DGL 감초
DGL (Deglycyrrhizinated Licorice)
📚 관련 논문 (25편)
1. Endocrine. 2026 Feb 2;91(1):51. doi: 10.1007/s12020-025-04476-5. Randomized Double-blind Placebo-controlled study to evaluate the efficacy of fermented deglycyrrhizinated licorice for treatment of diabetic polyneuropathy. Massoud AMA(1), Massoud HMA(2), El-Shawarby AA(3), Elseidy MI(4). Autho
2. Licorice. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. 2025 Jun 15. Licorice (Glycyrrhiza glabra) root contains glycyrrhizin (also called glycyrrhizic acid or glycyrrhizinic acid) and a mixture of the potas
3. Toxicol Mech Methods. 2022 Mar;32(3):180-193. doi: 10.1080/15376516.2021.1977881. Epub 2021 Sep 22. Evaluating the protective role of Deglycyrrhizinated licorice root supplement on bleomycin induced pulmonary oxidative damage. Gad El-Hak HN(1), Mohamed OE(1), Nabil ZI(1). Author information:
4. Cells. 2020 Jan 5;9(1):125. doi: 10.3390/cells9010125. De-Glycyrrhizinated Licorice Extract Attenuates High Glucose-Stimulated Renal Tubular Epithelial-Mesenchymal Transition via Suppressing the Notch2 Signaling Pathway. Hsu YC(1)(2), Chang PJ(1)(2)(3), Tung CW(1)(2), Shih YH(1)(2), Ni WC(1)(
5. Integr Med (Encinitas). 2018 Aug;17(4):44-50. Naturopathic Treatment of Gastrointestinal Dysfunction in the Setting of Parkinson's Disease. Neiworth-Petshow EM, Baldwin-Sayre C. Parkinson's disease is associated with multiple nonmotor symptoms including gastrointestinal (GI) distress, which
6. Anaerobe. 2012 Dec;18(6):590-6. doi: 10.1016/j.anaerobe.2012.10.005. Epub 2012 Oct 30. The antimicrobial effects of deglycyrrhizinated licorice root extract on Streptococcus mutans UA159 in both planktonic and biofilm cultures. Ahn SJ(1), Cho EJ, Kim HJ, Park SN, Lim YK, Kook JK. Author info
1. J Nutr Biochem. 2020 May;79:108340. doi: 10.1016/j.jnutbio.2020.108340. Epub 2020 Jan 17. Fecal metatranscriptomics and glycomics suggest that bovine milk oligosaccharides are fully utilized by healthy adults. Westreich ST(1), Salcedo J(2), Durbin-Johnson B(3), Smilowitz JT(4), Korf I(5), Mills DA(6), Barile D(7), Lemay DG(8). Author information: (1)Department of Molecular and Cellular Biology, University of California-Davis, Davis, California, United States; Genome Center, University of California-Davis, Davis, California, United States. Electronic address: stwestreich@ucdavis.edu. (2)Department of Food Science and Technology, University of California-Davis, Davis, California, United States. Electronic address: jsalcedodominguez@ucdavis.edu. (3)Genome Center, University of California-Davis, Davis, California, United States. Electronic address: bpdurbin@phs.ucdavis.edu. (4)Department of Food Science and Technology, University of California-Davis, Davis, California, United States; Foods for Health Institute, University of California, Davis, California, United States. Electronic address: jensm@ucdavis.edu. (5)Department of Molecular and Cellular Biology, University of California-Davis, Davis, California, United States; Genome Center, University of California-Davis, Davis, California, United States. Electronic address: ifkorf@ucdavis.edu. (6)Department of Food Science and Technology, University of California-Davis, Davis, California, United States; Foods for Health Institute, University of California, Davis, California, United States. Electronic address: damills@ucdavis.edu. (7)Department of Food Science and Technology, University of California-Davis, Davis, California, United States; Foods for Health Institute, University of California, Davis, California, United States. Electronic address: dbarile@ucdavis.edu. (8)Genome Center, University of California-Davis, Davis, California, United States; Foods for Health Institute, University of California, Davis, California, United States; USDA ARS Western Human Nutrition Research Center, Davis, California, United States. Electronic address: Danielle.Lemay@usda.gov. Human milk oligosaccharides play a vital role in the development of the gut microbiome in the human infant. Although oligosaccharides derived from bovine milk (BMO) differ in content and profile with those derived from human milk (HMO), several oligosaccharide structures are shared between the species. BMO are commercial alternatives to HMO, but their fate in the digestive tract of healthy adult consumers is unknown. Healthy human subjects consumed two BMO doses over 11-day periods each and provided fecal samples. Metatranscriptomics of fecal samples were conducted to determine microbial and host gene expression in response to the supplement. Fecal samples were also analyzed by mass spectrometry to determine levels of undigested BMO. No changes were observed in microbial gene expression across all participants. Repeated sampling enabled subject-specific analyses: four of six participants had minor, yet statistically significant, changes in microbial gene expression. No significant change was observed in the gene expression of host cells exfoliated in stool. Levels of BMO excreted in feces after supplementation were not significantly different from baseline and were not correlated with dosage or expressed microbial enzyme levels. Collectively, these data suggest that BMO are fully fermented in the human gastrointestinal tract upstream of the distal colon. Additionally, the unaltered host transcriptome provides further evidence for the safety of BMO as a dietary supplement or food ingredient. Further research is needed to investigate potential health benefits of this completely fermentable prebiotic that naturally occurs in cow's milk. Published by Elsevier Inc. DOI: 10.1016/j.jnutbio.2020.108340 PMCID: PMC7233280 PMID: 32028108 [Indexed for MEDLINE] Conflict of interest statement: Conflicts of interest D.G.L., I.K., D.A.M. and D.B. received funding from Arla Food Ingredients for this project. D.B., J.T.S. and D.A.M. received research funding from National Dairy Council for the parent clinical trial. D.B. and D.A.M. are co-founders of Evolve Biosystems Inc., a company focused on diet-based manipulation of the fecal microbiota. None of the funding sponsors, nor Evolve Biosystems Inc., had any role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
2. Lancet Glob Health. 2025 Jun;13(6):e1043-e1056. doi: 10.1016/S2214-109X(25)00055-5. Epub 2025 Apr 22. The aetiologies, mortality, and disability of non-traumatic coma in African children: a systematic review and meta-analysis. Ray STJ(1), Fuller CE(2), Boubour A(3), Tshimangani T(4), Kafoteka E(3), Muiruri-Liomba A(3), Malenga A(3), Tebulo A(3), Pensulo P(3), Gushu MB(3), Nielsen M(5), Raees M(6), Stockdale E(3), Langton J(7), Birbeck GL(8), Waithira N(9), Bonnett LJ(10), Henrion MY(11), Fink EL(12), Postels DG(13), O'Brien N(14), Page AL(15), Baron E(15), Gordon SB(11), Molyneux E(7), Dondorp A(9), George EC(16), Maitland K(17), Michael BD(18), Solomon T(19), Chimalizeni Y(20), Lalloo DG(11), Moxon CA(21), Taylor T(22), Mallewa M(7), Idro R(23), Seydel K(24), Griffiths MJ(25). Author information: (1)Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; Department of Paediatric Infectious Disease and Immunology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Wilson Lab, Weil Institute for Neurosciences, University of San Francisco, San Francisco, CA, USA. Electronic address: stephen.ray@paediatrics.ox.ac.uk. (2)The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; Department of Paediatric Immunology, Allergy and Infectious Diseases, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK. (3)Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi. (4)Hôpital Pédiatrique de Kalembe Lembe, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo. (5)Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi. (6)Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. (7)Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi. (8)Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Neurology, University of Rochester, Rochester, NY, USA. (9)Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Nakhon Pathom, Thailand. (10)Department of Health Data Science, University of Liverpool, Liverpool, UK. (11)Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, UK. (12)Division of Critical Care Medicine, Department of Anaesthesiology and Critical Care, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, PA, USA. (13)Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Division of Neurology, George Washington University and Children's National Health System, Washington, DC, USA. (14)Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Hôpital Pédiatrique de Kalembe Lembe, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo; Department of Pediatrics, Division of Critical Care Medicine, Nationwide Children's Hospital and Ohio State University, Columbus, OH, USA. (15)Epicentre, Paris, France. (16)Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK. (17)Department of Infectious Disease and Institute of Global Health and Innovation, Faculty of Medicine, Imperial College, London, UK; Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya. (18)The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Walton Centre NHS Foundation Trust, Liverpool, UK. (19)The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Walton Centre NHS Foundation Trust, Liverpool, UK; The Pandemic Institute, University of Liverpool, Liverpool, UK. (20)Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. (21)Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; School of Infection and Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA. (22)Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA. (23)Department of Paediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda. (24)Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Paediatrics and Child Health, Kamzu University of Health Sciences, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA. (25)The Brain Infection and Inflammation Group, University of Liverpool, Liverpool, UK; Centre for Child and Adolescent Health Research, Western Sydney (Baludarri) Precinct, Faculty of Medicine & Health, University of Sydney, Sydney, NSW, Australia. Erratum in Lancet Glob Health. 2026 Jan;14(1):e20. doi: 10.1016/S2214-109X(25)00176-7. BACKGROUND: Non-traumatic coma in African children is a common life-threatening presentation often leading to hospital attendance. We aimed to estimate the distribution of non-traumatic coma causes and outcomes, including disease-specific outcomes, for which evidence is scarce. METHODS: We systematically reviewed MEDLINE, Embase, and Scopus databases from inception to Feb 6, 2024. We included studies recruiting children (aged 1 month to 16 years) with non-traumatic coma (Blantyre Coma Scale score ≤2, ie deep coma or comparable alternative) from any African country. Disease-specific studies were included if outcomes were reported. Primary data were requested where required. We used a DerSimonian-Laird random effects model to calculate pooled estimates for prevalence of causes, mortality, and morbidity (in-hospital and post-discharge), including analysis of mortality by temporality. This study was registered with PROSPERO (CRD4202014193). FINDINGS: We screened 16 666 articles. 138 studies were eligible for analysis, reporting causes, outcome data, or both from 35 027 children with non-traumatic coma in 30 African countries. 114 (89%) of 128 studies were determined to be high quality. Among the causes, cerebral malaria had highest pooled prevalence at 58% (95% CI 48-69), encephalopathy of unknown cause was associated with 23% (9-36) of cases, and acute bacterial meningitis was the cause of 10% (8-12) of cases, with all other causes representing lower proportions of cases. Pooled overall case-fatality rates were 17% (16-19) for cerebral malaria, 37% (20-55) for unknown encephalopathy, and 45% (34-55) for acute bacterial meningitis. By meta-regression, there was no significant difference in cerebral malaria (p=0·98), acute bacterial meningitis (p=0·99), or all-cause coma (p=0·081) mortality by year of study. There was no substantial difference in deaths associated with cerebral malaria in-hospital compared with post-discharge (17% [16-19] vs (18% [16-20]). Mortality was higher post-discharge than in-hospital in most non-malarial comas, including acute bacterial meningitis (39% [26-52]) vs 53% [38-69]). Disability associated with cerebral malaria was 11% (9-12). Pooled disability outcomes associated with other non-malarial diseases were largely absent. INTERPRETATION: The prevalence and outcomes of cerebral malaria and meningitis associated with non-traumatic coma were strikingly static across five decades. Enhanced molecular and radiological diagnostics, investment, policy making, community awareness, and health service provision are all required to facilitate earlier referral to specialist centres, to drive a step-change in diagnostic yield and treatment options to improve these outcomes. FUNDING: Wellcome Trust. TRANSLATIONS: For the Chichewa, French and Portuguese translations of the abstract see Supplementary Materials section. Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/S2214-109X(25)00055-5 PMID: 40280144 [Indexed for MEDLINE] Conflict of interest statement: Declaration of interests DGL, MYRH, and SBG are supported by The Wellcome core award (award number 206545/Z/17/Z) to Malawi–Liverpool–Wellcome Trust. STJR and MN are also supported by Wellcome to conduct paediatric infectious diseases research (203919/Z/16/Z). STJR is also supported by a Thrasher child health early career award, Academy of Medical Sciences starter grant, and European Society of Paediatric Infectious Diseases Society diagnostic grant; and is a Centre for Human Genetics Well Institute Olink-48 grant prize winner and early research career committee member, both at The University of Oxford. MN is also supported by Roche Diagnostics for a Baby and Mother Biomarkers of Infection study; Liverpool School of Tropical Medicine as a clinical fellow for The DIAMONDS Research Consortia; FIND Diagnostics for a literature review on the utility of CRP testing in primary care in low-resource settings for supporting patient management and antibiotic stewardship; is an invited speaker at The Paediatric Infectious Diseases Games; and is deputy convenor, research co-lead, and winter meeting lead at the Royal College Of Paediatrics and Child Health's International Child Health group. MJG is supported to conduct neuroscience and infection research internationally by the Medical Research Council (MRC) Newton Fund (MR/S019960/1), MRC Developmental Pathway Funding Scheme (MR/R015406/1), and National Institute of Health and Care Research (NIHR; 153195 17/60/67, 126156 17/63/11, and 200907). CAM is a UKRI MRC Future Leaders Fellow (MR/V025856/1). TS is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (IS-HPU-1112–10117 and NIHR200907), NIHR Global Health Research Group on Brain Infections (17/63/110), the UK MRC Global Effort on COVID-19 Programme (MR/V033441/1), the EU's Horizon 2020 research and innovation programme (ZikaPLAN; 734584), and The Pandemic Institute; receives royalties from Oxford University Press, Liverpool University Press, Cambridge University, and Elsevier for published books he has written on brain infections; co-chaired the Medicines and Healthcare Products Regulatory Agency (MHRA) Expert Working Group on COVID-19 vaccines between 2020 and 2023; was a member of the COVID-19 Vaccines Benefit Risk Expert working group for the Commission on Human Medicines (CHM) committee of MHRA between 2020 and 2023; is a Committee Member of the Wellcome Trust Pathogen Biology and Disease Transmission Discovery advisory group; was a member of the MRC's Infections and Immunity Board between 2018 and 2022; sat on the Research Excellence Framework Panel between 2021 and 2022; and was on the data safety monitoring committee of the GSK Study to Evaluate the Safety and Immunogenicity of a Candidate Ebola Vaccine in Children (ChAd3 EBO-Z) vaccine (GSK3390107A). BDM is supported for COVID-19 neuroscience research by UK Research and Innovation (UKRI) and MRC (MR/V03605X/1); and for additional neurological inflammation due to viral infection research by grants from the MRC and UKRI (MR/V007181/1), MRC (MR/T028750/1), and the Wellcome Trust (ISSF201902/3). TTa is supported by a research grant from the US National Institutes of Health (NIH); is the President-Elect for the American Society of Tropical Medicine and Hygiene; and is a member of the Malaria Advisory Council for Novartis Pharma. GB is supported by two active and two recent research grants from US NIH; consults on educational materials for Neurotorium, Temp Traq, and similar devices at Blue Spark Technologies; lectures for The University of Calgary; participates on an advisory board for the BRIDGE clinical trial; and is on the editorial board of the Lancet Neurology, Neurotorium, and Zambian League against Epilepsy. ECG is funded by the MRC as core support to the Medical Research Council Clinical Trials Unit at University College London (MC_UU_00004/05). STJR, BDM, and TS are members of the Encephalitis International Scientific Advisory Panel—BDM is Scientific Chair and TS is President. All other authors declare no competing interests.
3. Thyroid. 2021 Dec;31(12):1829-1838. doi: 10.1089/thy.2021.0302. A Systematic Review and Meta-Analysis of the Relationship Between the Radiation Absorbed Dose to the Thyroid and Response in Patients Treated with Radioiodine for Graves' Disease. Taprogge J(1)(2), Gape PMD(1)(2), Carnegie-Peake L(1)(2), Murray I(1)(2), Gear JI(1)(2), Leek F(1)(2), Hyer SL(3), Flux GD(1)(2). Author information: (1)Joint Department of Physics, Royal Marsden NHSFT, Sutton, United Kingdom. (2)The Institute of Cancer Research, London, United Kingdom. (3)Department of Endocrinology, Epsom and St Helier University Hospitals NHS Trust, Carshalton, Surrey, United Kingdom. Background: Patients with Graves' disease are commonly treated with radioiodine. There remains controversy over whether the aim of treatment should be to achieve euthyroidism or hypothyroidism, and whether treatments should be administered with standard levels of radioactivity or personalized according to the radiation absorbed doses delivered to the thyroid. The aim of this review was to investigate whether a relationship exists between radiation absorbed dose and treatment outcome. Methods: A systematic review and meta-analysis of all reports published before February 13, 2020, were performed using PubMed, Web of Science, OVID MEDLINE, and Embase. Proportion of patients achieving nonhyperthyroid status was the primary outcome. Secondary outcomes were proportion of patients who were specifically euthyroid or hypothyroid. A random-effects meta-analysis of proportions was performed for primary and secondary outcomes, and the impact of the radiation absorbed dose on treatment outcome was assessed through meta-regression. The study is registered with PROSPERO (CRD42020175010). Results: A total of 1122 studies were identified of which 15, comprising 2303 Graves' disease patients, were eligible for the meta-analysis. A strong association was found between radiation absorbed dose and nonhyperthyroid and hypothyroid outcomes (odds ratio [OR] = 1.11 [95% confidence interval {CI} 1.08-1.14] and OR = 1.09 [CI 1.06-1.12] per 10 Gy increase). Higher rates of euthyroid outcome were found for radiation absorbed doses within the range 120-180 Gy when compared with outside this range (n = 1172, OR = 2.50 [CI 1.17-5.35], p = 0.018). A maximum euthyroid response of 38% was identified at a radiation absorbed dose of 128 Gy. Conclusions: The presented radiation absorbed dose-response relationships can facilitate personalized treatment planning for radioiodine treatment of patients with Graves' disease. Further studies are required to determine how patient-specific covariates can inform personalized treatments. DOI: 10.1089/thy.2021.0302 PMCID: PMC8721505 PMID: 34598656 [Indexed for MEDLINE] Conflict of interest statement: J.T., P.M.D.G., L.C.P., J.I.G., I.M., and G.D.F. report grants from Euratom research and training program 2014–2018 and National Institute for Health Research (NIHR) and funding from National Health Service to the NIHR Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research and NIHR Royal Marsden Clinical Research Facility outside the work of the study. J.I.G. reports personal fees and honoraria from The EANM outside the work of the study.
4. J Nematol. 2019;51:1-17. doi: 10.21307/jofnem-2019-011. Agricultural intensification and urbanization negatively impact soil nematode richness and abundance: a meta-analysis. Pothula SK(1), Grewal PS(2), Auge RM(3), Saxton AM(4), Bernard EC(1). Author information: (1)Department of Entomology & Plant Pathology, University of Tennessee , 370 Plant Biotechnology Building, 2505 E J Chapman Drive, Knoxville, TN, 37996-4560. (2)School of Earth, Environmental, and Marine Sciences, University of Texas Rio Grande Valley , 1201 West University Drive, Edinburg, TX, 78539-2999. (3)Department of Plant Sciences, University of Tennessee , 2431 Joe Johnson Drive, Knoxville, TN, 37996. (4)Department of Animal Science, University of Tennessee , 2506 River Drive, Knoxville, TN, 37996. Human activity has extensively transformed the land surface by agricultural intensification and urbanization. In soil, nematodes are the most abundant invertebrates. The effect of human interventions was assessed on overall richness, overall abundance, richness and abundance of nematodes of each trophic group and colonizer-persister (c-p) guild by comparing urban, agriculture and disturbed grassland (DGL) with natural grassland (NGL) and forest ecosystems. Meta-analyses were conducted to generate quantitative summaries from 111 published articles that met the inclusion criteria, 91 expressed data in grams and 20 expressed data in cm3. Results from data expressed per 100 g of soil indicated that overall richness was higher in forest than in NGL, DGL, urban, and agriculture ecosystems. The richness of all c-p guilds and of all trophic groups except herbivores was highest in forest ecosystems. In contrast, overall abundance was highest in DGL, agriculture and forest ecosystems. The abundance of c-p 1, c-p 2 and c-p 3 guilds and bacterivores, fungivores and herbivores was highest in disturbed ecosystems, while the abundance of c-p 4 and c-p 5 guilds and predators and omnivores was highest in relatively undisturbed ecosystems. Results from data expressed as nematodes per 100 cm3 of soil indicated that abundance followed a similar pattern, but richness often differed between the two methodologies. These meta-analyses strengthen the concept that human interventions adversely impact both richness and abundance using nematodes as soil health bioindicators. Human activity has extensively transformed the land surface by agricultural intensification and urbanization. In soil, nematodes are the most abundant invertebrates. The effect of human interventions was assessed on overall richness, overall abundance, richness and abundance of nematodes of each trophic group and colonizer-persister (c-p) guild by comparing urban, agriculture and disturbed grassland (DGL) with natural grassland (NGL) and forest ecosystems. Meta-analyses were conducted to generate quantitative summaries from 111 published articles that met the inclusion criteria, 91 expressed data in grams and 20 expressed data in cm3. Results from data expressed per 100 g of soil indicated that overall richness was higher in forest than in NGL, DGL, urban, and agriculture ecosystems. The richness of all c-p guilds and of all trophic groups except herbivores was highest in forest ecosystems. In contrast, overall abundance was highest in DGL, agriculture and forest ecosystems. The abundance of c-p 1, c-p 2 and c-p 3 guilds and bacterivores, fungivores and herbivores was highest in disturbed ecosystems, while the abundance of c-p 4 and c-p 5 guilds and predators and omnivores was highest in relatively undisturbed ecosystems. Results from data expressed as nematodes per 100 cm3 of soil indicated that abundance followed a similar pattern, but richness often differed between the two methodologies. These meta-analyses strengthen the concept that human interventions adversely impact both richness and abundance using nematodes as soil health bioindicators. DOI: 10.21307/jofnem-2019-011 PMCID: PMC6916142 PMID: 31088023
5. RMD Open. 2025 Jun 3;11(2):e005250. doi: 10.1136/rmdopen-2024-005250. Identification of distinct disease activity trajectories in patients with psoriatic arthritis receiving tofacitinib: a post hoc analysis of two phase 3 studies. Gladman D(1), Tillett W(2), Gruben D(3), Coates LC(4), Hahne S(5), Volkov M(6). Author information: (1)Department of Medicine, University Health Network Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada dafna.gladman@utoronto.ca. (2)Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, UK. (3)Pfizer Inc, Groton, Connecticut, USA. (4)Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. (5)Pfizer Pharma GmbH, Berlin, Germany. (6)Pfizer BV, Capelle aan den IJssel, The Netherlands. OBJECTIVE: To capture variations in tofacitinib treatment response in psoriatic arthritis (PsA) by identifying patient groups with distinct disease activity trajectories. METHODS: Data were pooled post hoc from two phase 3 studies (OPAL Broaden, OPAL Beyond) in patients with PsA receiving tofacitinib 5 or 10 mg twice daily (n=225, n=226, respectively). Psoriatic Arthritis Disease Activity Score (PASDAS) to month 6 was used in group-based trajectory modelling to identify distinct treatment response groups based on disease state (very low/low/moderate/high disease activity (VLDA/LDA/MoDA/HDA, respectively)). Baseline characteristics, PASDAS components to month 6 and adverse events (AEs) were assessed. RESULTS: Five trajectory groups were identified for both tofacitinib doses: groups improved from MoDA→VLDA/LDA (group 1); HDA→VLDA (group 2); HDA→MoDA rapidly (group 3) or gradually (group 4) or remained in HDA (group 5). Groups 4/5 generally had significantly higher baseline PsA clinical domain scores than groups 1‒3, except for Psoriasis Area and Severity Index/Nail Psoriasis Severity Index. Baseline Leeds Enthesitis Index/Spondyloarthritis Research Consortium of Canada enthesitis scores and tender joint counts were significantly higher in group 4 vs group 2. PASDAS components generally improved to month 6 in all groups, consistent with modelled trajectories. There were no clear trends in AEs across groups. CONCLUSIONS: In patients with PsA receiving tofacitinib, five distinct trajectory groups were identified with different baseline characteristics and treatment outcomes, but no clear trends in AEs. The tofacitinib 5 and 10 mg twice daily models showed comparable trajectories and baseline characteristics. In patients with HDA, enthesitis and tender joint count may impact timing and/or magnitude of response to tofacitinib. Identifying characteristics that impact treatment response may aid personalised treatment algorithm development. TRIAL REGISTRATION NUMBERS: NCT01877668/NCT01882439. © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. DOI: 10.1136/rmdopen-2024-005250 PMCID: PMC12142151 PMID: 40461265 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: DGl has acted as a consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc and UCB and has received grants and/or research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc and UCB. WT has acted as a consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono-Pharma, Pfizer Inc and UCB, has received grants and/or research support from AbbVie, Eli Lilly, Janssen, Pfizer Inc and UCB and has been a member of the speaker bureau for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono-Pharma, Pfizer Inc and UCB. DGr is an employee and a stockholder of Pfizer Inc. LCC has acted as a consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, MoonLake, Novartis, Pfizer Inc and UCB, has received grants and/or research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc and UCB and has been a member of the speaker bureau for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead Sciences, GSK, Janssen, Medac, Novartis, Pfizer Inc and UCB. SH is an employee of Pfizer Pharma and a stockholder of Pfizer Inc. MV was an employee of Pfizer BV at the time of this analysis and is a stockholder of Pfizer Inc.
