Environmental change, strategic entrepreneurial action, and success: Introduction to a special issue on an important, neglected topic

Research Summary: The two premises that underpin this SEJ Special Issue on Environmental Change, Strategic Entrepreneurial Action, and Success are that all environmental changes provide positive potentials for some ventures, and that this has been under-emphasized in past theory and research. After stating these premises and illustrating how present research treats the environment, we proceed to explain how the five articles selected for the special issue advance our thinking in this domain. We then broaden our discussion to how future entrepreneurship research can make further progress by studying interaction among environmental changes as well as their links to entrepreneurial agents, contexts (sectoral, spatial, organizational, etc.) and the entrepreneurial artifact (emerging venture). Throughout, the focus is on the enabling rather than constraining role of environmental changes. Managerial Summary: The COVID-19 pandemic, the digital revolution, and the sustainability transition forced by climate change demonstrate significant business impact of environmental changes, including potentials for new business initiatives. This editorial and the five vanguard articles included in this SEJ Special Issue on Environmental Change, Strategic Entrepreneurial Action, and Success outline how future research can develop better theory and evidence on this important topic. The articles address matters ranging from how COVID-19 facilitated some technology firms' recruiting and reignited media firms' dormant initiatives to how environmental degradations sparked entrepreneurial ecosystem development in Kenya, how the level of environmental dynamism at a venture's birth impact its current ability to benefit from change, and the consequences of passing on potentials provided by environmental change.

Covid-19 Vaccine-Induced Myositis

Background/Aims Through the COVID pandemic there have emerged reports of autoimmunity or new rheumatic diseases presenting in patients after they had COVID-19. This is thought to be caused by cross-reactivity of the COVID-19 spike protein to human antigens. Given the use of mRNA COVID-19 vaccinations which express the spike protein we might expect to see presentation of new rheumatic diseases following their use. We discuss a case where this appears to have occurred. Methods Our patient is a 24-year-old male with mixed phenotype acute leukaemia who had been treated with allogenic stem cell transplant and was currently in remission. He presented with fevers, palpitations, myalgia and bilateral arm and leg swelling. Symptoms began the day after receiving the first dose of an mRNA COVID-19 vaccination (Pfizer/BioNTech.) There were no other symptoms or recent change in medications. Physical examination revealed tender oedema in his forearms, biceps and thighs bilaterally with sparring of the hands. He had reduced power with shoulder (MRC 3/5), elbow (4), wrist (4+) and hip (4) movements. Observations revealed tachycardia and fevers up to 40C. Results Laboratory studies showed markedly elevated C-reactive protein (202), creatinine kinase (6697) and troponin (593) whilst investigations for infection were negative. An autoimmune panel was positive for anti- PM-SCL-75-Ab. An electrocardiogram showed sinus tachycardia. Echocardiogram was normal. Bilateral upper limb dopplers revealed no deep vein thrombus. An MRI of his thighs showed diffuse symmetrical oedema within the muscles, in keeping with an inflammatory myositis. A quadricep muscle biopsy showed evidence of MHC class 1 up-regulation, suggesting an inflammatory process. In addition, there were numerous macrophages evident in the endomysium. While this can be seen in graft-versus-host disease (GVHD), they would usually be found in the perimysium. After discussion between haematology, rheumatology and neurology, this was felt to be a case of vaccine induced myositis and myocarditis. Autoimmune myositis was thought to be less likely due to the relative sparing of the hands and the absence of Raynaud's phenomenon. 1 gram of intravenous methylprednisolone was then given for 3 days. The patient had a marked response with defervescence, improving laboratory markers, improved myalgia and decreased limb swelling. The patient was stepped down to a reducing regime of prednisolone and discharged. Due to relapse whilst weaning he has started on mycophenalate mofetil and rituximab and now continues to improve. Conclusion There are case reports of myositis following COVID-19 vaccination but our patient's case is complicated by the differential diagnosis of GVHD and concurrent myocarditis. Ongoing work is needed to clarify the exact link between vaccination and the presentation of a new inflammatory myositis, but it is important to recognise and start treatment early in order to preserve muscle bulk and ensure recovery.

