Evidence-based recruitment strategies for clinical research: Study personnel's and research participants' perceptions about successful methods of outreach for a U.S. Autism-Research Cohort.

Introduction: Under enrollment of participants in clinical research is costly and delays study completion to impact public health. Given that research personnel make decisions about which strategies to pursue and participants are the recipients of these efforts, we surveyed research staff (n = 52) and participants (n = 4,144) affiliated with SPARK (Simons Foundation Powering Autism for Knowledge) - the largest study of autism in the U.S. - to understand their perceptions of effective recruitment strategies. Methods: In Study 1, research personnel were asked to report recruitment strategies that they tried for SPARK and to indicate which ones they would and would not repeat/recommend. In Study 2, SPARK participants were asked to indicate all the ways they heard about the study prior to enrollment and which one was most influential in their decisions to enroll. Results: Staff rated speaking with a SPARK-study-team member (36.5%), speaking with a medical provider (19.2%), word of mouth (11.5%), and a live TV news story (11.5%) as the most successful strategies. Participants most often heard about SPARK via social media (47.0%), speaking with a medical provider (23.1%), and an online search (20.1%). Research personnel's and participants' views on effective recruitment strategies often differed, with the exception of speaking with a medical provider. Conclusion: Results suggest that a combination of strategies is likely to be most effective in reaching diverse audiences. Findings have implications for the selection of strategies that meet a study's specific needs, as well as recruitment-strategy "combinations" that may enhance the influence of outreach efforts.

Effectiveness of multimodal participant recruitment in SPARK, a large, online longitudinal research study of autism.

Background: SPARK launched in 2016 to build a US cohort of autistic individuals and their family members. Enrollment includes online consent to share data and optional consent to provide saliva for genomic analysis. SPARK's recruitment strategies include social media and support of a nation-wide network of clinical sites. This study evaluates SPARK's recruitment strategies to enroll a core study population. Methods: Individuals who joined between January 31, 2018, and May 29, 2019 were included in the analysis. Data include sociodemographic characteristics, clinical site referral, the website URL used to join, how the participant heard about SPARK, enrollment completion (online registration, study consents, and returning saliva sample), and completion of the baseline questionnaire. Logistic regressions were performed to evaluate the odds of core participant status (completing enrollment and baseline questionnaire) by recruitment strategy. Results: In total, 31,715 individuals joined during the study period, including 40% through a clinical site. Overall, 88% completed online registration, 46% returned saliva, and 38% were core participants. Those referred by a clinical site were almost twice as likely to be core participants. Those who directly visited the SPARK website or performed a Google search were more likely to be core participants than those who joined through social media. Discussion: Being a core participant may be associated with the "personal" connection and support provided by a clinical site and/or site staff, as well as greater motivation to seek research opportunities. Findings from this study underscore the value of adopting a multimodal recruitment approach that combines social media and a physical presence.

Suicidal Thoughts and Behaviors Among Children and Adolescents With Autism Spectrum Disorder.

This survey study uses data from the Mental Health and Suicidal Behaviors Questionnaire to examine the age at onset of suicidal thoughts and behaviors among children and adolescents aged 8 to 17 years who have been diagnosed with autism spectrum disorder (ASD).

A practical evidence-based approach to management of type 2 diabetes in children and young people (CYP): UK consensus.

BACKGROUND: Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. METHODS: Multidisciplinary professionals from The Association of Children's Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS AND DISCUSSION: Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. CONCLUSIONS: This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

Clinical tests for confirming tracheal intubation or excluding oesophageal intubation: a diagnostic test accuracy systematic review and meta-analysis.

Unrecognised oesophageal intubation causes preventable serious harm to patients undergoing tracheal intubation. When capnography is unavailable or doubted, clinicians still use clinical findings to confirm tracheal intubation, or exclude oesophageal intubation, and false reassurance from clinical examination is a recurring theme in fatal cases of unrecognised oesophageal intubation. We conducted a systematic review and meta-analysis of the diagnostic accuracy of five clinical examination tests and the oesophageal detector device when used to confirm tracheal intubation. We searched four databases for studies reporting index clinical tests against a reference standard, from inception to 28 February 2023. We included 49 studies involving 10,654 participants. Methodological quality was overall moderate to high. We looked at misting (three studies, 115 participants); lung auscultation (three studies, 217 participants); combined lung and epigastric auscultation (four studies, 506 participants); the oesophageal detector device (25 studies, 3024 participants); 'hang-up' (two non-human studies); and chest rise (one non-human study). The reference standards used were capnography (22 studies); direct vision (10 studies); and bronchoscopy (three studies). When used to confirm tracheal intubation, misting has a false positive rate (95%CI) of 0.69 (0.43-0.87); lung auscultation 0.14 (0.08-0.23); five-point auscultation 0.18 (0.08-0.36); and the oesophageal detector device 0.05 (0.02-0.09). Tests to exclude events that invariably lead to severe damage or death must have a negligible false positive rate. Misting or auscultation have too high a false positive rate to reliably exclude oesophageal intubation and there is insufficient evidence to support the use of 'hang-up' or chest rise. The oesophageal detector device may be considered where other more reliable means are not available, though waveform capnography remains the reference standard for confirmation of tracheal intubation.