6. Lancet Respir Med. 2025 Jun;13(6):517-529. doi: 10.1016/S2213-2600(25)00048-7. Epub 2025 Apr 14. Efficacy, safety, and immunogenicity of the AS01(E)-adjuvanted respiratory syncytial virus prefusion F protein vaccine (RSVPreF3 OA) in older adults over three respiratory syncytial virus seasons (AReSVi-006): a multicentre, randomised, observer-blinded, placebo-controlled, phase 3 trial. Ison MG(1), Papi A(2), Athan E(3), Feldman RG(4), Langley JM(5), Lee DG(6), Leroux-Roels I(7), Martinon-Torres F(8), Schwarz TF(9), van Zyl-Smit RN(10), Cuadripani S(11), Deraedt Q(12), Dezutter N(12), Gerard C(13), Fissette L(12), Xavier S(14), David MP(12), Olivier A(12), Van der Wielen M(15), Descamps D(12); AReSVi-006 study group. Collaborators: Adams M, Adams M, Agutu C, Akite EJ, Alt I, Andrews C, Antonelli-Incalzi R, Asatryan A, Bahrami G, Bargagli E, Bhorat Q, Bird P, Borowy P, Boutry C, Brotons Cuixart C, Browder D, Brown J, Buntinx E, Cameron D, Cartier C, Chinsky K, Choi M, Choo EJ, Collete D, Corral Carrillo M, Davis MG, de Heusch M, de Looze F, De Meulemeester M, De Negri F, DeAtkine D, Dedkova V, Dzongowski P, Eckermann T, Essink B, Faulkner K, Ferguson M, Fuller G, Galan Melendez IM, Gentile I, Ghesquiere W, Grimard D, Gruselle O, Halperin S, Heer A, Helman L, Hotermans A, Jelinek T, Kamerbeek J, Kim HY, Kimmel M, Koch M, Kokko S, Koski S, Kotb S, Lalueza A, Lee JS, Lins M, Lombaard J, Mahomed A, Malerba M, Marechal C, Marion S, Martinot JB, Masuet-Aumatell C, McNally D, Medina Pech CE, Mendez Galvan J, Mercati L, Mesotten D, Mitha E, Mngadi K, Moeckesch B, Montgomery B, Murray L, Nally R, Narejos Perez S, Newberg J, Nugent P, Ochoa Mazarro D, Oda H, Orso M, Ortiz Molina J, Pak T, Park DW, Patel M, Patel M, Pedro Pijoan AM, Perez AB, Perez-Breva L, Perez Vera M, Pileggi C, Pregliasco F, Pretswell C, Quinn D, Reynolds M, Romanenko V, Rosen J, Roy N, Ruiz Antoran B, Sakata H, Sauter J, Schaefer A, Sein Anand I, Serra Rexach JA, Shu D, Siig A, Simon W, Smakotina S, Steenackers K, Stephan B, Tafuri S, Takazawa K, Tellier G, Terryn W, Tharenos L, Thomas N, Toursarkissian N, Ukkonen B, Vale N, Van Landegem PJ, Vanden Abeele C, Vermeersch L, Vitale F, Voloshyna O, White J, Wie SH, Wilson J, Ylisastigui P, Zocco M. Author information: (1)Bethesda, MD, USA. (2)Pulmonary Division, University of Ferrara, St Anna University Hospital, Ferrara, Italy. (3)Barwon Health, University Hospital Geelong, Geelong, VIC, Australia; Centre for Innovation in Infectious Diseases and Immunology Research, Deakin University, Geelong, VIC, Australia. (4)Senior Clinical Trials, Laguna Hills, CA, USA. (5)Canadian Center for Vaccinology, Dalhousie University, IWK Health and Nova Scotia Health, Halifax, NS, Canada. (6)Division of Infectious Diseases, Department of Internal Medicine, Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea. (7)Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium. (8)Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain; Genetics, Vaccines, Infectious Diseases, and Pediatrics Research Group, Instituto de Investigación Sanitaria de Santiago, Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. (9)Institute of Laboratory Medicine and Vaccination Center, Klinikum Würzburg Mitte, Campus Juliusspital, Würzburg, Germany. (10)Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa. (11)GSK, Stevenage, UK. (12)GSK, Wavre, Belgium. (13)GSK, Rixensart, Belgium. (14)GSK, Bengaluru, India. (15)GSK, Wavre, Belgium. Electronic address: marie.x.van-der-wielen@gsk.com. BACKGROUND: Duration of protection after respiratory syncytial virus (RSV) vaccination is unknown. This study aimed to evaluate efficacy and safety over three RSV seasons of the AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) against RSV-related lower respiratory tract disease (RSV-LRTD) in older adults. METHODS: In this randomised, observer-blind, placebo-controlled, phase 3 trial (AReSVi-006), participants aged 60 years or older in 275 centres (ie, GP practices and clinical research sites) across 17 countries in Africa, Asia, Oceania, Europe, and North America were randomly assigned (1:1) to receive RSVPreF3 OA or placebo before RSV season one. RSVPreF3 OA recipients were re-randomly assigned (1:1) before RSV season two to receive a second RSVPreF3 OA dose (RSV revaccination group) or placebo (RSV single-dose group). Recipients of placebo before RSV season one also received placebo before season two (placebo group). The primary objective (efficacy against first occurrence of RSV-LRTD over one RSV season) was reported previously. Confirmatory secondary objectives were to demonstrate efficacy over three RSV seasons of a single RSVPreF3 OA dose and of a first dose followed by revaccination 1 year later, against RSV-LRTD, overall and by RSV subtype (success criteria: lower limits of two-sided CIs around efficacy estimates >20% [RSV-LRTD] and >0% [RSV-LRTD by RSV subtype]). This study is registered with ClinicalTrials.gov, NCT04886596, and is complete. FINDINGS: Participants were enrolled between May 25, 2021, and Jan 31, 2022. Efficacy analyses included 12 468 RSVPreF3 OA recipients and 12 498 placebo recipients. Cumulative efficacy over three seasons of one RSVPreF3 OA dose was 62·9% (97·5% CI 46·7-74·8) against RSV-LRTD, 69·8% (42·2-85·7) against RSV A-related LRTD, and 58·6% (35·9-74·1) against RSV B-related LRTD (median follow-up from day 15 post-dose one 30·6 months [IQR 26·2-32·0]). Efficacy was observed over three seasons among participants aged 60-69 years, participants aged 70-79 years, pre-frail participants (ie, those with a walking speed of 0·4-0·99 m/s in a gait speed test), and participants with pre-existing conditions that increase the RSV-LRTD risk. Efficacy against RSV-LRTD decreased over time. A first RSVPreF3 OA dose followed by revaccination 1 year later had an efficacy that was within the same range as that of one dose. RSVPreF3 OA showed a clinically acceptable safety profile. Between dose one and trial end, eight (<1%) participants in the RSV single-dose group, 12 (<1%) in the RSV revaccination group, and 12 (<1%) in the placebo group had a serious adverse event considered to be related to the trial intervention by the investigator. Five deaths were assessed as related to the trial intervention by the investigator: three in the vaccine groups (cardiopulmonary failure, cardiac arrest, and left ventricular failure) and two in the placebo group (death of unknown cause and pulmonary embolism). INTERPRETATION: A single RSVPreF3 OA dose was efficacious against RSV-LRTD over three RSV seasons in people aged 60 years or older, despite a decrease in efficacy over time. Further research is needed to establish the optimal revaccination strategy. These results support the favourable benefit-risk profile of RSVPreF3 OA to help protect against RSV-LRTD for at least three RSV seasons. FUNDING: GSK. Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. DOI: 10.1016/S2213-2600(25)00048-7 PMID: 40245915 [Indexed for MEDLINE] Conflict of interest statement: Declaration of interests MGI declares that research support from GSK was paid to his previous institution, Northwestern University; he received consulting fees paid by Adagio Therapeutics, ADMA Biologics, Adamis Pharmaceuticals, AlloVir, Atea, Cidara Therapeutics, Genentech/Roche, Janssen, Shionogi, Takeda, Talaris, and Eurofins Viracor; and payment for participation in data safety monitoring boards or advisory boards from Adamis Pharmaceuticals, AlloVir, National Institutes of Health, CSL Behring, Janssen, Merck, Seqirus, Takeda, and Talaris; all of these ended in December, 2022. MGI also receives author royalties from UpToDate, which is ongoing, and serves as Chair of the International Society for Influenza and other Respiratory Virus Diseases Antiviral Group, and was Editor-in-Chief of Transplant Infectious Disease. MGI's involvement was separate from his government service, and the comments are his own. MGI was a consultant for Romark but received no consulting fees. AP declares funding from GSK for conducting the trial; grants paid to his institution from GSK, Chiesi, AstraZeneca, Sanofi, and Agenzia Italiana del Farmaco; consulting fees from GSK, Chiesi, AstraZeneca, Sanofi, Novartis, Avillion, ELPEN Pharmaceuticals, Zambon, and Edmond Pharma; payment for participation in advisory boards from GSK, Chiesi, AstraZeneca, Sanofi, Novartis, Avillion, ELPEN Pharmaceuticals, Zambon, Edmond Pharma, and IQVIA; and honoraria from GSK, Chiesi, AstraZeneca, Sanofi, Novartis, Avillion, ELPEN Pharmaceuticals, Menarini, Zambon, Mundipharma, Edmond Pharma, and IQVIA. RGF declares having received payment from GSK for congress and speaking events lectures and support for travel related to these activities. JML reports grants paid to her institution from GSK, Pfizer, Merck, Moderna, Sanofi, Inventprise, and VBI Vaccines for conducting trials; and participation on a data safety monitoring board or advisory board for Vaxcyte, Sanofi, GSK, Merck, and Seqirus. IL-R declares grants or research support paid to her institution from GSK, Icosavax, Janssen Vaccines, Curevac, Moderna, Osivax, MSD, and OSE Immunotherapeutics for conducting trials; and payment for participation on a data safety monitoring board or advisory board from Janssen Vaccines and MSD. FM-T declares grants or research support payments to his institution from GSK, Sanofi, Moderna, MSD, Novavax, and Pfizer for conducting vaccine trials; and consulting fees or participation on advisory boards for GSK, Sanofi, MSD, Moderna, AstraZeneca, Biofabri, CSL-Seqirus, Novavax, and Janssen. TFS reports participation on data safety monitoring boards or advisory boards from AstraZeneca, Bavarian Nordic, Biogen, BioNTech, CSL-Seqirus, CSL-Vifor, Diasorin, GSK, Janssen-Cilag, Merck-Serono, Moderna, MSD, Novavax, Pfizer, Roche, Sanofi-Aventis, Synlab, and Takeda. RNvZ-S reports that his institution received support from Boehringer Ingelheim for the Interstitial Lung Disease registry and consulting fees from GSK and honoraria for lectures from Glenmark, Boehringer Ingelheim, Cipla, and Novartis; and payment for participation on data safety monitoring boards or advisory boards for OnQ SA. SC, QD, ND, CG, LF, SX, M-PD, AO, MVdW, and DD are employed by GSK; SC, QD, ND, CG, LF, M-PD, AO, MVdW, and DD hold financial equities in GSK. ND is co-applicant on a pending patent for vaccination against RSV and a patent regarding methods for eliciting an immune response to RSV and Streptococcus pneumoniae infections. MVdW has stock options from Haleon. LF, M-PD, AO, and MVdW are part of vaccine patents filed by GSK. The authors declare no other financial or non-financial relationships. EA and D-GL declare no competing interests.
