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Journal of Clinical Laboratory Analysis Apr 2021This research aimed to explore the effects of probiotic administration on glycemic control and renal function in patients with diabetic nephropathy (DN). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This research aimed to explore the effects of probiotic administration on glycemic control and renal function in patients with diabetic nephropathy (DN).
METHODS
The 101 participants were randomly divided into two treatment groups and 76 patients were included in the final analysis. In 76 patients with diabetic nephropathy of type 2 diabetes, a randomized double-blind and placebo-controlled clinical trial was conducted to evaluate the administration of 3.2 × 10 CFU probiotic supplements per day (Bifidobacterium bifidum, 1.2 × 10 CFU, Lactobacillus acidophilus 4.2 × 10 CFU, Streptococcus thermophilus 4.3 × 10 CFU) for 12 weeks on glycemic control of patients, including fasting blood glucose, 2 h postprandial blood glucose, glycosylated hemoglobin (HbA1c), microalbuminuria/creatinine (mAlb/Cr) and estimated glomerular filtration rate (eGFR) levels. The placebo group daily received empty capsules filled with starch.
RESULTS
After 12 weeks, the administration of probiotics demonstrated a significant reduction in fasting blood glucose (10.68 ± 3.24 mmol/L before vs. 7.81 ± 2.77 mmol/L after, p < 0.05), HbA1c (8.19 ± 1.60% before vs. 7.32 ± 1.20% after, p < 0.05) and mAlb/Cr (101.60 ± 22.17 mg/g before vs. 67.53 ± 20.11 mg/g after, p < 0.05), while only mAlb/Cr level was significantly lower in the probiotic group than in the placebo group after intervention (67.53 ± 20.11 mg/g vs. 87.71 ± 23.01, p < 0.05). Meanwhile, there was no significant reduction of 2 h postprandial blood glucose level (18.95 ± 5.23 mmol/L vs. 17.35 ± 6.28 mmol/L, p = 0.24) and eGFR (84.34 ± 6.97 ml/min vs. 82.8 ± 8.72 ml/min, p = 0.45) in patients before and after probiotic intake. In addition, the placebo group failed to show any significant change of these parameters.
CONCLUSION
This clinical study revealed probiotic administration could ameliorate glycemic control of patients with diabetic nephropathy, potentiating its therapeutic potential in clinical application.
Topics: Albuminuria; Blood Glucose; Creatinine; Diabetic Nephropathies; Fasting; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Glycemic Control; Humans; Male; Middle Aged; Placebos; Postprandial Period; Probiotics
PubMed: 33666270
DOI: 10.1002/jcla.23650 -
The Cochrane Database of Systematic... Mar 2021Mechanical ventilation is a potentially painful and discomforting intervention that is widely used in neonatal intensive care. Newborn infants demonstrate increased... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mechanical ventilation is a potentially painful and discomforting intervention that is widely used in neonatal intensive care. Newborn infants demonstrate increased sensitivity to pain, which may affect clinical and neurodevelopmental outcomes. The use of drugs that reduce pain might be important in improving survival and neurodevelopmental outcomes.
OBJECTIVES
To determine the benefits and harms of opioid analgesics for neonates (term or preterm) receiving mechanical ventilation compared to placebo or no drug, other opioids, or other analgesics or sedatives.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 9), in the Cochrane Library; MEDLINE via PubMed (1966 to 29 September 2020); Embase (1980 to 29 September 2020); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 29 September 2020). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials comparing opioids to placebo or no drug, to other opioids, or to other analgesics or sedatives in newborn infants on mechanical ventilation. We excluded cross-over trials. We included term (≥ 37 weeks' gestational age) and preterm (< 37 weeks' gestational age) newborn infants on mechanical ventilation. We included any duration of drug treatment and any dosage given continuously or as bolus; we excluded studies that gave opioids to ventilated infants for procedures.
