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JAMA Pediatrics Apr 2021Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP).
OBJECTIVE
To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants.
DESIGN, SETTING, AND PARTICIPANTS
The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020.
INTERVENTIONS
Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age.
MAIN OUTCOMES AND MEASURES
The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth.
RESULTS
A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P < .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died.
CONCLUSIONS AND RELEVANCE
This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03201588.
Topics: Arachidonic Acid; Dietary Fats; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Enteral Nutrition; Female; Humans; Infant, Newborn; Infant, Premature; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Patient Acuity; Poisson Distribution; Retinopathy of Prematurity; Treatment Outcome
PubMed: 33523106
DOI: 10.1001/jamapediatrics.2020.5653 -
Lung Cancer (Amsterdam, Netherlands) Apr 2023The efficacy and safety of first-line immune checkpoint inhibitors plus chemotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC)... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of first-line immune checkpoint inhibitors plus chemotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) remains unevaluated, and there are no reports to directly compare the efficacy and safety among different immunotherapy (especially adebrelimab and surplulimab). Suitable phase III randomized controlled trials with two or more different arms were included. Independent reviewers screened and extracted relevant data and disagreements were resolved through consensus. Fixed-effect consistency models were used to calculate the overall survival (OS), progression-free survival (PFS), objective response rate, adverse events ≥ 3, and safety outcomes in the clinically relevant subgroups. In this network meta-analysis, six randomized controlled clinical trials (CAPSTONE-1, ASTRUM-005, CASPIAN, IMpower133, KEYNOTE-604, and an ipilimumab + chemotherapy trial) with totaling 3662 patients were involved. Compared to chemotherapy, immune checkpoint inhibitors plus chemotherapy present higher possibilities to bring about better OS and PFS. Serplulimab + chemotherapy significantly showed a better survival profit in comparison with ipilimumab + chemotherapy (0.67; 0.50-0.90). Compared with chemotherapy, adebrelimab + chemotherapy (0.72; 0,58-0.90), atezolizumab + chemotherapy (0.76; 0.60-0.96) durvalumab + chemotherapy (0.75; 0.62-0.91), and serplulimab + chemotherapy (0.63;0.49-0.82) all presented significantly better overall survival. In terms of progression-free survival, serplulimab + chemotherapy showed better efficacy in comparison with adebrelimab + chemotherapy (0.72; 0,53-0.97), atezolizumab + chemotherapy (0.62; 0.46-0.84), durvalumab + chemotherapy (0.60; 0.45-0.80). Compared with chemotherapy, adebrelimab + chemotherapy (0.67; 0.54-0.83) and serplulimab + chemotherapy (0.48; 0.48-0.86) all presented significantly better PFS. Immunotherapy plus chemotherapy had similar probabilities to cause adverse events of grade ≥ 3. In comparison with chemotherapy, immune checkpoint inhibitors plus chemotherapy were likely to be more suitable for the first-line treatment of ES-SCLC. According to our analysis, serplulimab plus chemotherapy and adebrelimab plus chemotherapy present higher possibilities to show better efficacy and safety, however, the level of evidence of this type of comparison is limited.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Immune Checkpoint Inhibitors; Ipilimumab; Network Meta-Analysis; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic
PubMed: 36774774
DOI: 10.1016/j.lungcan.2023.02.003 -
Ontario Health Technology Assessment... 2012In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework. Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis. Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model. Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature. For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty member_giacomini.htm. For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx. The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
OBJECTIVE
The objective of this evidence-based review was to determine the effectiveness and cost-effectiveness of pulmonary rehabilitation in the management of chronic obstructive pulmonary disease (COPD).
TECHNOLOGY
Pulmonary rehabilitation refers to a multidisciplinary program of care for patients with chronic respiratory impairment that is individually tailored and designed to optimize physical and social performance and autonomy. Exercise training is the cornerstone of pulmonary rehabilitation programs, though they may also include components such as patient education and psychological support. Pulmonary rehabilitation is recommended as the standard of care in the treatment and rehabilitation of patients with COPD who remain symptomatic despite treatment with bronchodilators. For the purpose of this review, the Medical Advisory Secretariat focused on pulmonary rehabilitation programs as defined by the Cochrane Collaboration—that is, any inpatient, outpatient, or home-based rehabilitation program lasting at least 4 weeks that includes exercise therapy with or without any form of education and/or psychological support delivered to patients with exercise limitations attributable to COPD.
