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Abstract Background There is no globally accepted definition for dosing error in adult or pediatric practice. The definition of pediatric dosing error varies greatly in the literature. The objective of this study was to develop a framework, informed by a set of principles, for a clinician-based definition of drug dosing errors in critically ill children, and to identify the range that practitioners agree is a dosing error for different drug classes and clinical scenarios. Methods We conducted a nationwide three staged modified Delphi from May to December 2019. Expert clinicians included Canadian pediatric intensive care unit (PICU) physicians, pharmacists and nurses, with a least 5 years’ experience. Outcomes were underlying principles of drug dosing, and error thresholds, as defined by proportion above and below reference range, for common PICU medications and clinical scenarios. Results Forty-four participants met eligibility, and response rates were 95, 86 and 84% for all three rounds respectively. Consensus was achieved for 13 of 15 principles, and 23 of 30 error thresholds. An over-dosed drug that is intercepted, an under-dose of a possibly life-saving medication, dosing 50% above or below target range and not adjusting for a drug interaction were agreed principles of dosing error. Altough there remained much uncertainty in defining dosing error, expert clinicians agreed that, for most medication categories and clinical scenarios, dosing over or below 10% of reference range was considered an error threshold. Conclusion Dosing principles and threshold are complex in pediatric critical care, and expert clinicians were uncertain about whether many scenarios were considered in error. For most intermittent medications, dosing over 10% below or above reference range was considered a dosing error, although this was largely influenced by clinical context and drug properties. This consensus driven error threshold will help guide routine clinical dosing practice, standardized reporting and drug quality improvement in pediatric critical care.

Summary: Background: SARS-Cov-2 infection rates are high among residents of long-term care (LTC) homes. We used machine learning to identify resident and community characteristics predictive of SARS-Cov-2 infection. Methods: We linked 26 population-based health and administrative databases to identify the population of all LTC residents tested for SARS-Cov-2 infection in Ontario, Canada. Using ensemble-based algorithms, we examined 484 factors, including individual-level demographics, healthcare use, comorbidities, functional status, and laboratory results; and community-level characteristics to identify factors predictive of infection. Analyses were performed separately for January to April (early wave 1) and May to August (late wave 1). Findings: Among 80,784 LTC residents, 64,757 (80.2%) were tested for SARS-Cov-2 (median age 86 (78–91) years, 30.6% male), of whom 10.2% of 33,519 and 5.2% of 31,238 tested positive in early and late wave 1, respectively. In the late phase (when restriction of visitors, closure of communal spaces, and universal masking in LTC were routine), regional-level characteristics comprised 33 of the top 50 factors associated with testing positive, while laboratory values and comorbidities were also predictive. The c-index of the final model was 0.934, and sensitivity was 0.887. In the highest versus lowest risk quartiles, the odds ratio for infection was 114.3 (95% CI 38.6–557.3). LTC-related geographic variations existed in the distribution of observed infection rates and the proportion of residents at highest risk. Interpretation: Machine learning informed evaluation of predicted and observed risks of SARS-CoV-2 infection at the resident and LTC levels, and may inform initiatives to improve care quality in this setting. Funding: Funded by a Canadian Institutes of Health Research, COVID-19 Rapid Research Funding Opportunity grant (# VR4 172736) and a Peter Munk Cardiac Centre Innovation Grant. Dr. D. Lee is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. Dr. Austin is supported by a Mid-Career investigator award from the Heart and Stroke Foundation. Dr. McAlister is supported by an Alberta Health Services Chair in Cardiovascular Outcomes Research. Dr. Kaul is the CIHR Sex and Gender Science Chair and the Heart & Stroke Chair in Cardiovascular Research. Dr. Rochon holds the RTO/ERO Chair in Geriatric Medicine from the University of Toronto. Dr. B. Wang holds a CIFAR AI chair at the Vector Institute.

