Infectious Diseases and Therapy最新文献

{"title":"A Response to: A Letter to the Editor Regarding 'Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework'.","authors":"Ekkehard Beck, Mary T Bausch-Jurken, Nicolas Van de Velde, Xuan Wang, Mia Malmenäs","doi":"10.1007/s40121-024-01020-2","DOIUrl":"https://doi.org/10.1007/s40121-024-01020-2","url":null,"abstract":"","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Reported Outcomes in COVID-19 Treatment with Monoclonal Antibodies Reveal Benefits in Return to Usual Activities.","authors":"Diana Rofail, Mohamed Hussein, Ulrike Naumann, Anna J Podolanczuk, Thomas Norton, Shazia Ali, Vera Mastey, Cristina Ivanescu, Boaz Hirshberg, Gregory P Geba","doi":"10.1007/s40121-024-01013-1","DOIUrl":"10.1007/s40121-024-01013-1","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess the effects of a monoclonal antibody (mAb) combination on symptoms, daily function, and overall health-related quality of life.</p><p><strong>Methods: </strong>We analyzed patient-reported outcomes data from symptomatic outpatients in a phase 1/2/3 trial. Patients with confirmed SARS-CoV-2 infection and ≥ 1 risk factor for severe COVID-19 received mAb treatment (casirivimab plus imdevimab 1200 mg) or placebo. Prespecified exploratory assessments included time to sustained symptoms resolution, usual health, and return to usual activities (assessed daily for 29 days). The trial was conducted from September 2020 to February 2021, prior to widespread COVID-19 vaccination programs and Omicron-lineage variants against which casirivimab + imdevimab is not active.</p><p><strong>Results: </strong>In this analysis 736 outpatients received mAb and 1341 received placebo. Median time to sustained symptoms resolution was consistently shorter with mAb versus placebo (≥ 2 consecutive days: 14 vs 17 days, [nominal p = 0.0017]; ≥ 3 consecutive days: 17 vs 21 days, [nominal p = 0.0046]). Median time to sustained return to usual health and usual activities were both consistently shorter with mAb versus placebo (≥ 2 consecutive days: 12 vs 15 days [nominal p = 0.0001] and 9 vs 11 days [nominal p = 0.0001], respectively; ≥ 3 consecutive days: 14 vs 18 days [nominal p = 0.0003] and 10 vs 13 days [nominal p = 0.0041], respectively).</p><p><strong>Conclusions: </strong>mAb treatment against susceptible SARS-CoV-2 strains improved how patients feel and function, as evidenced by shortened time to sustained symptoms resolution and return to usual health and activities. Future studies are warranted to assess the patient experience with next generation mAbs.</p><p><strong>Clinicaltrials: </strong>GOV: Registration number, NCT04425629; Submission date June 11, 2020.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of Viral Infectious Diseases Reported in Saudi Arabia.","authors":"Munirah S Aleyiydi, Noura M Alshiban, Areej M Alajmi, Nada F Alosaimi, Maryam Alotaibi, Majed S Nassar, Nada K Alhumaid, Thamer A Almangour, Ziad A Memish, Abdulwahab Z Binjomah, Saeed M Algarni, Ahmed Al-Jedai, Abdulaziz S Almutairi, Atef Shibl, Essam A Tawfik","doi":"10.1007/s40121-024-01014-0","DOIUrl":"10.1007/s40121-024-01014-0","url":null,"abstract":"<p><strong>Introduction: </strong>Efficient epidemiological monitoring of virus diseases is crucial in evaluating general public health, the prevalence of specific diseases, the pattern of spread, and implementing preventative and control strategies into action.</p><p><strong>Methods: </strong>This study analyzed data obtained from the Field Epidemiology Program (FETP) which is part of the Ministry of Health (MOH) in Saudi Arabia, which contained reported cases of infectious diseases over four years, from January 2018 to December 2021, to investigate and highlight the significant trend and incidence rate for each viral infectious disease.</p><p><strong>Results: </strong>Of the reported viral infectious diseases, hepatitis B and C, dengue fever (DF), influenza, chickenpox, and measles were the highest reported viral cases over four years. For the aforementioned diseases, males were often more susceptible to viral infections than females. Except for DF, this viral infection was more common in Saudi citizens. Viral illnesses like hand, foot, and mouth disease were less prevalent, while neurological viral disorders such as acute flaccid paralysis were rarely detected. There was an overall reduction in viral cases recorded during 2020-2021, which may be attributed to the implementation of preventive measures during the Coronavirus Disease 2019 (COVID-19) pandemic or an underreporting of cases during the lockdown of that time.