7. Nat Med. 2025 Jan;31(1):267-277. doi: 10.1038/s41591-024-03355-2. Epub 2025 Jan 3. Proteomic changes upon treatment with semaglutide in individuals with obesity. Maretty L(1)(2), Gill D(3)(4), Simonsen L(5), Soh K(1), Zagkos L(3), Galanakis M(1)(6), Sibbesen J(1), Iglesias MT(1), Secher A(7), Valkenborg D(6), Purnell JQ(8), Knudsen LB(9), Tahrani AA(#)(10)(11), Geybels M(#)(1)(12). Author information: (1)Data Science, Novo Nordisk A/S, Søborg, Denmark. (2)QIAGEN A/S, Aarhus, Denmark. (3)Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. (4)Sequoia Genetics, London, UK. (5)Obesity Research, Novo Nordisk A/S, Måløv, Denmark. (6)Center for Statistics and Data Science Institute, Hasselt University, Hasselt, Belgium. (7)Brain and Adipose Biology, Novo Nordisk A/S, Måløv, Denmark. (8)Oregon Health & Science University (OHSU), Portland, OR, USA. (9)Chief Scientific Advisor Office, Novo Nordisk A/S, Måløv, Denmark. (10)Medical & Science, Novo Nordisk A/S, Søborg, Denmark. a.a.tahrani@bham.ac.uk. (11)Department of Metabolism and Systems Science, University of Birmingham, Birmingham, UK. a.a.tahrani@bham.ac.uk. (12)Genmab A/S, Valby, Denmark. (#)Contributed equally Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials. © 2025. The Author(s). DOI: 10.1038/s41591-024-03355-2 PMCID: PMC11750704 PMID: 39753963 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: L.S., K.S., M. Galanakis, M.T.I., J.S., A.S., L.B.K. and A.A.T. are employees and shareholders of Novo Nordisk. D.G., L.M. and M. Geybels were employees and shareholders of Novo Nordisk at the time of the analysis. M. Galanakis, M. Geybels and D.V. have received a grant from the Danish Innovation Fund (204000005B). J.Q.P. has received consulting fees from Boehringer Ingelheim and Novo Nordisk. L.Z. declares no competing interests.
8. Sci Rep. 2024 Jul 13;14(1):16195. doi: 10.1038/s41598-024-66448-5. High-intensity interval training improves bone remodeling, lipid profile, and physical function in multiple sclerosis patients. Amato A(1), Proia P(2), Alioto A(3), Rossi C(3), Pagliaro A(3), Ragonese P(4), Schirò G(4), Salemi G(4), Caldarella R(5), Vasto S(6), Nowak R(7)(8), Kostrzewa-Nowak D(9), Musumeci G(1), Baldassano S(6). Author information: (1)Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Science, School of Medicine, University of Catania, Via S. Sofia No 97, 95123, Catania, Italy. (2)Sport and Exercise Sciences Research Unit, Department of Psychology, Educational Science and Human Movement, University of Palermo, 90144, Palermo, Italy. patrizia.proia@unipa.it. (3)Sport and Exercise Sciences Research Unit, Department of Psychology, Educational Science and Human Movement, University of Palermo, 90144, Palermo, Italy. (4)Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127, Palermo, Italy. (5)Department of Laboratory Medicine, "P. Giaccone" University Hospital, University of Palermo, 90127, Palermo, Italy. (6)Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128, Palermo, Italy. (7)Institute of Physical Culture Sciences, University of Szczecin, 17C Narutowicza St, 70-240, Szczecin, Poland. (8)Department of Pathology, Pomeranian Medical University in Szczecin, 1 Unii Lubelskiej St, 71-242, Szczecin, Poland. (9)Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, 72 Powstańców Wlkp. Al, 70-111, Szczecin, Poland. Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease due to an autoimmune chronic inflammatory response, yet the etiology is currently not completely understood. It is already known that physical activity plays an essential role in improving quality of life, especially in neuropathological conditions. The study was aimed to investigate the possible benefits of high-intensity interval training (HIIT) in bone and lipid metabolism markers, and neuromotor abilities in MS patients. 130 participants were recruited; 16 subjects with MS met the inclusion criteria and were included in the data analysis. The patients were randomly assigned to two groups: a Control group (CG) (34.88 ± 4.45 yrs) that didn't perform any physical activity and the Exercise group (EG) (36.20 ± 7.80 yrs) that performed HIIT protocol. The training program was conducted remotely by a kinesiologist. It was performed three times a week for 8 weeks. At the beginning (T0) and the end of the study (T1) physical function tests, bone remodelling markers, and lipid markers analyses were performed. After 8 weeks of training the wall squat (s) (T0 = 27.18 ± 4.21; T1 = 41.68 ± 5.38, p ≤ 0.01) and Time Up and Go test (s) (T0 = 7.65 ± 0.43; T1 = 6.34 ± 0.38 p ≤ 0.01) performances improved; lipid markers analysis showed a decrease in Total (mg/dl) (T0 = 187.22 ± 15.73; T1 = 173.44 ± 13.03, p ≤ 0.05) and LDL (mg/dl) (T0 = 108 ± 21.08; T1 = 95.02 ± 17.99, p < 0.05) cholesterol levels. Additionally, the levels of osteocalcin (µg/L), a marker of bone formation increased (T0 = 20.88 ± 4.22; T1 = 23.66 ± 6.24, p < 0.05), 25-OH Vitamin D (µg/L) improved after 8 weeks (T0 = 21.11 ± 7.11; T1 = 27.66 ± 7.59, p < 0.05). HIIT had an effect on lower limb strength and gait control, improved bone formation, and lipid management, in MS patients. © 2024. The Author(s). DOI: 10.1038/s41598-024-66448-5 PMCID: PMC11246443 PMID: 39003295 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no competing interests.
9. Nat Med. 2024 Jul;30(7):1888-1897. doi: 10.1038/s41591-024-02951-6. Epub 2024 May 8. Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial. Bermingham KM(#)(1)(2), Linenberg I(#)(1)(2), Polidori L(2), Asnicar F(3), Arrè A(2), Wolf J(2), Badri F(2), Bernard H(2), Capdevila J(2), Bulsiewicz WJ(2)(4), Gardner CD(5), Ordovas JM(6)(7)(8), Davies R(2), Hadjigeorgiou G(2), Hall WL(1), Delahanty LM(9), Valdes AM(10)(11), Segata N(3), Spector TD(1)(12), Berry SE(13). Author information: (1)Department of Nutritional Sciences, King's College London, London, UK. (2)Zoe Ltd, London, UK. (3)Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy. (4)Emory University School of Medicine, Atlanta, GA, USA. (5)Stanford University, Stanford, CA, USA. (6)Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. (7)IMDEA Food Institute, Campus of International Excellence, Universidad Autónoma de Madrid, Consejo Superior de Investigaciones Científicas, Madrid, Spain. (8)Universidad Camilo José Cela, Madrid, Spain. (9)Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. (10)School of Medicine, University of Nottingham, Nottingham, UK. (11)Nottingham National Institute for Health and Care Research Biomedical Research Centre, Nottingham, UK. (12)Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. (13)Department of Nutritional Sciences, King's College London, London, UK. sarah.e.berry@kcl.ac.uk. (#)Contributed equally Large variability exists in people's responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020-2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41-70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = -0.13 mmol l-1; log-transformed 95% confidence interval = -0.07 to -0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268 . © 2024. The Author(s). DOI: 10.1038/s41591-024-02951-6 PMCID: PMC11271409 PMID: 38714898 [Indexed for MEDLINE] Conflict of interest statement: T.D.S., J.W. and G.H. are co-founders of ZOE Ltd. F.A., L.M.D., A.M.V., W.L.H., N.S., T.D.S. and S.E.B. are consultants to ZOE Ltd. K.M.B., I.L., L.P., A.A., J.W., F.B., H.B., J.C., W.J.B., R.D. and G.H. are or have been employees of ZOE Ltd. K.M.B., I.L., L.P., A.A., J.W., F.B., H.B., J.C., W.J.B., R.D., G.H., L.M.D., A.M.V., N.S., T.D.S. and S.E.B. have received options in ZOE Ltd. A.M.V., C.D.G., L.M.D., J.M.O. and N.S. are members of the Scientific Advisory Board of ZOE Ltd.
