-
1.
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.
-
2.
Homeopathic Medicines in Second Wave of COVID-19: Prognostic Factor Research.
Manchanda, RK, Miglani, A, Chakraborty, M, Kalsi, A, Meena, BS, Kaur, P, Saini, B, Arora, A, Nagrath, C, Kannoth, JT, et al
Homeopathy : the journal of the Faculty of Homeopathy. 2023;(1):12-21
Abstract
BACKGROUND The clinical profile and course of COVID-19 evolved perilously in a second wave, leading to the use of various treatment modalities that included homeopathy. This prognostic factor research (PFR) study aimed to identify clinically useful homeopathic medicines in this second wave. METHODS This was a retrospective, multi-centred observational study performed from March 2021 to May 2021 on confirmed COVID-19 cases who were either in home isolation or at COVID Care Centres in Delhi, India. The data were collected from integrated COVID Care Centres where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the prescribed medicines. An LR of 1.3 or greater was considered meaningful. RESULTS Out of 769 confirmed COVID-19 cases reported, 514 cases were selected for analysis, including 467 in home isolation. The most common complaints were cough, fever, myalgia, sore throat, loss of taste and/or smell, and anxiety. Most cases improved and there was no adverse reaction. Certain new symptoms, e.g., headache, dryness of mouth and conjunctivitis, were also seen. Thirty-nine medicines were prescribed, the most frequent being Bryonia alba followed by Arsenicum album, Pulsatilla nigricans, Belladonna, Gelsemium sempervirens, Hepar sulphuris, Phosphorus, Rhus toxicodendron and Mercurius solubilis. By calculating LR, the prescribing indications of these nine medicines were ascertained. CONCLUSION Add-on use of homeopathic medicines has shown encouraging results in the second wave of COVID-19 in integrated care facilities. Further COVID-related research is required to be undertaken on the most commonly prescribed medicines.
-
3.
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.
-
4.
Rugby Fans in Training New Zealand (RUFIT NZ): a randomized controlled trial to assess the effectiveness of a healthy lifestyle program for overweight men delivered through professional rugby clubs.
Maddison, R, Hargreaves, EA, Jiang, Y, Calder, AJ, Wyke, S, Gray, CM, Hunt, K, Lubans, DR, Eyles, H, Draper, N, et al
The international journal of behavioral nutrition and physical activity. 2023;(1):37
Abstract
BACKGROUND A healthy lifestyle program that appeals to, and supports, overweight and obese New Zealand (NZ) European, Māori (indigenous) and Pasifika men to achieve weight loss is urgently needed. A pilot program inspired by the successful Football Fans in Training program but delivered via professional rugby clubs in NZ (n = 96) was shown to be effective in weight loss, adherence to healthy lifestyle behaviors, and cardiorespiratory fitness in overweight and obese men. A full effectiveness trial is now needed. AIMS To determine the effectiveness and cost effectiveness of Rugby Fans In Training-NZ (RUFIT-NZ) on weight loss, fitness, blood pressure, lifestyle change, and health related quality of life (HRQoL) at 12- and 52-weeks. METHODS We conducted a pragmatic, two-arm, multi-center, randomized controlled trial in NZ with 378 (target 308) overweight and obese men aged 30-65 years, randomized to an intervention group or wait-list control group. The 12-week RUFIT-NZ program was a gender-sensitised, healthy lifestyle intervention delivered through professional rugby clubs. Each intervention session included: i) a 1-h workshop-based education component focused on nutrition, physical activity, sleep, sedentary behavior, and learning evidence-based behavior change strategies for sustaining a healthier lifestyle; and 2) a 1-h group-based, but individually tailored, exercise training session. The control group were offered RUFIT-NZ after 52-weeks. The primary outcome was change in body weight from baseline to 52-weeks. Secondary outcomes included change in body weight at 12-weeks, waist circumference, blood pressure, fitness (cardiorespiratory and musculoskeletal), lifestyle behaviors (leisure-time physical activity, sleep, smoking status, and alcohol and dietary quality), and health-related quality of life at 12- and 52-weeks. RESULTS Our final analysis included 200 participants (intervention n = 103; control n = 97) who were able to complete the RUFIT-NZ intervention prior to COVID-19 restrictions. At 52-weeks, the adjusted mean group difference in weight change (primary outcome) was -2.77 kg (95% CI -4.92 to -0.61), which favored the intervention group. The intervention also resulted in favorable significant differences in weight change and fruit and vegetable consumption at 12-weeks; and waist circumference, fitness outcomes, physical activity levels, and health-related quality of life at both 12 and 52 weeks. No significant intervention effects were observed for blood pressure, or sleep. Incremental cost-effective ratios estimated were $259 per kg lost, or $40,269 per quality adjusted life year (QALY) gained. CONCLUSION RUFIT-NZ resulted in sustained positive changes in weight, waist circumference, physical fitness, self-reported physical activity, selected dietary outcomes, and health-related quality of life in overweight/obese men. As such, the program should be recommended for sustained delivery beyond this trial, involving other rugby clubs across NZ. TRIAL REGISTRATION Australia New Zealand Clinical Trials Registry, ACTRN12619000069156. Registered 18 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376740 Universal Trial Number, U1111-1245-0645.
