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Adolescents and young adults (AYA) with sickle cell disease (SCD) experience high rates of acute care utilization and increased morbidity. At this high-risk time, they also face the need to transition from pediatric to adult services, which, if poorly coordinated, adds to heightened morbidity and acute care utilization. The study objective was to characterize the feasibility, acceptability, and short-term efficacy of a protocolized transition navigator (TN) intervention in AYA with SCD.We developed a protocolized TN intervention that used ecological assessment and motivational interviewing to assess transition readiness, identify goals, and remove barriers to transition, and to provide disease and pain management education and skills to AYAs with SCD.Ninety-three percent (56/60) of enrolled individuals completed the intervention. Participation in the TN program was associated with significant improvement in mean transition readiness scores (3.58-4.15, P.0001), disease knowledge scale (8.91-10.13, P.0001), Adolescent Medication Barriers Scale (40.05-35.39, P = .003) and confidence in both disease (22.5-23.96, P = .048) and pain management (25.07-26.61, P = .003) for youth with SCD.The TN intervention was acceptable to youth with SCD, feasible to implement at an urban academic medical center, and addressed barriers to transition identified by the youth. Longer-term assessment is needed to determine if the TN intervention improved successful transfer to and retention in adult care.

Background Cooling thermal burns with running water is a recommended first aid intervention. However, guidance on the ideal duration of cooling remains controversial and inconsistent across organisations. Aim To perform a systematic review of the evidence for the question; Among adults and children with thermal burn, does active cooling using running water as an immediate first aid intervention for 20 minutes or more, compared with active cooling using running water for any other duration, change the outcomes of burn size, burn depth, pain, adverse outcome (hypothermia) or complications? Method We searched Medline, Embase, Cochrane Database of Systematic Reviews and used ROBINS-I to assess for risk of bias. We used Grading of Recommendations, Assessment, Development and Evaluation methodology for determining the certainty of evidence. We included all studies that compared the selected outcomes of the duration of cooling of thermal burns with water in all patient ages. (PROSPERO registration number: CRD42021180665). From 560 screened references, we included four observational studies. In these studies, 48% of burns were cooled for 20 minutes or more. We found no benefit for a duration of 20 minutes or more of cooling when compared with less than 20 minutes of cooling for the outcomes of size and depth of burn, re-epithelialization, or the need for skin grafting. The evidence is of very low certainty owing to limitations in study design, risk of bias and indirectness. Conclusion The optimal duration of cooling for thermal burns remains unknown and future prospective research is required to better define this treatment recommendation.

Background Although several Utstein variables are known to independently improve survival, how they moderate the effect of emergency medical service (EMS) response times on survival is unknown. Objectives To quantify how public location, witnessed status, bystander CPR, and bystander AED shock individually and jointly moderate the effect of EMS response time delays on OHCA survival. Methods This retrospective cohort study was a secondary analysis of the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest database (December 2005 to June 2015). We included all adult, non-traumatic, non-EMS witnessed, and EMS-treated OHCAs from eleven sites across the US and Canada. We trained a logistic regression model with standard Utstein control variables and interaction terms between EMS response time and the four aforementioned OHCA characteristics. Results 102,216 patients were included. Three of the four characteristics – witnessed OHCAs (OR = 0.962), bystander CPR (OR = 0.968) and public location (OR = 0.980) – increased the negative effect of a one-minute delay on the odds of survival. In contrast, a bystander AED shock decreased the negative effect of a one-minute response time delay on the odds of survival (OR = 1.064). The magnitude of the effect of a one-minute delay in EMS response time on the odds of survival ranged from 1.3% to 9.8% (average: 5.3%), depending on the underlying OHCA characteristics. Conclusions Delays in EMS response time had the largest reduction in survival odds for OHCAs that did not receive a bystander AED shock but were witnessed, occurred in public, and/or received bystander CPR. A bystander AED shock appears to be protective against a delay in EMS response time.

Ovarian reserve is an important determinant of a woman’s reproductive potential, and women with diminished ovarian reserve (DOR) often seek in vitro fertilization (IVF). The underlying etiology of DOR is unknown, but follicular fluid cytokine concentrations likely play a role in follicular development and maturation. The present study seeks to investigate the expression of cytokines in follicular fluid (FF) of women with DOR undergoing IVF and explore correlated functional pathways. One hundred ninety-four women undergoing ovarian stimulation were recruited at the time of oocyte retrieval. Women were classified as having DOR if they met one or more of the following criteria: AMH 10 mIU/ml, and/or AFC

Importance Emergency research is challenging to do well as it involves time sensitive interventions in unstable patients. There is limited time to obtain informed consent from the patient or their legally authorized representative (LAR). Such research is permitted under exception from informed consent (EFIC) if specific criteria are met, including notification after enrollment. Some question whether the risks of EFIC outweighs its benefits. To date, there is limited empiric information about time to notification (TTN) and rates of withdrawal in such trials. Objective To describe variation in TTN and rates of withdrawal among that patients enrolled in EFIC trials over a twelve-year period. Design We performed post hoc descriptive analyses of data from five trials conducted under EFIC. Setting Emergency medical services and receiving hospitals participating in the Resuscitation Outcomes Consortium in the United States and Canada. Participants Patients with out-of-hospital cardiac arrest or life-threatening traumatic injury. Exposures Notification strategies were specified at each site before initiation of enrollment by a local institutional review board. We monitored TTN within each site centrally throughout each study’s enrollment period. Outcomes TTN was defined as time from randomization to first-reported notification of patient or LAR of enrollment. Withdrawal was defined as patient or LAR opt out of ongoing participation at the time of notification. Results Of 35,442 patients enrolled in five trials, 33,805 had cardiac arrest; and 1636 had traumatic injury. TTN varied overall and by patient outcome. Among those with cardiac arrest, TTN ranged from median (5%ile, 95%ile) of 6 (1,27) days to 28 (2, 53) days across sites. 0.3% of notified patients with cardiac arrest withdrew. Among those with traumatic injury, TTN ranged from 0 (0, 5) days to 36 (5, 68) days across sites. 7.7% of notified patients with traumatic injury withdrew. Conclusions and Relevance There is large variation in TTN in trials conducted under EFIC for emergency research. This may be due to several factors. It may or may not be modifiable. Overall rates of withdrawal are low, which suggests current practices related to EFIC are acceptable to those who have participated in emergency research.