Due to their low expression levels, complex multi-pass transmembrane structure, and the current lack of highly specific antibodies, the assessment of endogenous G protein-coupled receptors (GPCRs) remains challenging. While most of the research regarding their functions was performed in heterologous systems overexpressing the receptor, recent advances in genetic engineering methods have allowed the generation of several unique mouse models. These animals proved to be useful to investigate numerous aspects underlying the physiological functions of GPCRs, including their endogenous expression, distribution, interactome, and trafficking processes. Given their significant pharmacological importance and central roles in the nervous system, opioid peptide receptors (OPr) are often referred to as prototypical receptors for the study of GPCR regulatory mechanisms. Although only a few GPCR knock-in mouse lines have thus far been generated, OPr are strikingly well represented with over 20 different knock-in models, more than half of which were developed within the last 5 years. In this review, we describe the arsenal of OPr (mu-, delta-, and kappa-opioid), as well as the opioid-related nociceptin/orphanin FQ (NOP) receptor knock-in mouse models that have been generated over the past years. We further highlight the invaluable contribution of such models to our understanding of the in vivo mechanisms underlying the regulation of OPr, which could be conceivably transposed to any other GPCR, as well as the limitations, future perspectives, and possibilities enabled by such tools.

Abstract Background Although hospital readmission for heart failure (HF) is an issue for both men and women, little is known about differences in readmission rates by sex. Consequently, strategies to optimize readmission reduction programs and care strategies for women and men remain unclear. Our study aims were: (1) to identify studies examining readmission rates according to sex, and (2) to provide a qualitative overview of possible considerations for the impact of sex or gender. Methods We conducted a scoping review using the Arksey and O’Malley framework to include full text articles published between 2002 and 2017 drawn from multiple databases (MEDLINE, EMBASE), grey literature (i.e. National Technical information, Duck Duck Go), and expert consultation. Eligible articles included an index heart failure episode, readmission rates, and sex/gender-based analysis. Results The search generated 5887 articles, of which 746 underwent full abstract text consideration for eligibility. Of 164 eligible articles, 34 studies addressed the primary outcome, 103 studies considered sex differences as a secondary outcome and 25 studies stratified data for sex. Good inter-rater agreement was reached: 83% title/abstract; 88% full text; kappa: 0.69 (95%CI: 0.53–0.85). Twelve of 34 studies reported higher heart failure readmission rates for men and six studies reported higher heart failure readmission rates for women. Using non composite endpoints, five studies reported higher HF readmission rates for men compared to three studies reporting higher HF readmission rates for women. Overall, there was heterogeneity between studies when examined by sex, but one observation emerged that was related to the timing of readmissions. Readmission rates for men were higher when follow-up duration was longer than 1 year. Women were more likely to experience higher readmission rates than men when time to event was less than 1 year. Conclusions Future studies should consider different time horizons in their designs and avoid the use of composite measures, such as readmission rates combined with mortality, which are highly skewed by sex. Co-interventions and targeted post-discharge approaches with attention to sex would be of benefit to the HF patient population.

Abstract Background The lack of a reporting guideline for scaling of evidence-based practices (EBPs) studies has prompted the registration of the Standards for reporting studies assessing the impact of scaling strategies of EBPs (SUCCEED) with EQUATOR Network. The development of SUCCEED will be guided by the following main steps recommended for developing health research reporting guidelines. Methods Executive Committee. We established a committee composed of members of the core research team and of an advisory group. Systematic review. The protocol was registered with the Open Science Framework on 29 November 2019 (https://osf.io/vcwfx/). We will include reporting guidelines or other reports that may include items relevant to studies assessing the impact of scaling strategies. We will search the following electronic databases: EMBASE, PsycINFO, Cochrane Library, CINAHL, Web of Science, from inception. In addition, we will systematically search websites of EQUATOR and other relevant organizations. Experts in the field of reporting guidelines will also be contacted. Study selection and data extraction will be conducted independently by two reviewers. A narrative analysis will be conducted to compile a list of items for the Delphi exercise. Consensus process . We will invite panelists with expertise in: development of relevant reporting guidelines, methodologists, content experts, patient/member of the public, implementers, journal editors, and funders. We anticipated that three rounds of web-based Delphi consensus will be needed for an acceptable degree of agreement. We will use a 9-point scale (1 = extremely irrelevant to 9 = extremely relevant). Participants’ response will be categorized as irrelevant (1–3), equivocal (4–6) and relevant (7–9). For each item, the consensus is reached if at least 80% of the participants’ votes fall within the same category. The list of items from the final round will be discussed at face-to-face consensus meeting. Guideline validation . Participants will be authors of scaling studies. We will collect quantitative (questionnaire) and qualitative (semi-structured interview) data. Descriptive analyses will be conducted on quantitative data and constant comparative techniques on qualitative data. Discussion Essential items for reporting scaling studies will contribute to better reporting of scaling studies and facilitate the transparency and scaling of evidence-based health interventions.