-
5.
Association of the presence of a COVID-19 infection at the time of birth and the rates of exclusive breastfeeding upon discharge in BFHI hospitals: a multicenter, prospective cohort study.
Marín Gabriel, MÁ, Martín Lozoya, S, de Las Heras Ibarra, S, Domingo Comeche, L, González Carrasco, E, Lalaguna Mallada, P, Villó Sirerol, N, García Fernández, L, Jiménez Martínez, J, Royuela Vicente, A
International breastfeeding journal. 2023;(1):54
Abstract
BACKGROUND Very few studies have assessed the association between COVID-19 infection and the rates of exclusive breastfeeding (EBF) upon discharge following the first waves of the pandemic and after initiation of vaccination. The primary objective of this study is to compare the rates of EBF since birth upon discharge in mothers diagnosed with COVID-19 infection at the time of the delivery versus a group of non-infected mothers in maternity hospitals with Baby Friendly Hospital Initiative (BFHI) accreditation. The secondary objectives include determining the rates of any breastfeeding at three and six months of life in both groups, as well as determining the possible factors associated with EBF rates observed upon discharge. METHODS An observational, Spanish multi-center hospital, prospective cohort study conducted from 1 to 2021 to 31 March 2022 and with follow-up during the first six months of life. Follow-up was performed via telephone contact with calls performed at three and six months. A multivariate logistic regression analysis model was used to identify the factors related to a lower probability of EBF upon discharge. RESULTS 308 mother-infant pairs participated in the study, 111 in the cohort of women with COVID infection and 197 in the comparison group. EBF upon discharge was 62.7% in the COVID group vs. 81.2% in the comparison group (p = 0.002); at three months; 52.4% vs. 57.0% (p = 0.33) were performing EBF, with the rates of EBF at six months being 43.0% vs. 39.3% (p = 0.45), respectively. Exposure to COVID-19 at delivery (AOR 5.28; 95% CI 2.01, 13.86), not practicing BF previously (AOR 36.3; 95% CI 7.02, 187.74), birth via Cesarean section (AOR 5.06; 95% CI 1.62, 15.79) and low birth weight of the newborn (AOR 1.01; 95% CI 1.01, 1.01) were associated with a greater risk of not performing EBF upon discharge. CONCLUSIONS Mothers with a mild or asymptomatic COVID-19 infection at the time of the delivery were less likely to have exclusively breastfed during their hospital stay than other mothers in these BFHI-accredited hospitals. However, there were no differences in breastfeeding rates between the groups at three and six months postpartum.
-
6.
The added effect of non-pharmaceutical interventions and lifestyle behaviors on vaccine effectiveness against severe COVID-19 in Chile: A matched case-double control study.
Urquidi, C, Santelices, E, Lagomarcino, AJ, Teresa Valenzuela, M, Larrañaga, N, Gonzalez, E, Pavez, A, Wosiack, A, Maturana, M, Moller, P, et al
Vaccine. 2023;(18):2947-2955
-
-
Free full text
-
Abstract
BACKGROUND World Health Organization approved vaccines have demonstrated relatively high protection against moderate to severe COVID-19. Prospective vaccine effectiveness (VE) designs with first-hand data and population-based controls are nevertheless rare. Neighborhood compared to hospitalized controls, may differ in compliance to non-pharmacuetical interventions (NPI) compliance, which may influence VE results in real-world settings. We aimed to determine VE against COVID-19 intensive-care-unit (ICU) admission using hospital and community-matched controls in a prospective design. METHODS We conducted a multicenter, observational study of matched cases and controls (1:3) in adults ≧18 years of age from May to July 2021. For each case, a hospital control and two community controls were matched by age, gender, and hospital admission date or neighborhood of residence. Conditional logistic regression models were built, including interaction terms between NPIs, lifestyle behaviors, and vaccination status; the model's β coefficients represent the added effect these terms had on COVID-19 VE. RESULTS Cases and controls differed in several factors including education level, obesity prevalence, and behaviors such as compliance with routine vaccinations, use of facemasks, and routine handwashing. VE was 98·2% for full primary vaccination and 85·6% for partial vaccination when compared to community controls, and somewhat lower, albeit not significantly, compared to hospital controls. A significant added effect to vaccination in reducing COVID-19 ICU admission was regular facemask use and VE was higher among individuals non-compliant with the national vaccine program, and/or tonroutine medical visits during the prior year. CONCLUSION VE against COVID-19 ICU admission in this stringent prospective case-double control study reached 98% two weeks after full primary vaccination, confirming the high effectiveness provided by earlier studies. Face mask use and hand washing were independent protective factors, the former adding additional benefit to VE. VE was significantly higher in subjects with increased risk behaviors.