Periplasmic stress contributes to a tradeoff between protein secretion and cell growth in E. Coli Nissile.

Maximizing protein secretion is an important target in the design of engineered living systems. In this paper, we characterize a tradeoff between cell growth and per cell protein secretion in the curli biofilm secretion system of E Coli Nissile 1917. Initial characterization using 24-hour continuous growth and protein production monitoring confirms decreased growth rates at high induction leading to a local maximum in total protein production at intermediate induction. Propidium iodide staining at the endpoint indicates that cellular death is a dominant cause of growth reduction. Assaying variants with combinatorial constructs of inner and outer membrane secretion tags, we find that diminished growth at high production is specific to secretory variants associated with accumulation of protein containing the outer membrane transport tag in the periplasmic space. RNA sequencing experiments indicate upregulation of known periplasmic stress response genes in the highly secreting variant, further implicating periplasmic stress in the growth-secretion tradeoff. Overall, these results motivate additional strategies for optimizing total protein production and longevity of secretory engineered living systems.

The incidence of awake tracheal intubation in anesthetic practice is decreasing: a historical cohort study of the years 2014-2020 at a single tertiary care institution.

PURPOSE: Awake tracheal intubation (ATI) is recommended in airway management guidelines when significant difficulty is predicted with airway management. Use of the technique may be declining, which may have implications for patient safety or for skills acquisition and maintenance. This historical cohort database study sought to determine if the use of ATI was decreasing in our adult tertiary care center. METHODS: With institutional research ethics board approval, we queried our anesthesia information management system for cases with ATI descriptors for each year from 2014 to 2020. Records of the retrieved cases were independently reviewed by all three authors to verify they met inclusion criteria for the ATI cohort prior to analysis for the primary outcome. Secondary outcome measures included airway device and route used for ATI, first attempt and ultimate success rates, and reported adverse issues recorded in cases of failed ATI or those requiring more than one attempt. RESULTS: A total of 692 cases of ATI were identified between 2014 and 2020. There was a statistically significant decrease in yearly ATIs over the seven-year study period (Chi square goodness of fit, P < 0.001), with ATI use decreasing by about 50%. First attempt success was significantly greater with use of flexible bronchoscopy vs video laryngoscopy to facilitate ATI (84% vs 60%; P < 0.001), while there was no difference in first attempt success with the oral vs nasal route (82% vs 82%; P = 1.0). CONCLUSION: In this single-center historical cohort study, the use of ATI decreased significantly from 2014 to 2020. Whether this decrease will result in morbidity or mortality related to airway management is currently unclear. Regardless, it has implications for training opportunities and maintenance of competence in performing the procedure.