</p><p><strong>Conclusion: </strong>The prevalence of these common viral infections in the Saudi population suggests that understanding the mechanisms influencing changes in these viruses, methods of transmission, and the burden of these diseases is a priority for health policy. This understanding is necessary to develop effective intervention and preventive strategies.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetic Modeling of Abacavir/Dolutegravir/Lamivudine to Support a Fixed-Dose Combination in Children with HIV-1.","authors":"Hardik Chandasana, Sven C van Dijkman, Rashmi Mehta, Mark Bush, Helena Rabie, Patricia Flynn, Tim R Cressey, Edward P Acosta, Kristina M Brooks","doi":"10.1007/s40121-024-01008-y","DOIUrl":"10.1007/s40121-024-01008-y","url":null,"abstract":"<p><strong>Introduction: </strong>Once-daily fixed-dose combinations (FDC) containing abacavir (ABC), dolutegravir (DTG), and lamivudine (3TC) have been approved in the US for adults and children with HIV weighing ≥ 6 kg. This analysis assessed the ability of previously developed ABC, DTG, and 3TC pediatric population pharmacokinetic (PopPK) models using multiple formulations to describe and predict PK data in young children using dispersible tablet (DT) and tablet formulations of ABC/DTG/3TC FDC in the IMPAACT 2019 study.</p><p><strong>Methods: </strong>IMPAACT 2019 was a Phase I/II study assessing the PK, safety, tolerability, and efficacy of ABC/DTG/3TC FDC in children with HIV-1. Intensive and sparse PK samples were collected over 48 weeks. Existing drug-specific pediatric PopPK models for ABC (2-compartment), DTG (1-compartment), and 3TC (1-compartment) were applied to the IMPAACT 2019 drug concentration data without re-estimation (external validation) of PopPK parameters. Drug exposures were then simulated across World Health Organization weight bands for children weighing ≥ 6 to < 40 kg for each drug and compared with pre-defined exposure target ranges.</p><p><strong>Results: </strong>Goodness-of-fit and visual predictive check plots demonstrated that the previously developed pediatric PopPK models sufficiently described and predicted the data. Thus, new PopPK models describing the IMPAACT 2019 data were unnecessary. Across weight bands, the predicted geometric mean (GM) for ABC AUC_0-24 ranged from 14.89 to 18.50 μg*h/ml, DTG C24 ranged from 0.74 to 0.95 μg/ml, and 3TC AUC_0-24 ranged from 10.50 to 13.20 μg*h/ml. These exposures were well within the pre-defined target ranges set for each drug.</p><p><strong>Conclusion: </strong>This model-based approach leveraged existing pediatric data and models to confirm dosing of ABC/DTG/3TC FDC formulations in children with HIV-1. This analysis supports ABC/DTG/3TC FDC dosing in children weighing ≥ 6 kg.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness of a Third Dose of mRNA-1273 Versus BNT162b2 on Inpatient and Medically Attended COVID-19 Among Immunocompromised US Adults.","authors":"Tianyu Sun, Linwei Li, Katherine E Mues, Mihaela V Georgieva, Brenna Kirk, James A Mansi, Nicolas Van de Velde, Ekkehard C Beck","doi":"10.1007/s40121-024-01005-1","DOIUrl":"10.1007/s40121-024-01005-1","url":null,"abstract":"<p><strong>Introduction: </strong>Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US).</p><p><strong>Methods: </strong>This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method.</p><p><strong>Results: </strong>In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506-0.887), 29.3% (0.707; 0.573-0.858), and 23.4% (0.766; 0.626-0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860-0.976), 6.4% (0.936; 0.895-0.978), and 2.4% (0.976; 0.935-1.017), respectively.