Unanticipated Events Research Articles

Two-year outcomes of the ARTISAN-SNM study for the treatment of urinary urgency incontinence using the Axonics rechargeable sacral neuromodulation system.

AimsSacral neuromodulation (SNM) is a guideline‐recommended treatment with proven therapeutic benefit for urinary urgency incontinence (UUI) patients. The Axonics® System is the first Food and Drug Administration‐approved rechargeable SNM system and is designed to deliver therapy for a minimum of 15 years. The ARTISAN‐SNM study was designed to evaluate UUI participants treated with the Axonics System. Two‐year follow‐up results are presented.MethodsOne hundred and twenty‐nine UUI participants underwent implantation with the Axonics System. Therapeutic response rate, participant quality of life (QoL), and satisfaction were determined using 3‐day voiding diaries, ICIQ‐OABqol, and satisfaction questionnaires. Participants were considered responders if they had a 50% or greater reduction in UUI episodes post‐treatment. As‐treated and Completers analyses are presented.ResultsAt 2 years, 93% of the participants (n = 121 Completers at 2 years) were therapy responders, of which 82% achieved ≥ 75% reduction in UUI episodes and 37% were dry (100% reduction). Daily UUI episodes reduced from 5.6 ± 0.3 at baseline to 1.0 ± 0.2 at 2 years. Statistically significant improvements in ICIQ‐OABqol were reported. All participants were able to recharge their device and 94% of participants reported that the recharging frequency and duration were acceptable. Participant demographics nor condition severity were correlated with clinical outcomes or recharging experience. No unanticipated or serious device‐related adverse events occurred.ConclusionsAt 2 years, participants treated with the Axonics System demonstrated sustained safety and efficacy, high levels of satisfaction with therapy and recharging. Participant‐related factors were not associated with efficacy or recharging outcomes, indicating the reported results are applicable to a diverse population.

Resilient multivariable perimeter control of urban road networks under cyberattacks

The Macroscopic Fundamental Diagram (MFD) concept has become a very valuable tool for modeling the aggregated dynamic of large-scale urban traffic networks. This advance in traffic modeling has fueled the development of many urban traffic control (UTC) policies based on the MFD concept. In particular, perimeter control policies with the aim of maintaining a large-scale urban traffic network operating at its maximum capacity by manipulating the transfer flow of vehicles between adjacent homogeneous regions. In addition to achieve a satisfactory performance level, it is desirable that the control system would maintain a reliable operation under unanticipated events such as cyberattacks. It is important to note that modern UTC systems extensively rely on information technology infrastructures making them vulnerable to cyberattacks. Due to the occurrence of real-world cyberattacks affecting controlled physical systems in different fields, the threat of cyberattacks is becoming a serious and increasing concern for the proper operation of UTC. This paper presents a resilient multivariable control framework for large-scale urban traffic networks subject to several types of cyberattacks such as deception attacks and denial of service (DoS) attacks. Additionally, a feedforward–feedback control scheme combining a time-optimal controller with the resilient multivariable controller is also proposed. The aim of this feedforward–feedback controller is to steer the accumulations to their desired values after a large deviation. Finally, the performance of the proposed resilient controller is demonstrated by means of some realistic simulations of urban traffic networks, including stochastic errors in the traffic demands and in the MFD model, in addition to cyberattacks.

Unanticipated events, perceptions, and household labor allocation in Zimbabwe

• This paper evaluates labor allocation as a strategy to cope with unanticipated events during hyperinflation in Zimbabwe. • In this period households are already stressed by hyperinflation and so further labor reallocations delineate the bounds of possible labor responses. • In this stressed environment, new shocks compound existing stresses. • We find that different types of shocks disparately affect labor allocation; perceptions about experienced shocks also shift labor behavior. • Perceived rainfall shocks affect the share of labor allocated to migration activities and to non-labor participation. This paper investigates labor allocation as a strategy for coping with unanticipated events. We evaluate household responses to unforeseen death and rainfall shocks in Zimbabwe, during a period in which many households were already stressed due to the country’s long-term economic crisis. In this context, shocks compound existing stresses. Different types of shocks disparately affect household labor allocation. Household perceptions about the shocks experienced also shift labor use. Perceived rainfall shocks positively affect the share of labor allocated to migration-related activities and negatively affect the share of labor allocated to non-participation.