Lung transplant and COVID-19: A single centre experience in Ireland

As of April 2022, the Mater Hospital serves 190 patients who have been the recipient of a lung transplant in Ireland. During the COVID-19 pandemic, solid organ transplant was recognised as a risk factor for progression to severe disease. In January 2022, the European Medicines Agency (EMA) approved the use of Sotrovimab for high risk patients. Sotrovimab is a monoclonal antibody which neutralises SARS-CoV-2 with recent data showing efficacy in reducing the risk of progression to severe disease in high risk patients . We aim to describe our patient cohort and the rates of COVID-19 infection seen before and after the introduction of monoclonal antibody therapy. While likely reflecting emerging variants resulting in less severe disease, we observe variation in morbidity and mortality in this time. From March 2020 to April 2022, 116 post-lung transplant patients tested positive for COVID-19 infection. This represents 61% of our overall population. Since January 2022, coinciding with the surge of the omicron variant, 57 patients contracted COVID-19. 47 were deemed to be suitable for treatment with 10 presenting outside the window for therapeutic intervention. 3.5% (n=2) required ICU admission and 2 died directly as a result of COVID-19. Prior to this, 58 patients contracted COVID-19, 31 of which (53.5%) required hospital admission with 18 (58%) requiring ICU admission. Overall we saw 13 deaths representing 22.4% of this group and 6.8% of the overall population.

Infection with Covid Variants of Concern in a Lung Transplant Population

The COVID pandemic has evolved as the SARS-2 Coronavirus (CoV-2) mutated into unique variants of concern (VOC). The clinical approach to COVID has evolved as new therapeutics have become available. Previous reports demonstrate differences in patient outcomes based on VOC, however outcomes in a lung transplant population have not been described. Our lung transplant program follows over 300 transplant recipients. Relevant information including date of first positive test, hospital admission, monoclonal antibody (mAb) or oral anti-viral treatment, CoV-2 vaccination history, tixagevimab/cilgavimab (T/C) and COVID attributed mortality have been tracked for quality improvement purposes. Outcomes were stratified by predominant US VOC at time of positive testing: wild strain 02/2020-02/2021, alpha strain 02/2021-05/2021, delta strain 06/2021-12/2021, omicron strain 01/2022- 09/25/2022. From 03/20/2020 through 09/25/2022, 142 recipients were diagnosed with COVID 152 times, including 9 recipients infected twice and 1 recipient infected 3 times. Most infected recipients tested positive with CoV-2 during the omicron wave. All recurrent infections occurred during the omicron wave. 8 deaths (5.6%) were attributed to COVID: 6 due to COVID respiratory failure, 1 stroke and 1 new restrictive-chronic lung allograft dysfunction. Therapies directed against CoV-2 were more likely administered in delta and omicron waves. Recipients were more likely to require hospital admission in wild type and alpha waves of CoV-2. Most deaths occurred in the wild type and delta waves. Deceased recipients, and those requiring hospital admission received less vaccinations and were less likely to have received T/C. (Table) This analysis shows changing trends in management and outcomes over the COVID pandemic. Future research should focus on transplant specific outcomes, including post-infection changes in allograft function and risk of developing chronic lung allograft dysfunction based on likely infecting VOC. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An Observational Study of Guideline-Directed Medical Therapy Optimization for Patients With Heart Failure With Reduced Ejection Fraction in Telehealth versus In-Person Visits