DATA COLLECTION AND ANALYSIS
For each of the included trials, we independently extracted data (e.g. number of participants, birth weight, gestational age, types of opioids) using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria and assessed the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included 23 studies (enrolling 2023 infants) published between 1992 and 2019. Fifteen studies (1632 infants) compared the use of morphine or fentanyl versus placebo or no intervention. Four studies included both term and preterm infants, and one study only term infants; all other studies included only preterm infants, with five studies including only very preterm infants. We are uncertain whether opioids have an effect on the Premature Infant Pain Profile (PIPP) Scale in the first 12 hours after infusion (MD -5.74, 95% confidence interval (CI) -6.88 to -4.59; 50 participants, 2 studies) and between 12 and 48 hours after infusion (MD -0.98, 95% CI -1.35 to -0.61; 963 participants, 3 studies) because of limitations in study design, high heterogeneity (inconsistency), and imprecision of estimates (very low-certainty evidence - GRADE). The use of morphine or fentanyl probably has little or no effect in reducing duration of mechanical ventilation (MD 0.23 days, 95% CI -0.38 to 0.83; 1259 participants, 7 studies; moderate-certainty evidence because of unclear risk of bias in most studies) and neonatal mortality (RR 1.12, 95% CI 0.80 to 1.55; 1189 participants, 5 studies; moderate-certainty evidence because of imprecision of estimates). We are uncertain whether opioids have an effect on neurodevelopmental outcomes at 18 to 24 months (RR 2.00, 95% CI 0.39 to 10.29; 78 participants, 1 study; very low-certainty evidence because of serious imprecision of the estimates and indirectness). Limited data were available for the other comparisons (i.e. two studies (54 infants) on morphine versus midazolam, three (222 infants) on morphine versus fentanyl, and one each on morphine versus diamorphine (88 infants), morphine versus remifentanil (20 infants), fentanyl versus sufentanil (20 infants), and fentanyl versus remifentanil (24 infants)). For these comparisons, no meta-analysis was conducted because outcomes were reported by one study.
AUTHORS' CONCLUSIONS
We are uncertain whether opioids have an effect on pain and neurodevelopmental outcomes at 18 to 24 months; the use of morphine or fentanyl probably has little or no effect in reducing the duration of mechanical ventilation and neonatal mortality. Data on the other comparisons planned in this review (opioids versus analgesics; opioids versus other opioids) are extremely limited and do not allow any conclusions. In the absence of firm evidence to support a routine policy, opioids should be used selectively - based on clinical judgement and evaluation of pain indicators - although pain measurement in newborns has limitations.
Topics: Analgesics, Opioid; Bias; Child Development; Fentanyl; Heroin; Humans; Hypnotics and Sedatives; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Midazolam; Morphine; Pain, Procedural; Placebos; Randomized Controlled Trials as Topic; Remifentanil; Respiration, Artificial; Sufentanil
PubMed: 33729556
DOI: 10.1002/14651858.CD013732.pub2 -
The Cochrane Database of Systematic... Jul 2021Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral...
BACKGROUND
Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the early stages of infection. Currently, evidence on efficacy and safety of ivermectin for prevention of SARS-CoV-2 infection and COVID-19 treatment is conflicting.
OBJECTIVES
To assess the efficacy and safety of ivermectin compared to no treatment, standard of care, placebo, or any other proven intervention for people with COVID-19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS-CoV-2 (postexposure prophylaxis).
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), medRxiv, and Research Square, identifying completed and ongoing studies without language restrictions to 26 May 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing ivermectin to no treatment, standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity, treated in inpatient or outpatient settings, and for prevention of SARS-CoV-2 infection. Co-interventions had to be the same in both study arms. We excluded studies comparing ivermectin to other pharmacological interventions with unproven efficacy.
DATA COLLECTION AND ANALYSIS
We assessed RCTs for bias, using the Cochrane risk of bias 2 tool. The primary analysis excluded studies with high risk of bias. We used GRADE to rate the certainty of evidence for the following outcomes 1. to treat inpatients with moderate-to-severe COVID-19: mortality, clinical worsening or improvement, adverse events, quality of life, duration of hospitalization, and viral clearance; 2. to treat outpatients with mild COVID-19: mortality, clinical worsening or improvement, admission to hospital, adverse events, quality of life, and viral clearance; (3) to prevent SARS-CoV-2 infection: SARS-CoV-2 infection, development of COVID-19 symptoms, adverse events, mortality, admission to hospital, and quality of life.