Digital Pathology Operations at an NYC Tertiary Cancer Center During the First 4 Months of COVID-19 Pandemic Response

Implementation of an infrastructure to support digital pathology began in 2006 at Memorial Sloan Kettering Cancer Center. The public health emergency and COVID-19 pandemic regulations in New York City required a novel workflow to sustain existing operations. While regulatory enforcement discretions offered faculty workspace flexibility, a substantial portion of laboratory and digital pathology workflows require on-site presence of staff. Maintaining social distancing and offering staggered work schedules. Due to a decrease in patients seeking health care at the onset of the pandemic, a temporary decrease in patient specimens was observed. Hospital and travel regulations impacted onsite vendor technical support. Digital glass slide scanning activities onsite proceeded without interruption throughout the pandemic, with challenges including staff who required quarantine due to virus exposure, unrelated illness, family support, or lack of public transportation. During the public health emergency, we validated digital pathology systems for a remote pathology operation. Since March 2020, the departmental digital pathology staff were able to maintain scanning volumes of over 100 000 slides per month. The digital scanning team reprioritized archival slide scanning and participated in a remote sign-out validation and successful submission of New York State approval for a laboratory developed test. Digital pathology offers a health care delivery model where pathologists can perform their sign out duties at remote location and prevent disruptions to critical pathology services for patients seeking care at our institution during emergencies. Development of standard operating procedures to support digital workflows will maintain turnaround times and enable clinical operations during emergency or otherwise unanticipated events.

Integrated therapy as a tool to help fight asymptomatic COVID-19: A case report

COVID-19 is a rapidly changing and evolving situation and is extremely challenging to the humankind since it is highly infectious. Around 80% of the COVID-19 patients are asymptomatic but still need special care so that they don’t develop any further serious complications in due course of infection. The aim of present case study was to assess the effect of integrated therapy of yoga and Ayurveda on vital parameters of a COVID-19 positive asymptomatic patient. He was found to be COVID-19 positive with ORF CT value of 29.85. He remained asymptomatic throughout the course of disease. Vital parameters such as body temperature, oxygen saturation, and heart rate remained optimal throughout the course of infection. This was probably due to physical activity such as walking, yoga and Ayurvedic medications which helped in building of immunity. This further prevented progression of the disease to moderate/severe stage and there were no unanticipated events. The patient was rechecked after 8 days and was found to be COVID-19 negative. This implies that Yoga and Ayurveda treatment is effective in controlling symptoms of COVID-19 and prevention of disease progression.

The Stock Market’s Reaction to Unanticipated Catastrophic Event

Several factors influence the stock market; they trigger market over-or under-reactions. The paper aims to identify the effect of a major catastrophic event on stock returns. For this, daily data of stock market indices was used with a total of 210 observations and the effect of catastrophic event, Nepal Earthquake 2015, was tested using the method of event analysis for different event windows. The catastrophic event did not affect stock returns significantly and was resilient to earthquake-induced shocks. The event window (+2, +10) shows the higher and positive abnormal returns which depicts that the market has recovered from the shock in as many as three days. The study shows that stock market in Nepal is semi-strongly inefficient.

Imputação de dados na análise de variância em experimentos no Delineamento Inteiramente Casualizado

Unanticipated events often occur in the development of an experiment, especially in field experiments, often causing data loss. Through the present study, we sought to verify whether there is a difference in the result of the analysis of variance (ANOVA) test for unbalanced data in the Completely Randomized Design (DIC) when the inclusion of data obtained from the data imputation technique was performed of Predictive Average. Experiments were simulated in the DIC with 5 treatments and 10 repetitions, generating complete databases. From each database, 10% of the plots were removed and after the imputation method was applied, comparing the ANOVA results in each step. The imputation yielded acceptable results, but not better than those obtained when performing the specific ANOVA test for unbalanced data.

