Association between regular physical activity and the protective effect of vaccination against SARS-CoV-2 in a South African case-control study.

BACKGROUND: Both vaccination and physical activity have been shown to independently decrease the likelihood of severe COVID-19 infection. OBJECTIVE: To assess the association between regular physical activity and vaccination against COVID-19 among healthcare workers. METHODS: A test negative case-control study design was used to estimate the risk of having an associated COVID-19-related hospital admission, among individuals who were unvaccinated compared with those who were fully vaccinated with Ad26.COV2.S (>28 days after a single dose). 196 444 participant tests were stratified into three measured physical activity subgroups with low, moderate and high activity, to test the hypothesis that physical activity is an effect modifier on the relationship between vaccination and hospitalisation. RESULTS: Vaccine effectiveness against a COVID-19-related admission among vaccinated individuals within the low activity group was 60.0% (95% CI 39.0 to 73.8), 72.1% (95% CI 55.2 to 82.6) for the moderate activity group, and 85.8% (95% CI 74.1 to 92.2) for the high activity group. Compared with individuals with low activity levels, vaccinated individuals with moderate and high activity levels had a 1.4 (95% CI 1.36 to 1.51) and 2.8 (95% CI 2.35 to 3.35) times lower risk of COVID-19 admission, respectively (p value <0.001 for both groups). CONCLUSIONS: Regular physical activity was associated with improved vaccine effectiveness against COVID-19 hospitalisation, with higher levels of physical activity associated with greater vaccine effectiveness. Physical activity enhances vaccine effectiveness against severe COVID-19 outcomes and should be encouraged by greater public health messaging.

Small steps, strong shield: directly measured, moderate physical activity in 65 361 adults is associated with significant protective effects from severe COVID-19 outcomes.

OBJECTIVE: To determine the association between directly measured physical activity and hospitalisation, intensive care unit (ICU) admission, ventilation and mortality rates in patients with a confirmed diagnosis of COVID-19. METHODS: Directly measured physical activity data from 65 361 adult patients with a COVID-19 diagnosis from 19 March 2020 to 30 June 2021, were grouped by activity level: low (<60 min/week), moderate (60-149 min/week) and high activity (≥150 min/week). The association of physical activity levels and the risk of adverse outcomes was analysed using modified Poisson regression. We accounted for demographics and comorbidities including conditions known to influence COVID-19 outcomes, as well as patient complexity as measured by the Johns Hopkins Adjusted Clinical Group system. The regression approach was further validated with a Bayesian network model built off a directed acyclic graph. RESULTS: High physical activity was associated with lower rates of hospitalisation (risk ratio, RR 0.66, 95% CI 0.63 to 0.70), ICU admission (RR 0.59, 95% CI 0.52 to 0.66), ventilation (RR 0.55, 95% CI 0.47 to 0.64) and death (RR 0.58, 95% CI 0.50 to 0.68) due to COVID-19 than those who engaged in low physical activity. Moderate physical activity also was associated with lower rates of hospitalisation (RR 0.87, 95% CI 0.82 to 0.91), admission to ICU (RR 0.80, 95% CI 0.71 to 0.89), ventilation (RR 0.73, 95% CI 0.62 to 0.84) and death (RR 0.79, 95% CI 0.69 to 0.91). CONCLUSIONS: Adults with high and moderate physical activity levels had significantly better outcomes than those with low activity when contracting COVID-19. The apparent protective effects of regular physical activity extended to those with concomitant chronic medical conditions.

Neurodevelopmental Outcomes of Extremely Low Birth Weight Survivors in Johannesburg, South Africa.

Background: Improved survival in extremely low birth weight infants (ELBWI) in Sub-Saharan Africa has raised the question whether these survivors have an increased chance of adverse neurodevelopmental outcomes. Objectives: To describe neurodevelopmental outcomes of ELBWI in a neonatal unit in South Africa. Methods: This was a prospective follow-up study. All ELBWI who survived to discharge between 1 July 2013 and 31 December 2017 were invited to attend the clinic. Bayley Scales of Infant and Toddler Development (version III) were conducted at 9 to 12 months and 18 to 24 months. Results: There were 723 ELBWI admissions during the study period, 292 (40.4%) survived to hospital discharge and 85/292 (29.1%) attended the neonatal follow up clinic. The mean birth weight was 857.7 g (95% CI: 838.2-877.2) and the mean gestational age was 27.5 weeks (95% CI 27.1-27.9). None of the infants had any major complication of prematurity. A total of 76/85 (89.4%) of the infants had a Bayley-III assessment at a mean corrected age of 17.21 months (95% CI: 16.2-18.3). The mean composite scores for cognition were 98.4 (95% CI 95.1-101.7), language 89.9 (95% CI 87.3-92.5) and motor 97.6 (95% CI 94.5-100.6). All mean scores fell within the normal range, The study found 28 (36.8%) infants to be "at risk" for neurodevelopmental delay. Conclusion: Our study demonstrates good neurodevelopmental outcome in a small group of surviving ELBWI, but these results must be interpreted in the context of the high mortality in this group of infants.

