Gender equity of authorship in pulmonary medicine over the past decade.

BACKGROUND: Gender disparity in authorship broadly persists in medical literature, little is known about female authorship within pulmonary medicine. METHODS: A bibliometric analysis of publications from 2012 to 2021 in 12 journals with the highest impact in pulmonary medicine was conducted. Only original research and review articles were included. Names of the first and last authors were extracted and their genders were identified using the Gender-API web. Female authorship was described by overall distribution and distribution by country/region/continent and journal. We compared the article citations by gender combinations, evaluated the trend in female authorship, and forecasted when parity for first and last authorship would be reached. We also conducted a systematic review of female authorship in clinical medicine. RESULTS: 14,875 articles were included, and the overall percentage of female first authors was higher than last authors (37.0% vs 22.2%, p<0.001). Asia had the lowest percentage of female first (27.6%) and last (15.2%) authors. The percentages of female first and last authors increased slightly over time, except for a rapid increase in the COVID-19 pandemic periods. Parity was predicted in 2046 for the first authors and 2059 for the last authors. Articles with male authors were cited more than articles with female authors. However, male-male collaborations significantly decreased, whereas female-female collaborations significantly increased. CONCLUSIONS: Despite the slow improvement in female authorship over the past decade, there is still a substantial gender disparity in female first and last authorship in high-impact medical journals in pulmonary medicine.

Increasing incidence of lung transplantation in patients with post-COVID-19 pulmonary fibrosis.

Twenty months into the COVID-19 pandemic, we are still learning about the various long-term consequences of COVID-19 infection. While many patients do recover with minimal long-term consequences, some patients develop irreversible parenchymal and interstitial lung damage leading to diffuse pulmonary fibrosis. Unfortunately, these are some of the consequences of post-SARS-CoV-2 infection which thousands more people around the world will experience and which will outlast the pandemic for a long time to come. It is now being observed at various leading medical centres around the world that lung transplantation may be the only meaningful treatment available to a select group of patients experiencing serious lung damage and non-resolving COVID-19-associated respiratory failure, resulting from the triad of coronavirus infection, a hyper-inflammatory immune response to it and the inability of the human body to repair that injury.

Baricitinib against severe COVID-19: effectiveness and safety in hospitalised pretreated patients.

OBJECTIVES: To analyse the effectiveness and safety of baricitinib for severe COVID-19 in cytokine storm syndrome based on its potential role as an anti-inflammatory immunomodulator and inhibitor of viral endocytosis. METHODS: This was an observational retrospective study of hospitalised patients treated with baricitinib for severe COVID-19. Outcomes were clinical improvement on an ordinal scale of 1-8 on day 1 of baricitinib compared with day 14 (where 8=death and 1=not hospitalised with no limitations of activities), overall survival, time to recovery since baricitinib treatment started (days until hospital discharge) and laboratory parameters related to COVID-19 poor prognosis. Adverse events related to baricitinib during the admission period were also reported. RESULTS: Forty-three patients (70% men, mean age 70 years (IQR 54-79)) treated with baricitinib daily for 6 days (IQR 5-7) were included. Thirty-six patients were treated with corticosteroids (84%). Clinical improvement was 3 points (IQR 1-4) in patients on an ordinal scale of 4-6, overall survival was 100% at day 30 and day 60 with a mean time to recovery of 12 days (IQR 9-25) from start of baricitinib treatment. No adverse events of interest were found and all poor prognosis risk factors improved at day 14: interleukin-6, C-reactive protein, ferritin, lymphocytes, platelets and D-dimers. CONCLUSIONS: Patients treated with baricitinib for severe COVID-19 showed improvements in clinical and analytical values without relevant adverse events and 100% overall survival. Clinical randomised trials are needed to confirm the clinical benefit of baricitinib.

The dynamics in applied COVID-19 pharmacotherapy and the influence of national guidance in The Netherlands: a quantitative and qualitative study.