Perceptions of Institutional Support for “Second Victims” Are Associated with Safety Culture and Workforce Well-Being

This study was performed to determine whether health care worker (HCW) assessments of good institutional support for second victims were associated with institutional safety culture and workforce well-being. HCWs' awareness of work colleagues emotionally traumatized by an unanticipated clinical event (second victims), their perceptions of level of institutional support for such colleagues, safety culture, and workforce well-being were assessed using a cross-sectional survey (SCORE [Safety, Communication, Operational Reliability, and Engagement] survey). Safety culture scores and workforce well-being scores were compared across work settings with high (top quartile) and low (bottom quartile) perceptions of second victim support. Of the 10,627 respondents (81.5% response rate), 36.3% knew at least one work colleague who had been traumatized by an unanticipated clinical event. Across 396 work settings, the percentage of respondents agreeing (slightly or strongly) that second victims receive appropriate support ranged from 0% to 100%. Across all respondents, significant correlations between perceived support for second victims and all SCORE domains (Improvement Readiness, Local Leadership, Teamwork Climate, Safety Climate, Emotional Exhaustion, Burnout Climate, and Work-Life Balance) were found. The 24.9% of respondents who knew an actual second victim and reported inadequate institutional support were significantly more negative in their assessments of safety culture and well-being than the 42.2% who reported adequate institutional support. Perceived institutional support for second victims was associated with a better safety culture and lower emotional exhaustion. Investment in programs to support second victims may improve overall safety culture and HCW well-being.

Low-Dose Total Skin Electron Beam Therapy Combined With Mogamulizumab for Refractory Mycosis Fungoides and Sézary Syndrome

PurposeManagement of patients with refractory mycosis fungoides and Sézary syndrome (SS) is often challenging, as available therapies lack durable response and consistent activity across disease compartments. Combining low-dose total skin electron beam therapy (LD-TSEBT) upfront with mogamulizumab could optimize the clinical outcome of these patients. LD-TSEBT is effective in clearing skin disease, and mogamulizumab is an antitumor immunotherapy with long-term tolerability, suggesting its potential as a maintenance therapy after maximal response. We examine the combination regimen in patients with SS who were previously treated. Methods and MaterialsTwo patients with SS were treated with combination LD-TSEBT and mogamulizumab. Both patients received mogamulizumab 1 mg/kg weekly × 4 and then bi-weekly; LD-TSEBT (12 Gy) was initiated within 2 days of starting mogamulizumab and given over 2-3 weeks. Safety and clinical response were evaluated. ResultsTotal skin electron beam therapy plus mogamulizumab (TSE-Moga) was well-tolerated without any unanticipated adverse events. Patient 1 (T4N2bM0B2) was a 63-year-old woman with 4 prior systemic therapies; time to global response with TSE-Moga was 9 weeks. Patient 2 (T4NxM0B2) was a 75-year-old man with 5 prior systemic therapies; time to global response was 4 weeks. Both patients lacked global response to their prior therapies but achieved global complete response (blood and skin) with TSE-Moga. After a follow-up of 72 weeks and 43 weeks, respectively, global complete response continued. ConclusionsTSE-Moga demonstrated excellent tolerability and promising clinical activity with ongoing global complete responses in 2 patients with refractory SS. This encouraging experience supports our ongoing clinical trial evaluating the efficacy and safety of TSE-Moga in mycosis fungoides and SS.