RESEARCH QUESTIONS
1. What is the effectiveness and cost-effectiveness of pulmonary rehabilitation compared with usual care (UC) for patients with stable COPD? 2. Does early pulmonary rehabilitation (within 1 month of hospital discharge) in patients who had an acute exacerbation of COPD improve outcomes compared with UC (or no rehabilitation)? 3. Do maintenance or postrehabilitation programs for patients with COPD who have completed a pulmonary rehabilitation program improve outcomes compared with UC?
RESEARCH METHODS
LITERATURE SEARCH: SEARCH STRATEGY: For Research Questions 1and 2, a literature search was performed on August 10, 2010 for studies published from January 1, 2004 to July 31, 2010. For Research Question 3, a literature search was performed on February 3, 2011 for studies published from January 1, 2000 to February 3, 2011. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists and health technology assessment websites were also examined for any additional relevant studies not identified through the systematic search. INCLUSION CRITERIA: Research questions 1 and 2: published between January 1, 2004 and July 31, 2010; randomized controlled trials, systematic reviews, and meta-analyses. COPD study population; studies comparing pulmonary rehabilitation with UC (no pulmonary rehabilitation); duration of pulmonary rehabilitation program ≥ 6 weeks; pulmonary rehabilitation program had to include at minimum exercise training. Research question 3: published between January 1, 2000 and February 3, 2011; randomized controlled trials, systematic reviews, and meta-analyses. COPD study population; studies comparing a maintenance or postrehabilitation program with UC (standard follow-up); duration of pulmonary rehabilitation program ≥ 6 weeks; initial pulmonary rehabilitation program had to include at minimum exercise training. EXCLUSION CRITERIA: Research questions 1, 2, and 3: grey literature; duplicate publications; non-English language publications; study population ≤ 18 years of age; studies conducted in a palliative population; studies that did not report primary outcome of interest. Additional exclusion criteria for research question 3: studies with ≤ 2 sessions/visits per month. OUTCOMES OF INTEREST: The primary outcomes of interest for the stable COPD population were exercise capacity and health-related quality of life (HRQOL). For the COPD population following an exacerbation, the primary outcomes of interest were hospital readmissions and HRQOL. The primary outcomes of interest for the COPD population undertaking maintenance programs were functional exercise capacity and HRQOL. QUALITY OF EVIDENCE: The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses. The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence: [Table: see text]
SUMMARY OF FINDINGS
RESEARCH QUESTION 1: EFFECT OF PULMONARY REHABILITATION ON OUTCOMES IN STABLE COPD: Seventeen randomized controlled trials met the inclusion criteria and were included in this review. The following conclusions are based on moderate quality of evidence. Pulmonary rehabilitation including at least 4 weeks of exercise training leads to clinically and statistically significant improvements in HRQOL in patients with COPD. Pulmonary rehabilitation also leads to a clinically and statistically significant improvement in functional exercise capacity (weighted mean difference, 54.83 m; 95% confidence interval, 35.63–74.03; P < 0.001). RESEARCH QUESTION 2: EFFECT OF PULMONARY REHABILITATION ON OUTCOMES FOLLOWING AN ACUTE EXACERBATION OF COPD: Five randomized controlled trials met the inclusion criteria and are included in this review. The following conclusion is based on moderate quality of evidence. Pulmonary rehabilitation (within 1 month of hospital discharge) after acute exacerbation significantly reduces hospital readmissions (relative risk, 0.50; 95% confidence interval, 0.33–0.77; = 0.001) and leads to a statistically and clinically significant improvement in HRQOL. RESEARCH QUESTION 3: EFFECT OF PULMONARY REHABILITATION MAINTENANCE PROGRAMS ON COPD OUTCOMES: Three randomized controlled trials met the inclusion criteria and are included in this review. The conclusions are based on a low quality of evidence and must therefore be considered with caution. Maintenance programs have a nonsignificant effect on HRQOL and hospitalizations. Maintenance programs have a statistically but not clinically significant effect on exercise capacity ( = 0.01). When subgrouped by intensity and quality of study, maintenance programs have a statistically and marginally clinically significant effect on exercise capacity.