BACKGROUND Multimodal analgesia (MMA) during breast surgery reduces postoperative pain and opioid requirements, but the relative contribution of local anesthetic dosing as a component of MMA is not well defined among patients undergoing lumpectomy and sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS We identified consecutive patients who underwent lumpectomy and SLNB with MMA from 1/2019 to 4/2020. Univariable and multivariable linear and logistic regression were used to examine associations between local anesthetics, opioid requirements in the post-anesthesia care unit (PACU), and pain scores in the PACU and on postoperative day (POD) 1. RESULTS In total, 1603 patients [median tumor size, 14 mm (interquartile range 8-20 mm)] were included. The median PACU opioid requirement was 0 morphine milligram equivalents (interquartile range 0-5). PACU maximum pain was none or mild in 58% of patients and moderate to severe in 42%; among 420 survey respondents, 56% reported no or mild pain and 44% reported moderate to severe pain on POD 1. On multivariable analysis that adjusted for routine components of MMA, increasing doses of 0.5% bupivacaine were associated with reduced PACU opioid requirements (β -0.04, 95% confidence interval -0.07 to -0.01, p = 0.011) and lower odds of moderate to severe pain (odds ratio 0.98, 95% confidence interval 0.97-0.99, p < 0.001). Local anesthetics were not associated with pain scores on POD 1. CONCLUSIONS Higher amounts of local anesthetics reduce acute postoperative pain and opioid requirement after lumpectomy and SLNB. Maximizing dosing within weight-based limits is a low-risk, cost-effective pain control strategy that can be used in diverse practice settings.

Background Analyses of data recorded by monitor-defibrillators that measure CPR depth with different methods show significant relationships between the process and outcome of CPR. Our objective was to evaluate whether chest compression depth was significantly associated with outcome based on accelerometer-recordings obtained with monitor-defibrillators from a single manufacturer, and to assess whether an accelerometer-based analysis corroborated evidence-based practice guidelines on performance of CPR. Methods and results We included 5434 adult patients treated from seven US and Canadian cities between January 2007 and May 2015. These had mean (SD) age of 64.2 (17.2) years, mean compression depth of 45.9 (12.7) mm, ROSC sustained to ED arrival of 26%, and survival to hospital discharge of 8%. For survival to discharge, the adjusted odds ratios were 1.15 (95% CI, 0.86, 1.55) for cases within 2005 depth range (38–51 mm), and 1.17 (95% CI, 0.91, 1.50) for cases within 2010 depth range (>50 mm) compared to those with an average depth of Conclusions This analysis of patients with OHCA demonstrated that increased chest compression depth measured by accelerometer is associated with better survival. It confirms that current evidence-based recommendations to compress within 50–60 mm are likely associated with greater survival than compressing to another depth.

Hip and knee replacement surgery is common, yet more than 10% of patients who undergo total hip replacement (THR) and total knee replacement (TKR) report postsurgery dissatisfaction. Recommendations for improving patient experience after total joint replacement surgery include increasing support to patients, including having a patient navigator available to patients before and after surgery. This article reports on THR and TKR patients' experiences of using an orthopaedic patient navigator. We employed qualitative description to understand THR and TKR patients' experiences of interacting with an orthopaedic patient navigator in a community teaching hospital. Telephone interviews were conducted with 15 purposefully selected total joint replacement patients (TKR: n = 11; THR: n = 4) who had at least one contact with the navigator. Interview transcripts were analyzed using thematic analysis. Patients described receiving physical support services, emotional support services, informational support services, and care coordination services from the patient navigator. All interactions with the patient navigator were positive. Knowing the patient navigator was available for any future concerns also provided indirect benefits of reassurance, comfort, and security. Patients described these direct and indirect benefits as potentially having long-lasting and resilient positive effects. An orthopaedic patient navigator can have a positive impact on patients' THR and TKR experience and fill gaps in support identified in earlier studies. Addressing patients' complex and varied care needs is well suited to a clinical nurse specialist in the role. Investing in an orthopaedic patient navigator provides reassurance to patients that their needs are a priority and will be addressed in a timely manner.

Purpose: We present seven cases of advanced cancer patients who initially underwent tumor testing utilizing smaller, panel-based tests, followed by a variety of therapeutic treatments which ultimately resulted in progression of their disease. These cases demonstrate the value of utilizing WES/RNA seq and characterization following disease progression in these patients and the determination of clinically targetable alterations as well as acquired resistance mutations. Materials and Methods: All patients are part of an IRB approved observational study. WES and RNA sequencing were performed, using GEM ExTra® on tumor and blood samples obtained during routine clinical care. To accurately determine somatic versus germline alterations the test was performed with paired normal testing from peripheral blood. Results: The presented cases demonstrate the clinical impact of actionable findings uncovered using GEM ExTra® in patients with advanced disease who failed many rounds of treatment. Unique alterations were identified resulting in newly identified potential targeted therapies, mechanisms of resistance, and variation in the genomic characterization of the primary versus the metastatic tumor. Conclusions: Taken together our results demonstrate that GEM ExTra® maximizes detection of actionable mutations, thus allowing for appropriate treatment selection for patients harboring both common and rare genomic alterations.

Objective Genomics is increasingly used for diagnostic testing in children. This study describes the expectations of parents whose child received genomic testing and whether or not they were met. Methods A diverse stratified, purposive sample of parents of 22 children in New York City was interviewed using a semi-structured guide. Genomic test results were positive, negative, or uncertain. Results Parents expressed their expectations in narrative and numeric fashion. Parents expected that their child’s test would have a direct effect on their child’s diagnosis. Some believed that results would be definitive, while others recognized testing limitations. Expectations reflected parents’ hope to find a diagnosis and led to disappointment when results were uninformative or did not impact clinical management. Conclusion Results suggest pre-test genetic counseling emphasize the low likelihood of actionable results; however, parents’ expectations of genomics’ diagnostic capabilities are strongly rooted in their need to end the diagnostic odyssey and may be difficult to manage. Practice Implications Parents’ hope for a resolution and effective treatment for their child is a powerful context in which genetic counseling is heard. Clinicians who provide genomic testing should continue to acknowledge parents’ preconceptions. Additional research in other settings will help understand how to best address and manage parent expectations of genomic medicine.

Objective To identify opportunities for discontinuing elective and nonemergency surgical cases in a regional surgical practice in response to coronavirus disease 2019 (COVID-19). Patients and Methods COVID-19 began to affect surgical practices across the United States in March 2020. On March 17, 2020, all elective and nonemergency surgical care was deferred to prepare the Mayo Clinic Health System sites in northwestern Wisconsin for an anticipated surge in patients with COVID-19. When the decision was made to reactivate the surgical practice, several major structural and operational changes were made to the regional surgical practice to optimize efficiencies. Results The structural and operational changes implemented during reactivation resulted in improved utilization of surgical resources including improvement in operating room (OR) block utilization, increased available OR time, and increased case volumes. Conclusion Surgical and procedural leaders should consider a limited-time deferral of elective surgical cases to implement widespread OR efficiency strategies. The time selected for deferral of surgical cases should target a period of historically low surgical volume to minimize disruption to patient care and impact on overall OR functions.

