Tolerance of ETD001, a long-acting inhaled epithelial sodium channel blocker, in humans

Background: To assess the safety, tolerability, and pharmacokinetic (PK) profile in humans of the novel inhaled epithelial sodium channel blocker ETD001. Method(s): Inhaled ETD001 or placebo, delivered via nebulizer, have been administered in a 3:1 ratio to 96 healthy subjects in a blinded, first-inhuman clinical trial (ClinicalTrials.gov Identifier: NCT04926701). The study consisted of two parts. Part A evaluated single ascending doses (SADs) up to 10.8 mg, and Part B evaluated multiple ascending doses (MADs) up to 3.1 mg once daily (QD) for 7 days and 4.65 mg twice daily (BID) for 14 days. Safety was assessed by monitoring for adverse events (AEs), laboratory safety tests (including blood potassium monitoring), vital signs, 12-lead electrocardiogram (ECG), and spirometry. Systemic exposurewas assessed using serial pharmacokinetic blood draws. Result(s): Therewere no serious AEs. Twenty-four subjects reported 38 AEs, all of mild to moderate intensity and all resolved. There were no clinically relevant changes in laboratory safety tests, vital signs, ECGs, or spirometry measurements. All blood potassium assessments were within normal range at all doses. Three subjects withdrew in Part B;all withdrawals were considered unrelated to study drug: one on day 6 from the 3.1-mg QD cohort for personal reasons, one after the first dose of the 3.1-mg BID cohort because of vasovagal syncope at time of venipuncture triggering atrial fibrillation that spontaneously resolved, and one on Day 4 of the 3.1- mg BID cohort because of a positive COVID-19 test. Pharmacokinetic parameters were approximately dose proportional in Part A, with peak concentrations 1 to 2 hours after dose and exposure out to 12 to 24 hours at all doses, indicating good lung retention. Part B plasma concentrations displayed dose-independent kinetics and showed minimal accumulation, with a mean of 1.11-fold observed over 14 days. Conclusion(s): ETD001 was well tolerated at single doses up to 10.8 mg and multiple doses of 3.1 mg QD for 7 days and 4.65 mg BID for 14 days. The wide safety margin is predicted to enable doses capable of durable target engagement in the lung, which are expected to enhance mucociliary clearance in people with cystic fibrosis.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Non-pharmaceutical interventions in the State of Georgia: Economic implications.

Background: As Covid-19 spread rapidly, many countries implemented a strict shelter-in-place to "flatten the curve" and build capacity to treat in the absence of effective preventative therapies or treatments. Policymakers and public health officials must balance the positive health effects of lockdowns with economic, social, and psychological costs. This study examined the economic impacts of state and county level restrictions during the 2020 Covid-19 pandemic for two regions of Georgia. Methods: Taking unemployment data from the Opportunity Insights Economic Tracker with mandate information from various sites, we examined trends before and after a mandate's implementation and relaxation using joinpoint regression. Results: We found mandates with the largest impact on unemployment claims rates were the shelters-in-place (SIPs) and closures of non-essential businesses. Specific to our study, mandates had an effect where first implemented, i.e., if the state implemented an SIP after the county, the state-wide SIP had no additional measurable effect on claims rates. School closures had a consistent impact on increasing unemployment claims rates, but to a lesser degree than SIPs or business closures. While closing businesses did have a deleterious effect, implementing social distancing for businesses and restricting gatherings did not. Notably, the Coastal region was less affected than the Metro Area. Additionally, our findings indicate that race ethnicity may be a larger predictor of adverse economic effects than education, poverty level, or geographic area. Conclusions: Our findings coincided with other studies in some areas but showed differences in what indicators may best predict adverse effects and that coastal communities may not always be as impacted as other regions in a state. Ultimately, the most restrictive measures consistently had the largest negative economic impacts. Social distancing and mask mandates can be effective for containment while mitigating the economic impacts of strict SIPs and business closures.