RéSUMé: OBJECTIF: L'intubation trachéale éveillée (ITE) est recommandée dans les lignes directrices de prise en charge des voies aériennes lorsque des difficultés significatives sont anticipées dans la prise en charge des voies aériennes. L'utilisation de cette technique pourrait être en déclin, ce qui pourrait avoir des répercussions sur la sécurité des patients ou sur l'acquisition et le maintien des compétences. Cette étude de cohorte historique visait à déterminer si l'utilisation de l'ITE était en diminution dans notre centre de soins tertiaires pour adultes. MéTHODE: Après avoir obtenu l'approbation du comité d'éthique de la recherche de notre institution, nous avons extrait les données des patients ayant des descripteurs d'ITE de 2014 à 2020 à partir de notre système de gestion de l'information en anesthésie. Les données des dossiers de ces patients ont été examinées de manière indépendante par les trois auteurs afin de vérifier s'ils répondaient aux critères d'inclusion de la cohorte ITE avant l'analyse du critère d'évaluation principal. Les critères d'évaluation secondaires comprenaient le dispositif d'intubation et la voie d'accès utilisés pour l'ITE, les taux de réussite de la première tentative et de la réussite finale, et les problèmes indésirables signalés enregistrés dans les cas d'échec de l'ITE ou ceux nécessitant plus d'une tentative. RéSULTATS: Au total, 692 cas d'ITE ont été identifiés entre 2014 et 2020. Il y a eu une diminution annuelle statistiquement significative des ITE au cours de la période d'étude de sept ans (test d'adéquation du Chi carré, P < 0,001), l'utilisation de l'ITE diminuant d'environ 50 %. Le succès de l'intubation à la première tentative a été significativement plus important avec l'utilisation de la bronchoscopie flexible en comparaison à la vidéolaryngoscopie pour faciliter l'ITE (84 % vs 60 %; P < 0,001), bien qu'aucune différence n'ait été observée dans le succès de la première tentative par voie orale en comparaison à nasale (82 % versus 82 %; P = 1,0). CONCLUSION: Dans cette étude de cohorte historique monocentrique, l'utilisation de l'intubation trachéale éveillée a diminué de manière significative de 2014 à 2020. Il n'est pas clair si cette diminution entraînera une morbidité ou une mortalité liée à la prise en charge des voies aériennes. Quoi qu'il en soit, cela a des implications pour la formation et le maintien des compétences dans l'exécution de la procédure.

Re-Consenting Pediatric Research Participants as Legal Adulthood Approaches: Lessons from the SPARK Autism Study.

To explore issues surrounding re-consenting youth in longitudinal studies as they reach legal adulthood interviews were conducted with 46 parents plus 13 autistic teens enrolled in the Simons Foundation Powering Autism Research for Knowledge (SPARK) study. Qualitative analysis focused on family sensitivities regarding guardianship decisions, transition concerns, and the re-consenting process. Questions regarding guardianship were difficult for parents unsure of a teen's future status. Mothers were key facilitators of re-consenting for soon-to-be-independent teens. As legal adulthood approached, parents were willing to assist teens with re-consenting but needed support, asking for multiple contacts, transition resources, and explanatory materials from the research team. Most teens were not cognizant of SPARK but willing to continue participation once made aware.

Preventing unrecognised oesophageal intubation: a consensus guideline from the Project for Universal Management of Airways and international airway societies.

Across multiple disciplines undertaking airway management globally, preventable episodes of unrecognised oesophageal intubation result in profound hypoxaemia, brain injury and death. These events occur in the hands of both inexperienced and experienced practitioners. Current evidence shows that unrecognised oesophageal intubation occurs sufficiently frequently to be a major concern and to merit a co-ordinated approach to address it. Harm from unrecognised oesophageal intubation is avoidable through reducing the rate of oesophageal intubation, combined with prompt detection and immediate action when it occurs. The detection of 'sustained exhaled carbon dioxide' using waveform capnography is the mainstay for excluding oesophageal placement of an intended tracheal tube. Tube removal should be the default response when sustained exhaled carbon dioxide cannot be detected. If default tube removal is considered dangerous, urgent exclusion of oesophageal intubation using valid alternative techniques is indicated, in parallel with evaluation of other causes of inability to detect carbon dioxide. The tube should be removed if timely restoration of sustained exhaled carbon dioxide cannot be achieved. In addition to technical interventions, strategies are required to address cognitive biases and the deterioration of individual and team performance in stressful situations, to which all practitioners are vulnerable. These guidelines provide recommendations for preventing unrecognised oesophageal intubation that are relevant to all airway practitioners independent of geography, clinical location, discipline or patient type.

An in vitro assessment of light intensity provided during direct laryngeal visualization by videolaryngoscopes with Macintosh geometry blades.