Europa Clipper planetary protection probabilistic risk assessment summary

Protecting Jupiter’s Icy Moons from the Earth’s biological contamination is a key consideration for the Europa Clipper mission. The mission’s goal is to explore Jupiter’s moon, Europa, and investigate its habitability. The mission must satisfy NASA’s Planetary Protection (PP) requirements specified in the NASA Procedural Requirement (NPR) 8020.12D. The NPR states, “The probability of inadvertent contamination of an ocean or other liquid water body must be less than 1 ​× ​10−4 per mission.” The NPR defines contamination as “the introduction of a single viable terrestrial microorganism into a liquid-water environment”. The probabilistic nature of the requirement demands a probabilistic response. The Europa Clipper team at NASA’s Jet Propulsion Laboratory has developed an end-to-end probabilistic risk assessment (PRA) in order to demonstrate requirement compliance and inform design decisions.This Planetary Protection PRA conservatively assesses the unanticipated events that would need to coincide for the Europa Clipper mission to contaminate an ocean on one of Jupiter’s icy moons. This quantification requires a model of: spacecraft failure scenarios and the potential that these scenarios result in an icy body impact; expected geological resurfacing timescales that may introduce transported Earth biology to interstitial liquid water; and an assessment of biological mortality throughout the journey from Earth to the subsurface ocean. The motivation behind the development of this PRA is to determine the proper amount of bioburden reduction required prelaunch in order to achieve the NPR risk threshold, while minimizing programmatic and mission risk. Previous mathematical approaches have failed to offer such guidance, resulting in over or under-specified microbial reduction protocols and greater risk either to the exploration target or to the mission.If sterilizing spacecraft hardware is the sole solution employed to meet NASA’s planetary protection requirement, the PRA results show a 13-log bioburden reduction prelaunch is necessary. Most spaceflight electronics and optics cannot endure such microbial reduction protocols, or doing so would decrease part reliability to the point of being counter-productive. The Project, therefore, seeks to show compliance with the NPR by demonstrating the probability is sufficiently small that Europa Clipper inadvertently impacts an icy moon and subsequently delivers a fragment of hardware onto a piece of Europa that resurfaces by the year 3000 (within the 1000 year period of biological exploration). The Project does not seek to demonstrate that the hardware would be sterile if such an unlikely event sequence were to occur.This model introduces key improvements over previous planetary protection models. It affords an exact, interdependent, mathematically rigorous, end-to-end methodology for quantifying the probability of transmitting biologically viable contaminants from one planetary body to another. The model and specific findings, as they relate to the Europa Clipper mission, are explored at a summary level in this paper, along with implications of the model’s improvements. This work provides a cornerstone for future missions that are required to perform a planetary protection probabilistic risk assessment, such as Europa Lander and Mars Sample Return.

MIT shocks imply market incompleteness

The allocation after an unanticipated event (often called an “MIT shock”) is different from the allocation of a corresponding complete-market model that explicitly considers the possibility of the shock, even when the probability of the event approaches zero.

Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial

Among patients with out-of-hospital cardiac arrest (OHCA) and ventricular fibrillation, more than half present with refractory ventricular fibrillation unresponsive to initial standard advanced cardiac life support (ACLS) treatment. We did the first randomised clinical trial in the USA of extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation versus standard ACLS treatment in patients with OHCA and refractory ventricular fibrillation. For this phase 2, single centre, open-label, adaptive, safety and efficacy randomised clinical trial, we included adults aged 18-75 years presenting to the University of Minnesota Medical Center (MN, USA) with OHCA and refractory ventricular fibrillation, no return of spontaneous circulation after three shocks, automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System, and estimated transfer time shorter than 30 min. Patients were randomly assigned to early ECMO-facilitated resuscitation or standard ACLS treatment on hospital arrival by use of a secure schedule generated with permuted blocks of randomly varying block sizes. Allocation concealment was achieved by use of a randomisation schedule that required scratching off an opaque layer to reveal assignment. The primary outcome was survival to hospital discharge. Secondary outcomes were safety, survival, and functional assessment at hospital discharge and at 3 months and 6 months after discharge. All analyses were done on an intention-to-treat basis. The study qualified for exception from informed consent (21 Code of Federal Regulations 50.24). The ARREST trial is registered with ClinicalTrials.gov, NCT03880565. Between Aug 8, 2019, and June 14, 2020, 36 patients were assessed for inclusion. After exclusion of six patients, 30 were randomly assigned to standard ACLS treatment (n=15) or to early ECMO-facilitated resuscitation (n=15). One patient in the ECMO-facilitated resuscitation group withdrew from the study before discharge. The mean age was 59 years (range 36-73), and 25 (83%) of 30 patients were men. Survival to hospital discharge was observed in one (7%) of 15 patients (95% credible interval 1·6-30·2) in the standard ACLS treatment group versus six (43%) of 14 patients (21·3-67·7) in the early ECMO-facilitated resuscitation group (risk difference 36·2%, 3·7-59·2; posterior probability of ECMO superiority 0·9861). The study was terminated at the first preplanned interim analysis by the National Heart, Lung, and Blood Institute after unanimous recommendation from the Data Safety Monitoring Board after enrolling 30 patients because the posterior probability of ECMO superiority exceeded the prespecified monitoring boundary. Cumulative 6-month survival was significantly better in the early ECMO group than in the standard ACLS group. No unanticipated serious adverse events were observed. Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment. National Heart, Lung, and Blood Institute.

