Using Randomized Controlled Trials in the Sports Medicine and Performance Environment: Is It Time to Reconsider and Think Outside the Methodological Box?

SYNOPSIS: Randomized controlled trials (RCTs) are ubiquitous in medicine and have facilitated great strides in clinical care. However, when applied in sport, RCTs have limitations that hinder implementing effective interventions in the real-world clinical setting. Pragmatic clinical trials offer some solutions. Yet due to the competitive, high-pressure nature of sport at the individual, team, and governing body level, RCTs are likely infeasible in certain sport settings. The small number of athletes at the elite team level, along with the potential financial consequences of randomizing at the individual athlete and team level, also restricts study power and feasibility, limiting conclusions. Consequently, researchers may need to "think outside the box" and consider other research methodology, to help improve athlete care. In this Viewpoint, we detail alternative study designs that can help solve real-world problems in sports medicine and performance, while maintaining robust research standards and accounting for the challenges that RCTs pose. We also provide practical examples of alternative designs. J Orthop Sports Phys Ther 2023;53(6):1-4. Epub: 18 April 2023. doi:10.2519/jospt.2023.11824.

Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes.

SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness, although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 postmortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID postmortem controls. SARS-CoV-2 anti-NP staining in the postmortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE2 expression, the entry receptor for SARS-CoV-2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS-CoV-2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms with the organ tropism of SARS-CoV-2 in contemporary cases as well as providing insights into potential long-term complications of COVID-19. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Histological findings of tracheal samples from COVID-19 positive critically ill mechanically ventilated patients.

OBJECTIVES: This study examines the histological findings of tracheal tissue samples obtained from COVID-19 positive mechanically ventilated patients, to assess the degree of tracheal inflammation/ulceration present. DESIGN AND PARTICIPANTS: Retrospective single-centre observational cohort study. All patients admitted to Adult Intensive Care Unit (AICU) with COVID-19 infection, requiring mechanical ventilation and surgical tracheostomy between 1 April and 1 May 2020, were included (Group 1). Tracheal windows excised at tracheostomy underwent histological analysis. Comparison was made with: tracheal windows from COVID-19 positive AICU ventilated patients admitted between 1 January and 1 March 2021 (Group 2); tracheal windows from COVID-19 negative AICU ventilated patients (Group 3); and, tracheal autopsy samples from COVID-19 positive patients that died without undergoing prolonged mechanical ventilation (Group 4). RESULTS: Group 1 demonstrated mild/moderate inflammation (tracheitis) in nearly all samples (15/16, 93.8%), with infrequent micro-ulceration (2/16, 12.5%). Group 2 demonstrated similar mild/moderate inflammation in all samples (17/17, 100%), with no ulceration. Histological findings of Groups 1 and 2 COVID-19 positive patients were similar to Group 3 COVID-19 negative patients, which demonstrated mild/moderate inflammation (5/5, 100%), with uncommon superficial erosion (1/5, 20%). Group 4 demonstrated mild chronic inflammation or no significant inflammation, with uncommon micro-ulceration (1/4, 25%). CONCLUSIONS: Severe tracheal inflammation was not demonstrated in mechanically ventilated COVID-19 positive patients at the level of the second/third tracheal rings, at the stage of disease patients underwent tracheostomy. Histological findings were similar between mechanically ventilated COVID-19 positive and negative patients. Tracheal ulceration may be a feature of early or severe COVID-19 disease.

Surgical Tracheostomy Outcomes in COVID-19-Positive Patients.

