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Train at home, but not alone: a randomised controlled multicentre trial assessing the effects of live-streamed tele-exercise during COVID-19-related lockdowns.
Wilke, J, Mohr, L, Yuki, G, Bhundoo, AK, Jiménez-Pavón, D, Laiño, F, Murphy, N, Novak, B, Nuccio, S, Ortega-Gómez, S, et al
British journal of sports medicine. 2022;(12):667-675
Abstract
OBJECTIVE Public life restrictions associated with the COVID-19 pandemic caused reductions in physical activity (PA) and decreases in mental and somatic health. Considering the interplay between these factors, we investigated the effects of digital home exercise (DHE) during government-enforced lockdowns. METHODS A multicentre randomised controlled trial was performed allocating healthy individuals from nine countries (N=763; 523 female) to a DHE or an inactive control group. During the 4-week main intervention, DHE members engaged in live-streamed multicomponent home exercise. Subsequently, both groups had access to prerecorded workouts for an additional 4 weeks. Outcomes, assessed weekly, included PA level (Nordic Physical Activity Questionnaire-Short), anxiety (Generalized Anxiety Disorder Scale-7), mental well-being (WHO-5 Questionnaire), sleep quality (Medical Outcome Study Sleep Scale), pain/disability (Chronic Pain Grade Scale) and exercise motivation (Self-Concordance Scale). Mixed models were used for analysis. RESULTS Live-streamed DHE consistently increased moderate PA (eg, week 1: 1.65 times more minutes per week, 95% CI 1.40 to 1.94) and vigorous PA (eg, week 1: 1.31 times more minutes per week, 95% CI 1.08 to 1.61), although the effects decreased over time. In addition, exercise motivation, sleep quality and anxiety were slightly improved for DHE in the 4-week live streaming period. The same applied to mental well-being (mean difference at week 4: +0.99, 95% CI 0.13 to 1.86), but an inverted trend was observed after live streaming was substituted by prerecorded exercise. CONCLUSIONS Live-streamed DHE represents an efficacious method to enhance PA and selected markers of health during pandemic-related public life restrictions. However, research on implementation is warranted to reduce dropout rates. TRIAL REGISTRATION NUMBER DRKS00021273.
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Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.
Wolfe, CR, Tomashek, KM, Patterson, TF, Gomez, CA, Marconi, VC, Jain, MK, Yang, OO, Paules, CI, Palacios, GMR, Grossberg, R, et al
The Lancet. Respiratory medicine. 2022;(9):888-899
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BACKGROUND Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING National Institute of Allergy and Infectious Diseases.
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Explaining the complex impact of the Covid-19 pandemic on children with overweight and obesity: a comparative ecological analysis of parents' perceptions in three countries.
Nowicka, P, Ek, A, Jurca-Simina, IE, Bouzas, C, Argelich, E, Nordin, K, García, S, Vasquez Barquero, MY, Hoffer, U, Reijs Richards, H, et al
BMC public health. 2022;(1):1000
Abstract
BACKGROUND The Covid-19 pandemic has changed children's eating and physical activity behaviours. These changes have been positive for some households and negative for others, revealing health inequalities that have ramifications for childhood obesity. This study investigates the pandemic's impact on families of children aged 2-6 years with overweight or obesity. METHODS Drawing on interviews conducted as part of a randomised controlled trial (RCT) for childhood obesity, thematic analysis was used to examine how parents of pre-schoolers perceived changes in their eating, screentime and physical activity behaviours between the first and second waves of Covid-19. Parents (n = 70, representing 68 families) were interviewed twice during a period of 6 months in three countries with markedly different pandemic policies - Sweden, Romania, and Spain. The analysis is informed by Bronfenbrenner's ecological systems theory, which embeds home- and school-based influences within societal and policy contexts. RESULTS The findings show that, although all participants were recruited from an RCT for families of children with excess weight, they reported different responses to the pandemic's second wave, with some children engaging in healthier eating and physical activity, and others engaging in comfort eating and a more sedentary lifestyle. Differences in children's obesity-related behaviours were closely related to differences in parents' practices, which were, in turn, linked to their emotional and social wellbeing. Notably, across all sites, parents' feeding and physical activity facilitation practices, as well as their emotional and social wellbeing, were embedded in household resilience. In resilient households, where parents had secure housing and employment, they were better able to adapt to the challenges posed by the pandemic, whereas parents who experienced household insecurity found it more difficult to cope. CONCLUSIONS As the Covid-19 pandemic is turning into a long-term public health challenge, studies that address household resilience are crucial for developing effective prevention and treatment responses to childhood obesity.
