Understanding the malignant potential of gastric metaplasia of the oesophagus and its relevance to Barrett's oesophagus surveillance: individual-level data analysis.

OBJECTIVE: Whether gastric metaplasia (GM) of the oesophagus should be considered as Barrett's oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance. DESIGN: We performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC). RESULTS: We found that 58 of 77 short-segment (<3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was significantly lower than in the IM-only cases (Kaplan-Meier, p=0.03). Genomic analysis revealed that the mutation burden in GM is significantly lower than in IM (p<0.01). Moreover, GM does not bear the mutational hallmarks of OAC, with an absence of associated signatures and driver gene mutations. Finally, we established that GM found adjacent to OAC is evolutionarily distant from cancer. CONCLUSION: SS-GM is a distinct entity from SS-IM and the malignant potential of GM is lower than IM. It is questionable whether SS-GM warrants inclusion in BO surveillance.

Improving equity of services for sexually transmitted infections through community pharmacies: A scoping review.

BACKGROUND: Pharmacists have the potential to improve care for marginalized populations. Stigmatized and racialized groups may not find traditional health services accessible in other settings. Research focused on health care access for these populations is fundamental in understanding how to improve health equity. OBJECTIVES: This scoping review aimed to determine how health equity is addressed within services offered through community pharmacies for sexually transmitted infections (STIs). METHODS: This scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Checklist. A comprehensive search strategy was developed with an academic librarian to capture studies containing search terms related to each of the following 3 topics: STIs, pharmacy, and underserved groups. PubMed and Embase were both searched up to July 2023 and search results were uploaded to the screening software Covidence. Two researchers independently screened titles, abstracts, and full texts. Articles were included if they reported evaluation of a pharmacy-based sexual health service and addressed health equity in service design or implementation. RESULTS: A total of 8 articles were identified that described services implemented for underserved groups. Four populations were identified: injection drug users, men who have sex with men, racial minorities, and those with low socioeconomic status. Equity was addressed through 2 mechanisms: location-based implementation of services in areas of high target population density or through specific targeting of marginalized populations in recruitment and promotion. All studies involved interventions for the prevention or testing services rather than assessment and treatment. CONCLUSIONS: Equity is not being readily addressed in pharmacy-based services for STIs yet evidence exists that considering equity in the design and implementation of services may improve reach to underserved populations.

A Systematic Review of Antimicrobial Stewardship Interventions to Improve Management of Bacteriuria in Hospitalized Adults.

OBJECTIVE: To determine whether implementation of antimicrobial stewardship (AMS) interventions improve management of bacteriuria in hospitalized adults. DATA SOURCES: EMBASE, MEDLINE, CINAHL, and Clinical Trials Registries via Cochrane CENTRAL were searched from inception through May 2021. Reference lists of included studies were searched, and Scopus was used to retrieve articles that cited included references. STUDY SELECTION AND DATA EXTRACTION: Randomized and nonrandomized trials, controlled before-after studies, interrupted time-series studies, and repeated measures studies evaluating AMS interventions for hospitalized adult inpatients with bacteriuria were included. Risk of bias was assessed independently by 3 team members and compared. Results were summarized descriptively. DATA SYNTHESIS: The search yielded 5509 articles, of which 13 met inclusion criteria. Most common interventions included education (N = 8) and audit and feedback (N = 5) alone or in combination with other interventions. Where assessed, resource and antimicrobial use primarily decreased and appropriateness of antimicrobial use improved; however, impact on guideline adherence was variable. All studies were rated as having unclear or serious risk of bias. This review summarizes and assesses the quality of evidence for AMS interventions to improve the management of bacteriuria. Results provide guidance to both AMS teams and researchers aiming to develop and/or evaluate AMS interventions for management of bacteriuria. CONCLUSIONS: This review demonstrated benefit of AMS interventions on management of bacteriuria. However, most studies had some risk of bias, and an overall effect across studies is unclear due to heterogeneity in outcome measures.

Deep phenotyping in 3q29 deletion syndrome: recommendations for clinical care.