MAIN RESULTS
We found 14 studies with 1678 participants investigating ivermectin compared to no treatment, placebo, or standard of care. No study compared ivermectin to an intervention with proven efficacy. There were nine studies treating participants with moderate COVID-19 in inpatient settings and four treating mild COVID-19 cases in outpatient settings. One study investigated ivermectin for prevention of SARS-CoV-2 infection. Eight studies had an open-label design, six were double-blind and placebo-controlled. Of the 41 study results contributed by included studies, about one third were at overall high risk of bias. Ivermectin doses and treatment duration varied among included studies. We identified 31 ongoing and 18 studies awaiting classification until publication of results or clarification of inconsistencies. Ivermectin compared to placebo or standard of care for inpatient COVID-19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.14 to 2.51; 2 studies, 185 participants; very low-certainty evidence) and clinical worsening up to day 28 assessed as need for invasive mechanical ventilation (IMV) (RR 0.55, 95% CI 0.11 to 2.59; 2 studies, 185 participants; very low-certainty evidence) or need for supplemental oxygen (0 participants required supplemental oxygen; 1 study, 45 participants; very low-certainty evidence), adverse events within 28 days (RR 1.21, 95% CI 0.50 to 2.97; 1 study, 152 participants; very low-certainty evidence), and viral clearance at day seven (RR 1.82, 95% CI 0.51 to 6.48; 2 studies, 159 participants; very low-certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on clinical improvement up to 28 days (RR 1.03, 95% CI 0.78 to 1.35; 1 study; 73 participants; low-certainty evidence) and duration of hospitalization (mean difference (MD) -0.10 days, 95% CI -2.43 to 2.23; 1 study; 45 participants; low-certainty evidence). No study reported quality of life up to 28 days. Ivermectin compared to placebo or standard of care for outpatient COVID-19 treatment We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality up to 28 days (RR 0.33, 95% CI 0.01 to 8.05; 2 studies, 422 participants; very low-certainty evidence) and clinical worsening up to 14 days assessed as need for IMV (RR 2.97, 95% CI 0.12 to 72.47; 1 study, 398 participants; very low-certainty evidence) or non-IMV or high flow oxygen requirement (0 participants required non-IMV or high flow; 1 study, 398 participants; very low-certainty evidence). We are uncertain whether ivermectin compared to placebo reduces or increases viral clearance at seven days (RR 3.00, 95% CI 0.13 to 67.06; 1 study, 24 participants; low-certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on the number of participants with symptoms resolved up to 14 days (RR 1.04, 95% CI 0.89 to 1.21; 1 study, 398 participants; low-certainty evidence) and adverse events within 28 days (RR 0.95, 95% CI 0.86 to 1.05; 2 studies, 422 participants; low-certainty evidence). None of the studies reporting duration of symptoms were eligible for primary analysis. No study reported hospital admission or quality of life up to 14 days. Ivermectin compared to no treatment for prevention of SARS-CoV-2 infection We found one study. Mortality up to 28 days was the only outcome eligible for primary analysis. We are uncertain whether ivermectin reduces or increases mortality compared to no treatment (0 participants died; 1 study, 304 participants; very low-certainty evidence). The study reported results for development of COVID-19 symptoms and adverse events up to 14 days that were included in a secondary analysis due to high risk of bias. No study reported SARS-CoV-2 infection, hospital admission, and quality of life up to 14 days.
AUTHORS' CONCLUSIONS
Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials.
Topics: Antiparasitic Agents; Antiviral Agents; COVID-19; Cause of Death; Humans; Ivermectin; Placebos; Post-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Time Factors; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34318930
DOI: 10.1002/14651858.CD015017.pub2 -
PloS One 2023The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse.
METHODS
This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture.
RESULTS
A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups.
CONCLUSIONS
The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion.