BACKGROUND: Adequate illumination of the larynx is needed during laryngoscopy to facilitate tracheal intubation. The International Organization for Standardization (ISO) has established a minimum light intensity for direct laryngoscopy (DL) of over 500 lux for at least ten minutes, but no such standard exists for Macintosh geometry videolaryngoscope (Mac-VL) blades, which allow for both direct or indirect (videoscopic) viewing of the larynx. Using in situ bench and in vitro testing in a human cadaver, we determined illumination and luminance values delivered by various Mac-VLs and compared these with published minimum lighting benchmarks as well as a reference direct laryngoscope. METHODS: We tested six Mac-VLs (i-view™, McGRATH™ MAC, GlideScope® Spectrum™ [single-use] DVM S4, GlideScope® Titanium [reusable] Mac T4, C-MAC® S [single-use] Macintosh #4, C-MAC® [reusable] Macintosh #4) together with one direct laryngoscope (Heine LED). Each laryngoscope was assessed with three measurements, as follows: part 1: illuminance (lux) was measured in situ using a purpose-designed benchtop light intensity measurement apparatus; part 2: luminance (light reflected back to the eye) was measured (in candela m-2 [cd·m-2]) during videolaryngoscopy (VL) and DL in a human cadaver using a spot meter pointed at the interarytenoid notch; part 3: illuminance (lux) was measured during VL and DL in a human cadaver using a light meter surgically implanted just proximal to the vocal cords. RESULTS: Illuminance and luminance varied significantly among the Mac-VLs. Mean (standard devitation) illuminance among the six tested Mac-VLs ranged from 117 (11) to 2,626 (42) lux in the measurement apparatus and from 228 (11) to 2,900 (374) lux by the surgically implanted light meter in the cadaver. All values were less than the reference Heine direct laryngoscope and some fell below the published ISO standard of 500 lux for DL. Luminance testing by spot meter had a similarly wide range, varying from 3.78 (0.60) to 49.1 (10.4) cd·m-2, with some Mac-VLs delivering less luminance than the reference Heine direct laryngoscope. CONCLUSIONS: Our results indicate that illuminance and luminance provided by Mac-VLs used for direct laryngeal viewing varies substantially between devices, with some falling below standards previously suggested as the minimum required for DL. While this may have no implications for the quality of image visible on a device's video monitor, the clinician should be aware that when Mac-VLs are used for direct viewing of the larynx, lighting may not be optimal. This might adversely affect ease or success of tracheal intubation.

RéSUMé: CONTEXTE: L'éclairage adéquat du larynx est nécessaire pendant la laryngoscopie pour faciliter l'intubation trachéale. Pour la laryngoscopie directe (LD), l'Organisation internationale de normalisation (ISO) a établi une intensité lumineuse minimale de plus de 500 lux pendant au moins dix minutes. Toutefois, il n'existe aucune norme de ce type pour les lames de vidéolaryngoscope à géométrie Macintosh (VL-Mac), qui permettent une visualisation directe ou indirecte (vidéoscopique) du larynx. Par des études en laboratoire et in vitro sur un cadavre humain, nous avons déterminé les valeurs d'éclairage et de luminance fournies par divers VL-Mac et les avons comparées aux valeurs repères d'éclairage minimal publiées ainsi qu'aux valeurs obtenues avec un laryngoscope direct de référence. MéTHODE: Nous avons testé six VL-Mac (i-view™, McGRATH™ MAC, GlideScope® Spectrum™ [à usage unique] DVM S4, GlideScope® Titanium [réutilisable] Mac T4, C-MAC® S [à usage unique] Macintosh #4, et C-MAC® [réutilisable] Macintosh #4) ainsi qu'un laryngoscope direct (Heine LED). Chaque laryngoscope a été évalué avec trois mesures, comme suit : partie 1: l'éclairage (lux) a été mesuré in situ à l'aide d'un appareil spécialement conçu de mesure de l'intensité lumineuse en laboratoire; partie 2 : la luminance (lumière réfléchie vers l'œil) a été mesurée (en candela m-2 [cd·m-2]) pendant la vidéolaryngoscopie (VL) et la LD sur un cadavre humain, à l'aide d'un posemètre pointé vers la commissure interaryténoïdienne; partie 3: l'éclairage (lux) a été mesuré pendant la VL et la LD sur un cadavre humain à l'aide d'un photomètre implanté chirurgicalement juste en amont des cordes vocales. RéSULTATS: L'éclairage et la luminance variaient considérablement entre les VL-Mac. L'éclairage moyen (écart type) parmi les six VL-Mac testés variait de 117 (11) à 2626 (42) lux avec l'appareil de mesure, et de 228 (11) à 2900 (374) lux lorsque mesuré par le photomètre implanté chirurgicalement dans le cadavre. Toutes les valeurs étaient inférieures au laryngoscope direct Heine de référence, et certaines étaient inférieures à la norme ISO publiée de 500 lux pour la LD. Les essais de luminance par posemètre ont rapporté une plage tout aussi large, variant de 3,78 (0,60) à 49,1 (10,4) cd·m-2, certains VL-Mac offrant moins de luminance que le laryngoscope direct Heine de référence. CONCLUSION: Nos résultats indiquent que l'éclairage et la luminance fournis par les VL-Mac utilisés pour la visualisation directe du larynx varient considérablement d'un appareil à l'autre, certains tombant en dessous des normes précédemment suggérées comme minimalement requises pour la LD. Bien que cela puisse n'avoir aucune incidence sur la qualité de l'image visible sur le moniteur vidéo d'un appareil, le clinicien doit être conscient que lorsqu'un VL-Mac est utilisé pour la visualisation directe du larynx, l'éclairage pourrait ne pas être optimal. Cela pourrait nuire à la facilité ou au succès de l'intubation trachéale.