The COVID-19 pandemic and parental substance use: a cross-sectional survey of substance use among pregnant and post-partum individuals and their partners

Background: This study was designed to investigate patterns and risk factors for substance use among obstetrical patients who gave birth during the early period of the pandemic, and their partners. Method(s): Cross-sectional survey of obstetrical patients between March 17th and June 16th, 2020, at The Ottawa Hospital, Ottawa, Canada. Substance use was a composite measure of any alcohol, tobacco, or cannabis use since COVID-19 began. Four outcomes included: any participant substance use or increase in substance use, any partner substance use or increase in substance use. Adjusted risk ratios (ARR) and 95% confidence intervals (CI) are presented. Finding(s): Of 216 participants, 113 (52.3%) and 15 (6.9%) obstetrical patients reported substance use and increased use, respectively. Those born in Canada (ARR: 2.03;95% CI: 1.27-3.23) and those with lower household income (ARR: 1.38;95% CI: 1.04-1.85) had higher risk of substance use. Those with postpartum depression (ARR: 5.78;95%CI: 2.22-15.05) had the highest risk of increased substance use. Families affected by school/daycare closure reported a higher risk of increased partner substance use (ARR: 2.46;95% CI:1.38-4.39). Conclusion(s): This study found that risk factors for substance use included demographics (i.e., being born in Canada, income), mental health (postpartum depression), and school/childcare closures.Copyright © 2023 Taylor & Francis Group, LLC.

Quality and reliability of YouTube as an educational tool for patients undergoing radiological musculoskeletal intervention

Purpose: With increasing demands and time constraints on physicians, compounded by the telemedicine era of COVID, patients are ill-equipped to make informed decisions regarding their treatments1. Patients are seeking further information on the internet, particularly the audio-visual platform YouTube2. Appropriate patient education is paramount for patients undergoing treatment, particularly intervention, as it provides appropriate expectations and reduces anxiety1. This aim of this study was to objectively evaluate videos on YouTube that related to commonly performed musculoskeletal procedures against validated scoring systems. Methods and Materials: YouTube was utilised to search for common musculoskeletal procedures including "facet joint injection", "knee injection" and "shoulder injection". The first thirty videos returned for each search were assessed for suitability as it was deemed this was likely to encompass a patient search results as average user's will only assess the first 5 search results 3. 90 total videos were identified, and after exclusion 51 were included for analysis by three independent reviewers. Data extracted from the videos included video authorship, year published, number of views and number of 'likes' and 'dislikes'. Videos were scored for quality and reliability using three separate and validated tools for online medical video assessment;Journal of American Medical Association (JAMA) benchmark criteria, the global quality scoring (GQS) and the DISCERN criteria. Result(s): Of the 51 videos analysed, 88% were authored by a medical doctor, and the average number of views were 67,552. The overall video quality and reliability was poor. The mean DISCERN score was 32.78 (<39 = poor). The mean JAMA score was 1.79 (<3 = low quality) and the GQS was 2.39 (<3 = poor). As per DISCERN standards 24.18% of videos were very poor, 46.70% were poor, 26.79% were fair, 2.61% were good, and 0% were excellent. There was no significant difference in quality or reliability across the three video categories. Conclusion(s): YouTube is a popular medium for individuals seeking health related information, however, it provides substandard information for patient education on three commonly performed radiological guided musculoskeletal procedures;failing to meet benchmark criteria. Radiologists and referring physicians should avoid the recommendation of YouTube as an education aid at this time, as it may misinform patients and provide misconceptions with altered expectations.

Considering equity in priority setting using transmission models: Recommendations and data needs.

OBJECTIVES: Disease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity. METHODS: We reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations. RESULTS: We provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration. CONCLUSIONS: Current developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use these frameworks more in priority setting to accurately represent health inequities. We provide guidance on the technical approaches to support this goal and ultimately, to achieve more equitable health policies.

Hybrid Pain Management Strategy Attenuated Acute Pain and Reduced Left-Over Opioid Doses

