use of autologous cell vaccination in treating hematologic cancers. Primary outcomes of interest were safety and clinical response, with secondary outcomes including survival, relapse rate, correlative immune assays and health-quality related metrics. We performed a search of MEDLINE, Embase and the Cochrane Register of Controlled Trials including any interventional trial employing an autologous, whole cell product in any hematologic malignancy. Risk of bias was assessed using a modified Institute of Health Economics tool. Across 20 single arm studies, only 341 of 592 enrolled participants received one or more vaccinations. Primary reasons for not receiving vaccination included rapid disease progression/death and manufacturing challenges. Overall, few high-grade adverse events were observed. One death was reported and attributed to a GM-CSF producing allogeneic cell line co-administered with the autologous vaccine. Of 58 evaluable patients, the complete response rate was 21.0% [95% CI, 10.4%-37.8%)] and overall response rate was 35.8% (95% CI, 24.4%-49.0%). Of 97 evaluable patients for survival, the 5-years overall survival rate was 64.9% (95% CI, 52.6%-77.2%) and disease-free survival was 59.7% (95% CI, 47.7%-71.7%). We conclude that, in hematologic malignancies, based on limited available data, autologous cell vaccines are safe and display a trend towards efficacy but that challenges exist in vaccine manufacture and administration., (© 2021 John Wiley & Sons Ltd.)

The global burden of infectious diseases and the increased attention to natural, accidental, and deliberate biological threats has resulted in significant investment in infectious disease research. Translating the results of these studies to inform prevention, detection, and response efforts often can be challenging, especially if prior relationships and communications have not been established with decision-makers. Whatever scientific information is shared with decision-makers before, during, and after public health emergencies is highly dependent on the individuals or organizations who are communicating with policy-makers. This article briefly describes the landscape of stakeholders involved in information-sharing before and during emergencies. We identify critical gaps in translation of scientific expertise and results, and biosafety and biosecurity measures to public health policy and practice with a focus on One Health and zoonotic diseases. Finally, we conclude by exploring ways of improving communication and funding, both of which help to address the identified gaps. By leveraging existing scientific information (from both the natural and social sciences) in the public health decision-making process, large-scale outbreaks may be averted even in low-income countries.

A challenge for evolutionary research is to uncover how new morphological traits evolve the coordinated spatial and temporal expression patterns of genes that govern their formation during development. Detailed studies are often limited to characterizing how one or a few genes contributed to a trait's emergence, and thus our knowledge of how entire GRNs evolve their coordinated expression of each gene remains unresolved. The melanic color patterns decorating the male abdominal tergites of Drosophila (D.) melanogaster evolved in part by novel expression patterns for genes acting at the terminus of a pigment metabolic pathway, driven by cis-regulatory elements (CREs) with distinct mechanisms of Hox regulation. Here, we examined the expression and evolutionary histories of two important enzymes in this pathway, encoded by the pale and Ddc genes. We found that while both genes exhibit dynamic patterns of expression, a robust pattern of Ddc expression specifically evolved in the lineage of fruit flies with pronounced melanic abdomens. Derived Ddc expression requires the activity of a CRE previously shown to activate expression in response to epidermal wounding. We show that a binding site for the Grainy head transcription factor that promotes the ancestral wound healing function of this CRE is also required for abdominal activity. Together with previous findings in this system, our work shows how the GRN for a novel trait emerged by assembling unique yet similarly functioning CREs from heterogeneous starting points., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To review sexual health screening practices during admission to an adolescent psychiatry unit., Method: Retrospective chart review of randomly selected youth admitted over a one-year period (2013). Data extracted included demographics, reasons for admission, sexual health history, as well as any comorbid behaviours noted. The main outcome measure was whether sexual health details were documented at any time during admission; if so, this information was extracted for analysis. Statistical analysis was done using univariate associations and logistic association., Results: Mean age of subjects (n=99, 79 females and 20 males) was 15.24 years (SD = 1.30). Most common reasons for admission were suicidal gestures/self harm (n=57, 58%) and mood disorders (n=53, 54%). Thirty-seven patients (37%) had sexual health information documented in their charts. No demographic variables were significantly associated with being asked sexual health questions. Patients who had mood disorder diagnoses had 6 times the odds (95%CI: 1.18 to 29.96, P=0.03) of sexual health questions being documented compared to those not diagnosed with mood disorders., Conclusions: Screening for sexual health concerns is not being documented in the majority of adolescent psychiatry inpatients. Omitting sexual health screening during hospitalizations represents a missed opportunity for investigation and management of sexual health issues in this high-risk group. As many adolescents, particular those struggling with mental illness, do not attend preventative health visits, screening for pregnancy risk and other reproductive health needs is recommended at every adolescent encounter and in all settings.