PURPOSE: To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care. METHODS: Thirty-two individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments. RESULTS: Medical manifestations were varied and reported across nearly every organ system. The most severe manifestations were congenital heart defects (25%) and the most common were gastrointestinal symptoms (81%). Physical examination revealed a high proportion of musculoskeletal findings (81%). Neurodevelopmental phenotypes represent a significant burden and include intellectual disability (34%), autism spectrum disorder (38%), executive function deficits (46%), and graphomotor weakness (78%). Psychiatric illness manifests across the lifespan with psychosis prodrome (15%), psychosis (20%), anxiety disorders (40%), and attention deficit-hyperactivity disorder (ADHD) (63%). Neuroimaging revealed structural anomalies of the posterior fossa, but on neurological exam study subjects displayed only mild or moderate motor vulnerabilities. CONCLUSION: By direct evaluation of 3q29 deletion study subjects, we document common features of the syndrome, including a high burden of neurodevelopmental and neuropsychiatric phenotypes. Evidence-based recommendations for evaluation, referral, and management are provided to help guide clinicians in the care of 3q29 deletion patients.

Craniofacial features of 3q29 deletion syndrome: Application of next-generation phenotyping technology.

3q29 deletion syndrome (3q29del) is a recurrent deletion syndrome associated with neuropsychiatric disorders and congenital anomalies. Dysmorphic facial features have been described but not systematically characterized. This study aims to detail the 3q29del craniofacial phenotype and use a machine learning approach to categorize individuals with 3q29del through analysis of 2D photos. Detailed dysmorphology exam and 2D facial photos were ascertained from 31 individuals with 3q29del. Photos were used to train the next-generation phenotyping algorithm DeepGestalt (Face2Gene by FDNA, Inc, Boston, MA) to distinguish 3q29del cases from controls and all other recognized syndromes. Area under the curve of receiver operating characteristic curves (AUC-ROC) was used to determine the capacity of Face2Gene to identify 3q29del cases against controls. In this cohort, the most common observed craniofacial features were prominent forehead (48.4%), prominent nose tip (35.5%), and thin upper lip vermillion (25.8%). The FDNA technology showed an ability to distinguish cases from controls with an AUC-ROC value of 0.873 (p = 0.006) and led to the inclusion of 3q29del as one of the supported syndromes. This study found a recognizable facial pattern in 3q29del, as observed by trained clinical geneticists and next-generation phenotyping technology. These results expand the potential application of automated technology such as FDNA in identifying rare genetic syndromes, even when facial dysmorphology is subtle.

Segregation of two variants suggests the presence of autosomal dominant and recessive forms of WFS1-related disease within the same family: expanding the phenotypic spectrum of Wolfram Syndrome.

BACKGROUND: WFS1 was initially described as causative agent of autosomal recessive (AR) Wolfram syndrome, a childhood-onset disorder involving diabetes, optic atrophy, hearing loss and neurodegenerative features. However, the discovery of autosomal dominant (AD) disorders caused by this gene has resulted in clinical counselling and result interpretation challenges. OBJECTIVE: We seek to report a family that appears to segregate dominant and recessive forms of WFS1-related disease. METHODS/RESULTS: A 19-year-old woman presented with progressive childhood sensorineural hearing loss and recent optic atrophy, with biallelic mutations in WFS1: c.2486T>C (likely pathogenic) and c.2470G>A (uncertain significance). Her A1C was normal. Her sister carried the same variants and had a similar phenotype. Their father carried c.2486T>C and was found to have mild-moderate hearing loss but no optic atrophy or neurological symptoms. The mother carried c.2470G>A and had a normal audiogram and ophthalmological exam. Providing anticipatory guidance for this family was difficult given the phenotypic variability of WFS1-related disorders and the uncertainty surrounding whether the inheritance pattern was AR or AD. CONCLUSION: The clinical correlation of the variants identified in this family suggests an AR Wolfram-like syndrome, without the typical diabetes mellitus or diabetes insipidus nor neurological decline. To our knowledge, this is a novel WFS1-related phenotype.

