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Impact of COVID-19 in patients with heart failure with mildly reduced or preserved ejection fraction enrolled in the DELIVER trial.
Bhatt, AS, Kosiborod, MN, Claggett, BL, Miao, ZM, Vaduganathan, M, Lam, CSP, Hernandez, AF, Martinez, FA, Inzucchi, SE, Shah, SJ, et al
European journal of heart failure. 2023;(12):2177-2188
Abstract
AIM: COVID-19 may affect clinical risk in patients with heart failure. DELIVER began before and was conducted during the COVID-19 pandemic. This study aimed to evaluate the association between COVID-19 and clinical outcomes among DELIVER participants. METHODS AND RESULTS Participants with chronic heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) were randomized to dapagliflozin or placebo across 350 sites in 20 countries. COVID-19 was investigator-reported and the contribution of COVID-19 to death was centrally adjudicated. We assessed (i) the incidence of COVID-19, (ii) event rates before/during the pandemic, and (iii) risks of death after COVID-19 diagnosis compared to risks of death in participants without COVID-19. Further, we performed a sensitivity analysis assessing treatment effects of dapagliflozin vs. placebo censored at pandemic onset. Of 6263 participants, 589 (9.4%) developed COVID-19, of whom 307 (52%) required/prolonged hospitalization. A total of 155 deaths (15% of all deaths) were adjudicated as definitely/possibly COVID-19-related. COVID-19 cases and deaths did not differ by randomized assignment. Death rate in the 12 months following diagnosis was 56.1 (95% confidence interval [CI] 48.0-65.6) versus 6.4 (95% CI 6.0-6.8)/100 participant-years among trial participants with versus without COVID-19 (adjusted hazard ratio [aHR] 8.60, 95% CI 7.18-10.30). Risk was highest 0-3 months following diagnosis (153.5, 95% CI 130.3-180.8) and remained elevated at 3-6 months (12.6, 95% CI 6.6-24.3/100 participant-years). After excluding investigator-reported fatal COVID-19 events, all-cause death rates in the 12 months following diagnosis among COVID-19 survivors (n = 458) remained higher (aHR 2.46, 95% CI 1.83-3.33) than rates for all trial participants from randomization, with censoring of participants who developed COVID-19 at the time of diagnosis. Dapagliflozin reduced cardiovascular death/worsening HF events when censoring participants at COVID-19 diagnosis (HR 0.81, 95% CI 0.72-0.91) and pandemic onset (HR 0.72, 95% CI 0.58-0.89). There were no diabetic ketoacidosis or major hypoglycaemic events within 30 days of COVID-19. CONCLUSION DELIVER is one of the most extensive experiences with COVID-19 of any cardiovascular trial, with >75% of follow-up time occurring during the pandemic. COVID-19 was common, with >50% of cases leading to hospitalization or death. Treatment benefits of dapagliflozin persisted when censoring at COVID-19 diagnosis and pandemic onset. Patients surviving COVID-19 had a high early residual risk. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT03619213.
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Korean Red Ginseng Potentially Improves Maintaining Antibodies after COVID-19 Vaccination: A 24-Week Longitudinal Study.
Yoon, J, Park, B, Kim, H, Choi, S, Jung, D
Nutrients. 2023;(7)
Abstract
Despite the effectiveness and safety of COVID-19 vaccines, vaccine-induced responses decline over time; thus, booster vaccines have been approved globally. In addition, interest in natural compounds capable of improving host immunity has increased. This study aimed to examine the effect of Korean Red Ginseng (KRG) on virus-specific antibodies after COVID-19 vaccination. We conducted a 24 week clinical pilot study of 350 healthy subjects who received two doses of the COVID-19 vaccine and a booster vaccination (third dose). These subjects were randomized 1:2 to the KRG and control groups. We evaluated antibody response five times: just before the second dose (baseline), 2 weeks, 4 weeks, 12 weeks after the second dose, and 4 weeks after the third dose. The primary endpoints were changes in COVID-19 spike antibody titers and neutralizing antibody titers. The antibody formation rate of the KRG group was sustained higher than that of the control group for 12 weeks after the second dose. This trend was prominently observed in those above 50 years old. We found that KRG can help to increase and maintain vaccine response, highlighting that KRG could potentially be used as an immunomodulator with COVID-19 vaccines.