</p><p><strong>Conclusions: </strong>Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences Between RSV A and RSV B Subgroups and Implications for Pharmaceutical Preventive Measures.","authors":"Charles Nuttens, Juliette Moyersoen, Daniel Curcio, Zuleika Aponte-Torres, Marc Baay, Hilde Vroling, Bradford D Gessner, Elizabeth Begier","doi":"10.1007/s40121-024-01012-2","DOIUrl":"10.1007/s40121-024-01012-2","url":null,"abstract":"<p><strong>Introduction: </strong>Understanding the differences between respiratory syncytial virus (RSV) subgroups A and B provides insights for the development of prevention strategies and public health interventions. We aimed to describe the structural differences of RSV subgroups, their epidemiology, and genomic diversity. The associated immune response and differences in clinical severity were also investigated.</p><p><strong>Methods: </strong>A literature review from PubMed and Google Scholar (1985-2023) was performed and extended using snowballing from references in captured publications.</p><p><strong>Results: </strong>RSV has two major antigenic subgroups, A and B, defined by the G glycoprotein. The RSV F fusion glycoprotein in the prefusion conformation is a major target of virus neutralizing antibodies and differs in surface exposed regions between RSV A and RSV B. The subgroups co-circulate annually, but there is considerable debate as to whether clinical severity is impacted by the subgroup of the infecting RSV strain. Large variations between the studies reporting RSV subgroup impact on clinical severity were observed. A tendency for higher disease severity may be attributed to RSV A but no consensus could be reached as to whether infection by one of the subgroup caused more severe outcomes. RSV genotype diversity decreased over the last two decades, and ON and BA have become the sole lineages detected for RSV A and RSV B, since 2014. No studies with data obtained after 2014 reported a difference in disease severity between the two subgroups. RSV F is relatively well conserved and highly similar between RSV A and B, but changes in the amino acid sequence have been observed. Some of these changes led to differences in F antigenic sites compared to reference F sequences (e.g., RSV/A Long strain), which are more pronounced in antigenic sites of the prefusion conformation of RSV B. Initial results from the second season after vaccination suggest specific RSV B efficacy wanes more rapidly than RSV A for RSV PreF-based monovalent vaccines.</p><p><strong>Conclusions: </strong>RSV A and RSV B both contribute substantially to the global RSV burden. Both RSV subgroups cause severe disease and none of the available evidence to date suggests any differences in clinical severity between the subgroups. Therefore, it is important to implement measures effective at preventing disease due to both RSV A and RSV B to ensure impactful public health interventions. Monitoring overtime will be needed to assess the impact of waning antibody levels on subgroup-specific efficacy.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix in Healthy Adolescents: A Randomized Phase IIIb Multicenter Study.","authors":"Javier Díez-Domingo, Róbert Simkó, Giancarlo Icardi, Chan Poh Chong, Céline Zocchetti, Olga Syrkina, Siham Bchir, Isabelle Bertrand-Gerentes","doi":"10.1007/s40121-024-01009-x","DOIUrl":"10.1007/s40121-024-01009-x","url":null,"abstract":"<p><strong>Introduction: </strong>Many immunization programs in Europe recommend quadrivalent meningococcal vaccinations, which are often administered concomitantly with other vaccines. We compared the immune response of a tetanus toxoid conjugated quadrivalent meningococcal vaccine (MenACYW-TT, MenQuadfi^®) with another quadrivalent meningococcal conjugate vaccine (MCV4-TT; Nimenrix^®) when administered alone or concomitantly with Tdap-IPV and 9vHPV vaccines in adolescents.</p><p><strong>Methods: </strong>In this phase IIIb trial, healthy adolescents (MenC-naïve or MenC-primed before 2 years of age) from Spain, Italy, Hungary, and Singapore were randomized in a 3:3:2 ratio to receive either MenACYW-TT or MCV4-TT alone, or MenACYW-TT concomitantly with 9vHPV and Tdap-IPV. The primary objective was to demonstrate the non-inferiority of the seroprotection rate (human serum bactericidal assay [hSBA] titer ≥ 1:8) to serogroups A, C, W, and Y 30 days post-vaccination with a single dose of MenACYW-TT or MCV4-TT. Secondary objectives included describing hSBA titers for the four serogroups before and 1 month following vaccination and according to MenC priming status.