Self-care education across Canadian pharmacy schools: Curriculum survey findings.

BACKGROUND: Self-care instruction in pharmacy curricula is essential given the impact pharmacists have in caring for patients in the community and their evolving role in this area. The primary objective of this study was to strengthen our current understanding of self-care education across undergraduate Canadian pharmacy programs. METHODS: A national curriculum survey and follow-up phone interview was conducted in 2019 to assess the quantity and quality of self-care instruction across Canadian pharmacy schools. Representatives were selected based on theirparticipation in the Association of Faculties of Pharmacy of Canada Self-Care Therapeutics and Minor Ailments special interest group. RESULTS: Responses were received from all 10 pharmacy schools in Canada. Self-care education varies across Canadian pharmacy curricula, reflecting differences in scopes of practice across provinces, topics of interest and availability of space within curricula by the various faculties. Specifically, there was considerable variability in the number of hours devoted to self-care education, course content and methods for integration and teaching. CONCLUSIONS: Results of this study may help inform and evolve self-care curricula across the country. We argue that strategies for enhancing current programs may include establishing a minimum number of core hours and topics, expanding natural health product content and curricular content oversight by a lead faculty member. Can Pharm J (Ott) 2021;154:xx-xx.

Two Angelman families with unusually advanced neurodevelopment carry a start codon variant in the most highly expressed UBE3A isoform.

We present three children from two unrelated families with Angelman syndrome (AS) whose developmental skills are far more advanced than any other non-mosaic AS individual ever reported. All have normal gait and use syntactic language spontaneously to express their needs. All of them have a c.2T > C (p.Met1Thr) variant in UBE3A, which abrogates the start codon of isoform 1, but not of isoforms 2 and 3. This variant was maternally inherited in one set of siblings, but de novo in the other child from the unrelated family. This report underscores the importance of considering AS in the differential diagnosis even in the presence of syntactic speech.

A Systematic Review of Antimicrobial Stewardship Interventions in the Emergency Department.

BACKGROUND/OBJECTIVE: To improve antimicrobial utilization, development and implementation of antimicrobial stewardship programs in the emergency department (ED) has been recommended. The primary objective of this review was to characterize antimicrobial stewardship (AMS) in the ED and to identify interventions that improve patient outcomes or process of care and/or reduce consequences of antimicrobial use. METHODS: This study was completed as a systematic review. The following databases were searched from inception through November, 2016: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Web of Science. Randomized controlled trials, nonrandomized controlled trials, controlled and uncontrolled before-and-after studies, interrupted time series studies, and repeated-measures studies evaluating AMS interventions in the ED were included in the review. Studies published in languages other than English were excluded. RESULTS: A total of 43 studies meeting inclusion criteria were identified from our search. Patient or provider education and guideline or clinical pathway implementation were the most commonly reported interventions. Few studies reported on audit and feedback, and no study evaluated preauthorization. Impact of interventions showed variable results. Where identified, benefits of AMS interventions primarily included improvement in delivery of care or a decrease in antimicrobial utilization; however, most studies were rated as having unclear or high risk of bias. CONCLUSION: AMS interventions in the ED may improve patient care. However, the optimal combination of interventions is unclear. Additional studies with more rigorous design evaluating core components of AMS programs, including prospective audit and feedback are needed.

Describing student performance: a comparison among clinical preceptors across cultural contexts.