Problem: Clinicians treating postprocedure acute pain after third molar removal face a twofold challenge: attenuating pain levels while simultaneously limiting leftover opioid doses. Strategies for achieving the dual goals range from “letting patients decide,” which can lead to leftover doses and misuse, or “letting clinicians decide,” only prescribing opioids for those predicted to experience severe discomfort, which risks under-managing acute pain. A hybrid strategy relies on joint decision-making between the patient and clinician. The hypothesis for this IRB-approved prospective study was that a hybrid-strategy would be successful in moderating acute pain and reducing leftover opioid doses. Methods and Materials: This study included patients who met the American Society of Anesthesiologists, risk classification I or II, ages 18 to 35 years, with at least 2 mandibular third molars removed. Patients being treated for opioid addiction/abuse were excluded. All enrolled subject patients were consented and treated with a multimodal analgesic protocol consisting of intraoperative IV preventive antibiotics, dexamethasone, ketorolac, ondansetron, local anesthetics including liposomal bupivacaine and postoperative cold therapy, and scheduled ibuprofen. Patients were given 2 prescriptions (Rx), each for 4 doses of Hydrocodone/APAP 5/325, to be taken as needed for pain;1 Rx could be filled on the day of surgery, the second on any subsequent day. Opioid Rx data were retrieved from patient records and North Carolina Controlled Substances Reporting System. Pain scores and opioid-use data for each postsurgery day (PSD) were derived from a 14-day diary recorded by subjects. For the patients in this series, the goal was median pain levels ranked 1 or 2 on a 7-point scale, meaning no pain and minimal pain by postoperative day (POD) 3. Descriptive statistics were used for analyses. Results: Data were analyzed from 96 eligible patients treated consecutively from 2018 to 22, with a 15-month hiatus from COVID-19. Fifty-two patients (54%) did not fill an opioid prescription. Twenty-seven patients (28%) filled 1 opioid prescription and 17 patients (18%) filled 2 of the prescriptions. The patients who filled 1 prescription had 72 leftover doses (67% of possible doses), and the patients who filled 2 prescriptions had 50 leftover doses (74% of possible doses). Median worst pain levels reached 1 to 2 out of 7 on POD 4;median average pain on POD 3. Conclusions: The hybrid strategy reduced the number of opioid doses in circulation without compromising the patient's postoperative pain level. Decreasing the number of leftover opioid doses is an important step toward addressing opioid addiction and overdose. References: 1 Magraw CBL, Pham M, Neal T, Kendell B, Reside G, Phillips C, White RP Jr: A multimodal analgesic protocol may reduce opioid use after third molar surgery: A pilot study. Oral Surg Oral Med Oral Path Oral Radiol 126:214, 2018. 2 Pham M, Magraw C, Neal T, Kendell B, Reside G, Phillips C, White R: A Multi-modal Analgesic Protocol reduced opioid use/misuse after 3rd Molar Surgery: An Exploratory Study. Submitted Oral Surg Oral Med Oral Path Oral Radiol March 2019 3 Pham M, Magraw C, Neal T, Kendell B, Reside G, Phillips C, White R: A Multimodal Analgesic Protocol reduced acute pain levels after 3rd molar surgery. In preparation JOMS 4 White RP Jr, Shugars DA, Shafer DM, Laskin DM, Buckley MJ, Phillips C: Recovery after third molar surgery: clinical and health-related quality of life outcomes. J Oral and Maxillofacial Surgery 61:535, 2003. 5 American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 116:248, 2012 6-Savarese JJ, Tabler NG Jr: Multimodal analgesia as an alternative to the risks of opioid monotherapy in surgical pain management. J Health Care Risk Manag 37:24, 2017

Importance of ventilation and occupancy to Mycobacterium tuberculosis transmission rates in congregate settings.

BACKGROUND: Ventilation rates are a key determinant of the transmission rate of Mycobacterium tuberculosis and other airborne infections. Targeting infection prevention and control (IPC) interventions at locations where ventilation rates are low and occupancy high could be a highly effective intervention strategy. Despite this, few data are available on ventilation rates and occupancy in congregate locations in high tuberculosis burden settings. METHODS: We collected carbon dioxide concentration and occupancy data in congregate locations and public transport on 88 occasions, in Cape Town, South Africa. For each location, we estimated ventilation rates and the relative rate of infection, accounting for ventilation rates and occupancy. RESULTS: We show that the estimated potential transmission rate in congregate settings and public transport varies greatly between different settings. Overall, in the community we studied, estimated infection risk was higher in minibus taxis and trains than in salons, bars, and shops. Despite good levels of ventilation, infection risk could be high in the clinic due to high occupancy levels. CONCLUSION: Public transport in particular may be promising targets for infection prevention and control interventions in this setting, both to reduce Mtb transmission, but also to reduce the transmission of other airborne pathogens such as measles and SARS-CoV-2.