Hemophilia Natural History Study (ATHN 7): Baseline Characteristics, Adverse Events, and Self-Reported Health Status of Individuals with Hemophilia a and B

Hemophilia Natural History Study (ATHN 7): Baseline Characteristics, Adverse Events, and Self-Reported Health Status of Individuals with Hemophilia a and B

In Utero Stem Cell Transplantation in Patients with Alpha Thalassemia Major: Interim Results of a Phase 1 Clinical Trial

Introduction: In utero hematopoietic cell transplantation (IUHCT) has the potential to treat patients with blood disorders by taking advantage of bidirectional maternal-fetal tolerance during pregnancy. Although engraftment has only been seen in immunodeficient patients in the past, recent preclinical studies indicate that a higher dose of maternal cells should be given intravascularly to maximize engraftment in other settings. We hypothesized that: 1) fetuses will tolerate a maternal IUHCT without conditioning and develop low engraftment with sustained tolerance to maternal alloantigens; and 2) tolerant patients could receive a postnatal booster maternal transplant with minimal immunoablative conditioning and thereby achieve a cure. To test the first of these hypotheses in a controlled setting, we have initiated a phase 1 clinical trial of IUHCT in fetuses with alpha thalassemia major (ATM), who already require a fetal intervention (in utero transfusions (IUT)) to survive the pregnancy. We present interim results from the first two patients. Methods: After obtaining IND approval, we initiated the clinical trial in 2017 (NCT02986698). Fetuses with ATM between 18-26 weeks' gestation without other major anomalies were included. To date, we have evaluated 19 patients for possible inclusion: 15 patients terminated the pregnancy, 2 patients were outside the inclusion window and underwent IUT alone, and 2 have been transplanted and completed the 1 year follow up. For IUHCT, 300 ml of maternal bone marrow was harvested, CD34+ cells were selected and transplanted fresh into the fetus via the umbilical vein, along with a standard IUT. IUTs were repeated every 3 weeks until delivery. Maternal cell chimerism was detected using qRT-PCR for non-inherited maternal HLA-DR alleles on sorted cell populations in cord blood and after birth. Mixed lymphocyte reactions (MLRs) were performed by culturing CFSE-labeled host CD4 and CD8 responder cells with maternal (or third-party) derived antigen presenting cells (APC; direct pathway) or self APC/maternal lysate (indirect pathway). Results: Both fetuses were diagnosed with severe hydrops on ultrasound and received an initial IUT prior to the IUHCT. Patient 1 was transplanted at 23 weeks with 1x 108CD34+ cells/kg + 1 x 107T cells/kg and Patient 2 was transplanted at 25 weeks with 5x 107CD34+ cells/kg + 5 x 106T cells/kg; both received 4 more IUTs until birth. Prenatal hydrops resolved in both and neonatal hospitalizations were 16 and 13 days, respectively. Maternal chimerism was detected in both patients, but levels were higher and persisted throughout the year only in patient 1 (Fig 1A). We detected 70-fold higher levels of erythrocyte precursors (Fig 1B) but normal levels of CD34+ cells in the cord blood of patients compared to healthy controls, highlighting a potential barrier to engraftment in a disease with prenatal hypoxia. Patient 1 demonstrated sustained tolerance to maternal antigens by MLR throughout the year, whereas patient 2 showed reactivity against maternal antigens (Fig 1C). HLA antibodies were negative in both. Based on the finding of donor-specific tolerance in patient 1, we offered a booster transplant with maternal cells but the parents declined. Both patients are undergoing monthly transfusions and have had normal development and Bayley neurologic testing at 1 year. There were no unanticipated safety events in either mother/child pair. Conclusions: These results demonstrate the safety of IUHCT in fetuses with ATM and the potential of fetal transplantation in the second trimester to sustain tolerance to maternal cells after birth. Low engraftment levels are predicted in the setting of host hyperproliferation and lack of space-making conditioning, confirming the need for a two-step strategy (IUHCT and postnatal booster transplant) for a definitive cure. The earlier transplantation in patient 1 enabled a higher dose of cells and may explain the improved outcome observed. Implementation of earlier screening in at-risk patient groups could allow earlier diagnosis and enrollment in the future. Although parents of fetuses with ATM are commonly counseled for pregnancy termination due to concern for poor outcomes, our results indicate that fetal therapy with IUTs can result in survival to term and excellent quality of life. This strategy of maternal IUHCT could be employed to treat fetuses with other hematologic disorders in the future. Figure 1 Disclosures MacKenzie: Acrigen: Membership on an entity's Board of Directors or advisory committees; Ultragenyx: Research Funding. Vichinsky:Global Blood Therapeutics: Consultancy; Agios: Research Funding; Pfizer: Research Funding.