TRIAL REGISTRATION
CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).
Topics: Humans; Cholecalciferol; Dietary Supplements; Treatment Outcome; Vitamin D; Vitamins; Tuberculosis, Pulmonary; Double-Blind Method; Recurrence
PubMed: 36996065
DOI: 10.1371/journal.pone.0272682 -
International Journal of Nanomedicine 2020In the past few years, we have witnessed great development and application potential of various up-conversion luminescent nanoparticles (UCNPs) in the nanomedicine... (Review)
Review
In the past few years, we have witnessed great development and application potential of various up-conversion luminescent nanoparticles (UCNPs) in the nanomedicine field. Based on the unique luminescent mechanism of UCNPs and the distinguishable features of cancer biomarkers and the microenvironment, an increasing number of smart UCNPs nanoprobes have been designed and widely applied to molecular imaging, cancer diagnosis, and treatment. Considerable technological success has been achieved, but the main obstacles to oncology nanomedicine is becoming an incomplete understanding of nano-bio interactions, the challenges regarding chemistry manufacturing and controls required for clinical translation and so on. This review highlights the progress of the design principles, synthesis and surface functionalization preparation, underlying applications and challenges of UCNPs-based probes for cancer bioimaging, diagnosis and treatment that capitalize on our growing understanding of tumor biology and smart nano-devices for accelerating the commercialization of UCNPs.
Topics: Humans; Luminescence; Molecular Imaging; Nanoparticles; Neoplasms; Theranostic Nanomedicine; Tumor Microenvironment
PubMed: 33268986
DOI: 10.2147/IJN.S266006 -
CPT: Pharmacometrics & Systems... Apr 2021This study tested the hypothesis that analyzing longitudinal item scores of the Unified Parkinson's Disease Rating Scale could allow a smaller trial size and describe a... (Clinical Trial)
Clinical Trial
This study tested the hypothesis that analyzing longitudinal item scores of the Unified Parkinson's Disease Rating Scale could allow a smaller trial size and describe a drug's effect on symptom progression. Two historical studies of the dopaminergic drug ropinirole were analyzed: a cross-over formulation comparison trial in 161 patients with early-stage Parkinson's disease, and a 24-week, parallel-group, placebo-controlled efficacy trial in 393 patients with advanced-stage Parkinson's disease. We applied item response theory to estimate the patients' symptom severity and developed a longitudinal model using the symptom severity to describe the time course of the placebo response and the drug effect on the time course. Similarly, we developed a longitudinal model using the total score. We then compared sample size needs for drug effect detection using these two different models. Total score modeling estimated median changes from baseline at 24 weeks (90% confidence interval) of -3.7 (-5.4 to -2.0) and -9.3 (-11 to -7.3) points by placebo and ropinirole. Comparable changes were estimated (with slightly higher precision) by item-score modeling as -2.0 (-4.0 to -1.0) and -9.0 (-11 to -8.0) points. The treatment duration was insufficient to estimate the symptom progression rate; hence the drug effect on the progression could not be assessed. The trial sizes to detect a drug effect with 80% power on total score and on symptom severity were estimated (at the type I error level of 0.05) as 88 and 58, respectively. Longitudinal item response analysis could markedly reduce sample size; it also has the potential for assessing drug effects on disease progression in longer trials.
Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cross-Over Studies; Dopamine Agonists; Drug Development; Female; Humans; Indoles; Longitudinal Studies; Male; Mental Status and Dementia Tests; Middle Aged; Parkinson Disease; Placebos; Severity of Illness Index
PubMed: 33951753
DOI: 10.1002/psp4.12601 -
Nature Communications Jan 2022Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous...