Universal SARS-CoV-2 Testing Among Obstetrical Patients (UNIVERSE-OB) in Ottawa, Canada

Objectives: Universal testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within birthing units is an effective strategy to contain infection and estimate community prevalence. Given the high-prevalence of COVID-19 cases in Ontario, the objective of this study was to determine the prevalence of active and recovered SARS-CoV-2 infection among pregnant individuals in Ottawa through universal SARS-CoV-2 and serology testing. Methods: From October 19th to November 27th, 2020, pregnant individuals admitted to triage assessment units at The Ottawa Hospital (TOH) were consented for SARS-CoV-2 testing. Swab and serology samples were analyzed using digital droplet polymerase chain reaction (ddPCR) and enzyme-linked immunosorbent assays, respectively. SARS-CoV-2 seropositivity was defined as a positive result for immunoglobulin (Ig) G, either alone or in combination with IgM and/or IgA. Results: From the 395 enrolled participants, 284 swab and 353 serology samples were collected. We found that 18 of 395 (4.6%) participants had evidence of SARS-CoV-2 exposure: 2/284 (0.70%) were positive for SARS-CoV-2 and 16/353 (4.5%) were positive for anti–SARS-CoV-2 IgG. Seropositive participants were similar to seronegative participants in terms of demographics, clinical characteristics, and pregnancy outcomes. Conclusions: The prevalence of SARS-CoV-2 ddPCR positivity and seropositivity in the obstetrical population at TOH was 0.70% and 4.5%, respectively in the fall of 2020. According to local public health data, the infection rate peaked at 0.6% during the study time period. Universal SARS-CoV-2 testing programs may help approximate community prevalence, however, justification of this strategy depends on testing capabilities and the local context of COVID-19 infection. Keywords: pregnancy;COVID-19;SARS-CoV-2;universal testing;seroprevalence

Cardiac Effort to Compare Clinic and Remote 6-Minute Walk Testing in Pulmonary Arterial Hypertension.

BACKGROUND: The SARS-CoV-2 pandemic has limited objective physiologic assessments. A standardized remote alternative is not currently available. "Cardiac effort" (CE), that is, the total number of heart beats divided by the 6-minute walk test (6MWT) distance (beats/m), has improved reproducibility in the 6MWT and correlated with right ventricular function in pulmonary arterial hypertension. RESEARCH QUESTION: Can a chest-based accelerometer estimate 6MWT distance remotely? Is remote cardiac effort more reproducible than 6MWT distance when compared with clinic assessment? STUDY DESIGN AND METHODS: This was a single-center, prospective observational study, with institutional review board approval, completed between October 2020 and April 2021. Group 1 subjects with pulmonary arterial hypertension, receiving stable therapy for > 90 days, completed four to six total 6MWTs during a 2-week period to assess reproducibility. The first and last 6MWTs were performed in the clinic; two to four remote 6MWTs were completed at each participant's discretion. Masks were not worn. BioStamp nPoint sensors (MC10) were worn on the chest to measure heart rate and accelerometry. Two blinded readers counted laps, using accelerometry data obtained on the clinic or user-defined course. Averages of clinic variables and remote variables were used for Wilcoxon matched-pairs signed rank tests, Bland-Altman plots, or Spearman correlation coefficients. RESULTS: Estimated 6MWT distance, using the MC10, correlated strongly with directly measured 6MWT distance (r = 0.99; P < .0001; in 20 subjects). Remote 6MWT distances were shorter than clinic 6MWT distances: 405 m (330-464 m) vs 389 m (312-430 m) (P = .002). There was no difference between in-clinic and remote CE: 1.75 beats/m (1.48-2.20 beats/m) vs 1.86 beats/m (1.57-2.14 beats/m) (P = .14). INTERPRETATION: Remote 6MWT was feasible on a user-defined course; 6MWT distance was shorter than clinic distance. CE calculated by chest heart rate and accelerometer-estimated distance provides a reproducible remote assessment of exercise tolerance, comparable to the clinic-measured value.

Long-term effectiveness of Self-Help Plus in refugees and asylum seekers resettled in Western Europe: 12-month outcomes of a randomised controlled trial.