Due to concerns of infection and medication disruptions during the COVID-19 pandemic, rheumatology patients at the pandemic epicenter were at risk of distress and poor health outcomes. We sought to investigate medication disruptions and COVID-19-related distress in the Bronx, New York shortly after the peak of the pandemic and determine whether factors related to the pandemic were associated with flares, disease activity, and overall health.In the month following the epidemic peak, we surveyed adult patients and parents of pediatric patients from rheumatology clinics in the Bronx regarding medication access, medication interruptions, COVID-19 infection, COVID-19 hospitalization, and COVID-19-related distress. We examined which factors were associated with patient-reported flares, disease activity, and overall health scores in regression models accounting for sociodemographic characteristics and rheumatologic disease type.Of the 1,692 patients and parents of pediatric patients that were contacted, 361 (21%) responded; 16% reported medication access difficulty, 14% reported medication interruptions, and 41% reported experiencing flare(s). In a multivariable logistic regression model, medication access difficulty was associated with increased odds of flare (odds ratio [OR] 4.0 [95% confidence interval (95% CI) 1.5, 10.4]; P = 0.005), as was high COVID-19-related distress (OR 2.4 [95% CI 1.2, 4.6]; P = 0.01). In multivariable linear regression models, medication access difficulty and high COVID-19-related distress were associated with worse disease activity scores, and high COVID-19-related distress was associated with worse health scores.Medication access difficulties and flares were common among rheumatology patients from the Bronx, New York in the month following the peak of the epidemic. Medication access difficulty and COVID-19-related distress were highly associated with flare and disease activity. COVID-19-related distress was associated with overall health scores.

Background: Whether advances in identification and management of atrial fibrillation and atrial flutter (collectively, AF) have led to improved outcomes is unclear. We sought to study trends in clinical outcomes selected as quality indicators for nonvalvular AF in Canada. Methods: We identified hospitalized patients with a first diagnosis of nonvalvular AF between April 2006 and March 2015, in all of Canada except Quebec. We assessed trends in 1-year incidence of stroke/systemic embolism (SSE), major bleeding, and initial heart failure (HF) hospitalization. Results: The cohort included 466,476 patients. The median age was 77 years (interquartile range, 68-84 years), 46% were female, and 68% had a Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score > 3. Within 1 year of discharge, 3.5% were hospitalized for stroke or SSE, 1.6% for major bleeding, and 8.6% for new HF. Over the study period, the crude rate of SSE declined from 3.6% to 3.3% (P = 0.002), whereas the rates of hospitalization for new HF and for major bleeding did not significantly change. After adjustment for CHA2DS2-VASc score, the yearly rates of incident SSE (risk ratio, 0.99; 95% confidence interval [CI], 0.98-0.99; P = 0.002) and HF (risk ratio, 0.99; 95% CI, 0.99-1.00; P = 0.001) declined ≤ 1% absolute, whereas major bleeding remained unchanged (risk ratio, 1.00; 95% CI, 0.99-1.00; P = 0.28). Conclusions: Among hospitalized patients with nonvalvular AF in Canada, the rate of SSE and new HF decreased modestly over a 10-year period, with no significant change in major bleeding. Efforts to study process-based quality indicators, with increased focus on HF prevention, are needed. Résumé: Contexte: On ne sait pas si les avancées en matière de détection et de prise en charge de la fibrillation auriculaire et du flutter auriculaire (collectivement appelés « FA » ci-après) ont permis d’améliorer les résultats pour les patients. Nous avons donc étudié les tendances à l’égard de résultats cliniques particuliers pris comme indicateurs de qualité relatifs à la FA non valvulaire au Canada. Méthodologie: Nous avons recensé les patients hospitalisés au Canada (sauf au Québec) entre avril 2006 et mars 2015 en raison d’une FA non valvulaire nouvellement diagnostiquée. Nous avons évalué les tendances quant à la survenue d’un accident vasculaire cérébral ou d’une embolie systémique (AVC/ES), d’une hémorragie majeure et d’une première hospitalisation pour insuffisance cardiaque. Résultats: La cohorte comprenait 466 476 patients, dont l’âge médian était de 77 ans (intervalle interquartile : 68 à 84 ans); 46 % des patients étaient des femmes, et 68 % avaient un score CHA2DS2-VASc (Congestive Heart Failure [insuffisance cardiaque congestive], hypertension, âge [≥ 75 ans], diabète, Stroke/Transient Ischemic Attack [AVC/accident ischémique transitoire] – maladie vasculaire, âge [65-74 ans], sexe [femmes]) supérieur à 3. Dans l’année suivant la sortie de l’hôpital, 3,5 % des patients ont été hospitalisés en raison d’un AVC ou d’un AVC/ES, 1,6 %, en raison d’une hémorragie majeure et 8,6 %, en raison d’une nouvelle insuffisance cardiaque. Au cours de la période étudiée, le taux brut d’AVC/ES est passé de 3,6 % à 3,3 % (p = 0,002), tandis que les taux d’hospitalisation en raison d’une nouvelle insuffisance cardiaque ou d’une hémorragie majeure n’ont pas changé de manière significative. Après correction pour tenir compte du score CHA2DS2-VASc, les taux annuels de survenue d’un AVC/ES (rapport des risques de 0,99; intervalle de confiance [IC] à 95 % : de 0,98 à 0,99; p = 0,002) et d’une insuffisance cardiaque (rapport des risques de 0,99; IC à 95 % : de 0,99 à 1,00; p = 0,001) ont diminué de ≤ 1 % en valeur absolue, tandis que le taux de survenue d’une hémorragie majeure n’a pas changé (rapport des risques : 1,00; IC à 95 % : de 0,99 à 1,00; p = 0,28). Conclusions: Parmi les patients hospitalisés au Canada en raison d’une FA non valvulaire, les taux d’AVC/ES et de nouvelle insuffisance cardiaque ont affiché une réduction modeste sur une période de 10 ans, tandis que le taux d’hémorragie majeure n’a pas changé de manière significative. D’autres études évaluant les indicateurs de qualité fondés sur les procédés, notamment en matière de prévention de l’insuffisance cardiaque, s’imposent.

PurposeUse of genomic sequencing is increasing at a pace that requires technological solutions to effectively meet the needs of a growing patient population. We developed GUÍA, a web-based application, to enhance the delivery of genomic results and related clinical information to patients and families.MethodsGUÍA development occurred in 5 phases: formative research, content development, user interface design, stakeholder/community member input, and web application development. Development was informed by qualitative research involving parents (N=22) whose children underwent genomic testing. Participants enrolled in the NYCKidSeq pilot study (N=18) completed structured feedback interviews post-result disclosure using GUÍA. Genetic specialists, researchers, patients, and community stakeholders provided their perspectives on GUÍA’s design to ensure technical, cultural, and literacy appropriateness.ResultsNYCKidSeq participants responded positively to the use of GUÍA to deliver their children’s results. All participants (N=10) with previous experience with genetic testing felt GUÍA improved result disclosure, and 17 (94%) participants said the content was clear.ConclusionsGUÍA communicates complex genomic information in an understandable and personalized manner. Initial piloting demonstrated GUÍA’s utility for families enrolled NYCKidSeq pilot study. Findings from the NYCKidSeq clinical trial will provide insight into GUÍA’s effectiveness in communicating results among diverse, multilingual populations.