</p><p><strong>Results: </strong>A total of 463 participants were enrolled (MenACYW-TT, n = 173; MCV4-TT, n = 173; MenACYW-TT/9vHPV/Tdap-IPV n = 117). Non-inferiority based on seroprotection was demonstrated for MenACYW-TT versus MCV4-TT for all serogroups. Immune responses were comparable whether MenACYW-TT was administered alone or concomitantly with Tdap-IPV and 9vHPV. Post-vaccination hSBA GMTs were higher in MenACYW-TT vs. MCV4-TT for serogroups C, Y, and W and comparable for serogroup A. The percentages of participants with an hSBA vaccine seroresponse were higher in MenACYW-TT vs. MCV4-TT for all serogroups. For serogroup C, higher GMTs were observed in both MenC-naïve or -primed participants vaccinated with MenACYW-TT vs. MCV4-TT. Seroprotection and seroresponse were higher in MenC-naïve participants vaccinated with MenACYW-TT vs. MCV4-TT and comparable in MenC-primed. The safety profiles were comparable between groups and no new safety concerns were identified.</p><p><strong>Conclusions: </strong>These data support the concomitant administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines in adolescents.</p><p><strong>Trial registrations: </strong>Clinicaltrials.gov, NCT04490018; EudraCT: 2020-001665-37; WHO: U1111-1249-2973.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized, Open-Label Phase 3 Study Evaluating Immunogenicity, Safety, and Reactogenicity of RSVPreF3 OA Coadministered with FLU-QIV-HD in Adults Aged ≥ 65.","authors":"Robert Buynak, Kevin Cannon, David DeAtkine, John Kirby, Lisa Usdan, Amit Bhavsar, Catherine Gérard, Anastasia Kuznetsova, Amulya Jayadev, Hiwot Amare, Sofia Valenciano, Nadia Meyer","doi":"10.1007/s40121-024-00985-4","DOIUrl":"10.1007/s40121-024-00985-4","url":null,"abstract":"<p><strong>Introduction: </strong>Respiratory syncytial virus (RSV) and influenza pose major disease burdens in older adults due to an aging immune system and comorbidities; seasonal overlap exists between these infections. In 2023, the RSV prefusion protein F3 older adult (RSVPreF3 OA) vaccine was first approved in the USA as a single dose for prevention of lower respiratory tract disease due to RSV in adults aged ≥ 60 years. The vaccine has since been approved in the European Union and elsewhere. RSVPreF3 OA and FLU-QIV-HD could be coadministered if immunogenicity, safety, and reactogenicity are not affected.</p><p><strong>Methods: </strong>This open-label, randomized (1:1), controlled, phase 3 study in 1029 adults aged ≥ 65 years in the USA evaluated the immunogenicity (up to 1 month after last vaccine dose) and safety (up to 6 months after last vaccine dose) of RSVPreF3 OA coadministered with FLU-QIV-HD (co-ad group) versus FLU-QIV-HD alone followed by RSVPreF3 OA at a separate visit 1 month later (control group). Non-inferiority criterion was defined as an upper limit of the two-sided 95% confidence interval of the geometric mean titer (GMT) group ratio (control/co-ad) ≤ 1.5. Secondary endpoints included safety and reactogenicity.</p><p><strong>Results: </strong>Proportions of participants across age categories between groups and proportions of male (50.4%) and female (49.6%) participants were well balanced; most participants were white (68.7%). Group GMT ratios for RSV-A neutralizing titers, hemagglutination inhibition titers for four influenza vaccine strains, and RSV-B neutralizing titers were non-inferior in the co-ad group versus the control group. No clinically meaningful differences in local or systemic solicited and unsolicited adverse events (AEs), serious AEs, and potential immune-mediated diseases were identified. The most common solicited AEs in both groups were injection-site pain and myalgia.</p><p><strong>Conclusion: </strong>In adults aged ≥ 65 years, coadministration of RSVPreF3 OA and FLU-QIV-HD was immunogenically non-inferior to the sequential administration of both vaccines 1 month apart, and had clinically acceptable safety and reactogenicity profile.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05559476.