It has been widely recognised that transition into higher education (HE) can be challenging for incoming students. Literature identifies three main areas where students may benefit from support: social, practical and academic. This paper discusses a case study that explores the potential of a social networking environment to provide support in these areas during students' transition into HE. The Learning Development Unit (LDU) at Bucks New University has previously addressed transitional issues through pre-sessional campus-based programmes. However, to provide opportunities for a wider range of students, the LDU launched Startonline in 2010. This online pre-sessional environment used the social networking platform Ning to provide new students with access to non-subject-specific academic activities (e.g., critical thinking), social networking tools and practical information. As a pilot, the aim was to observe where students focussed their attention and explore the affordances of a social networking environment for facilitating transition. Startonline ran for the month leading up to the beginning of the academic year, during which time around 300 students signed up and participated. Quantitative analysis of platform user data was conducted and student and staff participants were interviewed, providing useful qualitative data. Findings highlighted that students' engaged intensely in social and informational aspects of the environment, but remained resolutely uninterested in generic academic activities. There was, however, considerable self-directed interest in finding subject-specific information and learning activities. Direct, personal involvement of subject-teaching staff seemed the determining factor in take up of these aspects. Social networking platforms are already used by students to maintain social capital and access emotional support from existing social networks when leaving secondary school. This project highlights that, equally, such environments also provide powerful opportunities for students to establish social networks as they transition into higher education. Lessons have also been learned with regard to effective pedagogical strategies for engaging students academically in social networking environments and areas identified for future research. (Contains 1 figure.)

Olivia Oxlade and co-authors introduce a Collection on tuberculosis preventive therapy in people with HIV infection.

Objective: Racial disparities are associated with increased healthcare costs and suboptimal resource utilization. We sought to evaluate racial disparities in the therapeutic management of liver lesions. Materials and Methods: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was queried for patients presenting with a liver lesion who had surgical resection (SR) or an ablative procedure (AP). Univariable and multivariable analysis were performed to identify disparities in the treatment rendered. A regression model was constructed to evaluate demographic characteristics favoring AP. Results: Between 2005 and 2016, 8,706 patients were diagnosed with a liver lesion, 7,290 (84%) had SR and 1,416 (16%) had AP. Compared to SR, the AP cohort had a higher number of Native Americans (0.5% vs. 2%; p

Background: Utilisation of the Endoscopic Vein Harvesting (EVH) technique has been increasing for coronary artery bypass grafting (CABG) for the last two decades. Some surgeons remain concerned about the long-term patency of the long saphenous vein harvested endoscopically compared to traditional Open Vein Harvesting (OVH). The aim of this study was to perform a retrospective analysis of the outcomes between EVH and OVH from three UK centres with 10 years follow-up. Methods: 27,024 patients underwent CABG with long saphenous vein harvested by EVH (n=13,794) or OVH (n=13,230) in three UK centres between 2007 and 2019. Propensity modelling was used to calculate the Inverse Probability of Treatment Weights (IPTW). The primary endpoint was mortality from all causes and secondary endpoints were length of hospital stay, postoperative complications, and incidence of repeat coronary re-vascularisation for symptomatic patients. IPTW was used to balance the two intervention groups for baseline and preoperative co-morbidities. Results: Median follow-up time was 4.54 years for EVH and 6.00 years for OVH. Death from any cause occurred in 13.8% of the EVH group versus 20.8% in the OVH group over the follow-up period. The hazard ratio of death (EVH to OVH) was 0.823 (95% CI: 0.767, 0.884). Length of hospital stay was similar between the groups (p=0.86). Post-operative pulmonary complications were more common in EVH vs OVH (14.7% vs. 12.8%, p