AIMS: As refugees and asylum seekers are at high risk of developing mental disorders, we assessed the effectiveness of Self-Help Plus (SH + ), a psychological intervention developed by the World Health Organization, in reducing the risk of developing any mental disorders at 12-month follow-up in refugees and asylum seekers resettled in Western Europe. METHODS: Refugees and asylum seekers with psychological distress (General Health Questionnaire-12 ⩾ 3) but without a mental disorder according to the Mini International Neuropsychiatric Interview (M.I.N.I.) were randomised to either SH + or enhanced treatment as usual (ETAU). The frequency of mental disorders at 12 months was measured with the M.I.N.I., while secondary outcomes included self-identified problems, psychological symptoms and other outcomes. RESULTS: Of 459 participants randomly assigned to SH + or ETAU, 246 accepted to be interviewed at 12 months. No difference in the frequency of any mental disorders was found (relative risk [RR] = 0.841; 95% confidence interval [CI] 0.389-1.819; p-value = 0.659). In the per protocol (PP) population, that is in participants attending at least three group-based sessions, SH + almost halved the frequency of mental disorders at 12 months compared to ETAU, however so few participants and events contributed to this analysis that it yielded a non-significant result (RR = 0.528; 95% CI 0.180-1.544; p-value = 0.230). SH + was associated with improvements at 12 months in psychological distress (p-value = 0.004), depressive symptoms (p-value = 0.011) and wellbeing (p-value = 0.001). CONCLUSIONS: The present study failed to show any long-term preventative effect of SH + in refugees and asylum seekers resettled in Western European countries. Analysis of the PP population and of secondary outcomes provided signals of a potential effect of SH + in the long-term, which would suggest the value of exploring the effects of booster sessions and strategies to increase SH + adherence.

Cardiac Effort Provides a Reproducible Remote Assessment of 6-Minute Walk Test

Rationale: 'Cardiac Effort' (CE), the total number of heart beats used during the 6-minute walk test (6MWT) divided by walk distance (beats/m), improves reproducibility in the 6MWT and correlates with right ventricular function in pulmonary arterial hypertension (PAH). The SARS-CoV-2 pandemic made in-office 6MWT challenging. We aimed to determine 1) whether a chestbased accelerometer could estimate 6MWT distance in the clinic and remotely;2) the reproducibility of CE measured during a remote 6MWT;and 3) the safety of remote 6MWT. We also compared measures of heart rate (HR) derived from electrocardiogram (ECG) and wrist-based photoplethysmography (PPG) during the 6MWT in PAH. Methods: This was a singlecenter, prospective observational study with IRB approval completed October 2020-April 2021. Group 1 PAH subjects on stable therapy for >90 days completed 4-6 total 6MWT during a 2 week period to assess reproducibility;we anticipated no clinical change during this short interval. The first and last 6MWT were performed in the clinic;2-4 remote 6MWT were completed at participant's discretion. Participants did not wear masks but did wear the MC10 Biostamp nPoint sensors to measure ECG HR and accelerometry. Two blinded readers estimated 6MWT distance using raw accelerometry data. We measured PPG HR with a wrist Nonin 3150 pulse oximeter during clinic 6MWT only. Averages of clinic variables and remote variables were used for paired Student's t test, Bland-Altman Plot, or Pearson correlation. Results: We enrolled 20 participants: 80% female;60% connective tissue disease;and 65% on initial combination therapy with ambrisentan and tadalafil. There was a wide range in baseline, clinicperformed 6MWT distance (220 -570 m). The median length of the remote 'hallway' was 40 ft. For clinic walks, there was 0.10% average difference between the directly observed and Biostamp accelerometry-estimated 6MWT distance with a strong correlation of r=0.99, p<0.0001 (figure 1). The 6MWT distance estimated using Biostamp in the clinic was greater than what was estimated remotely, 405 m vs. 389 m, p=0.007. There was no clear difference between clinic or remote CE, 1.83 beats/m vs 1.93 beats/m, p=0.14, or Borg Dyspnea Index, 3.5 vs 3.4, p=0.35. There were no safety concerns. PPG undercounted total HR expenditure during 6MWT compared to Biostamp (629 vs 719, p<0.0001). Conclusion: Remote 6MWT was feasible, appeared safe, and 6MWT distance was shorter than clinic distance. CE calculated by ECG HR and accelerometer-estimated distance provides a reproducible remote assessment of exercise tolerance, comparable to the clinic measured value. (Figure Presented).