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Burden of Respiratory Syncytial Virus (RSV) in Germany: A Comprehensive Data Analysis Suggests Underdetection of Hospitalisations and Deaths in Adults 60 Years and Older.","authors":"Stefan Scholz, Kristina Dobrindt, Jennifer Tufts, Sarah Adams, Parinaz Ghaswalla, Bernhard Ultsch, Jens Gottlieb","doi":"10.1007/s40121-024-01006-0","DOIUrl":"10.1007/s40121-024-01006-0","url":null,"abstract":"<p><strong>Introduction: </strong>In Germany, the estimation of the disease burden of respiratory syncytial virus (RSV) in older adults is limited. This makes it challenging for public health decision-makers to develop evidence-based recommendations for newly available vaccines against RSV for individuals aged 60 years and older (60+). This study investigates publicly available data sources in Germany to address the current gaps in evidence regarding the burden of RSV.</p><p><strong>Methods: </strong>Hospitalisation databases from the German Federal Statistical Office and national mortality statistic between 2000 and 2023, as well as regular surveillance reports from the national public health institute since 2014, were utilised to extract, combine and analyse data on RSV-related morbidity and mortality. These data were used to triangulate the age-specific burden of RSV.</p><p><strong>Results: </strong>The data indicate that the number of RSV-related outpatient consultations ranges between 1,313,100 and 3,911,800 cases per season from 2014/2015 to 2022/2023 for all age groups, with approximately 13.0% of outpatient consultations occurring in adults 60+. The significant increase in hospitalisations over time suggests that heightened testing due to the coronavirus disease 2019 (COVID-19) pandemic revealed the underdetection of inpatient RSV cases in pre-pandemic seasons. In the most recent season recorded, 2022/2023, the data show 12,800 RSV-related hospitalisations in adults 60+ (24% of all RSV-related hospitalisations) and 1340 in-hospital deaths in adults 60+ (93% of all RSV-related deaths).</p><p><strong>Conclusion: </strong>The comparison of pre- to post-pandemic seasons strongly suggest up to a sevenfold underdetection of RSV in individuals 60+, and the analysis of in-hospital mortality reveals higher mortality rates compared with the general German mortality statistics. These findings highlight the urgent need to improve surveillance and implement targeted prevention strategies to mitigate the impact of RSV in older adults.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing Day 1 Area Under the Curve Following Vancomycin Loading Dose Administration in Adult Hospitalized Patients Using Non-Trapezoidal Linear Pharmacokinetic Equations: A Retrospective Observational Study.","authors":"Abdulwhab Shremo Msdi, Jacinda C Abdul-Mutakabbir, Karen K Tan","doi":"10.1007/s40121-024-01004-2","DOIUrl":"10.1007/s40121-024-01004-2","url":null,"abstract":"<p><strong>Introduction: </strong>Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections, and achieving the recommended area under the curve (AUC) target has been linked to improved clinical outcomes. The current VAN therapeutic monitoring guidelines recommend a loading dose (LD) of 20-35 mg/kg to rapidly attain targeted VAN exposures within 24 h of therapy. However, there is a paucity of data describing the impact of VAN LD on day 1 area under the curve (AUC_0-24). This study aims to employ pharmacokinetic (PK) equations to calculate and describe the AUC_0-24 following a VAN LD of 20 mg/kg.</p><p><strong>Methods: </strong>This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC_0-24. Therapeutic AUC_0-24 was defined as 400-600 mg/l*h.</p><p><strong>Results: </strong>Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m² and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC_0-24, while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC_0-24, patients with subtherapeutic AUC_0-24 were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m² (67 vs. 52%). In contrast, patients with supratherapeutic AUC_0-24 were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC_0-24. CONCLUSIONS: Only 50% of patients achieve the target AUC_0-24 following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}