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Fermented Carica papaya and Morinda citrifolia as Perspective Food Supplements for the Treatment of Post-COVID Symptoms: Randomized Placebo-Controlled Clinical Laboratory Study.
Kharaeva, Z, Shokarova, A, Shomakhova, Z, Ibragimova, G, Trakhtman, P, Trakhtman, I, Chung, J, Mayer, W, De Luca, C, Korkina, L
Nutrients. 2022;(11)
Abstract
Food supplements based on fermented Carica papaya and Morinda citrifolia, known for their immune modulating, redox balancing, and anti-inflammatory effects, were added to conventional treatment protocols prescribed to patients recovering after severe and moderate COVID-19 disease in order to alleviate long-lasting post-COVID symptoms. A randomized single-center placebo-controlled clinical laboratory study was designed and performed (total number of participants 188, with delta variant of virus 157, with omicron 31). Clinical statuses were assessed using computer tomography, electrocardiography, a questionnaire, and physical endurance. Plasma cytokines (IL-6, IL-8, IL-17A, and INF-gamma), nitrate/nitrite ratio, antioxidant activity (AOA), and polymorphonuclear leukocyte (PMN) ATP levels were determined before and 20 days following the addition of 28 g of fermented supplements twice per day. The capacity of PMN to phagocyte and the oral-nasal-pharyngeal microbiota were assessed. Clinical symptoms, IL-6, IL-8, and nitric oxide metabolites diminished significantly compared to the placebo group and their background expression. The PMN capacity to phagocyte, AOA, and ATP content remarkably increased. The oral-nasal-pharyngeal microbiota were unchanged. On these grounds, we suggest that fermented tropical fruits could efficiently diminish post-COVID clinical symptoms through several immune-modulating, redox balancing, and pro-energy mechanisms.
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Dietary nitrate supplementation for preventing and reducing the severity of winter infections, including COVID-19, in care homes (BEET-Winter): a randomised placebo-controlled feasibility trial.
Bath, PM, Skinner, CJC, Bath, CS, Woodhouse, LJ, Korovesi, AAK, Long, H, Havard, D, Coleman, CM, England, TJ, Leyland, V, et al
European geriatric medicine. 2022;(6):1343-1355
Abstract
PURPOSE Infections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in care home residents. METHODS We performed a cluster-randomised placebo-controlled trial in UK residential and nursing care home residents and compared nitrate containing (400 mg) versus free (0 mg daily) beetroot juice given for 60 days. Outcomes comprised feasibility of recruitment, adherence, salivary and urinary nitrate, and ordinal infection/clinical events. RESULTS Of 30 targeted care homes in late 2020, 16 expressed interest and only 6 participated. 49 residents were recruited (median 8 [interquartile range 7-12] per home), mean (standard deviation) age 82 (8) years, with proxy consent 41 (84%), advance directive for hospital non-admission 8 (16%) and ≥ 1 doses of COVID-19 vaccine 37 (82%). Background dietary nitrate was < 30% of acceptable daily intake. 34 (76%) residents received > 50% of juice. Residents randomised to nitrate vs placebo had higher urinary nitrate levels, median 50 [18-175] v 18 [10-50] mg/L, difference 25 [0-90]. Data paucity precluded clinical between-group comparisons; the outcome distribution was as follows: no infection 32 (67%), uncomplicated infection 0, infection requiring healthcare support 11 (23%), all-cause hospitalisation 5 (10%), all-cause mortality 0. Urinary tract infections were most common. CONCLUSIONS Recruiting UK care homes during the COVID-19 pandemic was partially successful. Supplemented dietary nitrate was tolerated and elevated urinary nitrate. Together, infections, hospitalisations and deaths occurred in 33% of residents over 60 days. A larger trial is now required. TRIAL REGISTRATION ISRCTN51124684. Application date 7/12/2020; assignment date 13/1/2021.