CONTEXT: Health professional student evaluation during experiential training is notably subjective and assessor judgements may be affected by socio-cultural influences. OBJECTIVES: This study sought to explore how clinical preceptors in pharmacy conceptualise varying levels of student performance and to identify any contextual differences that may exist across different countries. METHODS: The qualitative research design employed semi-structured interviews. A sample of 20 clinical preceptors for post-baccalaureate Doctor of Pharmacy programmes in Canada and the Middle East gave personal accounts of how students they had supervised fell below, met or exceeded their expectations. Discussions were analysed following constructivist grounded theory principles. RESULTS: Seven major themes encompassing how clinical pharmacy preceptors categorise levels of student performance and behaviour were identified: knowledge; team interaction; motivation; skills; patient care; communication, and professionalism. Expectations were outlined using both positive and negative descriptions. Pharmacists typically described supervisory experiences representing a series of these categories, but arrived at concluding judgements in a holistic fashion: if valued traits of motivation and positive attitude were present, overall favourable impressions of a student could be maintained despite observations of a few deficiencies. Some prioritised dimensions could not be mapped to defined existing educational outcomes. There was no difference in thresholds for how student performance was distinguished by participants in the two regions. CONCLUSIONS: The present research findings are congruent with current literature related to the constructs used by clinical supervisors in health professional student workplace-based assessment and provide additional insight into cross-national perspectives in pharmacy. As previously determined in social work and medicine, further study of how evaluation instruments and associated processes can integrate these judgements should be pursued in this discipline.

The Role of Musical Experience in Hemispheric Lateralization of Global and Local Auditory Processing.

The global precedence effect is a phenomenon in which global aspects of visual and auditory stimuli are processed before local aspects. Individuals with musical experience perform better on all aspects of auditory tasks compared with individuals with less musical experience. The hemispheric lateralization of this auditory processing is less well-defined. The present study aimed to replicate the global precedence effect with auditory stimuli and to explore the lateralization of global and local auditory processing in individuals with differing levels of musical experience. A total of 38 college students completed an auditory-directed attention task while electroencephalography was recorded. Individuals with low musical experience responded significantly faster and more accurately in global trials than in local trials regardless of condition, and significantly faster and more accurately when pitches traveled in the same direction (compatible condition) than when pitches traveled in two different directions (incompatible condition) consistent with a global precedence effect. In contrast, individuals with high musical experience showed less of a global precedence effect with regards to accuracy, but not in terms of reaction time, suggesting an increased ability to overcome global bias. Further, a difference in P300 latency between hemispheres was observed. These findings provide a preliminary neurological framework for auditory processing of individuals with differing degrees of musical experience.

Parental Decision-Making Preferences in Neonatal Intensive Care.

OBJECTIVE: To explore how characteristics of medical decisions influence parents' preferences for control over decisions for their seriously ill infants. STUDY DESIGN: In qualitative interviews, parents of infants in the neonatal intensive care unit (NICU) were asked to consider all medical decisions they could recall, and were prompted with decisions commonly encountered in the NICU. For each decision, parents were asked detailed questions about who made each decision, whom they would have preferred to make the decision, and why. Using standard qualitative methods, responses were coded and organized such that decision-level characteristics could be analyzed according to preferred decision-making role. RESULTS: Parents identified 2 factors that were associated with a preference to delegate decisions to the medical team (high degree of urgency, high level of required medical expertise) and 4 factors associated with a preference to retain parental control (high perceived risk, high personal experience with the decision, involvement of foreign bodily fluids, and similarity to decisions that they perceived as part of the normal parental role). CONCLUSIONS: Characteristics of decisions influence preferences for control over medical decisions among parents of patients in the NICU. These insights may guide improvements in physician-parent communication and consent.

Neurohumoral Integration of Cardiovascular Function by the Lamina Terminalis.

The mechanisms involved in cardiovascular regulation, such as vascular tone, fluid volume and blood osmolarity, are quite often mediated by signals circulating in the periphery, such as angiotensin II and sodium concentration. Research has identified areas within the lamina terminalis (LT), specifically the sensory circumventricular organs (CVOs), the subfornical organ and the organum vasculosum of the lamina terminalis, as playing crucial roles detecting and integrating information derived from these circulating signals. The median preoptic nucleus (MnPO) is a third integrative structure within the LT that influences cardiovascular homeostasis, although to date, its role is not as clearly elucidated. More recent studies have demonstrated that the CVOs are not only essential in the detection of traditional cardiovascular signals but also signals primarily considered to be important in the regulation of metabolic, reproductive and inflammatory processes that have now also been implicated in cardiovascular regulation. In this review, we highlight the critical roles played by the LT in the detection and integration of circulating signals that provide critical feedback control information contributing to cardiovascular regulation.