Introduction: Rates of initiation and dose optimization of guideline-directed medical therapy (GDMT) for heart failure patients with reduced ejection fraction are suboptimal nationally. Recently, virtual medicine has been studied as a potential solution to help overcome barriers limiting GDMT optimization. We evaluated GDMT optimization during telehealth visits compared with in-person visits at Parkland Health, a large urban safety-net health system. Method(s): Parkland has a registry of all patients with an ejection fraction <= 40% on transthoracic echocardiography within the last three years. Using this registry data of patients seen in the Parkland cardiology clinic between September 2021 and February 2022, we compared GDMT prescriptions for patients before and after each clinic visit. We defined an optimization event as the initiation of a new class of GDMT, a switch to an angiotensin receptor/neprilysin inhibitor, or an increase in dosage of any class of GDMT. The rise of Omicron variant COVID-19 cases in Dallas led to a nearly universal shift of in-person to virtual visits in December 2021, allowing us to compare GDMT optimization rates between each visit type. Result(s): From 9/12/21 to 12/24/21, there were 147 visits of which 134 (91%) were in-person. Of these in-person visits, 58.2% led to an optimization event. From 12/25/21 to 2/12/22, there were 97 visits of which 84 (89%) were telehealth visits, all conducted by telephone. Of these telehealth visits, 16.1% led to an optimization event (p<0.001). Baseline characteristics of patients from each period were not significantly different (Table 1). Conclusion(s): Our study demonstrated GDMT optimization was significantly lower in telephone visits compared with in-person visits despite each group having similar demographics and medical co-morbidities. This observation should raise concern over increased reliance on telephone-only encounters, especially in urban resource limited populations. (Figure Presented).

Clinical Characteristics and Outcomes of Critically Ill COVID-19 Patients That Required Continuous Renal Replacement Therapy With and Without Adjuvant Blood Purification

Background: oXiris use received EUA by the FDA as a blood purification adjuvant for COVID-19 critical illness. We evaluated clinical characteristics and outcomes of patients with COVID-19 critical illness that received CRRT with vs. without oXiris. Method(s): Single-center, retrospective cohort study of adult ICU patients with COVID-19 critical illness requiring CRRT (3/2020 to 4/2021). oXiris exposure was defined as a minimum use of 48 h within the first 72 h of CRRT initiation and use of at least 50% of time if the patient died within the first 72 h of CRRT. Data were analyzed with and without propensity-score (PS) matching and with PS-regression. Result(s): 114 critically ill COVID adults admitted to the ICU required CRRT during the study period. Of these, 11 patients used oXiris without meeting the definition of exposure and were excluded. Of the 103 remaining patients, 31 used oXiris and 72 did not. Mean (SD) age of the cohort was 60 (12) years, 66% were male, and 81% white. There were no differences in demographics between both groups. Similarly, there was no difference in baseline kidney function or prevalence of ESRD. Patients that received oXiris had more frequently sepsis (90% vs. 63%, p=0.004) and more frequently received IL-6 inhibitors but CRRT indications were similar in both groups, being the most common one fluid overload in about two-third of patients. Critical illness parameters including SOFA scores (median of 11 in both groups) and extracorporeal organ support (ECMO or mechanical ventilation) were also similar in both groups. Inpatient mortality was not different between both groups (74% in the oXiris group vs. 65% in the non-oXiris group, p=0.37). Further, 28-day ventilator, CRRT and ICU free-days were comparable in both groups. Similarly, kidney recovery rates were not different based on oXiris exposure. These results were consistent in all adjusted analyses. There were no circuit or filter related complications attributed to oXiris. Conclusion(s): The use of oXiris as adjuvant treatment of blood purification during CRRT appears feasible and safe. We did not observe differences in mortality, kidney recovery, or resource utilization among patients exposed vs. non-exposed to oXiris. The clinical impact of oXiris needs to be further evaluated in interventional studies.

COVID-19, Cultural Competency, and Church Responsiveness in Nigeria

Amidst Nigeria's history of ethnic and religious conflicts, poverty, and government distrust, COVID-19 has added to the country's list of challenges. According to the World Health Organization, Nigeria has one of the highest infection rates in Africa. The Zion World Prayer and Missions (ZWPM) is a faith-based nonprofit headquartered in northern Nigeria providing church support to Christian minorities and their communities. This essay discusses how the ZWPM leveraged its cultural competency within a Muslim-dominated region to promote education and church response strategies to prevent COVID transmission. As of June 2021, the ZWPM had not recorded any active case of infection or death among its members or networks. © 2002 Taylor and Francis.