-
7.
FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial.
Guérin, E, Belin, L, Franchineau, G, Le Guennec, L, Hajage, D, Diallo, MH, Frapard, T, Le Fèvre, L, Luyt, CE, Combes, A, et al
Critical care (London, England). 2023;(1):331
Abstract
BACKGROUND Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. METHODS This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi). RESULTS Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009). CONCLUSIONS In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020.
-
8.
Long-term outcomes in critically ill patients who survived COVID-19: The NUTRICOVID observational cohort study.
Álvarez-Hernández, J, Matía-Martín, P, Cáncer-Minchot, E, Cuerda, C, ,
Clinical nutrition (Edinburgh, Scotland). 2023;(10):2029-2035
Abstract
BACKGROUND & AIMS Malnutrition and sarcopenia may last beyond hospital discharge, especially in patients admitted to intensive care units (ICU), having a negative impact on patient recovery and leading to disability, poor quality of life, and additional morbidity. No prior evidence is available for post-ICU management and follow-up of coronavirus disease 2019 (COVID-19) patients and their long-term evolution. This study reports on the one-year-long evolution of a cohort of COVID-19 survivors after ICU discharge, in terms of nutritional and functional status as well as health-related quality of life (HRQoL). METHODS A multicenter, ambispective, observational cohort study (NUTRICOVID study) was conducted in 16 public hospitals located in the Community of Madrid with COVID-19 survivors who were admitted to ICU during the first outbreak. Retrospective and prospective data were collected from hospital admission to one year after discharge. At hospital discharge and at 3, 6 and 12 months post-discharge, the following outcomes were recorded: weight, risk of malnutrition (MUST) and sarcopenia (SARC-F), medical nutrition therapy (MNT), functional status (Barthel index), and HRQoL (EQ-5D-5L). RESULTS A total of 199 patients (70.4% male, mean age [SD] of 60.7 [10.1]) were included in the study. At hospital discharge, mean weight loss was 16.4% (8.0%), whereas most patients gained weight after discharge with an increase of 16.5% (14.0%) at 12 months. The proportion of patients at high risk of malnutrition decreased from 83.2% at hospital discharge to 2.1% at 12 months. The proportion at risk of sarcopenia decreased from 86.9% at hospital discharge to 13.4% at 12 months. At hospital discharge, 69 patients received MNT by means of oral nutritional supplements (ONS) while two patients required enteral nutrition (EN). At 12 months, only 12 patients continued taking ONS, with no patients taking EN. Regarding functional status, 72.9% of patients were moderately or severely dependent at hospital discharge, whereas 87.2% showed low dependency or independency after 12 months. The EQ-VAS values increased from hospital discharge (39 [21.2]) to 6 months post-discharge and remained steady up to 12 months (72.7 [19.0]). The mean health value improved from hospital discharge (0.25 [0.41]) to 6 months post-discharge (0.80 [0.24]) and was maintained thereafter. CONCLUSIONS Patients' nutritional and functional impairment at hospital discharge was high, with high dependency status and low HRQoL; however, their situation improved progressively during the 12 months following hospital discharge. Nevertheless, there is a need to define early strategies to optimize the nutritional and functional recovery of COVID-19 patients.
-
9.
PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.
Navarese, EP, Podhajski, P, Gurbel, PA, Grzelakowska, K, Ruscio, E, Tantry, U, Magielski, P, Kubica, A, Niezgoda, P, Adamski, P, et al
Journal of the American College of Cardiology. 2023;(3):224-234
Abstract
BACKGROUND The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).
-
10.
Inhaled prostacyclin therapy in the acute respiratory distress syndrome: a randomized controlled multicenter trial.
Haeberle, HA, Calov, S, Martus, P, Serna-Higuita, LM, Koeppen, M, Goll, A, Bernard, A, Zarbock, A, Meersch, M, Weiss, R, et al
Respiratory research. 2023;(1):58
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS. METHODS We performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride (Placebo). The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events. RESULTS Of 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline PaO2/FiO2 ratio did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than Placebo (p = 0.17). Secondary analysis showed that the oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0.04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups. CONCLUSIONS The primary result of our study was negative. Our data suggest that inhaled prostacyclin might be beneficial treatment in patients with COVID-19 induced ARDS. TRIAL REGISTRATION The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016003168-37) and registered at clinicaltrials.gov (NCT03111212) on April 6th 2017.