Acute Impact of Inhaled Short Acting B2-Agonists on 5 Km Running Performance

Whilst there appears to be no ergogenic effect from inhaled salbutamol no study has investigated the impact of the acute inhalation of 1600 µg, the World Anti-Doping Agency (WADA) daily upper limit, on endurance running performance. To investigate the ergogenic effect of an acute inhalation of short acting β₂-agonists at doses up to 1600 µg on 5 km time trial performance and resultant urine concentration. Seven male non-asthmatic runners (mean ± SD; age 22.4 ± 4.3 years; height 1.80 ± 0.07 m; body mass 76.6 ± 8.6 kg) provided written informed consent. Participants completed six 5 km time-trials on separate days (three at 18 °C and three at 30 °C). Fifteen minutes prior to the initiation of each 5 km time-trial participants inhaled: placebo (PLA), 800 µg salbutamol (SAL800) or 1600 µg salbutamol (SAL1600). During each 5 km time-trial HR, VO₂, VCO₂, V_E, RPE and blood lactate were measured. Urine samples (90 ml) were collected between 30-180 minutes post 5 km time-trial and analysed for salbutamol concentration. There was no significant difference in total 5 km time between treatments (PLA 1714.7 ± 186.2 s; SAL800 1683.3 ± 179.7 s; SAL1600 1683.6 ± 190.7 s). Post 5 km time-trial salbutamol urine concentration between SAL800 (122.96 ± 69.22 ug·ml^-1) and SAL1600 (574.06 ± 448.17 ug·ml^-1) were not significantly different. There was no improvement in 5 km time-trial performance following the inhalation of up to 1600 µg of salbutamol in non-asthmatic athletes. This would suggest that the current WADA guidelines, which allow athletes to inhale up to 1600 µg per day, is sufficient to avoid pharmaceutical induced performance enhancement.

Key points

• Inhaling up to 1600 µg of Salbutamol does not result in improved 5 km time trial performance.
• The position of Salbutamol on the World Anti-Doping Agency list of prohibited appears justified.
• Athletes who use up to 1600 µg Salbutamol in one day need to review their therapy as it would suggest their respiratory condition is not under control.

Key Words: Anti-Doping, WADA code, asthma, treatment, athlete care     

The Importance of Voluntary Behavior in Rehabilitation Treatment and Outcomes

Most rehabilitation treatments are volitional in nature, meaning that they require the patient’s active engagement and effort. Volitional treatments are particularly challenging to define in a standardized fashion, because the clinician is not in complete control of the patient’s role in enacting these treatments. Current recommendations for describing treatments in research reports fail to distinguish between 2 fundamentally different aspects of treatment design: the selection of treatment ingredients to produce the desired functional change and the selection of ingredients that will ensure the patient’s volitional performance. The Rehabilitation Treatment Specification System (RTSS) is a conceptual scheme for standardizing the way that rehabilitation treatments are defined by all disciplines across all areas of rehabilitation. The RTSS highlights the importance of volitional behavior in many treatment areas and provides specific guidance for how volitional treatments should be specified. In doing so, it suggests important crosscutting research questions about the nature of volitional behavior, factors that make it more or less likely to occur, and ingredients that are most effective in ensuring that patients perform desired treatment activities.     

Human autoantibodies specific for the α1A calcium channel subunit reduce both P-type and Q-type calcium currents in cerebellar neurons

The pharmacological properties of voltage-dependent calcium channel (VDCC) subtypes appear mainly to be determined by the α₁ pore-forming subunit but, whether P-and Q-type VDCCs are encoded by the same α₁ gene presently is unresolved. To investigate this, we used IgG antibodies to presynaptic VDCCs at motor nerve terminals that underlie muscle weakness in the autoimmune Lambert–Eaton myasthenic syndrome (LEMS). We first studied their action on changes in intracellular free Ca²⁺ concentration [Ca²⁺]_i in human embryonic kidney (HEK293) cell lines expressing different combinations of human recombinant VDCC subunits. Incubation for 18 h with LEMS IgG (2 mg/ml) caused a significant dose-dependent reduction in the K⁺-stimulated [Ca²⁺]_i increase in the α_1A cell line but not in the α_1B, α_1C, α_1D, and α_1E cell lines, establishing the α_1A subunit as the target for these autoantibodies. Exploiting this specificity, we incubated cultured rat cerebellar neurones with LEMS IgG and observed a reduction in P-type current in Purkinje cells and both P- and Q-type currents in granule cells. These data are consistent with the hypothesis that the α_1A gene encodes for the pore-forming subunit of both P-type and Q-type VDCCs.     

ACS national surgical quality improvement program: Targeting quality improvement in Canadian pediatric surgery

Purpose

The pediatric NSQIP program is in the early stages of facilitated surgical quality improvement for children. The objective of this study is to describe the initial experience of the first Canadian Children’s Hospital participant in this program.