Metallic and semimetallic mesoporous frameworks are of great importance owing to their unique properties and broad applications. However, semimetallic mesoporous structures cannot be obtained by the traditional template-mediated strategies due to the inevitable hydrolytic reaction of semimetal compounds. Therefore, it is yet challenging to fabricate mesoporous semimetal nanostructures, not even mention controlling their pore sizes. Here we develop a facile and robust selective etching route to synthesize monodispersed mesoporous antimony nanospheres (MSbNSs). The pore sizes of MSbNSs are tunable by carefully controlling the partial oxidation of Sb nuclei and the selective etching of the as-formed SbO. MSbNSs show a wide absorption from visible to second near-infrared (NIR-II) region. Moreover, PEGylated MSbNSs are degradable and the degradation mechanism is further explained. The NIR-II photothermal performance of MSbNSs is promising with a high photothermal conversion efficiency of ~44% and intensive NIR-II photoacoustic signal. MSbNSs show potential as multifunctional nanomedicines for NIR-II photoacoustic imaging guided synergistic photothermal/chemo therapy in vivo. Our selective etching process would contribute to the development of various semimetallic mesoporous structures and efficient multimodal nanoplatforms for theranostics.
Topics: Animals; Antimony; Diagnostic Imaging; Drug Delivery Systems; Drug Therapy; Female; Humans; Mice; Mice, Inbred C57BL; Nanoparticles; Nanospheres; Nanostructures; Neoplasms; Photoacoustic Techniques; Phototherapy; Precision Medicine; Theranostic Nanomedicine
PubMed: 35087022
DOI: 10.1038/s41467-021-27835-y -
Theranostics 2021In recent years tremendous effort has been invested in the field of cancer diagnosis and treatment with an overall goal of improving cancer management, therapeutic... (Review)
Review
In recent years tremendous effort has been invested in the field of cancer diagnosis and treatment with an overall goal of improving cancer management, therapeutic outcome, patient survival, and quality of life. Photodynamic Therapy (PDT), which works on the principle of light-induced activation of photosensitizers (PS) leading to Reactive Oxygen Species (ROS) mediated cancer cell killing has received increased attention as a promising alternative to overcome several limitations of conventional cancer therapies. Compared to conventional therapies, PDT offers the advantages of selectivity, minimal invasiveness, localized treatment, and spatio-temporal control which minimizes the overall therapeutic side effects and can be repeated as needed without interfering with other treatments and inducing treatment resistance. Overall PDT efficacy requires proper planning of various parameters like localization and concentration of PS at the tumor site, light dose, oxygen concentration and heterogeneity of the tumor microenvironment, which can be achieved with advanced imaging techniques. Consequently, there has been tremendous interest in the rationale design of PS formulations to exploit their theranostic potential to unleash the imperative contribution of medical imaging in the context of successful PDT outcomes. Further, recent advances in PS formulations as activatable phototheranostic agents have shown promising potential for finely controlled imaging-guided PDT due to their propensity to specifically turning on diagnostic signals simultaneously with photodynamic effects in response to the tumor-specific stimuli. In this review, we have summarized the recent progress in the development of PS-based multifunctional theranostic agents for biomedical applications in multimodal imaging combined with PDT. We also present the role of different imaging modalities; magnetic resonance, optical, nuclear, acoustic, and photoacoustic in improving the pre-and post-PDT effects. We anticipate that the information presented in this review will encourage future development and design of PSs for improved image-guided PDT for cancer treatment.
Topics: Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Precision Medicine; Reactive Oxygen Species; Theranostic Nanomedicine; Tumor Microenvironment
PubMed: 34522227
DOI: 10.7150/thno.62479 -
Value in Health : the Journal of the... May 2022Emergence of severe acute respiratory syndrome coronavirus 2 infections and the resultant disease, COVID-19 led the world into 238 million cases and 4.8 million deaths...
OBJECTIVES
Emergence of severe acute respiratory syndrome coronavirus 2 infections and the resultant disease, COVID-19 led the world into 238 million cases and 4.8 million deaths over the first 22 months of the pandemic. While numerous vaccines have been developed to combat this pandemic, limited literature is available regarding the comparison of these vaccines. This study aims to systematically review and evaluate the immunogenicity and safety of COVID-19 vaccines compared with control arms in the healthy adult population.