Topics: Adult; Cost-Benefit Analysis; Evidence-Based Medicine; Exercise Therapy; Health Status; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Treatment Outcome
PubMed: 23074434
DOI: No ID Found -
The New England Journal of Medicine Jan 2012Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome.
METHODS
In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke.
RESULTS
Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04).
CONCLUSIONS
In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.).
Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Rivaroxaban; Secondary Prevention; Thiophenes
PubMed: 22077192
DOI: 10.1056/NEJMoa1112277 -
Antibiotics (Basel, Switzerland) Jan 2021Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are... (Review)
Review
Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.
PubMed: 33525684
DOI: 10.3390/antibiotics10020124 -
Complementary Therapies in Medicine Jun 2022The objective was to determine the effects of resveratrol supplementation on glucose homeostasis, oxidative stress, inflammation and microRNAs expression in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial.
OBJECTIVE
The objective was to determine the effects of resveratrol supplementation on glucose homeostasis, oxidative stress, inflammation and microRNAs expression in patients with diabetes mellitus type 2 on oral hypoglycemic drugs.
METHOD
This was a randomized, double blinded placebo-controlled parallel group trial. The diabetic patients (n = 110) were randomly assigned either to resveratrol (n = 55) and placebo (55) groups after informed consent and given once daily resveratrol 200 mg and cellulose capsules respectively for 24 weeks. Fasting glucose, insulin, HbA1c, lipid profile, TNF- α, IL-6, hs-CRP, MDA & circulatory microRNAs were measured at start and end of 24- week intervention.
RESULTS
Out of 110 patients recruited, 94 patients completed the study comprising of 45 in resveratrol and 46 in placebo group. The resveratrol supplementation after 24 weeks was resulted in significant reduction [mean difference (95%CI)] of plasma glucose[- 0.50(-0.94 to -0.06)], insulin[- 1.31(-2.24 to -0.38)], homeostatic model assessment of insulin resistance[- 0.83(-1.37 to -0.29)], malondialdehyde[- 0.36(-0.61 to -0.11)], high sensitive-C-reactive protein[- 0.35(-0.70 to -0.01)], tumor necrosis factor-alpha[- 1.25(-1.90 to -0.61)] and interleukin-6[- 1.99(-3.29 to -0.69)]. More than two-fold down regulation in miRNA-34a, miRNA-375, miRNA-21, miRNA-192 and up regulation in miRNA-126 and miRNA-132 expression was noted in patients receiving resveratrol as compared to placebo. No side effects were reported during the trial.
CONCLUSION
Resveratrol supplementation contributes in improvement of glycemic control by reducing insulin resistance. It has significant beneficial impact on chronic inflammation, oxidative stress and associated microRNA expression in diabetic patients. Thus, supplementation of resveratrol along with oral hypoglycemic agents may be useful in the reduction of diabetic associated complications.
Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Glucose; Hemostasis; Humans; Inflammation; Insulin Resistance; MicroRNAs; Oxidative Stress; Resveratrol
PubMed: 35240291
DOI: 10.1016/j.ctim.2022.102819 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2023Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine... (Randomized Controlled Trial)
Randomized Controlled Trial
Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial.
BACKGROUND & AIM
Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources.
METHODS
Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC-MS and reported in relative (mol%) and absolute concentration (μmol l) units.
RESULTS
Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645-5466) μmol l, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05).
CONCLUSIONS
Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health.
CLINICAL TRIAL REGISTRY
ClinicalTrials.gov, identifier: NCT03201588.