Sudden cardiac death during mountain sports activities

Sudden cardiac death (SCD) is an unanticipated and dramatic event resulting from cardiac causes. First reports on SCDs during mountain sports activities date back to the 1970s and 1980s of the last century. Relatively large datasets have been collected in Austria from 1985 onwards initiating systematic recordings and analyses of risk factors and triggers of SCDs during mountain sports activities. The results presented in this publication are derived from a literature search on reported SCDs that occurred during selected mountaineering activities with particular regard to study findings based on data collected in Austria. We found a relatively low SCD risk during mountaineering activities, amounting to about 1 SCD per 1 million activity days when hiking, trekking or ski touring, which is even lower during downhill skiing but higher in competitive cross-country skiing. The risk is much higher in men than in women and increases sharply above the age of 34. Main risk factors include prior myocardial infarction, coronary artery disease, arterial hypertension, hypercholesterolaemia and diabetes mellitus type 2, but regular and sport-specific activities turned out to be important protective factors. Unaccustomed physical exertion, in particular on the first days in the mountains (altitude), prolonged activities without rest and insufficient energy and fluid intake represent important SCD triggers. Besides considering these potential triggers during mountaineering activities, sports medical examination, appropriate pharmacological therapy of risk factors and physical preparation represent preventive key elements. Key Words: Exercise, Mountains, Cardiovascular, Risk, Triggers, Prevention

OxyChip Implantation and Subsequent Electron Paramagnetic Resonance Oximetry in Human Tumors Is Safe and Feasible: First Experience in 24 Patients.