Canadian Airway Focus Group updated consensus-based recommendations for management of the difficult airway: part 1. Difficult airway management encountered in an unconscious patient.

PURPOSE: Since the last Canadian Airway Focus Group (CAFG) guidelines were published in 2013, the literature on airway management has expanded substantially. The CAFG therefore re-convened to examine this literature and update practice recommendations. This first of two articles addresses difficulty encountered with airway management in an unconscious patient. SOURCE: Canadian Airway Focus Group members, including anesthesia, emergency medicine, and critical care physicians, were assigned topics to search. Searches were run in the Medline, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL databases. Results were presented to the group and discussed during video conferences every two weeks from April 2018 to July 2020. These CAFG recommendations are based on the best available published evidence. Where high-quality evidence was lacking, statements are based on group consensus. FINDINGS AND KEY RECOMMENDATIONS: Most studies comparing video laryngoscopy (VL) with direct laryngoscopy indicate a higher first attempt and overall success rate with VL, and lower complication rates. Thus, resources allowing, the CAFG now recommends use of VL with appropriately selected blade type to facilitate all tracheal intubations. If a first attempt at tracheal intubation or supraglottic airway (SGA) placement is unsuccessful, further attempts can be made as long as patient ventilation and oxygenation is maintained. Nevertheless, total attempts should be limited (to three or fewer) before declaring failure and pausing to consider "exit strategy" options. For failed intubation, exit strategy options in the still-oxygenated patient include awakening (if feasible), temporizing with an SGA, a single further attempt at tracheal intubation using a different technique, or front-of-neck airway access (FONA). Failure of tracheal intubation, face-mask ventilation, and SGA ventilation together with current or imminent hypoxemia defines a "cannot ventilate, cannot oxygenate" emergency. Neuromuscular blockade should be confirmed or established, and a single final attempt at face-mask ventilation, SGA placement, or tracheal intubation with hyper-angulated blade VL can be made, if it had not already been attempted. If ventilation remains impossible, emergency FONA should occur without delay using a scalpel-bougie-tube technique (in the adult patient). The CAFG recommends all institutions designate an individual as "airway lead" to help institute difficult airway protocols, ensure adequate training and equipment, and help with airway-related quality reviews.