Zoonotic pathogens have caused the majority of emerging infectious disease events in the past 6 decades. With most emerging infectious diseases arising from animal origins, including many of the select agents identified as most likely candidates for bioterrorism, linking human and animal surveillance systems will be critical to effective disease identification and control in the future. Lack of this linkage has been the focus of a number of important policy papers in recent years. These have expressed concern over the continued lack of preparedness for addressing zoonotic threats and have called for a new approach to integrating biosurveillance. However, these studies have been mainly Western-centric in viewpoint and have overlooked the example of the Russian Federation (RF) Anti-Plague System (AP system). In this article we submit that the RF AP system has select components that effectively address recent concerns and inform the US and UK intersectoral efforts on human-animal health surveillance, forming a basis for US, UK, and RF collaboration.

Disease surveillance networks in the Middle East, Southeast Asia, and Africa are models for the kind of transnational cooperation that can mount the needed flexible and coordinated response to the spread of 2009 H1N1 influenza and future pandemic threats. For example, members of the Middle East Consortium on Infectious Disease Surveillance (MECIDS), a regional disease surveillance network of public health experts and ministry of health officials from Israel, the Palestinian Authority, and Jordan, have coordinated the screening, laboratory testing, and risk communication strategies to detect and control 2009 H1N1 influenza. This coordination is made possible by trust and by well-exercised national and regional pandemic preparedness policies. The consortium illustrates the value of regional disease surveillance networks in shaping and managing cohesive policies on current and future threats. The MECIDS alliance partnership also exemplifies to other parts of the world that are experiencing conflict-like South Asia-that finding common ground is imperative to promoting health security and cooperation where it is most lacking and needed and that developing cohesive infectious disease control policies can build trust across the most difficult boundaries in the world. This article provides an overview of the history of MECIDS and similar networks and of the MECIDS response to 2009 H1N1 influenza.

Asthma is a prevalent chronic disorder that might substantially complicate pregnancy. Some recent reports suggest that the presence of a female fetus might be associated with worse maternal asthma symptoms during pregnancy. We tested this hypothesis using the sample of 719 pregnant women with asthma prospectively enrolled in the OTIS study. The presence of a female fetus was associated with a higher incidence of hospitalizations for asthma during pregnancy (OR = 1.84; 95% CI: 1.05; 3.21) independent of maternal age, BMI, ethnicity, smoking, and socioeconomic status. The current study suggests that pregnant asthmatic women carrying a girl might be more susceptible to asthma exacerbations.

Setting: San Diego, California public health department tuberculosis clinic., Objective: To evaluate the effectiveness of a behavioral intervention (the Treasure Chest) that employed the behavior modification techniques of self-monitoring and positive reinforcement to increase adherence to therapy for latent tuberculosis infection (LTBI) in children., Design: A retrospective study utilizing a historical comparison group. The treatment adherence of children who attended San Diego County TB Control Program (SDCTBCP) clinics with positive tuberculin skin tests who were started on LTBI treatment prior to Treasure Chest program implementation (n=841) was compared to that of SDCTBCP children enrolled in the Treasure Chest program (n=741)., Results: Logistic regression analysis demonstrated that children who participated in the Treasure Chest program were 2.4 times more likely to complete therapy than those who did not receive the intervention., Conclusion: The Treasure Chest intervention is effective in increasing adherence to LTBI therapy in children.

A randomized pretest and posttest comparative design was used to evaluate the outcome of implementing Think First for Kids (TFFK), an injury prevention program for children grades 1, 2, and 3, among intervention and controls schools. The study showed that children often lack basic knowledge regarding safety and do not recognize behaviors considered high risk for injury. By using multivariate analysis, the intervention children had a significantly greater increase in knowledge about the brain and spinal cord and safe behaviors to prevent traumatic injury, and a decrease in self-reported, high-risk behaviors (p < .001) when compared with control subjects, adjusting for the covariates gender, socioeconomic status, and race/ethnicity. African American and Hispanic children, although displaying the lowest test scores at baseline, had the largest absolute improvement in posttest scores. The TFKK prevention program addresses the leading causes of trauma among children including sports, motor vehicle crashes, falls, drowning, and pedestrian injuries., (Copyright 2001 by W.B. Saunders Company)