Introduction: Tumor hypoxia confers both a poor prognosis and increased resistance to oncologic therapies, and therefore, hypoxia modification with reliable oxygen profiling during anticancer treatment is desirable. The OxyChip is an implantable oxygen sensor that can detect tumor oxygen levels using electron paramagnetic resonance (EPR) oximetry. We report initial safety and feasibility outcomes after OxyChip implantation in a first-in-humans clinical trial (NCT02706197, www.clinicaltrials.gov).Materials and Methods: Twenty-four patients were enrolled. Eligible patients had a tumor ≤ 3 cm from the skin surface with planned surgical resection as part of standard-of-care therapy. Most patients had a squamous cell carcinoma of the skin (33%) or a breast malignancy (33%). After an initial cohort of six patients who received surgery alone, eligibility was expanded to patients receiving either chemotherapy or radiotherapy prior to surgical resection. The OxyChip was implanted into the tumor using an 18-G needle; a subset of patients had ultrasound-guided implantation. Electron paramagnetic resonance oximetry was carried out using a custom-built clinical EPR scanner. Patients were evaluated for associated toxicity using the Common Terminology Criteria for Adverse Events (CTCAE); evaluations started immediately after OxyChip placement, occurred during every EPR oximetry measurement, and continued periodically after removal. The OxyChip was removed during standard-of-care surgery, and pathologic analysis of the tissue surrounding the OxyChip was performed.Results: Eighteen patients received surgery alone, while five underwent chemotherapy and one underwent radiotherapy prior to surgery. No unanticipated serious adverse device events occurred. The maximum severity of any adverse event as graded by the CTCAE was 1 (least severe), and all were related to events typically associated with implantation. After surgical resection, 45% of the patients had no histopathologic findings specifically associated with the OxyChip. All tissue pathology was “anticipated” excepting a patient with greater than expected inflammatory findings, which was assessed to be related to the tumor as opposed to the OxyChip.Conclusion: This report of the first-in-humans trial of OxyChip implantation and EPR oximetry demonstrated no significant clinical pathology or unanticipated serious adverse device events. Use of the OxyChip in the clinic was thus safe and feasible.

Outcome selection, measurement and reporting for new surgical procedures and devices: a systematic review of IDEAL/IDEAL-D studies to inform development of a core outcome set.

BackgroundOutcome selection, measurement and reporting for the evaluation of new surgical procedures and devices is inconsistent and lacks standardization. A core outcome set may promote the safe and transparent evaluation of surgical innovations. This systematic review examined outcome selection, measurement and reporting in studies conducted within the IDEAL (Idea, Development, Exploration, Assessment and Long‐term monitoring) framework to examine current practice and inform the development of a core outcome set for early‐phase studies of surgical procedures/devices.MethodsWeb of Science and Scopus citation searches were performed to identify author‐reported IDEAL/IDEAL‐D studies for any surgical procedure/device. Outcomes were extracted verbatim, including contextual information regarding outcome selection and measurement. Outcomes were categorized to inform a conceptual framework of outcome domains relevant to evaluating innovation.ResultsSome 48 studies were identified. Outcome selection, measurement and reporting varied widely across studies in different IDEAL stages. From 1737 outcomes extracted, 22 domains specific to evaluating innovation were conceptualized under seven broad categories: procedure completion success/failure; modifications; unanticipated events; surgeons' experiences; patients' experiences; resource use specific to the innovative procedure/device; and other innovation‐specific outcomes. Most innovation‐specific outcomes were measured and reported in only a small number of studies.ConclusionThis review highlighted the need for guidance and standardization in outcome selection and reporting in the evaluation of new surgical procedures/devices. Novel outcome domains specific to innovation have been identified to establish a core outcome set for future evaluations of surgical innovations.