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Effects of combined training during the COVID-19 pandemic on metabolic health and quality of life in sedentary workers: A randomized controlled study.
Silva, FM, Duarte-Mendes, P, Carvalho, E, Soares, CM, Farinha, C, Serrano, J, Paulo, R, Massart, A, Rodrigues, RN, Teixeira, AM, et al
Frontiers in public health. 2022;:1040714
Abstract
This study aimed to analyze the effects of a combined training (CT) program performed during the first national lockdown due to the COVID-19 pandemic on body composition, metabolic profile, quality of life and stress in sedentary workers, and examines whether changes in the metabolic profile are associated with changes in health-related outcomes which are modifiable by exercise. We evaluated 31 sedentary workers (48.26 ± 7.89 years old). Participants were randomly assigned to a CT group (i.e., performed 16 weeks of exercise) or to a non-exercise control group. The CT program consisted of 16-week of resistance and aerobic exercise. Body composition, glycemic and lipidic profiles, cardiorespiratory fitness (CRF), health-related quality of life and stress levels were assessed pre- and post-intervention. After the intervention period, the CT group demonstrated significantly lower waist and hip circumference (p < 0.05) values than the control group. The control group significantly increased the fasting glucose and HOMA-IR after 16 weeks follow-up (+4.74 mg/dL, p = 0.029; and +0.41 units, p = 0.010, respectively), whiles no significant changes were observed in the CT group in the same parameters (+3.33 mg/dL, p = 0.176; and +0.04 units, p = 0.628, respectively). No changes were observed in the lipid profile for either group (p > 0.05). A significant positive relationship was detected between the change in BMI with the changes in insulin and HOMA-IR (r = 0.643, p = 0.024; and r = 0.605, p = 0.037, respectively). In addition, the changes in CRF were negatively associated with the changes in total cholesterol (r = -0.578, p = 0.049). We observed differences between groups on perceived stress levels and physical, psychological, and environmental domains of quality of life, with the CT group showing better results. Moreover, the CT group improved perceived life satisfaction (+3.17 points, p = 0.038). The findings of the present study suggest that the participants who remained physically active during the first pandemic-related lockdown were able to mitigate the deleterious effects associated with a sedentary lifestyle.
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Potential of Egg as Complementary Food to Improve Nutrient Intake and Dietary Diversity.
Faber, M, Malan, L, Kruger, HS, Asare, H, Visser, M, Mukwevho, T, Ricci, C, Smuts, CM
Nutrients. 2022;(16)
Abstract
The original aim was to determine the effect of egg consumption on infant growth in a low socioeconomic community in South Africa in a randomized controlled trial. Enrolment was, however, prematurely stopped due to COVID-19 lockdown regulations. The resultant small sample (egg group n = 70; control group n = 85) was followed up to assess the feasibility of egg consumption for eight months in terms of dietary intake, egg usage and perceived effects of lockdown on child feeding. Egg consumption remained low in the control group, <10% consumed egg ≥4 days/week at the follow-up points. In the egg group, egg was frequently consumed at midpoint (daily 87.1%, 4−6 days 8.1%) and endpoint (daily 53.1%, 4−6 days 21.9%). At endpoint, dietary intake of cholesterol and vitamin D was higher, and intake of niacin and vitamin B6 lower in the egg group compared to the control group. Dietary diversity was low, 36.2% of the egg group and 18.9% of the control group (p < 0.05) achieved minimum dietary diversity at endpoint. No babies developed egg allergy or sensitization, and adjusted regression analysis showed that frequency of egg intake was not related with the incidence or duration of allergy-related symptoms. This study showed that frequent egg consumption can contribute safely to complementary food for babies, especially in low- and middle-income countries.