OBJECTIVE: At the beginning of the COVID-19 pandemic in the Netherlands, the Dutch Working Party on Antibiotic Policy constructed an advisory document about off-label drug treatment options that was regularly updated with new scientific findings. The aim of this study is to describe the dynamics in applied COVID-19 pharmacotherapy during the first 100 days of the pandemic and to assess how the national advisory document influenced local hospital policies. METHODS: A multicentre observational cohort study was conducted in six hospitals in the Netherlands. Patients with confirmed COVID-19 admitted between 27 February and 7 June 2020 were studied. Drug prescription data were collected and percentages of patients receiving a specific treatment were calculated. These percentages were plotted together with release dates of the national advisory document. Semi-structured in-depth interviews with hospital pharmacists and infectious diseases specialists were conducted to gain insight into the development and implementation of pharmacotherapy treatment protocols in hospitals. RESULTS: Data from 1511 patients (60% men, mean age 66 years) were analysed. From mid-March (hydroxy)chloroquine was being prescribed in all six hospitals to approximately 70% of patients at admission. Frequencies of other off-label treatments were below 2%. In the week of 6 April 2020, the first hospital discontinued prescribing (hydroxy)chloroquine and the last hospital discontinued in the week of 4 May 2020 (total range -19 to +10 days after the national advisory document advised against its use (1 May 2020)). All interviewees (n=6) stated that the hospitals based their policies mainly on the national advisory document but also assessed scientific literature themselves. Order panels were constructed to support prescribing. CONCLUSION: Dutch hospitals opted en masse for (hydroxy)chloroquine as COVID-19 therapy at the start of the pandemic, although the time until the therapy was no longer prescribed differed by several weeks. The fact that hospitals defined pharmacotherapy regimens based on their own assessment of the scientific literature besides the national advisory document can explain this variation.

Administration of benralizumab in a patient with severe asthma admitted to the intensive care unit with COVID-19 pneumonia: case report.

A patient with severe asthma on benralizumab therapy was admitted to the intensive care unit (ICU) for a coronavirus disease 2019 (COVID-19) infection. At the end of the 8 week benralizumab dosing interval, discussion arose as to whether benralizumab should be administered or if treatment should be discontinued, due to the lack of experience with benralizumab in this situation. Severe broncho-obstruction developed, and the next injection of benralizumab was administered during ICU admission without detrimental symptoms. With this case report, we would like to share our experience with the safe administration of benralizumab during COVID-19 pneumonia, guiding doctors in future decision making.

Airflow dispersion during common neonatal resuscitation procedures: A simulation study.

BACKGROUND: Aerosol generating medical procedures (AGMPs) are common during newborn resuscitation. Neonates with respiratory viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may pose a risk to healthcare workers. International guidelines differ on methods to minimize the risk due to limited data. OBJECTIVE: We examined the expiratory airflow dispersion during common neonatal resuscitation AGMPs using infant simulators. METHODS: Expiratory airflow dispersion in term and preterm manikins was simulated (n = 288) using fine particle smoke at tidal volumes of 5 ml/kg. Using ImageJ, we quantified dispersion during common airway procedures including endotracheal tube (ETT) and T-piece ventilation. RESULTS: Maximal expiratory dispersion distances for the unsupported airway and disconnected uncuffed ETT scenarios were 30.2 and 22.7 cm (term); 22.1 and 17.2 cm (preterm), respectively. Applying T-piece positive end expiratory pressure (PEEP) via an ETT (ETTPEEP ) generated no expiratory dispersion but increased tube leak during term simulation, while ventilation breaths (ETTVENT ) caused significant expiratory dispersion and leak. There was no measurable dispersion during face mask ventilation. For term uncuffed ETT ventilation, the particle filter eliminated expiratory dispersion but increased leak. No expiratory dispersion and negligible leak were observed when combining a cuffed ETT and filter. Angulated T-pieces generated the greatest median dispersion distances of 35.8 cm (ETTPEEP ) and 23.3 cm (ETTVENT ). CONCLUSIONS: Airflow dispersion during neonatal AGMPs is greater than previously postulated and potentially could contaminate healthcare providers during resuscitation of infants infected with contagious viruses such as SARS-CoV-2. It is possible to mitigate this risk using particle filters and cuffed ETTs. Applicability in the clinical setting requires further evaluation.

COVID-19 in childhood: Transmission, clinical presentation, complications and risk factors.

Children less than 18 years of age account for an estimated 2%-5% of reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases globally. Lower prevalence of coronavirus disease 2019 (COVID-19) among children, in addition to higher numbers of mild and asymptomatic cases, continues to provide challenges in determining appropriate prevention and treatment courses. Here, we summarize the current evidence on the transmission, clinical presentation, complications and risk factors in regard to SARS-CoV-2 in children, and highlight crucial gaps in knowledge going forward. Based on current evidence, children are rarely the primary source of secondary transmission in the household or in child care and school settings and are more likely to contract the virus from an adult household member. Higher transmission rates are observed in older children (10-19 years old) compared with younger children ( <10 years old). While increasing incidence of COVID-19 in neonates raises the suspicion of vertical transmission, it is unlikely that breast milk is a vehicle for transmission from mother to infant. The vast majority of clinical cases of COVID-19 in children are mild, but there are rare cases that have developed complications such as multisystem inflammatory syndrome in children, which often presents with severe cardiac symptoms requiring intensive care. Childhood obesity is associated with a higher risk of infection and a more severe clinical presentation. Although immediate mortality rates among children are low, long-term respiratory, and developmental implications of the disease remain unknown in this young and vulnerable population.

Does timing matter on tocilizumab administration? Clinical, analytical and radiological outcomes in COVID-19.