A multi-centre retrospective cohort study to examine the effect of high-dose steroids in COVID-19 pneumonitis admitted to Intensive Care with ARDS

Introduction: The use of systemic corticosteroids to suppress SARS-CoV-2-induced lung inflammation is advocated in the treatment of COVID-19 ARDS.1,2 Whilst the evidence for low dose early corticosteroids in COVIDARDS is well established, the effect of larger steroid doses (i.e. short-term 'pulse-dose') is yet to be investigated. Objectives: The objective of this study was to examine the effect of pulse dose steroids on ventilatory parameters such as oxygenation in COVID-19 patients with and without established fibrosis or organising pneumonia (OP). Methods: This was a multi-centre, retrospective observational study performed at four teaching hospitals, with the following inclusion criteria: adult patients requiring invasive mechanical ventilation with confirmed PCR SARS-CoV-2 infection;and received high dose steroids for treatment for COVID-ARDS (defined as dose ≥ 20mg dexamethasone or an equivalent dose of methylprednisolone). This study was carried out as a service evaluation within the National Health Service (NHS) and recorded under the auspices of the clinical audit office at Imperial College HealthcareNHS Trust and Institutional Data Protection Office. Study patients were followed for 14 days or until they were discharged from the ICU and physiological or ventilatory variable data was retrospectively collected from patient records. Results: In total, 92 patients were included: 14 patients 20mg/day dexamethasone;5 patients 50mg/day dexamethasone;16 patients 500mg methylprednisolone;and 57 patients 1000mg methylprednisolone. Our data demonstrate a statistically significant improvement in PaO2/FiO2 (P/F) ratio over time, from baseline to day 14, in those patients who received 1000mg Methylprednisolone (baseline PaO2: 14.47 kPa, Day 3: 17.51 kPa, Day 7: 19.51 kPa, Day 14: 22.87 kPa, p<0.001). Whilst not statistically significant, there was a trend to higher P/F ratios by day 14 in patients who received 500mg Methylprednisolone group. There was no increase in P/F ratios in those patients who received 20mg or 50mg dexamethasone. The increase in P/F ratio was most apparent in those patients who had evidence of fibrosis on CT scan, although some benefit was seen in those patients who did not fibrosis on radiological imaging. Cross sectional random effects models were used to determine the effect of 1000mg methylprednisolone on improvement in P/F ratio and demonstrate that there was an increase of P/F ratio of more than 0.38 kPa per day in those patients that received 1000mg methylprednisolone. The was no significant effect on compliance measures. There was also a trend to more ventilator free days but no difference in mortality in those patients receiving large dose methylprednisolone. Reassuringly, rates of fungal infection and pneumothorax/pneumomediastinum for patients who received steroids, including those with high dose, were equivocal. Conclusion: In this study, we present novel data suggesting that large doses of methylprednisolone may be beneficial in patients with severe COVID-19, late in the disease course when ARDS is well established. This benefit was not demonstrated in patients treated with lesser (but still high) doses of steroids (i.e. 20mg or 50mg of dexamethasone) and suggest that larger pulsed-dose steroids may induce reversibility of the disease process, particularly in those who have developed fibrosis.

Understanding the Broader Impacts of COVID-19 on Women and Girls in the DRC through Integrated Outbreak Analytics to Reinforce Evidence for Rapid Operational Decision-Making

Whilst men and boys account for more COVID-19 cases and deaths, the secondary impacts of the outbreak on women and girls in the Democratic Republic of the Congo are cross-cutting and far-reaching. School closures put girls at increased risk of adolescent pregnancy, sexual violence and early marriage;more women working in the informal sector have lost jobs and been affected by closures of markets and borders;and frequent restrictions on sexual and reproductive healthcare have impacted access to services for women. Lessons learnt from previous health crises can help to highlight the extent of these issues. However, a lack of sex disaggregated data around COVID-19 morbidity and mortality in the DRC means that it is impossible to fully measure and understand the impact of the outbreak on women and girls or develop and implement appropriate interventions. This article presents a meta-synthesis of existing and ongoing analyses to highlight the broader impacts of COVID-19 on women and girls in the country.