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No evidence for stratified exercise therapy being cost-effective compared to usual exercise therapy in patients with knee osteoarthritis: Economic evaluation alongside cluster randomized controlled trial.
Knoop, J, Esser, J, Dekker, J, de Joode, JW, Ostelo, RWJG, van Dongen, JM
Brazilian journal of physical therapy. 2023;(1):100469
Abstract
BACKGROUND A stratified approach to exercise therapy may yield superior clinical and economic outcomes, given the large heterogeneity of individuals with knee osteoarthritis (OA). OBJECTIVE To evaluate the cost-effectiveness during a 12-month follow-up of a model of stratified exercise therapy compared to usual exercise therapy in patients with knee OA, from a societal and healthcare perspective. METHODS An economic evaluation was conducted alongside a cluster-randomized controlled trial in patients with knee OA (n = 335), comparing subgroup-specific exercise therapy for a 'high muscle strength subgroup', 'low muscle strength subgroup', and 'obesity subgroup' supplemented by a dietary intervention for the 'obesity subgroup' (experimental group), with usual ('non-stratified') exercise therapy (control group). Clinical outcomes included quality-adjusted life years - QALYs (EuroQol-5D-5 L), knee pain (Numerical Rating Scale) and physical functioning (Knee Injury and Osteoarthritis Outcome Score in daily living). Costs were measured by self-reported questionnaires at 3, 6, 9 and 12-month follow-up. Missing data were imputed using multiple imputation. Data were analyzed through linear regression. Bootstrapping techniques were applied to estimate statistical uncertainty. RESULTS During 12-month follow-up, there were no significant between-group differences in clinical outcomes. The total societal costs of the experimental group were on average lower compared to the control group (mean [95% confidence interval]: € 405 [-1728, 918]), albeit with a high level of uncertainty. We found a negligible difference in QALYs between groups (mean [95% confidence interval]: 0.006 [-0.011, 0.023]). The probability of stratified exercise therapy being cost-effective compared to usual exercise therapy from the societal perspective was around 73%, regardless of the willingness-to-pay threshold. However, this probability decreased substantially to 50% (willingness-to-pay threshold of €20.000/QALY) when using the healthcare perspective. Similar results were found for knee pain and physical functioning. CONCLUSIONS We found no clear evidence that stratified exercise therapy is likely to be cost-effective compared to usual exercise therapy in patients with knee OA. However, results should be interpreted with caution as the study power was lower than intended, due to the Coronavirus disease (COVID-19) pandemic.
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Effect of different types of supervised exercise programs on cardiorespiratory and muscular fitness, pain, fatigue, mental health and inflammatory and oxidative stress biomarkers in older patients with post-COVID-19 sequelae "EJerSA-COVID-19": a randomized controlled trial.
Pleguezuelos, E, Sánchez-Nuño, S, Del Carmen, A, Serra-Payá, N, Moreno, E, Molina-Raya, L, Robleda, G, Benet, M, Santos-Ruiz, S, Garrido, AB, et al
BMC geriatrics. 2023;(1):865
Abstract
BACKGROUND Many patients with COVID-19 present the so-called post-acute sequelae of COVID-19 such as fatigue, post-stress discomfort, dyspnea, headache, pain mental impairment, incapacity to perform daily physical tasks ant exercise intolerance. This study aims to investigate the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. METHODS The sample will be made up of 120 eligible participants, over the age of 60 years who have had COVID-19 disease and are survivors and present persistent COVID-19 symptomatology diagnosed by the corresponding physician. The participants will be randomly assigned to the experimental groups: supervised endurance group (SEG, n = 30), supervised strength group (SSG, n = 30), supervised concurrent group (SCG, n = 30), which will perform the corresponding exercise program 3 days a week compared to the control group (CG, n = 30), which will not carry out a supervised exercise program. The design of this project will include measurements of four relevant dimensions; 1) Cardiorespiratory fitness; 2) Muscle fitness; 3) Pain and mental health; and 4) Biomarkers of inflammation and oxidative stress. CONCLUSIONS The results of this study will provide insights into the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. These findings may be the basis for the formulation of health plans and rehabilitation programs that allow healthy aging and a reduction in the associated morbidity in patients with post-COVID-19 sequelae. TRIAL REGISTRATION NCT05848518. Registered on May 8, 2023.