1. Many neurodegenerative diseases are associated with pathological aggregation of proteins in neurons. 2. Autophagy is a natural self-cannibalization process that can act as a powerful mechanism to remove aged and damaged organelles as well as protein aggregates. It has been shown that promoting autophagy can attenuate or delay neurodegeneration by removing protein aggregates. 3. In this paper, we will review the role of autophagy in Alzheimer’s disease (AD), Parkinson’s Disease (PD), and Huntington’s Disease (HD) and discuss opportunities and challenges of targeting autophagy as a potential therapeutic avenue for treatment of these common neurodegenerative diseases.

ObjectiveTo delineate research priorities for improving clinical management of laryngeal dystonia, the NIH convened a multidisciplinary panel of experts for a 1-day workshop to examine the current progress in understanding its etiopathophysiology and clinical care.MethodsThe participants reviewed the current terminology of disorder and discussed advances in understanding its pathophysiology since a similar workshop was held in 2005. Clinical and research gaps were identified, and recommendations for future directions were delineated.ResultsThe panel unanimously agreed to adopt the term “laryngeal dystonia” instead of “spasmodic dysphonia” to reflect the current progress in characterizations of this disorder. Laryngeal dystonia was recognized as a multifactorial, phenotypically heterogeneous form of isolated dystonia. Its etiology remains unknown, whereas the pathophysiology likely involves large-scale functional and structural brain network disorganization. Current challenges include the lack of clinically validated diagnostic markers and outcome measures and the paucity of therapies that address the disorder pathophysiology.ConclusionResearch priorities should be guided by challenges in clinical management of laryngeal dystonia. Identification of disorder-specific biomarkers would allow the development of novel diagnostic tools and unified measures of treatment outcome. Elucidation of the critical nodes within neural networks that cause or modulate symptoms would allow the development of targeted therapies that address the underlying pathophysiology. Given the rarity of laryngeal dystonia, future rapid research progress may be facilitated by multicenter, national and international collaborations.

Aim To evaluate the optimal timing and doses of epinephrine for Infants and children suffering in-hospital or out-of-hospital cardiac arrest. Methods We searched Medline, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL) for human randomized clinical trials and observational studies including comparative cohorts. Two investigators reviewed relevance of studies, extracted the data, conducted meta-analyses and assessed the risk of bias using the GRADE and CLARITY frameworks. Authors of the eligible studies were contacted to obtain additional data. Critically important outcomes included return of spontaneous circulation, survival to hospital discharge and survival with good neurological outcome. Results We identified 7 observational studies suitable for meta-analysis and no randomized clinical trials. The overall certainty of evidence was very low. For the critically important outcomes, the earlier administration of epinephrine was favorable for both in-hospital and out-of-hospital cardiac arrest. Because of a limited number of eligible studies and the presence of severe confounding factors, we could not determine the optimal interval of epinephrine administration. Conclusions Earlier administration of the first epinephrine dose could be more favorable in non-shockable pediatric cardiac arrest. The optimal interval for epinephrine administration remains unclear.

Background: Studies examining gender-based differences in outcomes of patients experiencing out-of-hospital cardiac arrest have demonstrated that, despite a higher likelihood of return of spontaneous circulation, women do not have higher survival. Methods: Patients successfully resuscitated from out-of-hospital cardiac arrest enrolled in the CCC trial (Trial of Continuous or Interrupted Chest Compressions during CPR) were included. Hierarchical multivariable logistic regression models were constructed to evaluate the association between gender and survival after adjustment for age, gender, cardiac arrest rhythm, witnessed status, bystander cardiopulmonary resuscitation, episode location, epinephrine dose, emergency medical services response time, and duration of resuscitation. Do not resuscitate (DNR) and withdrawal of life-sustaining therapy (WLST) order status were used to assess whether differences in postresuscitation outcomes were modified by baseline prognosis. The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest) participants. Results: Among 4875 successfully resuscitated patients, 1825 (37.4%) were women and 3050 (62.6%) were men. Women were older (67.5 versus 65.3 years), received less bystander cardiopulmonary resuscitation (49.1% versus 54.9%), and had a lower proportion of cardiac arrests that were witnessed (55.1% versus 64.5%) or had shockable rhythm (24.3% versus 44.6%, P P =0.009) and had WLST (32.8% versus 29.8%, P =0.03). Discharge survival was significantly lower in women (22.5% versus 36.3%, P P =0.005). The association between gender and survival to discharge was modified by DNR and WLST order status such that women had significantly reduced survival to discharge among patients who were not designated DNR (31.3% versus 49.9%, P =0.005; adjusted odds ratio, 0.74 [95% CI, 0.60–0.91]) or did not have WLST (32.3% versus 50.7%, P =0.002; adjusted odds ratio, 0.73 [95% CI, 0.60–0.89]). In contrast, no gender difference in survival was noted among patients receiving a DNR order (6.7% versus 7.4%, P =0.90) or had WLST (2.8% versus 2.4%, P =0.93). Consistent patterns of association between gender and postresuscitation outcomes were observed in the secondary cohort. Conclusions: Among patients resuscitated after experiencing out-of-hospital cardiac arrest, discharge survival was significantly lower in women than in men, especially among patients considered to have a favorable prognosis.

Storytelling brings into vivid focus the emotions and affects that different classes and races of people experienced in the imperial Dutch Indies island worlds. The storyteller explored in this article is Maria Dermoût (1888–1962), a mixed-race Dutch woman (Indo) who was born and raised on Java in the Dutch East Indies and who spent more than thirty years there. This article argues that Dermoût is a key writer for understanding affective economies, because she devotes significant time and effort in her fiction to fleshing out Native characters, something that few writers of her time did. The novella Toetie, one of Dermoût’s last works, uncovers Indies and Dutch attitudes toward race and color, moving her work from the genre of Indies Letters, or Dutch colonial literature, to that of postcolonial critique, with an exploration of forms of servitude, affect, and the social relations of her time.

Sb2Se3 is a promising material for use in photovoltaics, but the optimum device structure has not yet been identified. This study provides band alignment measurements between Sb2Se3, identical to that used in high-efficiency photovoltaic devices, and its two most commonly used window layers, namely, CdS and TiO2. Band alignments are measured via two different approaches: Anderson’s rule was used to predict an interface band alignment from measured natural band alignments, and the Kraut method was used in conjunction with hard X-ray photoemission spectroscopy to directly measure the band offsets at the interface. This allows examination of the effect of interface formation on the band alignments. The conduction band minimum (CBM) of TiO2 is found by the Kraut method to lie 0.82 eV below that of Sb2Se3, whereas the CdS CBM is only 0.01 eV below that of Sb2Se3. Furthermore, a significant difference is observed between the natural alignment- and Kraut method-determined offsets for TiO2/Sb2Se3, whereas there is little difference for CdS/Sb2Se3. Finally, these results are related to device performance, taking into consideration how these results may guide the future development of Sb2Se3 solar cells and providing a methodology that can be used to assess band alignments in device-relevant systems.