METHODS
A literature search was conducted in PubMed, MEDLINE, Embase, and Cochrane up to July 4, 2021. Randomized controlled trials assessing the immunogenicity of any dose of COVID-19 vaccine in adults by anti-severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies geometric mean titers (GMTs) and neutralizing antibodies GMT response at 28 days postimmunization compared with the control groups in the healthy adults were considered for inclusion. Groups at day 28 with the highest GMT were further examined for their adverse events.
RESULTS
Of the 341 citations retrieved, 19 were included. This covered a total of 16 vaccines involving 8342 subjects aged between 30.8 and 69.7 years, comprising 52.13% females. All studies reported GMT at or close to 28 days postvaccination compared with placebo and comparator, and 13 of 19 studies reported seroconversion rates. While 15 of 16 vaccines reported adverse events that ranged from mild to severe, 1 of 16 (AD26.COV2.S) noted 1 case of a vaccine-related serious adverse event-high fever 6 hours after vaccination. Local reactions (such as redness, pain, and swelling) and systematic reactions (such as fatigue, fever, and headache) were commonly noted. Safety between vaccines was similar; however, higher rates of severe adverse events were noted in Ad5-vectored COVID-19, AD26.COV2.S, ChAdOx nCoV-19, and mRNA-1273. No all-cause mortality was documented in any vaccines.
CONCLUSIONS
All 16 vaccines elicited an immune response substantially higher than the control groups while maintaining tolerable safety profiles.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Ad26COVS1; COVID-19; COVID-19 Vaccines; Vaccination; Vaccines; Randomized Controlled Trials as Topic
PubMed: 35500945
DOI: 10.1016/j.jval.2021.09.003 -
Clinical Trials (London, England) Aug 2021Although several COVID-19 vaccines have been found to be effective in rigorous evaluation and have emerging availability in parts of the world, their supply will be...
BACKGROUND
Although several COVID-19 vaccines have been found to be effective in rigorous evaluation and have emerging availability in parts of the world, their supply will be inadequate to meet international needs for a considerable period of time. There also will be continued interest in vaccines that are more effective or have improved scalability to facilitate mass vaccination campaigns. Ongoing clinical testing of new vaccines also will be needed as variant strains continue to emerge that may elude some aspects of immunity induced by current vaccines. Randomized clinical trials meaningfully enhance the efficiency and reliability of such clinical testing. In clinical settings with limited or no access to known effective vaccines, placebo-controlled randomized trials of new vaccines remain a preferred approach to maximize the reliability, efficiency and interpretability of results. When emerging availability of licensed vaccines makes it no longer possible to use a placebo control, randomized active comparator non-inferiority trials may enable reliable insights.
METHODS
In this article, "hybrid" methods are proposed to address settings where, during the conduct of a placebo-controlled trial, a judgment is made to replace the placebo arm by a licensed COVID-19 vaccine due to emerging availability of effective vaccines in regions participating in that trial. These hybrid methods are based on proposed statistics that aggregate evidence to formally test as well as to estimate the efficacy of the experimental vaccine, by combining placebo-controlled data during the first period of trial conduct with active-controlled data during the second period.
RESULTS
Application of the proposed methods is illustrated in two important scenarios where the active control vaccine would become available in regions engaging in the experimental vaccine's placebo-controlled trial: in the first, the active comparator's vaccine efficacy would have been established to be 50%-70% for the 4- to 6-month duration of follow-up of its placebo-controlled trial; in the second, the active comparator's vaccine efficacy would have been established to be 90%-95% during that duration. These two scenarios approximate what has been seen with adenovirus vaccines or mRNA vaccines, respectively, assuming the early estimates of vaccine efficacy for those vaccines would hold over longer-term follow-up.
CONCLUSION
The proposed hybrid methods could readily play an important role in the near future in the design, conduct and analysis of randomized clinical trials performed to address the need for multiple additional vaccines reliably established to be safe and have worthwhile efficacy in reducing the risk of symptomatic disease from SARS-CoV-2 infections.
Topics: COVID-19; COVID-19 Vaccines; Control Groups; Humans; Placebos; Randomized Controlled Trials as Topic; SARS-CoV-2
PubMed: 34041932
DOI: 10.1177/17407745211018613