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Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.
Chopra, A, Tillu, G, Chuadhary, K, Reddy, G, Srivastava, A, Lakdawala, M, Gode, D, Reddy, H, Tamboli, S, Saluja, M, et al
PloS one. 2023;(3):e0282688
Abstract
OBJECTIVE Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION CTRI/2020/06/025557.
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Efficacy of a cardiac rehabilitation program in a municipal sports center compared to the hospital program: randomized controlled trial eCARCEX.
Izquierdo-García, J, Arranz-Escudero, A, Tello de Meneses, R, De la Torre, N, Amat-Macías, IM, Castillo Martín, JI, Sanz-Ayán, MP, Moreno, G
Anales del sistema sanitario de Navarra. 2023;(3)
Abstract
BACKGROUND This study aimed to analyze the effects of an outpatient cardiac rehabilitation program in a municipal sports center on functional capacity and adherence to physical exercise - among other variables - compared to an in-hospital program. METHODS Randomized clinical trial that included two parallel groups of acute coronary syndrome patients who performed a cardiac rehabilitation program that consisted of moderate physical exercise intervals along with learning healthy habits in a municipal sports center (experimental group) and in a tertiary hospital (control group) between September 2019 and June 2020. We collected the following data: compliance, anthropometrical, clinical, psychological variables, diet and tobacco habits, strength and functional capacity from ergospirometry. RESULTS Twenty-two patients completed the cardiac rehabilitation program (experimental group=12, control group=10). Significant improvement was observed for cholesterol, the sit-and-stand test, cardiac frequency in VT1 and VT2, and watts in VT1 in the control group, and for HDL-cholesterol, triglycerides, the sit-and-stand test, and frequency, and watts in VT1 in the experimental group. Better achievement was found in the control group for cardiac frequency in VT2 (11.17 vs 2.88 bpm) and in EG for HDL-cholesterol (11.0 vs 0.63 mg/dL). CONCLUSIONS We are unable to determine the effectiveness of the out-of-hospital cardiac rehabilitation program due to a lack of power (high number of withdrawals caused by COVID-19 lockdown). However, the experimented group achieved higher HDL-cholesterol levels, while cardiac frequency in VT2 was higher in the control group.
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"It's Gonna Be Okay"-A Qualitative Exploration of the COVID-19 Pandemic's Effects on African American Participants During a Dietary Intervention Study.
Bernhart, JA, Quattlebaum, M, Eustis, S, Okpara, N, Wilson, MJ, Sentman, C, Turner-McGrievy, GM
Journal of the Academy of Nutrition and Dietetics. 2023;(12):1763-1771
Abstract
BACKGROUND African American adults are at increased risk for chronic diseases. Limited research exists regarding how the COVID-19 pandemic affected African American adults in behavioral interventions. OBJECTIVE This study assessed how the early months of the COVID-19 pandemic, before vaccine availability and widespread testing, affected stress, nutrition, and exercise behaviors of African American adults participating in a dietary intervention study. DESIGN This was a qualitative interview study conducted with participants from both diet groups as part of the ongoing Nutritious Eating with Soul (NEW Soul) study. NEW Soul is a 2-year, randomized dietary intervention study with participants randomized to follow a vegan (intervention) or low-fat omnivorous diet (control), with both diets focused on soul food. PARTICIPANTS/SETTING Participants (n = 20) came from 2 cohorts of the larger intervention study in South Carolina and were purposefully recruited based on high and low attendance at intervention sessions. Participants in the first cohort were near the end of the intervention, and participants in the second cohort were near the mid-point. The interviews were conducted from June to July 2020. MAIN OUTCOME MEASURES Outcomes included participants' experiences related to stress, nutrition, and exercise behaviors during the early months of the COVID-19 pandemic. ANALYSIS Interviews were recorded and transcribed verbatim. Interview transcripts were coded by two coders using NVivo software. Interviews were coded through content analysis using a constant comparative method. RESULTS Participants discussed the following 3 themes in relation to health behaviors: increased stress, change in routines, and advice to follow health goals. CONCLUSIONS Findings provide perspectives for designing interventions for African American adults establishing new routines to overcome setbacks and changes in routines created by the COVID-19 pandemic.