A qualitative study evaluating barriers and enablers to improving antimicrobial use for the management of bacteriuria in hospitalized adults.

Objective: The objective of this study was to explore barriers and enablers to improving the management of bacteriuria in hospitalized adults. Design: Qualitative study. Setting: Nova Scotia, Canada. Participants: Nurses, physicians, and pharmacists involved in the assessment, diagnosis, and treatment of bacteriuria in hospitalized patients. Methods: Focus groups (FGs) were completed between May and July 2019. FG discussions were facilitated using an interview guide that consisted of open-ended questions coded to the theoretical domains framework (TDF) v2. Discussions were transcribed verbatim then independently coded to the TDFv2 by two members of the research team and compared. Thematic analysis was used to identify themes. Results: Thirty-three healthcare providers from five hospitals participated (15 pharmacists, 11 nurses, and 7 physicians). The use of antibiotics for the treatment of asymptomatic bacteriuria (ASB) was the main issue identified. Subthemes that related to management of ASB included: "diagnostic uncertainty," difficulty "ignoring positive urine cultures," "organizational challenges," and "how people learn." Barriers and/or enablers to improving the management of bacteriuria were mapped to 12 theoretical domains within these subthemes. Barriers and enablers identified by participants that were most extensively discussed related to the domains of environmental context and resources, belief about capabilities, social/professional role and identity, and social influences. Conclusions: Healthcare providers highlighted barriers and recognized enablers that may improve delivery of care to patients with bacteriuria. A wide range of barriers at the individual and organization level to address diagnostic challenges and improve workload should be considered to improve management of bacteriuria.

Neurological outcome following out of hospital cardiac arrest: Evaluation of performance of existing risk prediction models in a UK cohort.

Introduction: Out of hospital cardiac arrest (OHCA) is a common problem. Rates of survival are low and a proportion of survivors are left with an unfavourable neurological outcome. Four models have been developed to predict risk of unfavourable outcome at the time of critical care admission - the Cardiac Arrest Hospital Prognosis (CAHP), MIRACLE2, Out of Hospital Cardiac Arrest (OHCA), and Targeted Temperature Management (TTM) models. This evaluation evaluates the performance of these four models in a United Kingdom population and provides comparison to performance of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. Methods: A retrospective evaluation of the performance of the models was conducted over a 43-month period in 414 adult, non-pregnant patients presenting consecutively following non-traumatic OHCA to the five units in our regional critical care network. Scores were generated for each model for where patients had complete data (CAHP = 347, MIRACLE2 = 375, OHCA = 356, TTM = 385). Cerebral Performance Category (CPC) outcome was calculated for each patient at last documented follow up and an unfavourable outcome defined as CPC ⩾ 3. Performance for discrimination of unfavourable outcome was tested by generating receiver operating characteristic (ROC) curves for each model and comparing the area under the curve (AUC). Results: Best performance for discrimination of unfavourable outcome was demonstrated by the high risk group of the CAHP score with an AUC of 0.87 [95% CI 0.83-0.91], specificity of 97.1% [95% CI 93.8-100] and positive predictive value (PPV) of 96.3% [95% CI 92.2-100]. The high risk group of the MIRACLE2 model, which is significantly easier to calculate, had an AUC of 0.81 [95% CI 0.76-0.86], specificity of 92.3% [95% CI 87.2-97.4] and PPV of 95.2% [95% CI 91.9-98.4]. Conclusion: The CAHP, MIRACLE2, OHCA and TTM scores all perform comparably in a UK population to the original development and validation cohorts. All four scores outperform APACHE-II in a population of patients resuscitated from OHCA. CAHP and TTM perform best but are more complex to calculate than MIRACLE2, which displays inferior performance.

Disentangling oncogenic amplicons in esophageal adenocarcinoma.

Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons' origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma.

Propofol for procedural sedation in the emergency department: a qualitative systematic review.