10. Lancet Neurol. 2024 May;23(5):477-486. doi: 10.1016/S1474-4422(24)00073-5. Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial. Tawil R(1), Wagner KR(2), Hamel JI(1), Leung DG(2), Statland JM(3), Wang LH(4), Genge A(5), Sacconi S(6), Lochmüller H(7), Reyes-Leiva D(8), Diaz-Manera J(9), Alonso-Perez J(10), Muelas N(11), Vilchez JJ(12), Pestronk A(13), Gibson S(14), Goyal NA(15), Hayward LJ(16), Johnson N(17), LoRusso S(18), Freimer M(18), Shieh PB(19), Subramony SH(20), van Engelen B(21), Kools J(21), Leinhard OD(22), Widholm P(23), Morabito C(24), Moxham CM(24), Cadavid D(24), Mellion ML(24), Odueyungbo A(24), Tracewell WG(24), Accorsi A(24), Ronco L(24), Gould RJ(24), Shoskes J(24), Rojas LA(24), Jiang JG(25). Author information: (1)Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA. (2)Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. (3)University of Kansas, Lawrence, KS, USA. (4)University of Washington, Seattle, WA, USA. (5)Montreal Neurological Institute and Hospital, Montreal, QC, Canada. (6)Peripheral Nervous System and Muscle Department, Nice University Hospital and University of Côte d'Azur, Nice, France. (7)Children's Hospital of Eastern Ontario Research Institute, Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada. (8)Institut de Recerca IIB Sant Pau, Hospital Universitari Santa Creu i Sant Pau, Barcelona, Spain. (9)Institut de Recerca IIB Sant Pau, Hospital Universitari Santa Creu i Sant Pau, Barcelona, Spain; John Walton Muscular Dystrophy Research Center, Newcastle University, Newcastle, UK. (10)Neuromuscular Diseases Unit, Neurology Department, Hospital Universitario Nuestra Señora de Candelaria, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Santa Cruz de Tenerife, Tenerife, Spain; Neuromuscular Diseases Unit, Neurology Department, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. (11)Neuromuscular Diseases Unit, Neurology Department, Hospital Universitari i Politecnic La Fe and Neuromuscular Reference Centre, Valencia, Spain; Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain; Department of Medicine, University of Valencia, Valencia, Spain. (12)Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain. (13)Washington University in St Louis, St Louis, MO, USA. (14)University of Utah, Salt Lake City, UT, USA. (15)University of California at Irvine, Irvine, CA, USA. (16)University of Massachusetts, Worcester, MA, USA. (17)Virginia Commonwealth University, Richmond, VA, USA. (18)Ohio State University Wexner Medical Center, Columbus, OH, USA. (19)University of California at Los Angeles, Los Angeles, CA, USA. (20)University of Florida College of Medicine, Gainesville, FL, USA. (21)Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands. (22)AMRA Medical, Linköping, Sweden; Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden. (23)AMRA Medical, Linköping, Sweden; Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Department of Radiology, Linköping University, Linköping, Sweden. (24)Fulcrum Therapeutics, Cambridge, MA, USA. (25)Fulcrum Therapeutics, Cambridge, MA, USA. Electronic address: jjiang@fulcrumtx.com. Comment in Lancet Neurol. 2024 May;23(5):449-451. doi: 10.1016/S1474-4422(24)00129-7. BACKGROUND: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy. METHODS: We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4-driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. FINDINGS: Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45·7 (SD 12·5) years. Least squares mean changes from baseline in DUX4-driven gene expression did not differ significantly between the losmapimod (0·83 [SE 0·61]) and placebo (0·40 [0·65]) groups (difference 0·43 [SE 0·56; 95% CI -1·04 to 1·89]; p=0·56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drug-related) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. INTERPRETATION: Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy. FUNDING: Fulcrum Therapeutics. Copyright © 2024 Elsevier Ltd. All rights reserved. DOI: 10.1016/S1474-4422(24)00073-5 PMID: 38631764 [Indexed for MEDLINE] Conflict of interest statement: Declaration of interests RT reports grants from and contracts with the US National Institutes of Health, fees for consulting, participation on a data safety monitoring board, and data review, and support for attending meetings from Fulcrum Therapeutics. KRW is an employee of the Novartis Institute for Biomedical Research, Novartis. JIH reports consulting fees from Vertex Therapeutics and Dyne Therapeutics. DGL reports receiving institutional support for the ReDUX4 clinical trial and grant funding for administrative support for FSHD Clinical Trials Research Network, a K23 Career Development grant (paid to institution) to fund an imaging study in facioscapulohumeral muscular dystrophy, honoraria for co-chairing the annual research meeting of the FSHD Society, and institutional funding for facioscapulohumeral muscular dystrophy natural history studies by the FSHD Clinical Trials Research Network. JMS reports grants from or contracts with the US National Institutes of Health, the Muscular Dystrophy Association, the FSHD Society, Friends of FSH Research, FSHD Canada, and the US Centers for Disease Control and Prevention; consulting fees from Fulcrum Therapeutics, Epic Bio, Dyne, Avidity, Roche, EcoR1, and Treat NMD Advisory Committee for Therapeutics; and stock and stock options in Dyne. LHW reports consulting fees from Fulcrum Therapeutics and Avidity Therapeutics, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, educational events, and attending meetings or travel from Fulcrum Therapeutics, and payment for participation on a data safety monitoring and advisory board from Syneos. AG reports consulting fees from Fulcrum, Quralis, AL-S Pharma, Mitsubishi Tanabe Pharma America, Amylyx, Alexion, and Cytokinetics and support for attending meetings or travel from Amylyx, Quralis, Mitsubishi Tanabe Pharma America, Alexion, and AL-S Pharma; she serves on the Board of AL-S Canada and has stock or stock options in Quralis. SS reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, and educational events from Lupin and Fulcrum Therapeutics, payment for expert testimony from Axelys and Ology, support for attending meetings or travel from UCB, Sanofi, Biogen, and Fulcrum Therapeutics, and support for participation in data safety monitoring and advisory boards from Sanofi, Biogen, Amicus, UCB, and Alexion. HL receives support from the Canadian Institutes of Health Research, Muscular Dystrophy Canada, the Canada Foundation for Innovation, and the Canada Research Chairs program. SG reports being contracted as study-site principal investigator and receiving study-related equipment for the ReDUX4 phase 2 and 3 clinical trials from Fulcrum Therapeutics. LJH reports receiving consulting fees from Myocea and HC Wainwright, and support for attending meetings or travel from the Solve FSHD Foundation. NJ reports employment as a contractor for Fulcrum Therapeutics, Dyne, Avidity, Avexis, Biogen, Triplet, AMO Pharma, ML Bio solutions, and Askbio, consulting fees from Dyne, Avidity, Novartis Gene Therapies, Fulcrum, Biogen, and participation on data safety monitoring and advisory board for Biogen Idec. SHS reports institutional support from Fulcrum Therapeutics, including for participation on an advisory board. BvE reports grants from or contracts with Prinses Beatrix Spierfonds, the Dutch FSHD Foundation, and Stichting Spieren voor Spieren, royalties or licenses from patent EP2012740236, and institutional payments for consulting and participation on data safety monitoring and advisory boards from Fulcrum Therapeutics, Facio, Avidity, Dyne, Arrowhead, Biomarin, Pepgen, and Teva. JK reports institutional payment for ReDUX4. PW and ODL report receiving support for attending meetings or travel from, and stock or stock options in, AMRA Medical. CM, DC, MLM, AA, and LAR were full-time employees of Fulcrum Therapeutics at the time of manuscript preparation and own stock or have stock options in Fulcrum Therapeutics. MLM also received travel support from Fulcrum Therapeutics. RJG reports being an employee, board member, and consultant for Fulcrum Therapeutics, and holds stock or stock options in the company. JGJ is an employee of Fulcrum Therapeutics. All other authors report no competing interests.
11. Clin Drug Investig. 2023 Sep;43(9):681-690. doi: 10.1007/s40261-023-01282-7. Epub 2023 Sep 7. Pharmacokinetic and Exposure Response Analysis of the Double-Blind Randomized Study of Posaconazole and Voriconazole for Treatment of Invasive Aspergillosis. Maertens JA(1)(2), Rahav G(3)(4), Lee DG(5), Haider S(6), Ramirez-Sanchez IC(7), Klimko N(8), Ponce-de-León A(9), Han S(10), Wrishko R(10), Winchell GA(11), Grandhi A(10), Waskin H(10); study investigators. Author information: (1)Department of Microbiology, Immunology, and Transplantation, KU Leuven, Herestraat 49 Campus, 3000, Leuven, Belgium. johan.maertens@uzleuven.be. (2)Department of Hematology, University Hospitals Leuven, Leuven, Belgium. johan.maertens@uzleuven.be. (3)Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. (4)Sackler School of Medicine, Tel Aviv University, Ramat Gan, Israel. (5)Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea. (6)Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, ON, Canada. (7)Hospital Pablo Tobón Uribe, Universidad de Antioquia, Medellín, Colombia. (8)North-Western State Medical University, St. Petersburg, Russia. (9)Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. (10)Merck & Co., Inc., Rahway, NJ, USA. (11)Certara USA, Inc., Princeton, NJ, USA. BACKGROUND AND OBJECTIVE: A double-blind phase 3 study was conducted to compare posaconazole 300 mg intravenously (IV)/300 mg orally once daily (twice daily day 1) with voriconazole 4 mg/kg IV twice daily/200 mg orally twice daily (6 mg/kg day 1) for treatment of invasive aspergillosis. This analysis was conducted to summarize the pharmacokinetics and exposure-response relationships of posaconazole and voriconazole using plasma trough concentration (Ctrough) as a surrogate for exposure from the double-blind phase 3 study. METHODS: The pharmacokinetic evaluable population included all intention-to-treat (ITT) participants with at least one plasma concentration during the treatment period. Treatment blinding was maintained without therapeutic drug monitoring. Ctrough sampling occurred throughout treatment; efficacy and safety were evaluated using quartiles determined by mean Ctrough concentrations. Exposure efficacy variables included day 42 all-cause mortality (primary study endpoint) and global clinical response. Exposure safety variables included all adverse events and treatment-related adverse events. RESULTS: The pharmacokinetic analysis population included 506 of 575 ITT participants (437 with Ctrough concentrations: 228 posaconazole, 209 voriconazole). No trend was seen across quartiles of posaconazole Ctrough for the key efficacy endpoint of all-cause mortality through day 42. Participants in the highest quartile of voriconazole Ctrough had higher all-cause mortality through day 42 than participants in the lower three quartiles of voriconazole Ctrough. Similar findings were observed for global clinical response and Ctrough. No clear exposure safety trend by quartile was seen for posaconazole or voriconazole. CONCLUSIONS: A strong exposure-response relationship was not observed across the range of exposure from the administered doses and formulations for posaconazole or voriconazole. TRIAL REGISTRATION: NCT01782131; registered January 30, 2013. © 2023. The Author(s). DOI: 10.1007/s40261-023-01282-7 PMCID: PMC10514181 PMID: 37676612 [Indexed for MEDLINE] Conflict of interest statement: J.A.M. reports personal fees and non-financial support from MSD, grants, personal fees and non-financial support from Pfizer Inc., grants, personal fees and non-financial support from Gilead Sciences, personal fees and non-financial support from F2G, and personal fees and non-financial support from Cidara. G.R., S. Haider, I.C.R. and A.P. have nothing to disclose. D.