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Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial.
Reynolds, JV, Preston, SR, O'Neill, B, Lowery, MA, Baeksgaard, L, Crosby, T, Cunningham, M, Cuffe, S, Griffiths, GO, Parker, I, et al
The lancet. Gastroenterology & hepatology. 2023;(11):1015-1027
Abstract
BACKGROUND The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently). METHODS Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe. Patients aged 18 years or older with clinical tumour stage T2-3, nodal stage N0-3, and M0 adenocarcinoma of the oesophagus and oesophagogastric junction were randomly assigned to perioperative chemotherapy (three preoperative and three postoperative 3-week cycles of intravenous 50 mg/m2 epirubicin on day 1 plus intravenous 60 mg/m2 cisplatin or intravenous 130 mg/m2 oxaliplatin on day 1 plus continuous infusion of 200 mg/m2 fluorouracil daily or oral 625 mg/m2 capecitabine twice daily up to 2018, with four preoperative and four postoperative 2-week cycles of 2600 mg/m2 fluorouracil, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, and 50 mg/m2 docetaxel intravenously on day 1 as an option from 2018) or trimodality therapy (41·4 Gy in 23 fractions on days 1-5, 8-12, 15-19, 22-26, and 29-31 with intravenous area under the curve 2 mg/mL per min carboplatin plus intravenous 50 mg/m2 paclitaxel on days 1, 8, 15, 22, and 29). The primary endpoint was overall survival, assessed in all randomly assigned patients who received at least one dose of study drug, regardless of which study drug they received, by intention to treat. Secondary endpoints were disease-free survival, site of treatment failure, operative complications, toxicity, pathological response (complete [ypT0N0] and major [tumour regression grade 1 and 2]), margin-free resection (R0), and health-related quality of life. Toxicity and safety data were analysed in the safety population, defined as patients who took at least one dose of study drug, according to treatment actually received. The initial power calculation was based on superiority of trimodality therapy (n=366 patients); it was adjusted after FLOT became an option to a non-inferiority design with a margin of 5% for perioperative chemotherapy (n=540). This study is registered with ClinicalTrials.gov, NCT01726452. FINDINGS Between Jan 24, 2013, and Dec 23, 2020, 377 patients were randomly assigned, of whom 362 were included in the intention-to treat population (327 [90%] male and 360 [99%] White): 184 in the perioperative chemotherapy group and 178 in the trimodality therapy group. The trial closed prematurely in December, 2020, after the second interim futility analysis (143 deaths), on the basis of similar survival metrics and the impact of the COVID-19 pandemic. At a median follow-up of 38·8 months (IQR 16·3-55·1), median overall survival was 48·0 months (95% CI 33·6-64·8) in the perioperative chemotherapy group and 49·2 months (34·8-74·4) in the trimodality therapy group (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]; hazard ratio 1·03 [95% CI 0·77-1·38]; log-rank p=0·82). Median disease-free survival was 32·4 months (95% CI 22·8-64·8) in the perioperative chemotherapy group and 24·0 months (18·0-40·8) in the trimodality therapy group [hazard ratio 0·89 [95% CI 0·68-1·17]; log-rank p=0·41). The pattern of recurrence, locoregional or systemic, was not significantly different (odds ratio 1·35 [95% CI 0·63-2·91], p=0·44). Pathological complete response (odds ratio 0·33 [95% CI 0·14-0·81], p=0·012), major pathological response (0·21 [0·12-0·38], p<0·0001), and R0 rates (0·21 [0·08-0·53], p=0·0003) favoured trimodality therapy. The most common grade 3-4 adverse event was neutropenia (49 [27%] of 183 patients in the perioperative chemotherapy group vs 11 [6%] of 178 patients in the trimodality therapy group), followed by diarrhoea (20 [11%] vs none), and pulmonary embolism (ten [5%] vs nine [5%]). One (1%) patient in the perioperative chemotherapy group and three (2%) patients in the trimodality therapy group died from serious adverse events, two (one in each group) of which were possibly related to treatment. No differences were seen in operative mortality (five [3%] deaths in the perioperative chemotherapy group vs four [2%] in the trimodality therapy group), major morbidity, or in global health status at 1 and 3 years. INTERPRETATION Although underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise. FUNDING Health Research Board, Cancer Research UK, Irish Cancer Society, Oesophageal Cancer Fund, and French National Cancer Institute.