OBJECTIVE: The aim of this case series was to demonstrate that surgical tracheostomy can be undertaken safely in critically ill mechanically ventilated patients with coronavirus disease 2019 (COVID-19) and that it is an effective weaning tool. STUDY DESIGN: Retrospective case series. SETTING: Single academic teaching hospital in London. METHODS: All adult patients admitted to the adult intensive care unit (AICU), diagnosed with severe COVID-19 infection and requiring surgical tracheostomy between the March 10, 2020, and May 1, 2020, were included. Data collection focused upon patient demographics, AICU admission data, tracheostomy-specific data, and clinical outcomes. RESULTS: Twenty patients with COVID-19 underwent surgical tracheostomy. The main indication for tracheostomy was to assist in respiratory weaning. Patients had undergone mechanical ventilation for a median of 16.5 days prior to surgical tracheostomy. Tracheostomy remained in situ for a median of 12.5 days. Sixty percent of patients were decannulated at the end of the data collection period. There were no serious immediate or short-term complications. Surgical tracheostomy facilitated significant reduction in intravenous sedation at 48 hours after tracheostomy formation. There was no confirmed COVID-19 infection or reported sickness in the operating surgical or anesthetic teams. CONCLUSION: Surgical tracheostomy has been demonstrated to be an effective weaning tool in patients with severe COVID-19 infection.

Emergency Tracheal Intubation in Patients with COVID-19: Experience from a UK Centre.

This retrospective observational case series describes a single centre's preparations and experience of 53 emergency tracheal intubations in patients with COVID-19 respiratory failure. The findings of a contemporaneous online survey exploring technical and nontechnical aspects of airway management, completed by intubation team members, are also presented. Preparations included developing a COVID-19 intubation standard operating procedure and checklist, dedicated airway trolleys, a consultant-led mobile intubation team, and an airway education programme. Tracheal intubation was successful in all patients. Intubation first-pass success rate was 85%, first-line videolaryngoscopy use 79%, oxygen desaturation 49%, and hypotension 21%. Performance was consistent across all clinical areas. The main factor impeding first-pass success was larger diameter tracheal tubes. The majority of intubations was performed by consultant anaesthetists. Nonconsultant intubations demonstrated higher oxygen desaturation rates (75% vs. 45%, p=0.610) and lower first-pass success (0% vs. 92%, p < 0.001). Survey respondents (n = 29) reported increased anxiety at the start of the pandemic, with statistically significant reduction as the pandemic progressed (median: 4/5 very high vs. 2/5 low anxiety, p < 0.001). Reported procedural/environmental challenges included performing tasks in personal protective equipment (62%), remote-site working (48%), and modification of normal practices (41%)-specifically, the use of larger diameter tracheal tubes (21%). Hypoxaemia was identified by 90% of respondents as the most challenging patient-related factor during intubations. Our findings demonstrate that a consultant-led mobile intubation team can safely perform tracheal intubation in critically ill COVID-19 patients across all clinical areas, aided by thorough preparation and training, despite heightened anxiety levels.

Antiviral activity of a novel mixture of natural antimicrobials, in vitro, and in a chicken infection model in vivo.

The aim of this study was to test in vitro the ability of a mixture of citrus extract, maltodextrin, sodium chloride, lactic acid and citric acid (AuraShield L) to inhibit the virulence of infectious bronchitis, Newcastle disease, avian influenza, porcine reproductive and respiratory syndrome (PRRS) and bovine coronavirus viruses. Secondly, in vivo, we have investigated its efficacy against infectious bronchitis using a broiler infection model. In vitro, these antimicrobials had expressed antiviral activity against all five viruses through all phases of the infection process of the host cells. In vivo, the antimicrobial mixture reduced the virus load in the tracheal and lung tissue and significantly reduced the clinical signs of infection and the mortality rate in the experimental group E2 receiving AuraShield L. All these effects were accompanied by a significant reduction in the levels of pro-inflammatory cytokines and an increase in IgA levels and short chain fatty acids (SCFAs) in both trachea and lungs. Our study demonstrated that mixtures of natural antimicrobials, such AuraShield L, can prevent in vitro viral infection of cell cultures. Secondly, in vivo, the efficiency of vaccination was improved by preventing secondary viral infections through a mechanism involving significant increases in SCFA production and increased IgA levels. As a consequence the clinical signs of secondary infections were significantly reduced resulting in recovered production performance and lower mortality rates in the experimental group E2.