-G.L. has received grants and personal fees from Pfizer, Gilead Sciences, and Yuhan. N.K. has received research grants or honoraria as a speaker or advisor from Astellas, Gilead, MSD, and Pfizer. R.W. is an employee of Merck Sharp and Dohme LLC, a subsidiary of Merck and Co., Inc., Rahway, NJ, USA, and has stock in Merck and Co., Inc., Rahway, NJ, USA. G.A.W. is working under contract with Certara USA, Inc., Princeton, NJ, USA. S. Han, A.G., and H.W. are employees of Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
12. N Engl J Med. 2023 Feb 16;388(7):595-608. doi: 10.1056/NEJMoa2209604. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. Papi A(1), Ison MG(1), Langley JM(1), Lee DG(1), Leroux-Roels I(1), Martinon-Torres F(1), Schwarz TF(1), van Zyl-Smit RN(1), Campora L(1), Dezutter N(1), de Schrevel N(1), Fissette L(1), David MP(1), Van der Wielen M(1), Kostanyan L(1), Hulstrøm V(1); AReSVi-006 Study Group. Collaborators: Adams M, Adams M, Akite EJ, Alt I, Andrews C, Antonelli-Incalzi R, Asatryan A, Athan E, Bahrami G, Bargagli E, Bhorat Q, Bird P, Borowy P, Boutry C, Brotons Cuixart C, Browder D, Brown J, Buntinx E, Cameron D, Chinsky K, Choi M, Choo EJ, Collete D, Corral Carrillo M, Davis MG, de Heusch M, de Looze F, De Meulemeester M, De Negri F, DeAtkine D, Dedkova V, Descamps D, Dzongowski P, Eckermann T, Essink B, Faulkner K, Feldman R, Ferguson M, Fuller G, Galan Melendez IM, Gentile I, Ghesquiere W, Grimard D, Gruselle O, Halperin S, Heer A, Helman L, Hotermans A, Jelinek T, Kamerbeek J, Kim HY, Kimmel M, Koch M, Kokko S, Koski S, Kotb S, Lalueza A, Lee JS, Lins M, Lombaard J, Mahomed A, Malerba M, Marechal C, Martinot JB, Masuet-Aumatell C, McNally D, Medina Pech CE, Mendez Galvan J, Mesaros NE, Mesotten D, Mitha E, Mngadi K, Moeckesch B, Montgomery B, Murray L, Nally R, Narejos Perez S, Newberg J, Nugent P, Ochoa Mazarro D, Oda H, Olivier A, Orso M, Ortiz Molina J, Pak T, Park DW, Patel M, Patel M, Pedro Pijoan AM, Perez Vera M, Borobia Perez A, Perez-Breva L, Pileggi C, Pregliasco F, Pretswell C, Quinn D, Reynolds M, Romanenko V, Rosen J, Roy N, Ruiz Antoran B, Sakata H, Sauter J, Schaefer A, Sein Anand I, Serra Rexach JA, Shu D, Siig A, Simon W, Smakotina S, Steenackers K, Stephan B, Tafuri S, Takazawa K, Tellier G, Terryn W, Tharenos L, Thomas N, Toursarkissian N, Ukkonen B, Vale N, Van Landegem PJ, Vanden Abeele C, Verheust C, Vermeersch L, Vicco M, Vitale F, Voloshyna O, White J, Wie SH, Wilson J, Ylisastigui P. Author information: (1)From the Pulmonary Division, University of Ferrara, St. Anna University Hospital, Ferrara, Italy (A.P.); the Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago (M.G.I.); the Canadian Center for Vaccinology, Dalhousie University, IWK Health and Nova Scotia Health, Halifax, Canada (J.M.L.); the Division of Infectious Diseases, Department of Internal Medicine, the Catholic University of Korea, Seoul, South Korea (D.-G.L.); the Center for Vaccinology, Ghent University, and Ghent University Hospital, Ghent (I.L.-R.), GSK, Wavre (L.C., N.D., L.F., M.-P.D., M.V.W., L.K., V.H.), and GSK, Rixensart (N.S.) - all in Belgium; Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, the Genetics, Vaccines, Infectious Diseases, and Pediatrics Research Group, Instituto de Investigación Sanitaria de Santiago, Universidad de Santiago de Compostela, Santiago de Compostela, Consorcio Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid (F.M.-T.); the Institute of Laboratory Medicine and Vaccination Centre, Klinikum Würzburg Mitte, Campus Juliusspital, Würzburg, Germany (T.F.S.); and the Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town, and Groote Schuur Hospital, Cape Town, South Africa (R.N.Z.-S.). Comment in Ann Intern Med. 2023 Jun;176(6):JC62. doi: 10.7326/J23-0038. BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection. METHODS: In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01E-adjuvanted RSV prefusion F protein-based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20%. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated. RESULTS: A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR-confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups. CONCLUSIONS: A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting conditions. (Funded by GlaxoSmithKline Biologicals; AReSVi-006 ClinicalTrials.gov number, NCT04886596.). Copyright © 2023 Massachusetts Medical Society. DOI: 10.1056/NEJMoa2209604 PMID: 36791160 [Indexed for MEDLINE]
13. J Orofac Orthop. 2024 Mar;85(2):110-122. doi: 10.1007/s00056-022-00427-1. Epub 2022 Sep 21. Low-level laser therapy, piezocision, or their combination vs. conventional treatment for orthodontic tooth movement : A hierarchical 6-arm split-mouth randomized clinical trial. [Article in English] Moradinejad M(1), Chaharmahali R(2), Shamohammadi M(1)(3), Mir M(4)(5), Rakhshan V(6). Author information: (1)Department of Orthodontics, School of Dentistry, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. (2)Department of Orthodontics, School of Dentistry, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. charmahali.r@gmail.com. (3)Orthodontic Department, Faculty of Dentistry, Shahed University, Tehran, Iran. (4)Department of Conservative Dentistry (DGL), Rheinisch-Westfälische Technische Hochschule (RWTH) Hospital, Aachen, Germany. (5)Beckman Laser Institute, University of California, Irvine, CA, USA. (6)Dentist in private practice, Tehran, Iran. PURPOSE: The use non-invasive or minimally invasive methods to accelerate orthodontic tooth movements (OTM) is desirable. In this regard, low-level laser therapy (LLLT, photobiomodulation) and piezocision are suggested. However, because the efficacies of these methods remain controversial/inconclusive, we investigated and compared these two methods. METHODS: Sixty-four quadrants in 32 patients were randomized into three parallel intervention groups of 22, 22, and 20 (6 parallel arms, n = 64 treatment/control sides). Bilateral first premolars were extracted and canine retraction commenced. In each group, one side of the mouth was randomly selected as control, while the other side underwent each of three interventions: LLLT (940 nm, 8 J, 0.5 W, 16 s, 12 sites), piezocision, and "LLLT + piezocision". At the 3rd, 6th, and 9th follow-up weeks, canine retraction and anchorage loss were measured. Data were analyzed statistically (α = 0.05). RESULTS: After 9 weeks, LLLT, piezocision, and LLLT + piezocision improved canine retraction by 0.51, 1.14, and 1.93 mm, respectively. LLLT accelerated canine retraction (compared to control) by 1.6-, 1.4-, and 1.2-fold in the 3rd, 6th, and 9th week, respectively. These statistics were 2.1-, 1.7-, and 1.5-fold for piezocision and 2.7-, 2.1-, and 1.8-fold for LLLT + piezocision. Compared to controls, each intervention showed significant retraction acceleration (p < 0.05). The effect of LLLT + piezocision was greater than that of isolated piezocision (p < 0.05), which itself was greater than that for isolated LLLT (p < 0.05). CONCLUSION: All three methods accelerated OTM, with the combination of LLLT + piezocision producing the strongest and LLLT producing the weakest acceleration. Publisher: ZUSAMMENFASSUNG: ZIELSETZUNG: Die Anwendung nichtinvasiver oder minimal-invasiver Methoden zur Beschleunigung kieferorthopädischer Zahnbewegungen (OTM) ist wünschenswert. In diesem Kontext werden die Low-Level-Lasertherapie (LLLT, Photobiomodulation) und die Piezozision vorgeschlagen. Da die Wirksamkeit dieser Methoden jedoch nach wie vor umstritten bzw. nicht eindeutig ist, haben wir diese beiden Methoden untersucht und verglichen. METHODEN: Vierundsechzig Quadranten von 32 Patienten wurden nach dem Zufallsprinzip in 3 parallele Interventionsgruppen von 22, 22 und 20 (6 parallele Arme, n = 64 Behandlungs‑/Kontrollseiten) eingeteilt. Die bilateralen ersten Prämolaren wurden entfernt, die Eckzahnretraktion wurde eingeleitet. In jeder Gruppe wurde eine Seite des Mundes nach dem Zufallsprinzip als Kontrolle ausgewählt, während die andere Seite jeweils einer der 3 Behandlungsmethoden unterzogen wurde: LLLT (940 nm, 8 J, 0,5 W, 16 s, 12 Stellen), Piezozision und „LLLT + Piezozision“. In der 3., 6. und 9. Nachuntersuchungswoche wurden Eckzahnretraktion und Verankerungsverlust ermittelt. Die Daten wurden statistisch ausgewertet (α = 0,05). ERGEBNISSE: Nach 9 Wochen verbesserten LLLT, Piezozision und LLLT + Piezozision die Eckzahnretraktion um 0,51, 1,14 bzw. 1,93 mm. LLLT beschleunigte die Eckzahnretraktion (im Vergleich zur Kontrolle) in der 3., 6. und 9. Woche um das 1,6-, 1,4- bzw. 1,2-fache. Diese Werte waren 2,1-, 1,7- und 1,5-fach für die Piezozision und 2,7-, 2,1- und 1,8-fach für LLLT + Piezozision. Im Vergleich zu den Kontrollen zeigte jeder Eingriff eine signifikante Beschleunigung der Retraktion (p < 0,05). Die Wirkung von LLLT + Piezozision war größer als die der isolierten Piezozision (p < 0,05), die wiederum größer war als die der isolierten LLLT (p < 0,05). SCHLUSSFOLGERUNG: Alle 3 Behandlungsverfahren beschleunigten die OTM, die Kombination von LLLT + Piezozision am stärksten, die LLLT am wenigsten. © 2022. Springer Medizin Verlag GmbH, ein Teil von Springer Nature. DOI: 10.1007/s00056-022-00427-1 PMID: 36129485 [Indexed for MEDLINE]