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Effect of the povidone iodine, hypertonic alkaline solution and saline nasal lavage on nasopharyngeal viral load in COVID-19.
Batioglu-Karaaltin, A, Yigit, O, Cakan, D, Akgul, O, Yigit, E, Yilmaz, YZ, Cakir, KB, Ciftci, G, Boyoğlu, NS, Cagliyan, A, et al
Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2023;(4):623-629
Abstract
OBJECTIVE The present study aimed to investigate the in vivo activity of nasal irrigation (NI) with saline, NI with povidone-iodine (PVP-I) 1%, NI with a mix of hypertonic alkaline and PVP-I 1% against Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). DESIGN This study was a prospective randomised clinical trial. SETTING A multicenter study involving tertiary care centres. PARTICIPANTS The study included adult outpatients whose qualitative SARS-CoV-2 RT-PCR tests in nasopharyngeal swabs were positive. One hundred twenty patients were divided into four equal groups. Standard COVID-19 treatment was given to Group 1, NI containing saline was added to patients' treatment in Group 2, NI containing 1% PVP-I solution was added to patients' treatment in Group 3, and NI containing 1% PVP-I solution and the hypertonic alkaline solution was added to patients' treatment in Group 4. MAIN OUTCOME MEASURES On the first day of diagnosis (Day 0), nasopharyngeal swab samples were taken, on the third and fifth days the nasopharyngeal viral load (NVL) reduction in quantitative RT-PCR test was calculated. RESULTS Between the zeroth to third days and zeroth to fifth days, the NVL reduction was significant in all groups (p < .05). In paired comparisons of groups, the NVL decrease in Group 4 in the first 3 days was significantly lower than all groups (p < .05). The NVL decrease in Groups 3 and 4 in the first 5 days were significantly lower than Group 1 (p < .05). CONCLUSION This study revealed that the use of NI of 1% PVP-I and the hypertonic alkaline solution mixture was more effective in reducing NVL.
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Impact of a dissemination strategy on family day care educators' intentions to adopt outdoor free play guidelines introduced in response to COVID-19: a randomized controlled trial.
Lum, M, Yoong, SL, Wolfenden, L, Turon, H, Reilly, K, Grady, A
Health education research. 2023;(5):458-468
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Abstract
In 2021, guidelines for early childhood education and care were released recommending children are provided access to outdoor areas during all free play sessions to reduce the risk of coronavirus disease of 2019 transmission, aligning with the existing recommendations to increase children's physical activity. There is a need to understand how to disseminate guidelines in this setting as dissemination is a prerequisite of adoption and implementation. This randomized controlled trial explored the impact of a video-based strategy to disseminate guidelines on family day care educators' intentions to adopt outdoor free play guidelines. Educators (N = 255) were randomized to receive a video (intervention) or text-based (usual care) resource via email describing recommendations. Educators were invited to participate in a post-intervention survey at 5-week follow-up assessing intentions to adopt guidelines. The secondary outcomes included knowledge, beliefs about capabilities, beliefs about consequences, social/professional role and identity, goals, implementation of guidelines, acceptability of resource and intervention reach. There was no statistically significant difference between groups in intentions to adopt guidelines [ß = 0.01 (95% confidence interval -0.50 to 0.52), P = 0.97], nor for any secondary outcomes. Further investigation is needed to identify effective dissemination strategies in the family day care setting to increase the adoption of public health guidelines.