INTRODUCTION: While there are no pharmacological treatments with proven efficacy for coronavirus disease 2019 (COVID-19), tocilizumab has emerged as a candidate therapy. Some aspects of this therapy are still unknown, including the optimal timing of administration. OBJECTIVE: This observational study aimed to compare the 90-day mortality in two cohorts of patients when the drug was administered within the first 10 days from onset of symptoms or after day 11. METHODS: Patients hospitalised with severe COVID-19 pneumonia who had received tocilizumab were divided into two groups according to when the medication was administered. The primary outcome was 90-day mortality. Secondary outcomes were 30-day mortality, clinical improvement on a 6-item scale by day 6, biomarker improvement by day 6, radiological image improvement by day 10 and SaO₂ quotient by day 6. The results in the two groups were compared. Additionally, adverse events relating to tocilizumab were recorded. RESULTS: A total of 112 patients were analysed. Both groups were epidemiologically comparable. The results obtained in the primary efficacy variable of the study (90-day mortality) showed a statistically significant difference in the subgroups according to the time of administration of tocilizumab (18.6% vs 5.0%, p=0.048). There was clinical improvement in 24.1% of patients at 6 days, with similar behaviour in both subgroups. No statistically significant differences were found in the percentage of patients who achieved radiological improvement at 10 days or in the other inflammatory parameters, with the exception of significant reductions in lactate dehydrogenase and C-reactive protein. Administration of tocilizumab was not associated with relevant adverse events. CONCLUSION: To our knowledge, this is the first report of data regarding the timing of administration of tocilizumab in patients with COVID-19 pneumonia. A strategy involving tocilizumab administration after 10 days from onset of symptoms may decrease mortality. Further randomised controlled trials are needed to confirm this emerging hypothesis.

Observational study on off-label use of tocilizumab in patients with severe COVID-19.

BACKGROUND: In December 2019 a novel coronavirus designated SARS-CoV-2 was identified, and the disease COVID-19 has caused many deaths. SARS-CoV-2 infection has been associated with the development of cytokine storm (including interleukin 6 (IL-6)), which can cause lung damage and lack of oxygen. Tocilizumab (TCZ) inhibits ligand binding to the IL-6 receptor and may be a potential treatment for the hyperinflammation symptoms of COVID-19. However, data regarding the efficacy of TCZ in COVID-19 are lacking. The rapid spread of the pandemic in France, especially in the Paris region, constrained us to the off-label use of TCZ in patients with severe clinical conditions. METHODS: A single-centre observational cohort study of 44 patients infected with COVID-19 was carried out between 6 April and 21 April 2020 in Groupe Hospitalier Intercommunal Le Raincy-Montfermeil (GHILRM). Twenty-two patients diagnosed with COVID-19 were treated with TCZ and were compared with 22 patients not treated with TCZ matched for age, gender and length of hospital stay for COVID-19. Respiratory rate and oxygen supplementation as well as laboratory parameters (such as C-reactive protein (CRP), aspartate aminotransferase and alanine aminotransferase) were collected at baseline and during 14 days of follow-up. Our primary objective was to assess the efficacy of TCZ on respiratory clinical conditions. FINDINGS: The average respiratory rate was lower in the TCZ group than in the control group (21.5 vs 25.5 breaths/min at day 14, 95% CI -7.5 to -0.4; p=0.03). Treated patients tended to be intubated less during the course of the disease (2/22 vs 6/22, 95% CI -0.4 to 0.1; p=0.12). In each group, 10 patients no longer required oxygen therapy. We found a significant decrease in CRP in treated patients on day 7 (p=0.04). TCZ caused cytolysis in more than half (14/22) of the patients but without clinical impact. INTERPRETATION: There was a significant difference in the respiratory rate on day 14 of follow-up, with a greater decrease observed in the treated group. Fewer patients required mechanical ventilation in the TCZ group, especially among patients with more extensive CT lung damage, than in the control group. The same number of patients were weaned off oxygen on day 14 in the two groups, while the patients in the TCZ group had more severe impairment at inclusion. We consider that TCZ showed significant control of the biological inflammatory syndrome, suggesting that it may limit the effect of the cytokine storm. Our study seems to indicate the efficacy of TCZ, particularly in patients with severe initial pulmonary impairment. Selecting the best candidates and the best timing for TCZ therapy needs to be determined in randomised clinical trials.

Pulmonary Therapy 2020 Update and Podcast: Meet the Journal's Editors-in-Chief.

The Editors-in-Chief of Pulmonary Therapy have prepared podcasts summarizing their current research, recent highlights from the field, and future predictions. Audio-only versions and the transcripts can be downloaded here: https://doi.org/10.6084/m9.figshare.11938863. Following this is a written summary of the journal's recent developments and the transcripts from the podcasts.