14. N Engl J Med. 2022 Aug 18;387(7):599-610. doi: 10.1056/NEJMoa2201662. Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19. Bramante CT(1), Huling JD(1), Tignanelli CJ(1), Buse JB(1), Liebovitz DM(1), Nicklas JM(1), Cohen K(1), Puskarich MA(1), Belani HK(1), Proper JL(1), Siegel LK(1), Klatt NR(1), Odde DJ(1), Luke DG(1), Anderson B(1), Karger AB(1), Ingraham NE(1), Hartman KM(1), Rao V(1), Hagen AA(1), Patel B(1), Fenno SL(1), Avula N(1), Reddy NV(1), Erickson SM(1), Lindberg S(1), Fricton R(1), Lee S(1), Zaman A(1), Saveraid HG(1), Tordsen WJ(1), Pullen MF(1), Biros M(1), Sherwood NE(1), Thompson JL(1), Boulware DR(1), Murray TA(1); COVID-OUT Trial Team. Collaborators: Anderson B, Atwater RC, Avula N, Beckman KB, Belani HK, Boulware DR, Bramante CT, Brea J, Broedlow CA, Buse JB, Campora P, Charles J, Christensen G, Christiansen T, Cohen K, Connelly B, Datta S, Deng N, Dunn AT, Erickson SM, Fairbairn FM, Fenno SL, Fraser DJ, Fricton RD, Griffiths G, Hagen AA, Hartman KM, Hendrickson AF, Huling JD, Ingraham NE, Jeng AC, Johnson DM, Karger AB, Klatt NR, Kuehl EA, LaBar DD, Lee S, Liebovitz DM, Lindberg S, Luke DG, Machicado R, Mohamud Z, Murray TA, Ngonyama R, Nicklas JM, Odde DJ, Parrens E, Parra D, Patel B, Proper JL, Pullen MF, Puskarich MA, Rao V, Reddy NV, Reddy N, Rypka KJ, Saveraid HG, Seloadji P, Shahriar A, Sherwood N, Siegart JL, Siegel LK, Simmons L, Sinelli I, Singh P, Snyder A, Stauffer MT, Thompson J, Tignanelli CJ, Tople TL, Tordsen WJ, Watson RHB, Wu B, Zaman A, Zolik MR, Zinkl L. Author information: (1)From the Departments of Medicine (C.T.B., N.E.I., K.M.H., A.A.H., B.P., S.L.F., N.A., N.V.R., S.M.E., H.G.S., M.F.P., D.R.B.) and Surgery (C.J.T., N.R.K.), Emergency Medicine (M.A.P., M.B.), and Laboratory Medicine and Pathology (A.B.K.), Medical School, the Divisions of Biostatistics (J.D.H., J.L.P., L.K.S., V.R., S. Lindberg, T.A.M.) and Epidemiology and Community Health (N.E.S.), School of Public Health, and the Department of Biomedical Engineering (D.J.O.), University of Minnesota, the Department of Emergency Medicine, Hennepin County Medical Center (M.A.P., W.J.T., M.B.), and the Investigational Drug Service Pharmacy, University of Minnesota-Fairview (D.G.L.), Minneapolis, and UnitedHealth Group, Optum Labs, Minnetonka (K.C.) - all in Minnesota; the Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill (J.B.B.); the Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (D.M.L., R.F., S. Lee); the Department of Medicine, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora (J.M.N., A.Z.); the Department of Medicine, Olive View-University of California, Los Angeles (H.K.B.); Atlanta Veterans Affairs Medical Center and the Department of Medicine, Emory University School of Medicine - both in Atlanta (B.A.); and the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville (J.L.T.). Comment in N Engl J Med. 2022 Aug 18;387(7):654-655. doi: 10.1056/NEJMe2209017. N Engl J Med. 2022 Dec 15;387(24):e65. doi: 10.1056/NEJMc2212542. N Engl J Med. 2022 Dec 15;387(24):e65. doi: 10.1056/NEJMc2212542. BACKGROUND: Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications. RESULTS: A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS: None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.). Copyright © 2022 Massachusetts Medical Society. DOI: 10.1056/NEJMoa2201662 PMCID: PMC9945922 PMID: 36070710 [Indexed for MEDLINE]
15. N Engl J Med. 2022 Mar 24;386(12):1109-1120. doi: 10.1056/NEJMoa2111904. Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis. Jarvis JN(1), Lawrence DS(1), Meya DB(1), Kagimu E(1), Kasibante J(1), Mpoza E(1), Rutakingirwa MK(1), Ssebambulidde K(1), Tugume L(1), Rhein J(1), Boulware DR(1), Mwandumba HC(1), Moyo M(1), Mzinganjira H(1), Kanyama C(1), Hosseinipour MC(1), Chawinga C(1), Meintjes G(1), Schutz C(1), Comins K(1), Singh A(1), Muzoora C(1), Jjunju S(1), Nuwagira E(1), Mosepele M(1), Leeme T(1), Siamisang K(1), Ndhlovu CE(1), Hlupeni A(1), Mutata C(1), van Widenfelt E(1), Chen T(1), Wang D(1), Hope W(1), Boyer-Chammard T(1), Loyse A(1), Molloy SF(1), Youssouf N(1), Lortholary O(1), Lalloo DG(1), Jaffar S(1), Harrison TS(1); Ambition Study Group. Collaborators: Goodall J, Lechiile K, Mawoko N, Mbangiwa T, Milburn J, Mmipi R, Muthoga C, Ponatshego P, Rulaganyang I, Seatla K, Tlhako N, Tsholo K, April S, Bekiswa A, Boloko L, Bookholane H, Crede T, Davids L, Goliath R, Hlungulu S, Hoffman R, Kyepa H, Masina N, Maughan D, Mnguni T, Moosa S, Morar T, Mpalali M, Naude J, Oliphant I, Sayed S, Sebesho L, Shey M, Swanepoel L, Chasweka M, Chimang'anga W, Chimphambano T, Dziwani E, Gondwe E, Kadzilimbile A, Kateta S, Kossam E, Kukacha C, Lipenga B, Ndaferankhande J, Ndalama M, Shah R, Singini A, Stott K, Zambasa A, Banda T, Chikaonda T, Chitulo G, Chiwoko L, Chome N, Gwin M, Kachitosi T, Kamanga B, Kazembe M, Kumwenda E, Kumwenda M, Maya C, Mhango W, Mphande C, Msumba L, Munthali T, Ngoma D, Nicholas S, Simwinga L, Stambuli A, Tegha G, Zambezi J, Ahimbisibwe C, Akampurira A, Alice A, Cresswell F, Gakuru J, Kiiza D, Kisembo J, Kwizera R, Kugonza F, Laker E, Luggya T, Lule A, Musubire A, Muyise R, Namujju O, Ndyetukira J, Nsangi L, Okirwoth M, Sadiq A, Tadeo K, Tukundane A, Williams D, Atwine L, Buzaare P, Collins M, Emily N, Inyakuwa C, Kariisa S, Mwesigye J, Niwamanya S, Rodgers A, Rukundo J, Rwomushana I, Ssemusu M, Stead G, Boyd K, Gondo S, Kufa P, Makaha E, Moyo C, Mtisi T, Mudzingwa S, Mwarumba T, Zinyandu T, Alanio A, Dromer F, Sturny-Leclere A, Griffin P, Hafeez S. Author information: (1)From the Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (J.N.J., D.S.L., N.Y.), the Institute for Infection and Immunity, St. George's University London (A.L., S.F.M., T.S.H.), and the Clinical Academic Group in Infection and Immunity, St. George's University Hospitals NHS Foundation Trust (T.S.H.), London, Liverpool School of Tropical Medicine (H.C.M., E.W., D.W., D.G.L., S. Jaffar) and the Department of Public Health, Policy, and Systems, Institute of Population Health (T.C.), and the Department of Pharmacology and Therapeutics, Institute of Systems, Molecular, and Integrative Biology (W.H.), University of Liverpool, Liverpool, and the Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter (T.S.H.) - all in the United Kingdom; the Botswana-Harvard AIDS Institute Partnership (J.N.J., D.S.L., M. Mosepele, T.L., K. Siamisang, N.Y.), the Departments of Internal Medicine (M. Mosepele) and Family Medicine and Public Health (K. Siamisang), University of Botswana, and the Department of Health Services Management, Ministry of Health and Wellness (K. Siamisang) - all in Gaborone, Botswana; the Infectious Diseases Institute, College of Health Sciences (D.B.M., E.K., J.K., E.M., M.K.R., K. Ssebambulidde, L.T., J.R., D.R.B., S. Jjunju, E.N.), and the Department of Medicine, School of Medicine (D.B.M.), Makerere University, Kampala, and Mbarara University of Science and Technology, Mbarara (C. Muzoora, E.N.) - both in Uganda; the University of Minnesota, Minneapolis (D.B.M., J.R., D.R.B.); the Malawi-Liverpool-Wellcome Trust Clinical Research Programme (H.C.M., M. Moyo, H.M., D.G.L.) and the Department of Medicine, Kamuzu University of Health Sciences (H.C.M., M. Moyo), Blantyre, and the Lilongwe Medical Relief Fund Trust (University of North Carolina-Malawi Project), Lilongwe (C.K., M.C.H., C.C.) - all in Malawi; the Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill (M.C.H.); the Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine (G.M., C.S., K.C., A.S.), and the Department of Medicine (G.M., C.S., K.C.), University of Cape Town, and the Department of Radiology, Groote Schuur Hospital (A.S.) - both in Cape Town, South Africa; the Internal Medicine Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare (C.E.N., A.H., C. Mutata); Institut Pasteur, National Center for Scientific Research, Molecular Mycology Unit and National Reference Center for Invasive Mycoses and Antifungals, Unités Mixtes de Recherche 2000, and Université de Paris, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Institut Hospitalo-Universitaire Imagine - both in Paris (T.B.-C., O.L.). Comment in N Engl J Med. 2022 Mar 24;386(12):1179-1181. doi: 10.1056/NEJMe2201150. N Engl J Med. 2022 Jul 28;387(4):380-381. doi: 10.1056/NEJMc2206274. BACKGROUND: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.). Copyright © 2022 Massachusetts Medical Society. DOI: 10.1056/NEJMoa2111904 PMCID: PMC7612678 PMID: 35320642 [Indexed for MEDLINE]
16. Mycoses. 2019 Oct;62(10):969-978. doi: 10.1111/myc.12972. Epub 2019 Aug 18. Efficacy and safety of combination antifungal therapy in Korean haematological patients with invasive aspergillosis. Lee DG(1), Lee HJ(2), Yan JL(3), Lin SS(3), Aram JA(3). Author information: (1)Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea. (2)Pfizer Inc, Seoul, South Korea. (3)Pfizer Inc, New York, NY, USA. This randomised, double-blind, placebo-controlled trial assessed the efficacy, safety and tolerability of voriconazole+anidulafungin (combination) or voriconazole+placebo (monotherapy) for invasive aspergillosis (IA; NCT00531479). We present a post hoc analysis of Korean and non-Korean patients with IA (including baseline positive serum galactomannan [GM]). Immunocompromised patients ≥ 16 years with IA were randomised 1:1, combination or monotherapy, for ≥ 2 weeks' treatment. The primary endpoint was 6- and 12-week all-cause mortality (Korean modified intent-to-treat [mITT] population). Overall, 454 patients enrolled (Koreans: 56 [combination: 28, monotherapy: 28], non-Koreans: 398 [combination: 200, monotherapy: 198]). The mITT population comprised 40 Koreans (combination: 23; monotherapy: 17) and 237 non-Koreans (combination: 112; monotherapy: 125). Week 6 treatment difference in mortality rate between combination and monotherapy was -6.4% in non-Koreans. This reduction was more marked in Koreans (-22.4%). Week 12 difference in all-cause mortality between combination and monotherapy was -17.7% (Koreans) and -20.2% at Week 6 (Koreans; positive baseline GM). Week 6 mortality (Koreans [mITT]; baseline GM >0.5-2.0) was 0/13 (combination) and 2/6 (monotherapy). Serious adverse events were numerically higher for combination than monotherapy (Koreans: 57.1%, 46.4%; non-Koreans: 49.5%, 46.0%). In Koreans, combination therapy was associated with marginally better outcomes than monotherapy and more so than in non-Koreans. © 2019 The Authors. Mycoses published by Blackwell Verlag GmbH. DOI: 10.1111/myc.12972 PMCID: PMC7003761 PMID: 31355956 [Indexed for MEDLINE] Conflict of interest statement: D‐GL has received grants and personal fees from Astellas, Gilead Sciences, MSD, Pfizer and Yuhan, outside the submitted work. H‐JL is an employee of Pfizer Inc, Seoul. JLY, SS‐FL and JAA are employees of Pfizer Inc, New York.