RéSUMé: OBJECTIF: Depuis la dernière publication des lignes directrices du Canadian Airway Focus Group (CAFG) en 2013, la littérature sur la prise en charge des voies aériennes s'est considérablement étoffée. Le CAFG s'est donc réuni à nouveau pour examiner la littérature et mettre à jour ses recommandations de pratique. Ce premier article de deux traite de la prise en charge des voies aériennes difficiles chez un patient inconscient. SOURCES: Des sujets de recherche ont été assignés aux membres du Canadian Airway Focus Group, qui compte des médecins anesthésistes, urgentologues et intensivistes. Les recherches ont été menées dans les bases de données Medline, EMBASE, Cochrane Central Register of Controlled Trials et CINAHL. Les résultats ont été présentés au groupe et discutés lors de vidéoconférences toutes les deux semaines entre avril 2018 et juillet 2020. Les recommandations du CAFG sont fondées sur les meilleures données probantes publiées. Si les données probantes de haute qualité manquaient, les énoncés se fondent alors sur le consensus du groupe. CONSTATATIONS ET RECOMMANDATIONS CLéS: La plupart des études comparant la vidéolaryngoscopie à la laryngoscopie directe indiquent un taux de réussite plus élevé à la première tentative et globalement avec la vidéolaryngoscopie, ainsi que des taux de complication inférieurs. Ainsi, les ressources le permettant, le CAFG recommande dorénavant l'utilisation de vidéolaryngoscopes avec le type de lame convenablement sélectionné pour faciliter toutes les intubations trachéales. En cas d'échec de la première tentative d'intubation trachéale ou d'échec de positionnement du dispositif supraglottique (DSG), d'autres tentatives peuvent être entreprises tant que la ventilation et l'oxygénation du patient le permettent. Néanmoins, le nombre total de tentatives devrait être limité, à trois ou moins, avant de déclarer un échec et de considérer les options de « stratégie de retrait ¼. En cas d'échec de l'intubation, les options de stratégie de retrait chez un patient toujours oxygéné comprennent l'éveil (si possible), la temporisation avec un DSG, une dernière tentative d'intubation trachéale à l'aide d'une technique différente, ou une cricothyroïdotomie. L'échec de l'intubation trachéale, de la ventilation au masque facial et de la ventilation via un DSG accompagné d'une hypoxémie présente ou imminente, définit une urgence « impossible de ventiler, impossible d'oxygéner ¼. Le bloc neuromusculaire doit alors être confirmé ou mis en place, et une tentative finale de ventilation au masque, de positionnement du DSG ou d'intubation trachéale avec une lame de vidéolaryngoscopie hyper-angulée peut être réalisée, si cette approche n'a pas encore été essayée. Si la ventilation demeure impossible, une cricothyroïdotomie d'urgence devrait être réalisée sans délai utilisant une technique de scalpel-bougie-tube (chez le patient adulte). Le CAFG recommande à toutes les institutions de désigner une personne comme « leader des voies aériennes ¼ afin d'assister à la mise en place de protocoles pour les voies aériennes difficiles, d'assurer une formation et un équipement adéquats et d'aider aux examens de la qualité en rapport avec les voies aériennes.

Canadian Airway Focus Group updated consensus-based recommendations for management of the difficult airway: part 2. Planning and implementing safe management of the patient with an anticipated difficult airway.

PURPOSE: Since the last Canadian Airway Focus Group (CAFG) guidelines were published in 2013, the published airway management literature has expanded substantially. The CAFG therefore re-convened to examine this literature and update practice recommendations. This second of two articles addresses airway evaluation, decision-making, and safe implementation of an airway management strategy when difficulty is anticipated. SOURCE: Canadian Airway Focus Group members, including anesthesia, emergency medicine, and critical care physicians were assigned topics to search. Searches were run in the Medline, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL databases. Results were presented to the group and discussed during video conferences every two weeks from April 2018 to July 2020. These CAFG recommendations are based on the best available published evidence. Where high-quality evidence is lacking, statements are based on group consensus. FINDINGS AND KEY RECOMMENDATIONS: Prior to airway management, a documented strategy should be formulated for every patient, based on airway evaluation. Bedside examination should seek predictors of difficulty with face-mask ventilation (FMV), tracheal intubation using video- or direct laryngoscopy (VL or DL), supraglottic airway use, as well as emergency front of neck airway access. Patient physiology and contextual issues should also be assessed. Predicted difficulty should prompt careful decision-making on how most safely to proceed with airway management. Awake tracheal intubation may provide an extra margin of safety when impossible VL or DL is predicted, when difficulty is predicted with more than one mode of airway management (e.g., tracheal intubation and FMV), or when predicted difficulty coincides with significant physiologic or contextual issues. If managing the patient after the induction of general anesthesia despite predicted difficulty, team briefing should include triggers for moving from one technique to the next, expert assistance should be sourced, and required equipment should be present. Unanticipated difficulty with airway management can always occur, so the airway manager should have a strategy for difficulty occurring in every patient, and the institution must make difficult airway equipment readily available. Tracheal extubation of the at-risk patient must also be carefully planned, including assessment of the patient's tolerance for withdrawal of airway support and whether re-intubation might be difficult.