ONLINE AND SIMULATION BASED CARDIAC POINT OF CARE ULTRASOUND TRAINING FOR RESIDENTS, A RANDOMIZED PILOT STUDY

Background: Cardiac point of care ultrasound (cPOCUS) is becoming an important skill for residents. This study explores the feasibility and efficacy of a novel online and simulation-based curriculum for cPOCUS training during the COVID-19 pandemic. Methods: Between January 20th and August 1st, 2021, Internal Medicine PGY-1’s were block randomized in a 1:1 fashion to intervention and control arms based on prior cPOCUS experience. All participants were asked to interpret a standard, preselected set of echocardiographic images. After this testing, the intervention arm underwent an in-person, simulation-based teaching experience followed by a structured, online curriculum. Both study arms were given the same test again after completion of this curriculum. Test results were graded by two blinded reviewers (board certified in echocardiography) using a standardized rubric, creating a score of 0-16 [16 being the highest]. A subjective, dichotomous “scope of practice” score was created to evaluate interpretation appropriateness. The primary outcome was improvement in interpretation score. One-tailed Mann-Whitney and Fischer's exact were performed as appropriate (GraphPad Prism version 9.2.0). Results: A total of twenty-four participants were enrolled, twelve in each arm. Two participants in the intervention arm did not complete baseline testing and were excluded from the analysis. One PGY-1 in each arm had prior cPOCUS training. Baseline median interpretation scores were 9.1 in the intervention arm and 9.5 in the control arm (p=0.9). The median increase in echo interpretation score was 3.3 in the intervention arm vs. 1.1 in the control arm (p=0.11). Interpretation scores improved in 90% of the intervention arm and 67% in the control arm (p=0.21). Interpretation quality stayed within the scope of practice for 80% of participants in the intervention arm vs. 42% in the control arm (p=0.08) on post-testing. Conclusion: Our randomized pilot study showed a trend towards improvement in echo interpretation in a small sample size, demonstrating the potential utility and feasibility of online and simulation-based training. PGY-1 feedback for the experience was positive.

A 10-year impact assessment of the Efficacy and Mechanism Evaluation (EME) programme: an independent mixed-method evaluation study

