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Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials.
Furtado, RHM, Barros E Silva, PGM, Fonseca, HAR, Serpa-Neto, A, Correa, TD, Guimarães, HP, Pereira, AJ, Olivato, GB, Zampieri, FG, Lisboa, T, et al
The American journal of cardiology. 2024;:18-24
Abstract
The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.
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Increasing Natural Killer Cell Activity of Mineral Nanomaterial ALP1018 in Healthy Adults: A Randomized, Double-Blind, Placebo Comparative Clinical Trial.
Kim, SA, Kim, S, Chai, H, Cho, J, Paek, YJ
Nutrients. 2024;(6)
Abstract
This randomized, double-blind, placebo comparative clinical trial aimed to determine the immune-enhancing effects and safety of a nanomaterial with iron and zinc (ALP1018) in healthy adults. Participants who met the inclusion criteria were recruited for this study (n = 80) and randomly assigned to either the test group (n = 40), which was given Alp1018 in capsule form, or the placebo group (n = 40), which was given crystal cellulose capsules of identical appearance, weight, and flavor for 8 weeks. Compared to baseline, natural killer (NK) cell activity (%) increased in the test group after 8 weeks, although there were no changes in the placebo group. Furthermore, in the subgroup analysis of Coronavirus disease 2019 (COVID-19) affected participants, significantly increased NK cell activity was observed in the test group at 4 (p < 0.05) and 8 weeks (p < 0.05). No significant differences were observed in cytokine levels between the two groups. ALP1018 supplementation appeared to enhance immune function by improving NK cell activity without adverse effects in healthy adults.
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Plant stanol consumption increases anti-COVID-19 antibody responses, independent of changes in serum cholesterol concentrations: a randomized controlled trial.
van Brakel, L, Mensink, RP, Lütjohann, D, Plat, J
The American journal of clinical nutrition. 2024;(4):969-980
Abstract
BACKGROUND People with overweight/obesity generally have impaired immune responses, resulting among others in increased risk of severe complaints and hospitalization after infections with severe acute respiratory syndrome coronavirus 2 (COVID-19), as well as decreased antibody production after vaccinations. Plant stanol ester previously increased the combined IgM/IgG antibody titers toward a hepatitis A vaccination in patients with allergic asthma, but the underlying mechanism is unknown. OBJECTIVES We evaluated whether plant stanol ester consumption improved the immune response in subjects with overweight/obesity after a COVID-19 vaccination. METHODS A double-blind, randomized, placebo-controlled trial was performed. Thirty-two subjects with overweight/obesity consumed products with added plant stanols (4 g/d; provided as plant stanol ester) or control ≥2 wk before receiving their COVID-19 vaccination until 4 wk after vaccination. Antibody titers were analyzed weekly and statistically analyzed using mixed models. Serum metabolic markers and cytokine profiles were also analyzed. RESULTS IgM concentrations against the COVID-19 Spike protein were increased in the plant stanol ester group compared with the control group, with the largest difference observed 2 wk after vaccination [31.2 (0.43, 62.1) BAU/mL, or +139%; Group × Time: P = 0.031]. Subjects that produced very low IgM antibodies produced, as expected, hardly any IgG antibodies. In those with IgG seroconversion, IgG Spike concentrations were also increased in the plant stanol ester group compared with the control group [71.3 (2.51, 140.1) BAU/mL; Group P = 0.043]. Stimulated cytokine concentrations decreased in the plant stanol ester group compared with the control group in all 3 cytokine domains (that is, proinflammatory, T helper [Th1]/Th17, and Th2/regulatory T cells). Between-group differences in serum LDL cholesterol or other metabolic markers were not observed. CONCLUSIONS Consuming plant stanols (4 g/d) affects immune responses to COVID-19 vaccinations, translating into increased serum anti-COVID-19 IgM concentrations in subjects with overweight/obesity. Only in IgG seroconverted subjects, serum anti-COVID-19 IgG concentrations also increase. These effects are independent of reductions in LDL cholesterol. These results suggest that this high-risk group for COVID-19 complications could benefit from plant stanol consumption. This trial was registered at clinicaltrials.gov as NCT04844346.