This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 20 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 3 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

This2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendationsfor advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

Background Despite high-quality cardiopulmonary resuscitation (CPR), early defibrillation, and antiarrhythmic medications, some patients remain in refractory ventricular fibrillation (VF) during out-of-hospital cardiac arrest. These patients have worse outcomes compared to patients who respond to initial treatment. Double sequential external defibrillation (DSED) and vector change (VC) defibrillation have been proposed as viable options for patients in refractory VF. However, the evidence supporting the use of novel defibrillation strategies is inconclusive. The objective of this study is to compare two novel therapeutic defibrillation strategies (DSED and VC) against standard defibrillation for patients with treatment refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest. Research question Among adult (≥ 18 years) patients presenting in refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest, does DSED or VC defibrillation result in greater rates of survival to hospital discharge compared to standard defibrillation? Methods This will be a three-arm, cluster randomized trial with repeated crossover conducted in six regions of Ontario, Canada (Peel, Halton, Toronto, Simcoe, London, and Ottawa), over 3 years. All adult (≥ 18 years) patients presenting in refractory VF (defined as patients presenting in VF/pVT and remaining in VF/pVT after three consecutive standard defibrillation attempts during out-of-hospital cardiac arrest of presumed cardiac etiology will be treated by one of three strategies: (1) continued resuscitation using standard defibrillation, (2) resuscitation involving DSED, or (3) resuscitation involving VC (change of defibrillation pads from anterior-lateral to anterior-posterior pad position) defibrillation. The primary outcome will be survival to hospital discharge. Secondary outcomes will include return of spontaneous circulation (ROSC), VF termination after the first interventional shock, VF termination inclusive of all interventional shocks, and number of defibrillation attempts to obtain ROSC. We will also perform an a priori subgroup analysis comparing rates of survival for those who receive “early DSED,” or first DSED shock is shock 4–6, to those who receive “late DSED,” or first DSED shock is shock 7 or later. Discussion A well-designed randomized controlled trial employing a standardized approach to alternative defibrillation strategies early in the treatment of refractory VF is urgently required to determine if the treatments of DSED or VC defibrillation impact clinical outcomes. Trial registration ClinicalTrials.gov NCT04080986. Registered on 6 September 2019.

BACKGROUND No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3-12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later. RESULTS Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only. CONCLUSION While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE Diagnostic test, level III.

Background Multi-sectoral partnerships (MSPs) are frequently cited as a means by which governments can improve population health while leveraging the resources and expertise of the private and non-profit sectors. As part of their efforts in this area, the Public Health Agency of Canada (the Agency) introduced a novel funding programme requiring applicants to procure matched resources from private sources to support large-scale interventions for chronic disease prevention. The current literature on MSPs is limited in its applicability to this model of multi-sectoral engagement. The purpose of this study was to explore the experiences of Agency staff working with potential partners to develop programme applications, such that we might identify lessons from adopting this type of partnership approach. Methods Semi-structured interviews were conducted with the 12 staff working in the MSP programme. Interviews were recorded, transcribed and analysed using thematic analysis. Preliminary themes were used to inform follow up focus-groups sessions. A second round of analysis was conducted guided by a coding paradigm focused on understanding process. Results We identified “experiencing uncertainty” to be a central concept in participants’ accounts of the MSP process, related specifically to the MSP programme’s novel conditions, shifts that occurred in sectoral roles and demands for new capacities. In response, Agency staff employed strategies to clarify partner interests, build trust in inter-sectoral relationships, and support internal and partner capacity. Outcomes associated with this process include impacts on trust between the Agency and potential partners, a deeper understanding of other sectors, and programme adaptations and refinements to address challenges related to the programme model. Conclusions The co-funding model employed by the Agency is a potentially popular one for government bodies wanting to leverage funding from private sector sources. Our study identifies the potential challenges that can occur under this model. Some challenges are related to addressing material conditions related to partner capacity, whereas other challenges speak to deeper and more difficult to address concerns regarding trust and alignment of motivations and interests between partners. Future research exploring the challenges associated with specific models of MSP engagement is necessary to inform approaches to addressing complex problems through collaborative efforts.

Background Remote ischemic conditioning (RIC) is a noninvasive therapeutic strategy that uses brief cycles of blood pressure cuff inflation and deflation to protect the myocardium against ischemia-reperfusion injury. We sought to compare major adverse cardiovascular events (MACE) for patients who received RIC before PCI for ST-segment–elevation myocardial infarction (STEMI) compared with standard care. Methods We conducted a pre- and postimplementation study. In the preimplementation phase, STEMI patients were taken directly to the PCI lab. After implementation, STEMI patients received 4 cycles of RIC by paramedics or emergency department staff before PCI. The primary outcome was MACE at 90 days. Secondary outcomes included MACE at 30, 60, and 180 days. Inverse probability of treatment weighting using propensity scores estimated causal effects independent from baseline covariables. Results A total of 1667 (866 preimplementation, 801 postimplementation) patients were included. In the preimplementation phase, 13.4% had MACE at 90 days compared with 11.8% in the postimplementation phase (odds ratio [OR] 0.86, 95% CI 0.62-1.21). There were no significant differences in MACE at 30, 60, and 180 days. Patients presenting with cardiogenic shock or cardiac arrest before PCI were less likely to have MACE at 90 days (42.7% pre vs 27.8% post) if they received RIC before PCI (OR 0.52, 95% CI 0.27-0.98). Conclusions A strategy of RIC before PCI for STEMI did not reduce 90-day MACE. Future research should explore the impact of RIC before PCI for longer-term clinical outcomes and for patients presenting with cardiogenic shock or cardiac arrest.

BACKGROUND: Whether routinely prescribed opioids are necessary for pain control after discharge among lumpectomy/sentinel node biopsy (Lump/SLNB) patients is unclear. We hypothesized that Lump/SLNB patients could be discharged without opioids with a failure rate of

[Image: see text] Pan-BET inhibitors have shown profound efficacy in a number of in vivo preclinical models and have entered the clinic in oncology trials where adverse events have been reported. These inhibitors interact equipotently with the eight bromodomains of the BET family of proteins. To better understand the contribution of each domain to their efficacy and to improve from their safety profile, selective inhibitors are required. This Letter discloses the profile of GSK973, a highly selective inhibitor of the second bromodomains of the BET proteins that has undergone extensive preclinical in vitro and in vivo characterization.