Method

Randomly sampled surgical cases from the “included” case list were abstracted into the ACS-NSQIP database. These surgical procedure-specific data incorporate patient risk factors, intraoperative details, and 30 day outcomes to generate annual reports which provide hierarchical ranking of participant hospitals according to their risk-adjusted outcomes.

Results

Our first risk-adjusted report identified local improvement opportunities based on our rates of surgical site infection (SSI) and urinary tract infection (UTI). We developed and implemented an engagement strategy for our stakeholders, performed literature reviews to identify practice variation, and conducted case control studies to understand local risk factors for our SSI/UTI occurrences. We have begun quality improvement activities targeting reduction in rates of SSI and UTI with our general surgery division and ward nurses, respectively.

Conclusions

The NSQIP pediatric program provides high quality outcome data that can be used in support of quality improvement. This process requires multidisciplinary teamwork, systematic stakeholder engagement, clinical research methods and process improvement through engagement and culture change.     

Panostotic Expansile Bone Disease With Massive Jaw Tumor Formation and a Novel Mutation in the Signal Peptide of RANK

Precise regulation of bone resorption is critical for skeletal homeostasis. We report a 32‐year‐old man with a panostotic expansile bone disease and a massive hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and became bow‐legged during childhood. There was no family history of skeletal disease. Puberty occurred normally, but during adolescence he experienced difficulty straightening his limbs, sustained multiple fractures, and developed a bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular mass grew and protruded from the oral cavity, extending to the level of the lower ribs. Other bony defects included a similar maxillary mass and serpentine limbs. Upon referral at age 27 years, biochemical studies showed serum alkaline phosphatase of 1760 U/L (Nl: 29‐111) and other elevated bone turnover markers. Radiography of the limbs showed medullary expansion and cortical thinning with severe bowing. Although the jaw tumors were initially deemed inoperable, mandibular mass excision and staged partial maxillectomy were eventually performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a background of hypocellular fibrous tissue. Fibrous dysplasia of bone was suspected, but there was no mutation in codon 201 of GNAS in samples from blood or tumor. His clinical and radiographic findings, elevated serum markers, and disorganized bone morphology suggested amplified receptor activator of NF‐κB (RANK) signaling, even though his disorder differed from conditions with known constitutive activation of RANK signaling (eg, familial expansile osteolysis). We found a unique 12‐base pair duplication in the signal peptide of TNFRSF11A, the gene that encodes RANK. No exon or splice site mutations were found in the genes encoding RANK ligand or osteoprotegerin. Alendronate followed by pamidronate therapies substantially decreased his serum alkaline phosphatase activity. This unique patient expands the phenotypes and genetic basis of the mendelian disorders of RANK signaling activation. © 2014 American Society for Bone and Mineral Research.     

Ventricular structure,function, and focal fibrosis in anabolic steroid users: a CMR study

Purpose

Anabolic steroid (AS) misuse is widespread amongst recreational bodybuilders; however, their effects on the cardiovascular system are uncertain. Our aim was to document the impact of AS use on cardiac structure, function and the presence of focal fibrosis using the gold standard cardiovascular magnetic resonance imaging (CMR).

Methods

A cross-sectional cohort design was utilised with 21 strength-trained participants who underwent CMR imaging of the heart and speckle-tracking echocardiography. Thirteen participants (30 ± 5 years) taking AS for at least 2 years and currently on a “using”-cycle were compared with age and training-matched controls (n = 8; 29 ± 6 years) who self-reported never having taken AS (NAS).

Results

AS users had higher absolute left ventricular (LV) mass (220 ± 45 g) compared to NAS (163 ± 27 g; p < 0.05) but this difference was removed when indexed to fat-free mass. AS had a reduced right ventricular (RV) ejection fraction (AS 51 ± 4 % vs. NAS 59 ± 5 %; p < 0.05) and a significantly lower left ventricular E’:A’ myocardial tissue velocity ratio [AS 0.99(0.54) vs. NAS 1.78(0.46) p < 0.05] predominantly due to greater tissue velocities with atrial contraction. Peak LV longitudinal strain was lower in AS users (AS ?14.2 ± 2.7 % vs. NAS ?16.6 ± 1.9 %; p < 0.05). There was no evidence of focal fibrosis in any participant.

Conclusions

AS use was associated with significant LV hypertrophy, albeit in-line with greater fat-free mass, reduced LV strain, diastolic function, and reduced RV ejection fraction in male bodybuilders. There was, however, no evidence of focal fibrosis in any AS user.     

Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID‐19

The global pandemic of coronavirus disease 2019 (COVID‐19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID‐19 patients show elevated D‐dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI‐1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID‐19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre‐existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue‐type plasminogen activator (tPA), to treat COVID‐19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID‐19 patients to degrade fibrin and improving oxygenation in critically ill patients.     

Comprehensive Systematic Review Update Summary: Disorders of Consciousness: Report of the Guideline Development,Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability,Independent Living,and Rehabilitation Research

Objective

To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition for the minimally conscious state (MCS) by reviewing the literature on the diagnosis, natural history, prognosis, and treatment of disorders of consciousness lasting at least 28 days.