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Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial.
Labori, KJ, Bratlie, SO, Andersson, B, Angelsen, JH, Biörserud, C, Björnsson, B, Bringeland, EA, Elander, N, Garresori, H, Grønbech, JE, et al
The lancet. Gastroenterology & hepatology. 2024;(3):205-217
Abstract
BACKGROUND In patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma. METHODS NORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing. FINDINGS Between Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49-71) in the neoadjuvant FOLFIRINOX group versus 73% (62-84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2-34·9) versus 38·5 months (27·6-not reached; hazard ratio [HR] 1·52 [95% CI 1·00-2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46-67) in the neoadjuvant FOLFIRINOX group versus 70% (55-83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2-34·9) versus 34·4 months (19·4-not reached; HR 1·46 [95% CI 0·99-2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event. INTERPRETATION This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven. FUNDING Norwegian Cancer Society, South Eastern Norwegian Health Authority, The Sjöberg Foundation, and Helsinki University Hospital Research Grants.
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Effects of a telerehabilitation program and detraining on cardiorespiratory fitness in patients with post-COVID-19 sequelae: A randomized controlled trial.
Pleguezuelos, E, Del Carmen, A, Moreno, E, Miravitlles, M, Serra, M, Garnacho-Castaño, MV
Scandinavian journal of medicine & science in sports. 2024;(1):e14543
Abstract
BACKGROUND This study aimed to evaluate the effects of a 15-week telerehabilitation program and a detraining period on cardiorespiratory fitness and mechanical efficiency in patients with post-COVID-19 sequelae. METHODS 131 patients with post-COVID-19 sequelae were randomly assigned to one of two groups: patients who carried out the supervised telerehabilitation program (TRG, n = 66) and a control group (CG, n = 65). An incremental cardiopulmonary exercise testing (CPET) was performed on cycle ergometer to compare cardioventilatory responses between experimental groups. RESULTS A significant increase in the CPET duration, peak power output, and mechanical efficiency was observed in TRG compared to CG after the telerehabilitation program (p ≤ 0.001). A significant increase in the CPET duration, peak power output, and mechanical efficiency was verified at 3 months compared to the pretest and after detraining in TRG (p < 0.001). A significant increase in peak oxygen uptake (V̇O2peak ) was identified after the intervention and in the detraining period compared to the pretest in both experimental groups (p < 0.001). A higher ventilatory efficiency was observed after the telerehabilitation program (p = 0.021) than in pretest only in TRG. CONCLUSIONS A 15-week supervised home telerehabilitation program improved exercise capacity, power output, and mechanical efficiency in TRG compared to a CG. The telerehabilitation program was not more effective in improving V̇O2peak than the activities of the CG. However, ventilatory efficiency was improved only after the telerehabilitation program. The reported results after the detraining period highlight the need to maintain the rehabilitation program over time.
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The influence of propolis plus Hyoscyamus niger L. against COVID-19: A phase II, multicenter, placebo-controlled, randomized trial.
Kosari, M, Khorvash, F, Sayyah, MK, Ansari Chaharsoughi, M, Najafi, A, Momen-Heravi, M, Karimian, M, Akbari, H, Noureddini, M, Salami, M, et al
Phytotherapy research : PTR. 2024;(1):400-410
Abstract
The incubation period of COVID-19 symptoms, along with the proliferation and high transmission rate of the SARS-CoV-2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID-19 with acute disease conditions in a double-blinded approach. The study was performed on 140 patients with COVID-19 in a double-blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID-19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID-19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID-19. So, this syrup promises to be an effective treatment in the great challenge of COVID-19.
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Safety of bempedoic acid in patients at high cardiovascular risk and with statin intolerance.