17. Anesthesiology. 2019 Feb;130(2):203-212. doi: 10.1097/ALN.0000000000002509. Amisulpride for the Rescue Treatment of Postoperative Nausea or Vomiting in Patients Failing Prophylaxis: A Randomized, Placebo-controlled Phase III Trial. Habib AS(1), Kranke P, Bergese SD, Chung F, Ayad S, Siddiqui N, Motsch J, Leiman DG, Melson TI, Diemunsch P, Fox GM, Candiotti KA. Author information: (1)From the Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina (A.S.H.) Department of Anaesthesia and Critical Care, University Hospitals of Würzburg, Würzburg, Germany (P.K.) Department of Anesthesiology, Wexner Medical Center at The Ohio State University, Columbus, Ohio (S.D.B.) Department of Anesthesia, University Health Network, University of Toronto, Toronto, Ontario, Canada (F.C.) Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Anesthesiology Institute, Outcomes Research, Fairview Hospital, Cleveland, Ohio (S.A.) Department of Anesthesia, Mount Sinai Hospital, Toronto, Ontario, Canada (N.S.) Department of Anesthesiology, Universitätsklinikum Heidelberg, Heidelberg, Germany (J.M.) Hermann Drive Surgical Hospital, Houston, Texas (D.G.L.) Helen Keller Hospital, Sheffield, Alabama (T.I.M.) Service d'Anesthésie-Réanimation Chirurgicale, CHU de Hautepierre, Strasbourg, France (P.D.) Acacia Pharma Ltd, Cambridge, United Kingdom (G.M.F.) Department of Anesthesiology, Critical Care and Perioperative Medicine, University of Miami, Miami, Florida (K.A.C.). Comment in Anesthesiology. 2019 Feb;130(2):183-185. doi: 10.1097/ALN.0000000000002536. BACKGROUND: Although antiemetics are commonly used to prevent postoperative nausea or vomiting, the failure rate is appreciable and there is currently no generally accepted standard for rescue treatment of postoperative nausea or vomiting after failed prophylaxis. This prospective, randomized, double-blind, parallel-group, placebo-controlled, multicenter study was designed to test the hypothesis that intravenous amisulpride, a dopamine D2/D3-antagonist, is superior to placebo at treating established postoperative nausea or vomiting after failed prophylaxis. METHODS: A total of 2,285 adult patients undergoing surgery under general inhalational anesthesia and receiving standard antiemetic prophylaxis were enrolled at 23 sites in Canada, France, Germany, and the United States. Of these, 702 patients experienced postoperative nausea or vomiting in the 24-h period after surgery and were randomized to receive a single dose of 5 or 10 mg intravenous amisulpride or matching placebo. The primary endpoint was complete response, defined as no emesis or rescue antiemetic use for 24 h after study drug administration, excluding emesis in the first 30 min. Secondary endpoints included incidence of emesis and rescue medication use, nausea burden, time to treatment failure, and length of stay in postanesthesia care unit and hospital. RESULTS: Complete response occurred in significantly more patients receiving 10 mg amisulpride (96 of 230, 41.7%) than placebo (67 of 235, 28.5%), a 13.2% difference (95% CI, 4.6 to 21.8; odds ratio, 1.80; P = 0.006). A 5-mg dose of amisulpride did not show a significant benefit (80 of 237, 33.8%); the difference from placebo was 5.2% (95% CI, 3.1 to 13.6; odds ratio, 1.24; P = 0.109). The total number of adverse events recorded and proportion of patients with at least one adverse event were comparable between the placebo and amisulpride groups. No clinically relevant toxicities were observed. CONCLUSIONS: A single 10-mg dose of intravenous amisulpride was safe and more effective than placebo at treating established postoperative nausea or vomiting in patients failing postoperative nausea or vomiting prophylaxis. DOI: 10.1097/ALN.0000000000002509 PMID: 30475232 [Indexed for MEDLINE]
18. Anesthesiology. 2018 Jun;128(6):1099-1106. doi: 10.1097/ALN.0000000000002133. Amisulpride Prevents Postoperative Nausea and Vomiting in Patients at High Risk: A Randomized, Double-blind, Placebo-controlled Trial. Kranke P(1), Bergese SD, Minkowitz HS, Melson TI, Leiman DG, Candiotti KA, Liu N, Eberhart L, Habib AS, Wallenborn J, Kovac AL, Diemunsch P, Fox G, Gan TJ. Author information: (1)From the Department of Anaesthesia and Critical Care, University Hospitals of Würzburg, Würzburg, Germany (P.K.) Department of Anesthesiology, Wexner Medical Center at the Ohio State University, Columbus, Ohio (S.D.B.) Memorial Hermann Hospital, Houston, Texas (H.S.M.) Helen Keller Hospital, Sheffield, Alabama (T.I.M.) Hermann Drive Surgical Hospital, Houston, Texas (D.G.L.) Department of Anesthesiology, Jackson Memorial Hospital, Miami, Florida (K.A.C.) Service d'Anesthésie, Hôpital Foch, Suresnes, France (N.L.) Outcomes Research Consortium, Cleveland Clinic, Ohio (N.L.) Department of Anaesthesiology and Intensive Care, Philipps University Marburg, Marburg, Germany (L.E.) Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina (A.S.H.) Department of Anesthesiology and Intensive Care, HELIOS Clinic Aue, Aue, Germany (J.W.) Department of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas (A.L.K.) Department of Anesthesiology and Resuscitation, Centre Hospitalier Universitaire of Hautepierre, Strasbourg, France (P.D.) Acacia Pharma, Cambridge, United Kingdom (G.F.) Department of Anesthesiology, Stony Brook University Medical Center, New York (T.J.G.). BACKGROUND: Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated. METHODS: This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors. Patients were randomized to receive either intravenous amisulpride (5 mg) or matching placebo at induction of general anesthesia, in addition to one standard, nondopaminergic antiemetic, most commonly ondansetron or dexamethasone. Vomiting/retching, nausea, and use of rescue medication were recorded for 24 h after wound closure. The primary endpoint was complete response, defined as no emesis or rescue medication use in the 24-h postoperative period. RESULTS: Complete response occurred in 330 of 572 (57.7%) of the amisulpride group and 268 of 575 (46.6%) of the control group (difference 11.1 percentage points; 95% CI, 5.3 to 16.8; P < 0.001). The incidences of emesis (13.8% vs. 20.0%, P = 0.003), any nausea (50.0% vs. 58.3%, P = 0.002), significant nausea (37.1% vs. 47.7%, P < 0.001), and rescue medication use (40.9% vs. 49.4%, P = 0.002) were significantly lower in the amisulpride group. Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently with amisulpride than with placebo. CONCLUSIONS: Intravenous amisulpride was safe and effective as prophylaxis of postoperative nausea and vomiting when given in combination with an antiemetic from another class to adult patients at high risk for suffering postoperative nausea and vomiting undergoing elective surgery under inhalational general anesthesia. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B727. DOI: 10.1097/ALN.0000000000002133 PMID: 29543631 [Indexed for MEDLINE]
19. N Engl J Med. 2018 Mar 15;378(11):1004-1017. doi: 10.1056/NEJMoa1710922. Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa. Molloy SF(1), Kanyama C(1), Heyderman RS(1), Loyse A(1), Kouanfack C(1), Chanda D(1), Mfinanga S(1), Temfack E(1), Lakhi S(1), Lesikari S(1), Chan AK(1), Stone N(1), Kalata N(1), Karunaharan N(1), Gaskell K(1), Peirse M(1), Ellis J(1), Chawinga C(1), Lontsi S(1), Ndong JG(1), Bright P(1), Lupiya D(1), Chen T(1), Bradley J(1), Adams J(1), van der Horst C(1), van Oosterhout JJ(1), Sini V(1), Mapoure YN(1), Mwaba P(1), Bicanic T(1), Lalloo DG(1), Wang D(1), Hosseinipour MC(1), Lortholary O(1), Jaffar S(1), Harrison TS(1); ACTA Trial Study Team. Collaborators: Chimanganga W, Chilima E, Dziwani E, Gondwe E, Goodson P, Jassi C, Kukacha C, Keyla L, Likwinj M, Ming D, Segula D, Singimi A, Miyango S, Mwloza V, Matandika L, Mthunthama N, Ndaferankhande J, Rothe C, Sambakunsi C, Shumba F, Bagna E, Bella F, Dang A, Epupa J, Essaka H, Goula G, Luma H, Ngoula A, Banda T, Banda B, Chikaonda T, Chikasema M, Chipeta M, Chome N, Kanyemba C, Kasonkanji E, Kumwenda E, Kumwenda W, Mhango W, Msumba L, Mwangomba P, Namaluweso F, Phulusa J, Shumba I, Sichali D, Chanda D, Chansa A, Chikatula E, Kakusa Y, Mputu M, Mukasine M, Mwaba J, Mwambazi W, Mwanamoonga L, Mweeba A, Nglube J, Sichone M, Silumbe J, Tande A, Abdallah A, Buma D, Chande AA, Diarz E, Hassan M, Kalabashanga JM, Kalinga R, Kileo D, Kimambo A, Lawrence R, Massawa T, Mganga M, Mamboya S, Nyange MM, Okeng’o K, Simbaulanga R, Rugemalila J, Tarimo IB, Kouala-Shiro S, Delaporte E, Alma M, Dombu R, Djoukwe RE, Embolo C, Le Gac S, Kamdem A, Mounpou G, Owono EP, Pasquier E, Sonkeng E, Tongo S, Vigne P, Wodo M, Kaphale G, Nyondo E, Jusu A, Kalima K, Mataka Y, Khoriyo C, Silwamba L, Abdelmalik S, Burton S, Simms V. Author information: (1)From the Centre for Global Health, Institute for Infection and Immunity, St. George's University of London (S.F.M., A.L., N.S., N. Karunaharan, J.A., T.B., T.S.H.), University College London (R.S.H.), and the MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine (J.B.), London, and Liverpool School of Tropical Medicine, Liverpool (T.C., D.G.L., D.W., S.J.) - all in the United Kingdom; the University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe (C. Kanyama, C.C., C.H., M.C.H.), Malawi-Liverpool-Wellcome Trust Clinical Research Programme (R.S.H., N. Kalata, K.G., M.P., J.E.) and the College of Medicine, University of Malawi (R.S.H., N. Kalata, K.G., M.P., J.E., J.J.O.), Blantyre, and Dignitas International, Zomba Central Hospital, Zomba (A.K.C., P.B., D.L., J.J.O.) - all in Malawi; University of Dschang, Dschang (C. Kouanfack), Hôpital Central Yaoundé/Site Agence Nationale de Recherche sur le Sida (ANRS) Cameroun, Yaoundé (C. Kouanfack, S. Lontsi, J.-G.N., V.S.), and Douala General Hospital (E.T., Y.N.M.) and University of Douala (Y.N.M.), Douala - all in Cameroon; the Institute for Medical Research and Training (D.C., N.S., N. Karunaharan, P.B.), University Teaching Hospital (D.C., S. Lakhi, N.S., N. Karunaharan, P.B.), and the Department of Internal Medicine and Directorate of Research and Postgraduate Studies, Lusaka Apex Medical University (P.M.), Lusaka, Zambia; the National Institute for Medical Research, Muhimbili Medical Research Centre, Dar Es Salaam, Tanzania (S.M., S. Lesikari); Institut Pasteur, Molecular Mycology Unit (E.T., O.L.), and Paris Descartes University, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, IHU Imagine, Assistance Publique-Hôpitaux de Paris (O.L.), Paris; the Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto (A.K.C.); and the University of North Carolina, Chapel Hill (C.H., M.C.H.). BACKGROUND: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODS: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTS: A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen. CONCLUSIONS: One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509 .). DOI: 10.1056/NEJMoa1710922 PMID: 29539274 [Indexed for MEDLINE]
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