BACKGROUND: The Efficacy and Mechanism Evaluation (EME) programme - a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership - funds trials that evaluate the efficacy of interventions with the potential to promote health and studies that improve our understanding of the mechanisms of underlying diseases and their treatments. OBJECTIVE: To conduct an independent review of the EME programme's impact and identify opportunities for future improvement. DESIGN: A mixed-methods approach, including desk research, an analysis of secondary data, stakeholder consultation and the development of impact case studies. PARTICIPANTS: Chief investigators of EME awards, unfunded applicants to the EME programme and key opinion leaders relevant to the programme and research ecosystem. INTERVENTIONS: No interventions were tested, as this was a retrospective programme evaluation. MAIN OUTCOME MEASURES: The evaluation was guided by a set of 15 evaluation questions. RESULTS: The EME programme bridges the gap between proof-of-concept and effectiveness studies that are located among other MRC and NIHR schemes and grants from charities in the funding landscape. Mechanistic studies alongside EME trials add value by lending confidence to trial findings and providing insights into the underlying biology. Between 2009 and September 2018, 175.7M in funding was approved for 145 EME projects. EME programme-funded research has started to deliver value to the NHS and patients by improving treatments and providing more efficient use of resources. Of the 43 completed trials, 14% (n = 6) showed that the intervention had a positive effect, whereas 74% (n = 32) of trials did not. The remaining five (12%) trials were unable to recruit participants or did not proceed to the full-trial stage. Seven projects (i.e. 16% of completed trials) have informed clinical guidelines or regulatory approval decisions and another eight projects have the potential to do so in the future, given the nature of their findings. Projects in the EME programme portfolio address a range of UK health needs and government priority areas, but they do not fully align with the level of health needs present. Commissioned calls for applications steer applicants. However, many commissioned calls do not lead to funded awards, and a better understanding of the underlying reasons for this would enable targeted supported to address key health needs. The majority of EME projects investigate existing interventions of limited commercial interest, focusing on repurposing (67/136, 49%) and informing current practice (23/136, 17%). Although there is little evidence of wider economic impact from commercial benefits, the EME programme is important in funding research in which industry is unlikely to invest. Stronger co-ordination with other funders, such as charities, could lead to synergies, enhancing the potential for health impact and influence on other funders' agendas. The main challenges identified for EME projects were 'complex and slow contracting processes' (35/46, 76%), 'setting up of study sites' (30/46, 65%) and patient recruitment (28/46, 61%). Enablers of research included a clinical research fellow position on the project and support from Clinical Research Networks and Biomedical Research Centres. Nearly all of the chief investigators consulted had engaged in patient and public involvement at some project stage, and a lack of patient and public involvement did not emerge as a barrier to research or impact. Research ideas stemming from patients were, however, over-represented among unfunded applications, but the reason for this is unclear. LIMITATIONS: Only about one-third of all studies had been completed or had published their main findings, necessitating a purposive, rather than representative, sampling of the portfolio. The COVID-19 outbreak cut short the programme of interviews, limiting the depth to which some evaluation questions could be explored. Several data sources were based on self-reporting by chief investigators;whereas key self-reported aspects were verified through desk research, this was not possible for all findings. CONCLUSIONS: The EME programme plays an important role in the UK research funding landscape and has started to deliver value to the NHS and patients. Based on the evidence gathered, seven recommendations were developed to enhance the EME programme's health and economic impact and address challenges encountered by chief investigators in implementing research projects. FUNDING: This project was funded by the EME programme, a MRC and NIHR partnership. This will be published in full in Efficacy and Mechanism Evaluation;Vol. 8, No. 20. See the NIHR Journals Library website for further project information.

Healthy sleep as an important resource and buffer for intersectional discrimination: Results from COVID 19 study

Introduction: Our previous studies have highlighted sleep disparities for this underserved population, including how Grandparents Raising Grandchildren (GRG) experience troubled and disruptive sleep. Intersectional types of discrimination facing these families during COVID 19, include: race/ethnicity of self and children, income, age, essential workforce status, and impairments (mobility, vision, and hearing). This current study intends to explore how healthy sleep is an important resource (potential buffer) for GRG experiencing intersectional discrimination during COVID 19. Methods: We used community partnerships to recruit 600 GRG from all fifty states in USA and several tribes to complete an online survey on their experiences with caregiving and intersectional discrimination during COVID 19. We developed an index on intersectional discrimination based on GRG lived experiences to inform the survey and used descriptive and bivariate statistics to profile this group. Chi-square Automatic Interaction Detector (CHAID) analysis was used to build a predictive model to help determine how variables in our study best merge to explain intersectional discrimination. Results: Of the GRGs', 37% were between 54-65 years and 33% cared for children 6 to 10 years for at least 5 years. The types of discrimination that were more likely to be included in intersectional discrimination include: Black or African American [83.8% (31)], my child's race [59.5% (22)], my lower economic status [56.8% (21)], and my status as a caregiver [56.8% (21)]. The resource needs that showed the most disparity (higher rate showed higher priority/extreme concern) between those with ID and those without included: Information on how COVID impacts race and ethnicity differently (6.0 vs. 3.61), ability to pay utilities (3.7 vs. 1.99), and information on how to achieve healthy sleep (4.19 vs. 2.64). Conclusion: This study suggests that GRG facing intersectional discrimination identify the importance of attaining information on how to achieve healthy sleep as an important resource to them during COVID 19. These results can be used to help mobilize resources and disseminate information for this underserved group to improve healthy sleep and also model for their extended families and communities.