Bays, HE, Bloedon, LT, Lin, G, Powell, HA, Louie, MJ, Nicholls, SJ, Lincoff, AM, Nissen, SE
Journal of clinical lipidology. 2024;(1):e59-e69
Abstract
BACKGROUND Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. The Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes study demonstrated that bempedoic acid reduced cardiovascular (CV) risk in patients at high risk for CV events who were unwilling or unable to take guideline-recommended doses of statins. OBJECTIVE To describe detailed safety information from CLEAR Outcomes, including events in the United States (US) prescribing information based on previous phase 3 hyperlipidemia studies. METHODS CLEAR Outcomes was a double-blind trial conducted in 13,970 patients randomized to oral bempedoic acid 180 mg daily or placebo and followed for a median of 3.4 years. RESULTS In patients who received at least one dose (7,001 bempedoic acid, 6,964 placebo), treatment emergent adverse events (AE) occurred in 86.3 % and 85 % of patients, respectively. COVID-19 was the most frequently reported AE in both groups. Changes in serum creatinine, blood urea nitrogen, hemoglobin, aminotransaminases, and uric acid were consistent with the known safety profile of bempedoic acid. Gout or gouty arthritis occurred in 3.2 % of bempedoic acid and 2.2 % of placebo patients. AE associated with tendinopathies, including tendon rupture, occurred in 2 % of patients in both treatment groups. Cholelithiasis occurred in 2.2 % of bempedoic acid and 1.2 % of placebo patients; AE related to gallbladder disease were similar between treatment groups. CONCLUSIONS Bempedoic acid was well-tolerated compared with placebo. Safety data from the long-term CLEAR Outcomes study reinforce the positive benefit-risk profile of bempedoic acid.
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Remote delivery of a weight management intervention for adults with intellectual disabilities: Results from a randomized non-inferiority trial.
Ptomey, LT, Washburn, RA, Sherman, JR, Mayo, MS, Krebill, R, Szabo-Reed, AN, Honas, JJ, Helsel, BC, Bodde, A, Donnelly, JE
Disability and health journal. 2024;(2):101587
Abstract
BACKGROUND Remote delivery of multi-component weight management interventions results in clinically meaningful weight loss in adults without intellectual disabilities (ID), but the effectiveness of remotely delivered weight management interventions in adults with ID has not previously been evaluated. OBJECTIVE To determine if a weight management intervention delivered remotely could achieve weight loss (kg) at 6 months that is non-inferior to in-person visits in adults with ID and overweight or obesity (BMI ≥25 kg/m2). METHODS Participants were randomized to a 24-mo. trial (6 mos weight loss,12 mos weight maintenance, 6 mos. no-contact follow up) to compare weight loss achieved with the same multicomponent intervention delivered to individual participants in their home either remotely (RD) or during face-to-face home visits (FTF). RESULTS One hundred twenty adults with ID (∼32 years of age, 53 % females) were randomized to the RD (n = 60) or the FTF arm (n = 60). Six-month weight loss in the RD arm (-4.9 ± 7.8 kg) was superior to 6-month weight loss achieved in the FTF arm (-2.1 ± 6.7 kg, p = 0.047). However, this may be partially attributed to the COVID-19 pandemic, since weight loss in the FTF arm was greater in participants who completed the intervention entirely pre-COVID (n = 33,-3.2 %) compared to post-COVID (n = 22, -0.61 %). Weight loss across did not differ significantly between intervention arms at 18 (p = 0.33) or 24 months (p = 0.34). CONCLUSION Our results suggest that remote delivery is a viable option for achieving clinically relevant weight loss and maintenance in adults with ID. NCT REGISTRATION NCT03291509.
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The effect of Aromatherapy with Pelargonium graveolens (P. graveolens) on the fatigue and sleep quality of critical care nurses during the Covid-19 pandemic: A randomized controlled trial.