OBJECTIVE: To evaluate the efficacy and safety of propofol compared to other agents for procedural sedation of adults in the emergency department (ED) and to review the use of opioids in conjunction with propofol for procedural sedation in the ED. DATA SOURCES: PubMed (1949-December 2012) and EMBASE (1980-December 2012) were searched using combinations of the following search terms: (procedural sedation or conscious sedation [MESH]) and propofol. A manual search of references was also performed. STUDY SELECTION AND DATA EXTRACTION: English-language, full reports of randomized controlled trials (RCTs) and observational studies evaluating propofol use in adults undergoing procedural sedation in the ED were included if they reported efficacy or safety outcomes. Two reviewers independently assessed each article for inclusion, data extraction, and study limitations. DATA SYNTHESIS: Thirteen RCTs and 20 observational studies meeting our inclusion criteria were retrieved. Regardless of the agent used for sedation, pro ce du ral success was greater than 80% and most trials demonstrated no statistically significant difference in the incidence of respiratory depression with propofol compared to alternatives. One RCT showed a significantly greater percent decrease in systolic blood pressure from baseline in those who received propofol compared to ketamine. Where reported, no significant difference was found in patient recall, pain, and satisfaction when opioids were added to propofol com pared to propofol alone; the addition of opioids may have resulted in a higher incidence of respiratory adverse events. CONCLUSIONS: Propofol for procedural sedation is a reasonable alternative for use in the ED, with comparative efficacy and safety to other alternatives. Use of opioids in addition to propofol may not provide added benefit but does contribute to increased rates of adverse events.

Development of Quality Indicators to Evaluate the Appropriateness of Empiric Antimicrobial Use in Pediatric Patients.

Background: Use of quality indicators is one strategy recommended to assess antimicrobial prescribing for pediatric inpatients. Objective: To achieve consensus from infectious diseases clinicians on quality indicators that characterize appropriate empiric antimicrobial use for the management of infectious syndromes in pediatric inpatients. Methods: This study was completed using the Delphi technique. The research team developed an initial list of quality indicators, informed by a literature search. A multidisciplinary group of health care providers with expertise in infectious diseases was invited to participate. The list was disseminated to this panel of experts using Opinio survey software. The experts were asked to rate the indicators on a 9-point Likert scale in relation to the following criterion: "The importance of each item in determining appropriateness considering benefit or harm at the individual or population level". Consensus was defined as at least 75% agreement and a median score of 7 or higher. Results: Twelve of 31 invited experts completed at least 1 round of the survey, and 10 completed all rounds. Consensus was achieved on 28 of 31 proposed indicators after 3 rounds. Indicators with consensus were categorized under "empiric choice" (n = 12 indicators), "dose" (n = 5), "duration" (n = 2), "administration" (n = 4), "diagnosis" (n = 2), and "documentation" (n = 3). Six of the indicators for which consensus was achieved were rephrased by the experts. Conclusions: Consensus was achieved on quality indicators to assess the appropriateness of empiric antimicrobial use in pediatric patients. Clinicians and researchers can use these consensus-based indicators to assess adherence to best practice.