Prognostic factors affecting survival in children and adolescents with HIV and Hodgkin lymphoma in South Africa.

South African children with Hodgkin lymphoma (HL) and human immunodeficiency virus (HIV) have low 5-year overall survival (OS) rates. In this retrospective multicenter study, 271 South African pediatric patients with HL were studied to determine OS and prognostic factors in those with HIV and HL. Univariate risk factor analysis was performed to analyze prognostic factors. The 29 HIV-infected patients were younger (p = .021), more likely to present with wasting (0.0573), stunting (0.0332), and Stage IV disease (p = .000) than HIV-uninfected patients. The 5- and 10-year OS of HIV-infected patients of 49% and 45% versus 84% and 79%, respectively for HIV-uninfected patients (p = .0001) appeared to be associated with hypoalbuminemia (<20 g/dL) and CD4 percentage of <15%. Causes of death in the HIV-infected group included disease progression (6/14), infection (4/14), unknown (3/14), and second malignancy (1/14). HIV-infected pediatric patients with HL experience increased mortality due to post-therapy opportunistic and nosocomial infections.

Uncertainty in Antibiotic Dosing in Critically Ill Neonate and Pediatric Patients: Can Microsampling Provide the Answers?

PURPOSE: With a decreasing supply of antibiotics that are effective against the pathogens that cause sepsis, it is critical that we learn to use currently available antibiotics optimally. Pharmacokinetic studies provide an evidence base from which we can optimize antibiotic dosing. However, these studies are challenging in critically ill neonate and pediatric patients due to the small blood volumes and associated risks and burden to the patient from taking blood. We investigate whether microsampling, that is, obtaining a biologic sample of low volume (<50 µL), can improve opportunities to conduct pharmacokinetic studies. METHODS: We performed a literature search to find relevant articles using the following search terms: sepsis, critically ill, severe infection, intensive care AND antibiotic, pharmacokinetic, p(a)ediatric, neonate. For microsampling, we performed a search using antibiotics AND dried blood spots OR dried plasma spots OR volumetric absorptive microsampling OR solid-phase microextraction OR capillary microsampling OR microsampling. Databases searched include Web of Knowledge, PubMed, and EMbase. FINDINGS: Of the 32 antibiotic pharmacokinetic studies performed on critically ill neonate or pediatric patients in this review, most of the authors identified changes to the pharmacokinetic properties in their patient group and recommended either further investigations into this patient population or therapeutic drug monitoring to ensure antibiotic doses are suitable. There remain considerable gaps in knowledge regarding the pharmacokinetic properties of antibiotics in critically ill pediatric patients. Implementing microsampling in an antibiotic pharmacokinetic study is contingent on the properties of the antibiotic, the pathophysiology of the patient (and how this can affect the microsample), and the location of the patient. A validation of the sampling technique is required before implementation. IMPLICATIONS: Current antibiotic regimens for critically ill neonate and pediatric patients are frequently suboptimal due to a poor understanding of altered pharmacokinetic properties. An assessment of the suitability of microsampling for pharmacokinetic studies in neonate and pediatric patients is recommended before wider use. The method of sampling, as well as the method of bioanalysis, also requires validation to ensure the data obtained reflect the true result.

Is there a role for microsampling in antibiotic pharmacokinetic studies?

INTRODUCTION: Clinical pharmacokinetic studies of antibiotics can establish evidence-based dosing regimens that improve the likelihood of eradicating the pathogen at the site of infection, reduce the potential for selection of resistant pathogens, and minimize harm to the patient. Innovations in small volume sampling (< 50 µL) or 'microsampling' may result in less-invasive sample collection, self-sampling and dried storage. Microsampling may open up opportunities in patient groups where sampling is challenging. AREAS COVERED: The challenges for implementation of microsampling to assure suitability of the results, include: acceptable study design, regulatory agency acceptance, and meeting bioanalytical validation requirements. This manuscript covers various microsampling methods, including dried blood/plasma spots, volumetric absorptive microsampling, capillary microsampling, plasma preparation technologies and solid-phase microextraction. EXPERT OPINION: The available analytical technology is being underutilized due to a lack of bridging studies and validated bioanalytical methods. These deficiencies represent major impediments to the application of microsampling to antibiotic pharmacokinetic studies. A conceptual framework for the assessment of the suitability of microsampling in clinical pharmacokinetic studies of antibiotics is provided. This model establishes a 'contingency approach' with consideration of the antibiotic and the type and location of the patient, as well as the more prescriptive bioanalytical validation protocols.