Objective Familial hypercholesterolemia (FH), a prevalent genomic disorder that increases risk of coronary heart disease, remains significantly underdiagnosed. Clinical decision support (CDS) tools have the potential to increase FH detection. We describe our experience in the development and implementation of a genomic CDS for FH at a large academic medical center.Methods CDS development and implementation were conducted in four phases: (1) development and validation of an algorithm to identify “possible FH”; (2) obtaining approvals from institutional committees to develop the CDS; (3) development of the initial prototype; and (4) use of an implementation science framework to evaluate the CDS.Results The timeline for this work was approximately 4 years; algorithm development and validation occurred from August 2018 to February 2020. During this 4-year period, we engaged with 15 stakeholder groups to build and integrate the CDS, including health care providers who gave feedback at each stage of development. During CDS implementation six main challenges were identified: (1) need for multiple institutional committee approvals; (2) need to align the CDS with institutional knowledge resources; (3) need to adapt the CDS to differing workflows; (4) lack of institutional guidelines for CDS implementation; (5) transition to a new institutional electronic health record (EHR) system; and (6) limitations of the EHR related to genomic medicine.Conclusion We identified multiple challenges in different domains while developing CDS for FH and integrating it with the EHR. The lessons learned herein may be helpful in streamlining the development and deployment of CDS to facilitate genomic medicine implementation.

Introduction Bystander training to control life-threatening hemorrhage is an important intervention to decrease preventable trauma deaths. We asked if receiving a trauma first aid (TFA) kit in addition to Bleeding Control (BC) 1.0 training improves self-reported confidence among community members (CM) and medical professionals (MP). Methods Anonymous pre- and post-course surveys assessed exposure to severe bleeding, BC knowledge, and willingness to intervene with and without TFA kits. Surveys were compared using chi-squared tests. Results 80 CM and 60 MP underwent BC training. Both groups demonstrated improved confidence in their ability to stop severe bleeding after the class; however, post-class confidence was significantly modified by receiving a TFA kit. After training, CM confidence was 36.1% without versus 57.0% with a TFA kit(p = 0.008) and MP confidence was 53.8% without versus 87.6% with a TFA kit(p = 0.001). Conclusion Receiving a TFA kit was significantly associated with increased post-training confidence among CM and MP. Summary Stop the Bleed training improves confidence in stopping severe bleeding among both medical professionals and community members. By providing participants with a trauma first aid kit, post-class confidence improves significantly regardless of medical training.

Poor maternal environments, such as under- or overnutrition, can increase the risk for the development of obesity, type 2 diabetes and cardiovascular disease in offspring1-9. Recent studies in animal models have shown that maternal exercise before and during pregnancy abolishes the age-related development of impaired glucose metabolism10-15, decreased cardiovascular function16 and increased adiposity11,15; however, the underlying mechanisms for maternal exercise to improve offspring's health have not been identified. In the present study, we identify an exercise-induced increase in the oligosaccharide 3'-sialyllactose (3'-SL) in milk in humans and mice, and show that the beneficial effects of maternal exercise on mouse offspring's metabolic health and cardiac function are mediated by 3'-SL. In global 3'-SL knockout mice (3'-SL-/-), maternal exercise training failed to improve offspring metabolic health or cardiac function in mice. There was no beneficial effect of maternal exercise on wild-type offspring who consumed milk from exercise-trained 3'-SL-/- dams, whereas supplementing 3'-SL during lactation to wild-type mice improved metabolic health and cardiac function in offspring during adulthood. Importantly, supplementation of 3'-SL negated the detrimental effects of a high-fat diet on body composition and metabolism. The present study reveals a critical role for the oligosaccharide 3'-SL in milk to mediate the effects of maternal exercise on offspring's health. 3'-SL supplementation is a potential therapeutic approach to combat the development of obesity, type 2 diabetes and cardiovascular disease.

Background Multiple Myeloma (MM) is a cancer characterised by the proliferation of malignant plasma cells in the bone marrow. This study examined the treatment preferences of people living with MM compared to the treatment preferences of other groups involved in treatment decision making, including carers, as well as physicians and nurses who treat people living with MM in Australia. Methods Data were collected using discrete choice experiments (DCEs) through an online survey. The DCEs presented participants with a traditional treatment generic choice experiment (e.g., treatment A vs treatment B), focusing on the clinical benefits of treatments and the associated risks. The attributes and levels of the attributes were selected based on previous research, literature review, qualitative research and expert opinion. The DCE data were modelled using a Latent Class Model (LCM). Results The model revealed significant heterogeneity in preferences for treatment attributes. In particular, overall survival, remission period and annual out of pocket cost were the attributes with the most variation. In comparison to people living with MM, carers were less cost-sensitive and more concerned with quality of life (remission period). Physicians and nurses were generally more concerned with overall survival and more cost sensitive than people living with MM. Conclusions This study demonstrated that not all people living with MM valued the same treatment attributes equally. Further, not all groups involved in MM treatment decision making had preference alignment on all treatment attributes. This has important implications for healthcare policy decisions and shared decision making. Results from this study could be used to guide decisions around the value of new MM medicines or the medical plan surrounding the needs of those living with MM, as well as those caring for them.

Background There has been an exponential increase in the demand for transcatheter aortic valve replacement (TAVR). Our goal was to examine trends in TAVR capacity and wait-times across Canada. Methods All TAVR cases were identified from April 1, 2014, to March 31, 2017. Wait-time was defined as the duration in days from the initial referral to the TAVR procedure. TAVR capacity was defined as the number of TAVR procedures per million population/province/fiscal year. We performed multivariable multilevel Cox proportional hazards modelling of the time to TAVR as the dependant variable and the effect of provinces as random effects. We quantified the variation in wait-times among provinces using the median hazard ratio. Results We identified a total of 4906 TAVR procedures across 9 provinces. Despite a year over year increase in overall capacity, there was a greater than 3-fold difference in capacity between provinces. Crude median wait-times increased over time in all provinces, with marked variation from 71.5 days in Newfoundland to 190.5 and 203 days in Manitoba and Alberta, respectively. This suggests increasing demand outpaced the growth in capacity. We found a median hazard ratio of 1.62, indicating that in half of the possible pairwise comparisons, the time to TAVR for identical patients was at least 62% longer between different provinces. Conclusion We found substantial geographic inequity in TAVR access. This calls for policy makers, clinicians, and administrators across Canada to address this inequity through revaluation of provincial funding mechanisms, as well as implementation of efficient care pathways.

ObjectiveOur study objective was to describe the Canadian emergency medicine (EM) research community landscape prior to the initiation of a nationwide network.MethodsA two-phase electronic survey was sent to 17 Canadian medical schools. ThePhase 1 Environmental Scanwas administered to department chairs/hospital EM chiefs, to identify EM physicians conducting clinical or educational research. ThePhase 2 Surveywas sent to the identified EM researchers to assess four themes: 1) geographic distribution, 2) training/career satisfaction, 3) time/financial compensation, and 4) research facilitators/barriers. Descriptive analyses were conducted, and results were stratified by Canadian regions.ResultsA total of 92 EM researchers were identified inPhase 1; 67 (73%) responded to thePhase 2 Survey. Of those, 42 (63%) reported being clinical researchers, and 19 (45%) had a graduate degree. Three provinces encompassed most of the researchers (n = 35). Of the respondents, 61% had a research degree, 66% felt adequately trained for their research career, 73% had financial support, 83% had access to office spaces, 52% had no mentor during their first years of their career, 69% felt satisfied with their research career, and 82% suggested that they will still be conducting research in 5 years.ConclusionEM researchers reported being adequately trained, even though only a little over half had a graduate degree. Only two-thirds had financial support, and mentorship was lacking in one-third of the participants. Not all respondents had a form of infrastructure, but most felt optimistic about their careers. The Canadian EM research environment could be improved to ensure better research capacity.