Contexte: L'utilisation d'indicateurs de qualité est l'une des stratégies recommandées pour évaluer la prescription d'antimicrobiens aux patients pédiatriques hospitalisés. Objectif: Parvenir à un consensus, entre les cliniciens des maladies infectieuses, portant sur les indicateurs de qualité qui caractérisent l'utilisation empirique appropriée des antimicrobiens pour la prise en charge des syndromes infectieux chez les patients pédiatriques hospitalisés. Méthodes: Cette étude a été réalisée à l'aide de la technique Delphi. L'équipe de recherche a dressé une liste initiale d'indicateurs de qualité éclairée par une recherche documentaire. Un groupe multidisciplinaire de prestataires de soins de santé ayant une expertise dans le domaine des maladies infectieuses a été invité à participer. La liste a été diffusée à ce panel d'experts à l'aide du logiciel d'enquête Opinio. Les experts ont été invités à noter les indicateurs sur une échelle de Likert de 9 points par rapport au critère suivant : « L'importance de chaque élément pour déterminer la pertinence compte tenu du bienfait ou du dommage à l'échelle individuelle ou de la population ¼. Le consensus était défini comme « Un accord d'au moins 75 % et un score médian d'au moins 7 ¼. Résultats: Douze des 31 experts invités ont terminé au moins 1 cycle de l'enquête et 10 les ont tous terminés. Un consensus a été atteint pour 28 des 31 indicateurs proposés après 3 cycles. Les indicateurs qui ont atteint le consensus ont été classés en « choix empirique ¼ (n = 12 indicateurs), « dose ¼ (n = 5), « durée ¼ (n = 2), « administration ¼ (n = 4), « diagnostic ¼ (n = 2) et « documentation ¼ (n = 3). Six indicateurs faisant consensus ont été reformulés par les experts. Conclusions: Un consensus a été atteint pour les indicateurs de qualité visant à évaluer l'utilisation empirique appropriée des antimicrobiens chez les patients pédiatriques. Les cliniciens et les chercheurs peuvent utiliser ces indicateurs basés sur le consensus pour évaluer le respect des meilleures pratiques.

Crowd-sourced observations of a polyphagous moth reveal evidence of allochronic speciation varying along a latitudinal gradient.

Allochronic speciation, where reproductive isolation between populations of a species is facilitated by a difference in reproductive timing, depends on abiotic factors such as seasonality and biotic factors such as diapause intensity. These factors are strongly influenced by latitudinal trends in climate, so we hypothesized that there is a relationship between latitude and divergence among populations separated by life history timing. Hyphantria cunea (the fall webworm), a lepidopteran defoliator with red and black colour morphs, is hypothesized to be experiencing an incipient allochronic speciation. However, given their broad geographic range, the strength of allochronic speciation may vary across latitude. We annotated >11,000 crowd-sourced observations of fall webworm to model geographic distribution, phenology, and differences in colour phenotype between morphs across North America. We found that red and black morph life history timing differs across North America, and the phenology of morphs diverges more in warmer climates at lower latitudes. We also found some evidence that the colour phenotype of morphs also diverges at lower latitudes, suggesting reduced gene flow between colour morphs. Our results demonstrate that seasonality in lower latitudes may increase the strength of allochronic speciation in insects, and that the strength of sympatric speciation can vary along a latitudinal gradient. This has implications for our understanding of broad-scale speciation events and trends in global biodiversity.

Evaluating the impact of incorporating clinical practice guidelines for the management of infectious diseases into an electronic application (e-app).

OBJECTIVES: To improve dissemination and accessibility of guidelines to healthcare providers at our institution, guidance for infectious syndromes was incorporated into an electronic application (e-app). The objective of this study was to compare empiric antimicrobial prescribing before and after implementation of the e-app. DESIGN: This study was a before-and-after trial. SETTING: A tertiary-care, public hospital in Halifax, Canada. PARTICIPANTS: This study included pediatric patients admitted to hospital who were empirically prescribed an antibiotic for an infectious syndrome listed in the e-app. METHODS: Data were collected from medical records. Prescribing was independently assessed considering patient-specific characteristics using a standardized checklist by 2 members of the research team. Assessments of antimicrobial prescribing were compared, and discrepancies were resolved through discussion. Empiric antimicrobial prescribing before and after implementation of the e-app was compared using interrupted time-series analysis. RESULTS: In total, 237 patients were included in the preimplementation arm and 243 patients were included in the postimplementation arm. Pneumonia (23.8%), appendicitis (19.2%), and sepsis (15.2%) were the most common indications for antimicrobial use. Empiric antimicrobial use was considered optimal in 195 (81.9%) of 238 patients before implementation compared to 226 (93.0%) 243 patients after implementation. An immediate 15.5% improvement (P = .019) in optimal antimicrobial prescribing was observed following the implementation of the e-app. CONCLUSIONS: Empiric antimicrobial prescribing for pediatric patients with infectious syndromes improved after implementation of an e-app for dissemination of clinical practice guidelines. The use of e-apps may also be an effective strategy to improve antimicrobial use in other patient populations.