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Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.
Mann, DL, Givertz, MM, Vader, JM, Starling, RC, Shah, P, McNulty, SE, Anstrom, KJ, Margulies, KB, Kiernan, MS, Mahr, C, et al
JAMA cardiology. 2022;(1):17-25
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IMPORTANCE The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. OBJECTIVE To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. DESIGN, SETTING, AND PARTICIPANTS A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. INTERVENTION Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. MAIN OUTCOMES AND MEASURES The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. RESULTS Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. CONCLUSIONS AND RELEVANCE The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02816736.
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Reaching high-risk Black adults for diabetes prevention programming during a pandemic: The design of Fit & Faithful a randomized controlled community trial.
Williams, LB, Moser, DK, Gustafson, A, Waters, TM, Rayens, MK, Karle, ER, Kriska, AM
Contemporary clinical trials. 2022;:106973
Abstract
Obesity is a key risk factor for Type 2 diabetes (T2D). Alarmingly, 87% of US adults have overweight or obesity, with non-Hispanic black adults having higher obesity and T2D prevalence than non-Hispanic white. The Diabetes Prevention Program (DPP) demonstrated the clinical benefits of lifestyle intervention (LI). While the DPP LI is effective, some participants don't achieve clinically significant weight loss in the current group-based translation paradigm. Black adults have the lowest adjusted weight loss (3.2%) among all racial/ethnic groups. Early intervention nonresponse defined as ≤1% weight loss at intervention week 4 is linked to lower probability of achieving weight loss goals. This paper describes the design and methods of a cluster randomized controlled trial among black weight loss nonresponders nested in 20 community sites (primarily churches). Descriptions of the adaptations made to transition the program to virtual format during the COVID-19 pandemic are also included. Trained community health workers deliver a group-based, 6-month long DPP over 18 sessions via Zoom. Additionally, nonresponders in the enhanced group receive weekly telephone support to provide individual-level intervention to help overcome weight loss barriers. Outcomes include weight, physical activity level, blood pressure, and dietary behaviors; these are compared between nonresponders in the enhanced intervention group and nonresponders in the active control group. Cost, mediators, and moderators are explored. If found to efficacious, these enhanced strategies could be standardized as a supplement for use with DPP nonresponders.
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Efficacy and Safety of ELOM-080 as Add-On Therapy in COVID-19 Patients with Acute Respiratory Insufficiency: Exploratory Data from the Prospective Placebo-Controlled COVARI Trial.
Dreher, M, Grohè, C, Hartmann, NU, Kanzler, S, Kraft, K, Sarrazin, C, Doll, M, Spiesshöfer, J, Steiner, S, Wöhrle, J, et al
Advances in therapy. 2022;(6):3011-3018
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INTRODUCTION Enhancement of mucociliary clearance (MCC) might be a potential target in treating COVID-19. The phytomedicine ELOM-080 is an MCC enhancer that is used to treat inflammatory respiratory diseases. PATIENTS/METHODS This randomised, double-blind exploratory study (EudraCT number 2020-003779-17) evaluated 14 days' add-on therapy with ELOM-080 versus placebo in patients with COVID-19 hospitalised with acute respiratory insufficiency. RESULTS The trial was terminated early after enrolment of 47 patients as a result of poor recruitment. Twelve patients discontinued prematurely, leaving 35 in the per-protocol set (PPS). Treatment with ELOM-080 had no significant effect on overall clinical status versus placebo (p = 0.49). However, compared with the placebo group, patients treated with ELOM-080 had less dyspnoea in the second week of hospitalisation (p = 0.0035), required less supplemental oxygen (p = 0.0229), and were more often without dyspnoea when climbing stairs at home (p < 0.0001). CONCLUSION These exploratory data suggest the potential for ELOM-080 to improve respiratory status during and after hospitalisation in patients with COVID-19.