Trends in Front of Neck Access - A bibliometric analysis

Background: Front of Neck Access (FONA) is a critical skill Anaesthetists must be able to perform in the 'Can't Intubate, Can't oxygenate' (CICO) scenario, and is a core technical skill ANZCA registrars must develop during training (ANZCA 2020). However, since the Covid-19 pandemic, opportunities for first hand emergency airway experience have reduced. To gain an understanding of trends in the field of FONA and to guide future advancement, we conducted a bibliometric analysis of the 100 most cited papers for Front of Neck Access. Methods: The Thomas Reuters Web of Science database was searched on 13th of June 2021 using the terms;“Front of Neck Access”, “FONA”, “Cricothyroidotomy”, “Surgical cricothyroidotomy”, “Scalpel Cricothyroidotomy”, “Needle Cricothyroidotomy”. The 100 most cited papers relevant to FONA were analysed by design, topic, author, publication year and institution. The journal impact factor for the year 2019 along with Eigenfactor scores were recorded. Results: A total of 787 papers were retrieved from our search. These were ranked by total number of citations. The median number of citations for the top 100 articles was 56.5 (IQR 28), with 44% of articles originating from the USA. The top five cited papers made up 37% of total citations. Anesthesia (n=9) and The British Journal of Anesthesia (n=9) had the greatest number of papers, whilst the greatest number of citations came from Academic Emergency Medicine (n=2456). The years 2011 (n=9) and 2015 (n=9) had the greatest number of papers published. Technique for emergent FONA was the most common theme. Conclusions: The most influential articles in the FONA literature have each been cited at least 35 times, reflecting considerable impact and quality. The USA has produced most research in this area, allowing the widespread dispersion of indications, technique and guidelines at a time when practical experience may be limited due to the pandemic.

Transitioning selexipag to oral treprostinil in patients with pulmonary artery hypertension.

There are no prospective studies or guidelines describing transition between selexipag and oral treprostinil. We present two different transition strategies from selexipag to oral treprostinil, one started inpatient and then completed at home, and one completely under outpatient settings. Neither patient experienced worsening prostacyclin-type adverse effects; both were rigorous in their attention to a 7-8 hour administration schedule for oral treprostinil, and both experienced objective clinical benefit at follow-up. Prospective studies are needed to help guide clinical decisions when patients remain intermediate risk after a trial of either drug.

Oral treprostinil improves pulmonary vascular compliance in pulmonary arterial hypertension.

Oral treprostinil has been shown to improve exercise capacity and delay disease progression in patients with pulmonary arterial hypertension (PAH), but its effects on hemodynamics are not well-characterized. The FREEDOM-EV trial was a Phase III, international, placebo-controlled, double-blind, event-driven study in 690 participants with PAH who were taking a single oral PAH therapy. FREEDOM-EV demonstrated a significantly reduced risk for clinical worsening with oral treprostinil taken three times daily and did not uncover new safety signals in PAH patients. Sixty-one participants in the FREEDOM-EV trial volunteered for a hemodynamics sub-study. Pulmonary artery compliance (PAC), a ratio of stroke volume to pulmonary pulse pressure, significantly increased from Baseline to Week 24 in the oral treprostinil group compared with the placebo group (geometric mean 26.4% active vs. -6.0% placebo; ANCOVA p=0.007). There was a significant increase in cardiac output in the oral treprostinil group compared to the placebo group (geometric mean 11.3% active vs. -6.4% placebo; ANCOVA p=0.005) and a corresponding significant reduction in pulmonary vascular resistance (PVR) (geometric mean -21.5 active vs. -1.8% placebo; ANCOVA p=0.02) from Baseline to Week 24. These data suggest that increased compliance contributes to the physiological mechanism by which oral treprostinil improves exercise capacity and delays clinical worsening for patients with PAH.