RéSUMé: OBJECTIF: Depuis la dernière publication des lignes directrices du Canadian Airway Focus Group (CAFG) en 2013, la littérature sur la prise en charge des voies aériennes s'est considérablement étoffée. Le CAFG s'est donc réuni à nouveau pour examiner la littérature et mettre à jour ses recommandations de pratique. Ce deuxième article traite de l'évaluation des voies aériennes, de la prise de décision et de la mise en œuvre sécuritaire d'une stratégie de prise en charge des voies aériennes lorsque des difficultés sont anticipées. SOURCES: Des sujets de recherche ont été assignés aux membres du Canadian Airway Focus Group, qui compte des médecins anesthésistes, urgentologues et intensivistes. Les recherches ont été réalisées dans les bases de données Medline, EMBASE, Cochrane Central Register of Controlled Trials et CINAHL. Les résultats ont été présentés au groupe et discutés lors de vidéoconférences toutes les deux semaines entre avril 2018 et juillet 2020. Les recommandations du CAFG sont fondées sur les meilleures données probantes publiées. Si les données probantes de haute qualité manquaient, les énoncés se fondent alors sur le consensus du groupe. CONSTATATIONS ET RECOMMANDATIONS CLéS: Avant d'amorcer la prise en charge des voies aériennes, une stratégie documentée devrait être formulée pour chaque patient, en fonction de l'évaluation de ses voies aériennes. L'examen au chevet devrait rechercher les prédicteurs de difficultés pour la ventilation au masque, l'intubation trachéale utilisant la vidéolaryngoscopie ou la laryngoscopie directe, l'utilisation d'un dispositif supraglottique, ainsi que pour la cricothyroïdotomie d'urgence. La physiologie du patient et ses problématiques contextuelles devraient également être évaluées. Les difficultés anticipées devraient inciter à prendre des décisions éclairées sur la façon la plus sécuritaire de procéder à la prise en charge des voies aériennes. L'intubation trachéale éveillée peut procurer une marge de sécurité supplémentaire lorsqu'on s'attend à ce que la vidéolaryngoscopie ou la laryngoscopie directe soient impossibles, lorsqu'on prévoit des difficultés pour plus d'un mode de prise en charge des voies aériennes (p. ex., intubation trachéale et ventilation au masque), ou lorsque la difficulté prévue coïncide avec des problèmes physiologiques ou contextuels importants. En cas de choix de prise en charge des voies respiratoires du patient après induction de l'anesthésie générale malgré les difficultés prévues, les directives à l'équipe devraient inclure les déclencheurs pour passer d'une technique à l'autre, l'aide d'experts disponibles et l'équipement requis disponible. Des difficultés imprévues lors de la prise en charge des voies aériennes peuvent toujours survenir, de sorte que la personne responsable de la prise en charge des voies aériennes devrait avoir une stratégie pour chaque patient, et l'établissement doit rendre facilement disponible le matériel pour la prise en charge des voies aériennes difficiles. L'extubation trachéale du patient à risque doit également être soigneusement planifiée, y compris l'évaluation de la tolérance du patient lors du retrait du dispositif de soutien des voies aériennes et d'une ré-intubation potentiellement difficile.

Survival and Contaminants in Imperiled and Common Riverine Fishes Assessed with an In Situ Bioassay Approach.

An in situ bioassay approach was used to determine whether aquatic contaminant stressors in a large Atlantic river ecosystem affect the survival of 3 fish species: the largemouth bass (Micropterus salmoides, juveniles), the fathead minnow (Pimephales promelas, adults), and the robust redhorse (Moxostoma robustum, juveniles). Hatchery-propagated fish were placed into cages to assess site-specific survival in the Yadkin-Pee Dee River of North Carolina and South Carolina, USA. Contaminants were measured in caged fish and sediment and surface water at each site. No apparent longitudinal trends in fish survival were detected, and contaminant concentrations varied among sites. Juvenile largemouth bass and robust redhorse did not survive past 13 and 23 d, with corresponding Kaplan-Meier median survival estimates of 9.7 and 12.1 d, respectively. Survival of adult fathead minnows deployed in cages alongside the juvenile fish averaged 43% at the end of the 28-d exposure, with a 22-d median survival estimate. The intersex condition, an indicator of endocrine disruption, was not observed in any adult fathead minnow. Contaminant accumulation in surviving fathead minnows was apparent, with highest accumulated concentrations of polychlorinated biphenyls (34.6-93.4 ng/g dry wt), organochlorine pesticides (19.9-66.1 ng/g dry wt), and mercury (0.17-0.63 µg/g dry wt). Contaminants and other water quality stressors in this river system appear to detrimentally impact juvenile fish survival, with presumed effects at the fish assemblage and community levels. Environ Toxicol Chem 2021;40:2206-2219. © 2021 SETAC.

A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer.