Background Some electronic hand hygiene (HH) monitoring systems require a benchmark of HH opportunities. To establish a benchmark, we measured rates of HH opportunities among general surgery patients at a tertiary care hospital. Methods Trained observers recorded HH opportunities for newly admitted patients daily for up to 5 days. We used multivariable logistic regression to assess the relationship between patient variables and the HH opportunity rate. A subset of observed HH events was compared to event data from an electronic HH monitoring system. Results We observed 2,404 HH opportunities over 677.4 care-hours for 23 patients (median 3.25 per hour; IQR 2.2-4.7, range 0-13). Rates of HH opportunities were significantly higher on admission day 1, for sessions starting before 9 AM, and for patients without roommates. HH was performed using alcohol-based hand rub from dispensers at the door to a patient's room more often than bedside or pocket dispensers (72.7% vs 20.8% or 5.1%). Electronic dispenser event counts did not match observed event counts. Conclusions Our results provide a benchmark HH opportunity rate for general surgery patients, and highlight the importance of validating electronic HH event counts. Further research is needed to determine which patient factors affect HH opportunity rates.

Rationale & Objective Group-based care provides an opportunity to increase patient access to providers without increasing physician time and is effective in the management of chronic diseases in the general population. This model of care has not been investigated in chronic kidney disease (CKD). Study Design Randomized controlled trial in adults (n = 50); observational study in adolescents (n = 10). Setting & Participants Adults and adolescents with CKD and hypertension in the Bronx, NY. Intervention Group-based care (monthly sessions over 6 months) versus usual care in adults. All adolescents received group-based care and were analyzed separately. Outcomes Participant attendance and satisfaction with group-based care were used to evaluate intervention feasibility. The primary clinical outcome was change in mean 24-hour ambulatory blood pressure. Secondary outcomes included physical activity, medication adherence, quality of life, and sodium intake as assessed by 24-hour urinary sodium excretion and food frequency questionnaires. Results Among adults randomly assigned to group-based care, attendance was high (77% of participants attended ≥3 sessions) and most reported higher satisfaction. Mean 24-hour ambulatory systolic blood pressure decreased by −4.2 (95% CI, −13.3 to 5.8) mm Hg in group-based care patients compared with usual care at 6 months but this was not statistically significant. Similarly, we did not detect significant differences in health-related behaviors (such as medication adherence, sodium intake, and physical activity) or quality-of-life measures between the 2 groups. Among the adolescents, attendance was very poor; self-reported satisfaction, although high, did not change from baseline compared with the 6-month follow-up. Limitations Small study size, missing data. Conclusions Group-based care is feasible and acceptable among adults with hypertension and CKD. However, a larger trial is needed to determine the effect on blood pressure and health-related behaviors. Patient participation may limit the effectiveness of group-based care models in adolescents. Funding National Institutes of Health R34 DK102174. Trial registration https://clinicaltrials.gov/show/NCT02467894., Graphical Abstract

Objectives The primary objective was to determine the feasibility and safety of a cluster randomized controlled trial (RCT) with crossover comparing vector change defibrillation (VC) or double sequential external defibrillation (DSED) to standard defibrillation for patients experiencing refractory ventricular fibrillation (VF). Secondary objectives were to assess the rates of VF termination (VFT) and return of spontaneous circulation (ROSC). Methods We conducted a pilot cluster RCT with crossover in four Canadian paramedic services including all treated adult OHCA patients who presented in VF and received a minimum of three successive defibrillation attempts. Each EMS service was randomly assigned to provide standard defibrillation, VC or DSED. Agencies crossed over to an alternate defibrillation strategy after six months. Results 152 patients were enrolled. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no safety concerns reported. In the standard group, 66.6% of cases resulted in VFT, compared to 82.0% in VC and 76.3% in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusions Our findings suggest the DOSE-VF protocol is feasible and safe. Rates of VFT and ROSC were higher in the VC and DSED than standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact clinical outcomes.

Background: Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia. How this might be influenced by the route of drug administration is not known. Methods: In this prespecified analysis of a randomized, placebo-controlled clinical trial, we compared the differences in survival to hospital discharge in adults with shock-refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest who were randomly assigned by emergency medical services personnel to an antiarrhythmic drug versus placebo in the ALPS trial (Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study), when stratified by the intravenous versus intraosseous route of administration. Results: Of 3019 randomly assigned patients with a known vascular access site, 2358 received ALPS drugs intravenously and 661 patients by the intraosseous route. Intraosseous and intravenous groups differed in sex, time-to-emergency medical services arrival, and some cardiopulmonary resuscitation characteristics, but were similar in others, including time-to-intravenous/intrasosseous drug receipt. Overall hospital discharge survival was 23%. In comparison with placebo, discharge survival was significantly higher in recipients of intravenous amiodarone (adjusted risk ratio, 1.26 [95% CI, 1.06–1.50]; adjusted absolute survival difference, 5.5% [95% CI, 1.5–9.5]) and intravenous lidocaine (adjusted risk ratio, 1.21 [95% CI, 1.02–1.45]; adjusted absolute survival difference, 4.7% [95% CI, 0.7–8.8]); but not in recipients of intraosseous amiodarone (adjusted risk ratio, 0.94 [95% CI, 0.66–1.32]) or intraosseous lidocaine (adjusted risk ratio, 1.03 [95% CI, 0.74–1.44]). Survival to hospital admission also increased significantly when drugs were given intravenously but not intraosseously, and favored improved neurological outcome at discharge. There were no outcome differences between intravenous and intraosseous placebo, indicating that the access route itself did not demarcate patients with poor prognosis. The study was underpowered to assess intravenous/intraosseous drug interactions, which were not statistically significant. Conclusions: We found no significant effect modification by drug administration route for amiodarone or lidocaine in comparison with placebo during out-of-hospital cardiac arrest. However, point estimates for the effects of both drugs in comparison with placebo were significantly greater for the intravenous than for the intraosseous route across virtually all outcomes and beneficial only for the intravenous route. Given that the study was underpowered to statistically assess interactions, these findings signal the potential importance of the drug administration route during resuscitation that merits further investigation.