Topics: Infant; Infant, Newborn; Humans; Docosahexaenoic Acids; Fatty Acids; Arachidonic Acid; Cohort Studies; Infant, Extremely Premature; Phospholipids
PubMed: 37120902
DOI: 10.1016/j.clnu.2023.04.020 -
Nutrients Jan 20247-MEGA is a food product made from purified Alaska pollack fish oil containing palmitoleic acid (16:1), commonly referred to as omega-7. We sought to quantitatively... (Comparative Study)
Comparative Study Randomized Controlled Trial
7-MEGA is a food product made from purified Alaska pollack fish oil containing palmitoleic acid (16:1), commonly referred to as omega-7. We sought to quantitatively evaluate whether this substance inhibits skin aging. A total of 101 middle-aged females were randomly allocated to the intervention ( = 50) or placebo group ( = 51). Each participant was advised to take either 500 mg of 7-MEGA or a placebo twice daily for 12 weeks. The primary outcomes were the degree of improvement in wrinkles and the degree of moisture filling after consumption for 12 weeks compared to baseline. The secondary outcomes were improvement in skin wrinkles; moisture changes at 4 and 8 weeks from baseline; changes in transdermal water loss, skin elasticity, the melanin index, the erythema index, and the Global Photo Damage Score. We found a significant improvement in skin wrinkles and elasticity at 12 weeks in the 7-MEGA-consuming group compared to that in the placebo group; skin moisture, elasticity, and the melanin index were also improved. No supplement-related adverse reactions were observed and 7-MEGA was identified as safe. 7-MEGA was effective for human skin function in terms of wrinkles, moisture, elasticity, and melanin production and may be useful as a skin nutritional supplement.
Topics: Female; Humans; Middle Aged; Dietary Supplements; Elasticity; Melanins; Skin; Skin Aging; Double-Blind Method
PubMed: 38257104
DOI: 10.3390/nu16020212 -
Nature Communications Oct 2023The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants accentuates the...
The persistent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants accentuates the great demand for developing effective therapeutic agents. Here, we report the development of an orally bioavailable SARS-CoV-2 3C-like protease (3CL) inhibitor, namely simnotrelvir, and its preclinical evaluation, which lay the foundation for clinical trials studies as well as the conditional approval of simnotrelvir in combination with ritonavir for the treatment of COVID-19. The structure-based optimization of boceprevir, an approved HCV protease inhibitor, leads to identification of simnotrelvir that covalently inhibits SARS-CoV-2 3CL with an enthalpy-driven thermodynamic binding signature. Multiple enzymatic assays reveal that simnotrelvir is a potent pan-CoV 3CL inhibitor but has high selectivity. It effectively blocks replications of SARS-CoV-2 variants in cell-based assays and exhibits good pharmacokinetic and safety profiles in male and female rats and monkeys, leading to robust oral efficacy in a male mouse model of SARS-CoV-2 Delta infection in which it not only significantly reduces lung viral loads but also eliminates the virus from brains. The discovery of simnotrelvir thereby highlights the utility of structure-based development of marked protease inhibitors for providing a small molecule therapeutic effectively combatting human coronaviruses.
Topics: Mice; Female; Male; Animals; Humans; Rats; SARS-CoV-2; Protease Inhibitors; COVID-19; Antiviral Agents; Enzyme Inhibitors
PubMed: 37833261
DOI: 10.1038/s41467-023-42102-y -
Vaccines Jul 2021Human norovirus (HuNoV) is the leading cause of acute gastroenteritis (AGE) worldwide, which is highly stable and contagious, with a few virus particles being sufficient... (Review)
Review
Human norovirus (HuNoV) is the leading cause of acute gastroenteritis (AGE) worldwide, which is highly stable and contagious, with a few virus particles being sufficient to establish infection. Although the World Health Organization in 2016 stated that it should be an absolute priority to develop a HuNoV vaccine, unfortunately, there is currently no licensed HuNoV vaccine available. The major barrier to the development of an effective HuNoV vaccine is the lack of a robust and reproducible in vitro cultivation system. To develop a HuNoV vaccine, HuNoV immunogen alone or in combination with other viral immunogens have been designed to assess whether they can simultaneously induce protective immune responses against different viruses. Additionally, monovalent and multivalent vaccines from different HuNoV genotypes, including GI and GII HuNoV virus-like particles (VLPs), have been assessed in order to induce broad protection. Although there are several HuNoV vaccine candidates based on VLPs that are being tested in clinical trials, the challenges to develop effective HuNoV vaccines remain largely unresolved. In this review, we summarize the advances of the HuNoV cultivation system and HuNoV vaccine research and discuss current challenges and future perspectives in HuNoV vaccine development.
PubMed: 34358148
DOI: 10.3390/vaccines9070732