INTRODUCTION: MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690). METHODS: A standard 3 + 3 dose-escalation design was used. Binimetinib 30 mg BID (dose level 1 [DL1]) or 45 mg BID (dose level 2 [DL2]) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule. The primary outcome was determination of the recommended phase II dose (RP2D) and safety of binimetinib. Secondary outcomes included efficacy, pharmacokinetics, and an exploratory analysis of response based on mutation subtype. RESULTS: Thirteen patients (6 DL1, 7 DL2) were enrolled: 7 KRAS, 5 EGFR, and 1 NRAS mutation. The RP2D was binimetinib 30 mg BID. Eight patients (61.5%) had grade 3/4 adverse events, with dose limiting toxicities in 2 patients at DL2. Twelve patients were evaluated for response, with an investigator-assessed objective response rate (ORR) of 50% (95% CI 21.1%-78.9%; ORR 33.3% by independent-review, IR), and disease control rate 83.3% (95% CI 51.6%-97.9%). Median progression free survival (PFS) was 4.5 months (95% CI 2.6 months-NA), with a 6-month and 12-month PFS rate of 38.5% (95% CI 19.3%-76.5%) and 25.6% (95% CI 8.9%-73.6%), respectively. In an exploratory analysis, KRAS/NRAS-mutated patients had an ORR of 62.5% (ORR 37.5% by IR) vs. 25% in KRAS/NRAS wild-type patients. In MAP2K1-mutated patients, the ORR was 42.8%. CONCLUSION: The addition of binimetinib to carboplatin and pemetrexed appears to have manageable toxicity with evidence of activity in advanced non-squamous NSCLC.

Availability of Services and Caregiver Burden: Supporting Individuals With Neurogenetic Conditions During the COVID-19 Pandemic.

Because of the COVID-19 pandemic, in-person services for individuals with neurodevelopmental disabilities were disrupted globally, resulting in a transition to remote delivery of services and therapies. For individuals with neurogenetic conditions, reliance on nonclinical caregivers to facilitate all therapies and care was unprecedented. The study aimed to (1) describe caregivers' reported impact on their dependent's services, therapies, medical needs, and impact on themselves as a result of the COVID-19 pandemic and (2) assess the relationship between the extent of disruption of services and the degree of self-reported caregiver burden. Two online questionnaires were completed by caregivers participating in Simons Searchlight in April and May 2020. Surveys were completed by caregivers of children or dependent adults with neurodevelopmental genetic conditions in Simons Searchlight. Caregivers reported that the impact of the COVID-19 pandemic moderately or severely disrupted services, therapies, or medical supports. The majority of caregivers were responsible for providing some aspect of therapy. Caregivers reported "feeling stressed but able to deal with problems as they arise," and reported lower anxiety at follow-up. Caregivers reported that telehealth services were not meeting the needs of those with complex medical needs. Future surveys will assess if and how medical systems, educational programs, therapists, and caregivers adapt to the challenges arising during the COVID-19 pandemic.

Early Pandemic Experiences of Autistic Adults: Predictors of Psychological Distress.

The COVID-19 pandemic has disrupted lives around the world. Autistic adults are at higher risk for co-occurring medical and psychiatric conditions and may be more prone to difficulties adapting to pandemic-related changes and social distancing mandates and coping with ongoing uncertainties. On the other hand, the pandemic may lead to greater understanding and acceptance of accommodations in the broader community that may facilitate supports for autistic adults beyond the pandemic. To learn more about their early pandemic experiences, online surveys were sent to independent adults enrolled in the Simons Powering Autism Research Knowledge (SPARK). The first survey was open from March 30 to April 19, 2020; a follow-up survey sent to original responders was open from May 27 to June 6, yielding 396 participants with data for both surveys. We found that adults who were female, younger, had prior diagnoses of a mental health condition, personal COVID-19 experience (i.e., knowing someone who had symptoms or tested positive) or less frequent hope for the future reported the greatest negative impacts. Decrease in feelings of hopefulness over time predicted greater psychological distress at T2, accounting for T1 impact and distress levels and increases in total COVID-19 impact. Less perceived benefit of online services also predicted later distress. Although there tends to be a focus on coping with negative effects of the pandemic, mental health providers may consider approaches that focus on positives, such as fostering hope and understanding factors that facilitate benefit from online services. LAY SUMMARY: Autistic adults may be at risk for psychological distress during the COVID-19 pandemic. The current study suggests that autistic adults who were younger, female, had a mental health diagnosis before the pandemic and knew someone who showed symptoms or tested positive for COVID-19 reported more areas negatively impacted by COVID-19 and greater difficulty coping with those effects. Decreases in hope over time were associated with greater psychological distress. Less perceived benefit from online services also predicted distress 2 months later. These results suggest important areas to further explore as we develop supports for autistic adults during the pandemic.