BackgroundMobile app–based therapies are increasingly being employed by speech-language pathologists in the rehabilitation of people with aphasia as adjuncts or substitutes for traditional in-person therapy approaches. These apps can increase the intensity of treatment and have resulted in meaningful outcomes across several domains. ObjectiveVoiceAdapt is a mobile therapy app designed with user and stakeholder feedback within a user-centered design framework. VoiceAdapt uses two evidence-based lexical retrieval treatments to help people with aphasia in improving their naming abilities through interactions with the app. The purpose of the randomized controlled trial (RCT) proposed here is to examine the feasibility and clinical efficacy of training with VoiceAdapt on the language and communication outcomes of people with aphasia. MethodsA multicenter RCT is being conducted at two locations within Canada. A total of 80 people with aphasia will be recruited to participate in a two-arm, waitlist-controlled, crossover group RCT. After baseline assessment, participants will be randomized into an intervention group or a waitlist control group. The intervention group participants will engage in 5 weeks of training with the app, followed by posttreatment and follow-up assessments after an additional 5 weeks. Those in the waitlist control group will have no training for 5 weeks; this is followed by pretreatment assessment, training for 5 weeks, and posttreatment assessment. All trial procedures are being conducted remotely given the COVID-19 pandemic. ResultsRecruitment of participants started in September 2020, and the study is expected to be completed by March 2022. Publication of results is expected within 6 months of study completion. ConclusionsThe results of the RCT will provide information on evidence-based practice using technology-based solutions to treat aphasia. If positive results are obtained from this RCT, the VoiceAdapt app can be recommended as an efficacious means of improving lexical retrieval and communicative functioning in people with aphasia in an easily accessible and a cost-effective manner. Moreover, the implementation of this RCT through remote assessment and delivery can provide information to therapists on telerehabilitation practices and monitoring of app-based home therapy programs. Trial RegistrationClinicalTrials.gov NCT04108364; https://clinicaltrials.gov/ct2/show/NCT04108364 International Registered Report Identifier (IRRID)DERR1-10.2196/30621

Introduction. L’écriture manuelle est une tâche fonctionnelle essentielle au rendement occupationnel, enseignée très tôt dans le cursus scolaire. Lorsque des difficultés graphomotrices sont constatées, les enseignants et ergothérapeutes interviennent souvent dans le but de modifier la prise du crayon des élèves en privilégiant l’adoption d’une prise tripode dynamique. Toutefois, dans la littérature scientifique, cette prise n’est pas la seule à être répertoriée et considérée comme fonctionnelle. Objectifs. Cette étude vise à documenter les différents types de prise du crayon chez des élèves de 2e et 4e année du primaire, ainsi qu’à examiner la relation entre ces différentes prises et la vitesse et la lisibilité de l’écriture manuelle. Méthode. 57 élèves (2e année : n = 22 ; 4e année : n = 35) ont été filmés, lors d’une série de tâches de production écrite, de manière à identifier les différentes prises adoptées par les élèves. La vitesse et la lisibilité de l’écriture manuelle ont été évaluées par l’entremise d’une tâche de copie de phrases de près. Résultats. Les élèves utilisent différentes prises du crayon. Aucune relation significative n’a été identifiée entre ces prises et la vitesse et la lisibilité de l’écriture manuelle. La prise quadripode dynamique est la plus utilisée par les élèves de 2e année et de 4e année du primaire. Conclusion. La prise tripode dynamique n’est pas la seule prise fonctionnelle adoptée par les élèves. Les prises quadripode dynamique, tripode latérale et quadripode latérale sont toutes aussi fonctionnelles. Lors de l’enseignement de l’écriture, cette diversité quant à la prise du crayon devrait être prise en compte. _____________________________________________________________________________________________________________ Grasp patterns of Grade 2 and Grade 4 pupils and the effect of pencil grasp on speed and legibility in handwriting Background. Handwriting is a functional skill essential for occupational performance that is taught early on to pupils. When a pupil has some difficulties with handwriting, teachers and occupational therapists tend to focus on changing his pencil grasp by favorizing the dynamic tripod one. Therefore, it has been proven that this grasp isn’t the only functional one. Purpose. This study aims to describe grasp patterns of Grade 2 and Grade 4 pupils and evaluate the effect of pencil grasp on speed and legibility in handwriting. Method. 57 pupils (Grade 2: n = 22; Grade 4: n = 42) were filmed during a series of handwritten tasks to identify the different grasps adopted by pupils. The handwriting skills were evaluated by completing a near-point copying task. Findings. Pupils use different pencil grasps and none of the grasps described had an effect on speed and legibility of the handwriting. The dynamic quadrupod grasp is the most used by grade 2 and 4 pupils. Implications. The dynamic tripod grasp is not the only functional grasp. The dynamic quadrupod, lateral tripod and lateral quadrupod graps also allowed good speed and legibility when writing. When teaching handwriting, the different grasps should be taken into consideration.