Solar water splitting directly converts solar energy into H2 fuel that is suitable for storage and transport. To achieve a high solar-to-hydrogen (STH) conversion efficiency, elaborate strategies yielding a high photocurrent in a tandem configuration along with sufficient photovoltage should be developed. We demonstrated highly efficient solar water splitting devices based on emerging low-cost Sb2Se3 photocathodes coupled with semitransparent perovskite photovoltaics. A state-of-the-art Sb2Se3 photocathode exhibiting efficient long-wavelength photon harvesting enabled by judicious selection of junction layers was employed as a bottom absorber component. The top semitransparent photovoltaic cells, i.e., parallelized nanopillar perovskites using an anodized aluminum oxide scaffold, allowed the transmittance, photocurrent, and photovoltage to be precisely adjusted by changing the filling level of the perovskite layer in the scaffold. The optimum tandem device, in which similar current values were allocated to the top and bottom cells, achieved an STH conversion efficiency exceeding 10% by efficiently utilizing a broad range of photons at wavelength over 1000 nm.

Background Up to 1 in 5 patients who undergo total knee arthroplasty (TKA) express dissatisfaction with their surgery. Our goal was to understand the experiences of patients of South Asian origin who undergo TKA and to identify a research agenda for this patient population. Methods We undertook a modified Delphi study in British Columbia to generate and prioritize potential research topics. An initial list of topics was generated using 3 focus groups with patients of South Asian origin who underwent TKA and their caregivers. Focus group sessions were audiotaped and transcribed, and the data were analyzed using thematic analysis. The resulting Delphi question-naire was administered over 2 rounds to patients, caregivers and health professionals. The second-round questionnaire included only topics that were strongly supported in the first round. A patient-oriented approach was adopted, with 3 patient partners as full research team members, who contributed to scoping, design, data collection, analysis and interpretation. Results Twenty-one patients who had undergone TKA and 6 caregivers attended the focus groups. Our analyses resulted in 6 broad themes and 25 research topics, all of which were presented in the first round of the Delphi survey. The survey was completed by 27 patients and 5 caregivers (54% combined response rate) and by 25 clinicians (76% response rate). Top priorities both for patients and caregivers and for clinicians were promoting exercise following surgery and self-management after hospital discharge. One of the highest ranked topics for patients and caregivers was improving knee implants; this was supported by only 60% of clinicians. Interpretation The patients and caregivers in our study prioritized research on promotion of exercise and self-management following surgery and improvement in knee implants. Future patient-oriented research efforts in Canada should emphasize these topics for this patient population.

Background The coronavirus disease 2019 (COVID-19) pandemic has significantly influenced epidemiology, yet its impact on out-of-hospital cardiac arrest (OHCA) remains unclear. We aimed to evaluate the impact of the pandemic on the incidence and case fatality rate (CFR) of OHCA. We also evaluated the impact on intermediate outcomes and clinical characteristics. Methods PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases were searched from inception to May 3, 2021. Studies were included if they compared OHCA processes and outcomes between the pandemic and historical control time periods. Meta-analyses were performed for primary outcomes [annual incidence, mortality, and case fatality rate (CFR)], secondary outcomes [field termination of resuscitation (TOR), return of spontaneous circulation (ROSC), survival to hospital admission, and survival to hospital discharge], and clinical characteristics (shockable rhythm and etiologies). This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021253879). Results The COVID-19 pandemic was associated with a 39.5% increase in pooled annual OHCA incidence (p p Conclusion Compared to the pre-pandemic period, the COVID-19 pandemic period was significantly associated with increased OHCA incidence and worse outcomes.

Most raptor populations are declining and nearly a fifth are threatened with extinction; thus there is a need to increase collaboration to ensure efficient and effective research, management, and conservation. Here, we introduce the Global Raptor Impact Network (GRIN; www.globalraptors.org), a tool to enhance collaboration and conservation impact of the raptor research community. We provide an overview of the history and current state of GRIN, including plans for expansion. Predecessors to GRIN include The African Raptor DataBank, which was launched in 2012 to ascertain the conservation status of raptors across Africa; and the Global Raptor Information Network, which was launched in the late 1990s as a website to provide information regarding diurnal raptors and facilitate communication among researchers. GRIN expands the data collection and storage capabilities of the African Raptor DataBank to a global scale via mobile application. We have implemented data-sharing rules to ensure the safety of sensitive species, and users of the GRIN mobile app can designate their records as confidential. GRIN staff and partners are developing analyses of species' population trends and geographic distributions to aid in conservation assessments. GRIN is also developing systematic reviews, detailed bibliographies, and online accounts that will summarize the state of knowledge for each raptor species. We hope that GRIN will benefit the entire raptor research community and aid in the collaboration necessary to help raptor populations thrive in the Anthropocene.

Importance Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach. Objective To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. Design, Setting, and Participants From November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center. Intervention Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative. Main Outcome and Measures The primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC. Results Of 610 patients with cN1 breast cancer treated with NAC (median [IQR] age, 49 [40-58] years), 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. Median age was 49 years. Median tumor size was 3 cm; 144 (62%) wereERBB2(formerlyHER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC, 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences. Conclusions and Relevance This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.

Aim Quantifying the ratio describing the difference between “true route” and “straight-line” distances from out-of-hospital cardiac arrests (OHCAs) to the closest accessible automated external defibrillator (AED) can help correct likely overestimations in AED coverage. Furthermore, we aimed to examine to what extent the closest AED based on true route distance differed from the closest AED using “straight-line”. Methods OHCAs (1994–2016) and AEDs (2016) in Copenhagen, Denmark and in Toronto, Canada (2007–2015 and 2015, respectively) were identified. Three distances were calculated between OHCA and target AED: 1) the straight-line distance (“straight-line”) to the closest AED, 2) the corresponding true route distance to the same AED (“true route”), and 3) the closest AED based only on true route distance (“shortest true route”). The ratio between “true route” and “straight-line” distance was calculated and differences in AED coverage (an OHCA ≤ 100 m of an accessible AED) were examined. Results The “straight-line” AED coverage of 100 m was 24.2% (n = 2008/8295) in Copenhagen and 6.9% (n = 964/13916) in Toronto. The corresponding “true route” distance reduced coverage to 9.5% (n = 786) and 3.8% (n = 529), respectively. The median ratio between “true route” and “straight-line” distance was 1.6 in Copenhagen and 1.4 in Toronto. In 26.1% (n = 2167) and 22.9% (n = 3181) of all Copenhagen and Toronto OHCAs respectively, the closest AED in “shortest true route” was different than the closest AED initially found by “straight-line”. Conclusions Straight-line distance is not an accurate measure of distance and overestimates the actual AED coverage compared to a more realistic true route distance by a factor 1.4–1.6.

BackgroundTiming of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to genetic risk for neurodevelopmental disorders in the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia.MethodsWe use data from a genotyped sub-set (N = 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences.ResultsWe found that ADHD PGS were associated with earlier walking age (β = −0.033, padj < 0.001) in both males and females. Additionally, autism PGS were associated with later walking (β = 0.039, padj = 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment.ConclusionsGenetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.