Introduction to the special issue on the HEALing Communities Study

The severity of the overdose epidemic underscores the urgent need for innovative and high impact interventions that promote the rapid penetration and scale up of evidence-based practices (EBPs) in communities profoundly affected by fatal opioid overdose. This special issue shares scientific advancements in implementation research design and evaluation of a novel data-driven community-based intervention. The HEALing (Helping End Addiction Long-Term) Communities Study (HCS) is a four-year study that is designed to examine the effectiveness of the Communities That HEAL (CTH) intervention. The CTH intervention supports the dissemination of EBPs in 67 communities across four high-burdened states—Kentucky, Massachusetts, New York, and Ohio. The diversity in these communities in terms of rural-urban status, race-ethnicity and other social determinants of health facilitates generalizability of results to other communities across the US.The nine papers in this special issue describe critical elements that constitute the HCS framework and design. This includes the implementation of EBPs that have a substantial impact on fatal and non-fatal opioid overdose, the Opioid-overdose Reduction Continuum of Care Approach, communication campaigns to increase awareness and demand for EBPs and reduce stigma against people with OUD and MOUD interventions, and the process of community engagement. This includes how to form community coalitions and gain their commitment, and steps taken to mobilize coalitions to pursue EBP implementation and ensure EBPs are adapted for community needs.The collective papers in this issue demonstrate that the design of any complex study must adapt to unanticipated temporal events, including the rapidly emerging COVID-19 crisis. Readers will learn about the scientific process of the design and implementation of a community-engaged intervention, its methodologies, guiding conceptual models, and research implementation strategies that can be applied to address other health issues.

Do DJIA Firms Reflect Stationary Debt Ratios?

To form optimum firm capital structure strategies to face unanticipated economic events, firm managers should understand the stability of a firm’s capital structure. The aim of this research was to study whether the debt ratio is stationary in listed firms on the Dow Jones Industrial Average (DJIA). Two vital capital structure concepts regarding pecking order and trade-off theory are fairly contradictory. Using opposing theoretical contexts, the Sequential Panel Selection Method apparently categorizes which and how many series are stationary processes in the panel. This method was used to test the mean reverting properties of the 25 companies listed on Dow Jones Industrial Average between 2001 and 2017 in this study, which is expected to fill the current gap in the literature. The overall results show that stationary debt ratios exist in 10 of the 25 studied firms, supporting the trade-off theory. Moreover, the 10 firms utilizing trade-off theory are affected by firm size, profitability, growth opportunity, and dividend payout ratio. These results provide vital information for firms to certify strategies to optimize capital structure.

Rethinking and reinventing learning, education and collaboration in the digital age—from creating technologies to transforming cultures

PurposeThe digitalization of society results in challenges and opportunities for learning and education. This paper describes exemplary transformations from current to future practices. It illustrates multi-dimensional aspects of learning which complement and transcend current frameworks of learning focused on schools. While digital technologies are necessary for these transformations, they are not sufficient. The paper briefly illustrates the applicability of the conceptual framework to the COVID-19 pandemic. It concludes that design opportunities and design trade-offs in relation to digital technologies and learning should be explored by envisioning the cultural transformation that are desirable for making learning a part of life.Design/methodology/approachThis paper is based on the work conducted at the symposium “Rethinking and Reinventing Learning, Education, and Collaboration in the Digital Age—From Creating Technologies to Transforming Cultures” that took place in Engeltofta outside of Gävle, Sweden in September 2019. The symposium invited scholars in collaborative analysis of design opportunities and design trade-offs in relation to digital technologies and learning and explored design strategies for systematically and proactively increasing digital technology's contributions to learning and collaborating. The paper first provides a condensed introduction of a conceptual framework summarizing current practices, their problems and promising alternatives. Multi-dimensional aspects of learning and lifelong learning will be briefly described as promising future alternatives to school learning. Examples of transformative practices are supporting the major argument of the paper that creating new technologies is an important prerequisite to address the fundamental challenge of transforming cultures. The unanticipated but fundamental event of the occurrence of COVID-19 will be briefly described to provide further evidence for the need and the applicability of our conceptual framework for rethinking and reinventing learning, education and collaboration in the digital age.FindingsThe paper provides a condensed introduction of a conceptual framework summarizing current practices, their problems and promising alternatives. The framework includes multi-dimensional aspects of learning and lifelong learning as a promising future alternative to a focus on school learning.Originality/valueThis paper describes exemplary transformations from current to future practices. It illustrates multi-dimensional aspects of learning which complement and transcend current frameworks of learning focused on schools.