Objectives Evaluate gender differences in authorship of COVID-19 articles in high-impact medical journals compared with other topics.Design Cross-sectional review.Data sources Medline database.Eligibility criteria Articles published from 1 January to 31 December 2020 in the seven leading general medical journals by impact factor. Article types included primary research, reviews, editorials and commentaries.Data extraction Key data elements were whether the study topic was related to COVID-19 and names of the principal and the senior authors. A hierarchical approach was used to determine the likely gender of authors. Logistic regression assessed the association of study characteristics, including COVID-19 status, with authors’ likely gender; this was quantified using adjusted ORs (aORs).Results We included 2252 articles, of which 748 (33.2%) were COVID-19-related and 1504 (66.8%) covered other topics. A likely gender was determined for 2138 (94.9%) principal authors and 1890 (83.9%) senior authors. Men were significantly more likely to be both principal (1364 men; 63.8%) and senior (1332 men; 70.5%) authors. COVID-19-related articles were not associated with the odds of men being principal (aOR 0.99; 95% CI 0.81 to 1.21; p=0.89) or senior authors (aOR 0.96; 95% CI 0.78 to 1.19; p=0.71) relative to other topics. Articles with men as senior authors were more likely to have men as principal authors (aOR 1.49; 95% CI 1.21 to 1.83; p

The social, economic, and environmental determinants of health include employment, housing, and education; exposure to environmental factors like lead or access to healthy food; and poverty, racism and oppression. Many of these conditions can lead to Adverse Childhood Experiences that may put children and youth at risk for abuse or maltreatment leading to involvement in the child welfare or juvenile justice systems. All young people experience important developmental milestones on their path to becoming healthy adults, and while this time of change is full of promise, it can be a time of increased vulnerability or risk. For system-involved youth, navigating this time of change can be fraught with even more challenges or barriers. Without strong family and social networks, they may face increased risk of engaging in high-risk behaviors--such as unprotected sex and sex with multiple partners--as well as unintended pregnancy, HIV, and other sexually transmitted infections. Our study examined survey data to assess the overall sexual reproductive health behaviors for youth aged 14-21 in out-of-home care in an urban environment (n = 270; 60.7% male; 82% African American; 7.9% Latinx). Youth were recruited between 2012 and 2016; 76.4% of these teens had had sexual intercourse at some point in their lifetime. Of these, 86.0% were sexually active before the age of 16. Although there were numerous risk factors related to contraception and condom use as well as partner demographics, there were assets or strengths identified. A discussion of how these findings can be utilized to develop effective prevention intervention strategies is provided.

Summary: Polypharmacy is very common in older adults and increases the risk of inappropriate and unsafe prescribing for older adults. Older adults, particularly women (who make up the majority of this age group), are at the greatest risk for drug-related harm. Therefore, optimising drug prescribing for older people is very important. Identifying potentially inappropriate medications and opportunities for judicious deprescribing processes are intrinsically linked, complementary, and essential for optimising medication safety. This Review focuses on optimising prescribing for older adults by reducing doses or stopping drugs that are potentially harmful or that are no longer needed. We explore how sex (biological) and gender (sociocultural) factors are important considerations in safe drug prescribing. We conclude by providing a practical approach to optimising medication safety that clinicians can routinely apply to the care of their older patients, highlighting how sex and gender considerations inform medication decision making.

Si bien la era de las tasas de interés negativas no parece haber terminado, al menos por el momento, sigue siendo un tema sobre el que vale la pena reflexionar, especialmente en un intento por comprender sus raíces teóricas, y particularmente a la luz de una posible desaceleración en la actividad económica en Estados Unidos y en otras geografías (al momento de escribir este artículo). Este documento examina la evolución de la política monetaria desde la crisis y se centra en las llamadas políticas no convencionales como la flexibilización cuantitativa (QE) y las tasas de interés negativas, argumentando que desde una perspectiva teórica, aunque neoclásica, ambas políticas están relacionadas y basadas en el mismo modelo de multiplicador de dinero.