Karimi, N, Hasanvand, S, Beiranvand, A, Gholami, M, Birjandi, M
Explore (New York, N.Y.). 2024;(1):82-88
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Abstract
OBJECTIVES Measures to reduce nurses' fatigue are necessary to improve the patient's care and the nurse's health and well-being. This study investigated the effectiveness of aromatherapy with Pelargonium graveolens (P. graveolens) essential oil on fatigue and sleep quality of nurses working in intensive care units (ICU). METHODS In this double-blind, randomized, controlled clinical trial, 84 nurses working in the ICU of Covid-19 patients were assigned to two groups of P. graveolens and placebo by the stratified block method. The intervention group inhaled one drop of pure P. graveolens. The placebo group inhaled one drop of pure sunflower oil in three consecutive shifts (morning or evening) and each shift twice for 20 min. Using the Visual Analog Fatigue Scale (VAS-F), fatigue was measured 30 min before the intervention, immediately, and 60 min later. Also, on the morning of the intervention days, sleep quality was assessed with the Verran and Snyder-Halpern (VSH) Sleep Scale. Data analysis was performed using SPSS, version 24. Independent t-tests, Mann-Whitney, Chi-square tests, and MANOVA, were used. RESULTS The mean score of fatigue immediately and 60 min after aromatherapy in the P. graveolens group was lower than in the control group (P ˂ 0.05). There was no significant difference between the mean sleep scores of nurses in the P. graveolens group before and after the intervention (P > 0.05). CONCLUSION Inhalation aromatherapy with P. graveolens essential oil can reduce nurses' fatigue in the ICU. The findings of this study can make nurses interested in using aromatherapy as a self-care method.
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Preoperative dietitian-led Very Low Calorie Diet (VLCD) Clinic for adults living with obesity undergoing gynaecology, laparoscopic cholecystectomy and hernia repair procedures: a pilot parallel randomised controlled trial.
Griffin, SB, Palmer, MA, Strodl, E, Lai, R, Chuah, TL, Burstow, MJ, Ross, LJ
The British journal of nutrition. 2024;(8):1436-1446
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Abstract
Obesity can increase the risk of postoperative complications. Despite increased demand for patients living with obesity to lose weight prior to common surgical procedures, the impact of intentional weight loss on surgical outcomes is largely unknown. We aimed to conduct a pilot study to assess the feasibility of a full-scale randomised controlled trial (RCT) to examine the effect of preoperative dietitian-led Very Low Calorie Diet (VLCD) Clinic on surgical outcomes in gynaecology and general surgeries. Between August 2021 and January 2023, a convenience sample of adults living with obesity (BMI ≥ 30 kg/m2) awaiting gynaecology, laparoscopic cholecystectomy and ventral hernia repair procedures were randomised to dietitian-led VLCD (800-1000 kcal using meal replacements and allowed foods), or control (no dietary intervention), 2-12 weeks preoperatively. Primary outcome was feasibility (recruitment, adherence, safety, attendance, acceptability and quality of life (QoL)). Secondary outcomes were anthropometry and 30-d postoperative outcomes. Outcomes were analysed as intention-to-treat. Fifty-one participants were recruited (n 23 VLCD, n 28 control), mean 48 (sd 13) years, 86 % female, and mean BMI 35·8 (sd 4·6) kg/m2. Recruitment was disrupted by COVID-19, but other thresholds for feasibility were met for VLCD group: high adherence without unfavourable body composition change, high acceptability, improved pre/post QoL (22·1 ± 15 points, < 0·001), with greater reductions in weight (-5·5 kg VLCD v. -0·9 kg control, P < 0·05) waist circumference (-6·6 cm VLCD v. +0·6 control, P < 0·05) and fewer 30-d complications (n 4/21) than controls (n 8/22) (P > 0·05). The RCT study design was deemed feasible in a public hospital setting. The dietitian-led VLCD resulted in significant weight loss and waist circumference reduction compared with a control group, without unfavourable body composition change and improved QoL.