A multi-institutional study of the impact of the COVID-19 pandemic on pancreatic cancer diagnosis and management

Background: The impact of COVID-19 on cancer patients may be attributed not only to its direct effects on the immune system but also to delays in diagnosis and treatment. Data on the effects of COVID-19 on pancreatic ductal adenocarcinoma (PDAC) patients are scarce. Therefore, we set out to determine the impact of the pandemic on diagnosis and treatment initiation. We hypothesized that time from diagnosis to treatment would be increased in the COVID era compared to the pre-COVID era. Methods: We conducted an IRB-approved retrospective chart review of 488 patients diagnosed with PDAC from March 2019 to September 2020 at two academic medical centers. Patients were divided into two groups, based on the date of initial pathologic diagnosis. We defined the pre-COVID era as March 2019 to March 2020, the 12-month time period before California's statewide lockdown. The COVID era was defined as the 6 months following the lockdown, March 2020 to September 2020. Demographics, clinical stage, and treatment type were recorded. In addition, initial clinical encounter date, pathologic diagnosis date, and initial treatment date were also collected. All data were gathered at two large-scale academic institutions. Descriptive statistics were used in the analysis. Results: There were 333 patients diagnosed during the pre-COVID era and 155 patients during the COVID era. While race/ethnicity and age at diagnosis were statistically similar for both groups, females made up a significantly larger proportion of COVID era patients than preCOVID era patients (p= 0.02). There was no significant difference in clinical stage at diagnosis between the two groups (p= 0.84). In the pre-COVID era, 19.5% of cases were resectable, 11.1% borderline resectable, 20.1% locally advanced, and 31.8% metastatic. In the COVID era, 17.4% of patients were resectable, 11% borderline resectable, 23.9% locally advanced, and 32.9% metastatic. Median time from pathologic diagnosis to initiation of treatment was 32 days for the pre-COVID era patients and 28 days for the COVID era patients (p= 0.38). Initial treatment type was also similar between the two groups (p= 0.29). Conclusions: Fortunately, our data indicate that the COVID-19 pandemic has not significantly prevented PDAC patients from seeking care. Additionally, it does not appear that COVID-19 has delayed treatment initiation or changed initial treatment type. We believe that the successful adoption of telemedicine and other safety protocols have allowed patients with PDAC to continue receiving appropriate care during the pandemic.

To Work from Home (WFH) or Not to Work from Home? Lessons Learned by Software Engineers During the COVID-19 Pandemic

This research investigates software engineering during the COVID-19 pandemic with a focus on the lessons learned and predictions for future software engineering work. Four themes are explored: Remote work, Team management, Work/Life balance, and Technology/Software Engineering Methods. Our research has demonstrated that software companies will derive tangible benefits from supporting their employees during this uncertain time through ergonomic home offices, listening to their concerns, as well as encouraging breaks and hard stops to boost long term well-being and productivity. It shows that communication and collaboration tools, critical to project success, have been utilised. The hiring of new talent has been reimagined, with managers playing a vital role in the process. The insights gained are significant as they will assuage some pre-existing concerns regarding remote work, creating a new understanding of its role in the future. Looking to a post-COVID-19 future, we envision the rise of hybrid software development working arrangements, with a focus on the Working-From-Home to Not-Working-From-Home ratio - WFH: NWFH - perhaps colloquialised as Home: Not Home (HNH). For many this ratio will be neither 100:0 or 0:100, the former would lead to team breakdowns, developer isolation, difficulties onboarding and too many communication gaps, the latter would lead to disaffected employees. We identify plausible future software engineering working arrangements, noting that there are challenging times ahead for employers and employees as they navigate this HNH future, but there are benefits for both parties in getting the balance right. © 2021, Springer Nature Switzerland AG.

Global impact of the COVID-19 pandemic on stroke care and intravenous thrombolysis

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods. Background: The COVID-19 pandemic led to widespread repercussions on the delivery of health care worldwide. Design/Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by ICD-10 codes and/or classifications in stroke center databases. Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI,-11.7 to-11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI,-13.8 to-12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI,-13.7 to-10.3, p=0.001). There were greater declines in primary compared to comprehensive stroke centers (CSC) for stroke hospitalizations (-17.3% vs-10.3%, p<0.0001) and IVT (-15.5% vs-12.6%, p=0.0001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) months of the pandemic, with greater recovery in hospitals with lower COVID-19 hospitalization volume, high volume stroke center, and CSC. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months, with greater recovery in hospitals with lower COVID-19 hospitalizations, high volume stroke centers, and CSCs.