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47 ud af 47 tidsskrifter valgt, ingen søgeord valgt, emner højest 7 dage gamle, sorteret efter nyeste først.
265 emner vises.
Friedman, M. R., Badri, S., Bowleg, L., Haberlen, S. A., Jones, D. L., Kempf, M.-C., Konkle-Parker, D., Kwait, J., Martinson, J., Mimiaga, M. J., Plankey, M. W., Stosor, V., Tsai, A. C., Turan, J. M., Ware, D., Wu, K.
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
IntroductionThe increasing burden of non-communicable diseases, such as hypertension, diabetes and dyslipidaemia, presents key challenges to achieving optimal HIV care outcomes among ageing people living with HIV. These diseases are often comorbid and are exacerbated by psychosocial and structural inequities. This interaction among multiple health conditions and social factors is referred to as a syndemic. In the USA, there are substantial disparities by social position (ie, racial, ethnic and socioeconomic status) in the prevalence and/or control of non-communicable diseases and HIV. Intersecting stigmas, such as racism, classism and homophobia, may drive these health disparities by contributing to healthcare avoidance and by contributing to a psychosocial syndemic (stress, depression, violence victimisation and substance use), reducing success along the HIV and non-communicable disease continua of care. Our hypothesis is that marginalised populations experience disparities in non-communicable disease incidence, prevalence and control, mediated by intersectional stigma and the psychosocial syndemic. Methods and analysisCollecting data over a 4 year period, we will recruit sexual minority men (planned n=1800) enrolled in the MACS/WIHS Combined Cohort Study, a long-standing mixed-serostatus observational cohort in the USA, to investigate the following specific aims: (1) assess relationships between social position, intersectional stigma and the psychosocial syndemic among middle-aged and ageing sexual minority men, (2) assess relationships between social position and non-communicable disease incidence and prevalence and (3) assess relationships between social position and HIV and non-communicable disease continua of care outcomes, mediated by intersectional stigma and the psychosocial syndemic. Analyses will be conducted using generalised structural equation models using a cross-lagged panel model design. Ethics and disseminationThis protocol is approved as a single-IRB study (Advarra Institutional Review Board: Protocol 00068335). We will disseminate results via peer-reviewed academic journals, scientific conferences, a dedicated website, site community advisory boards and forums hosted at participating sites.
Læs mere Tjek på PubMedADEQUATE Paediatric Trial Group, Yau, Vitale, Vecchia, DAmbrosio, Bouwman, van Esschoten, Leus, de Pooter, Timbermont, Rodriguez Ruiz, Hommel, Tessonneau, Kohns Vasconcelos, Malhotra-Kumar, Allantaz, Vandepitte, Tissier, Cleuziat, Postma, van Asselt, van Dorst, van der Pol, Antonanzas, Rojas, Gonzales, Dawoud, Hawksworth, Lyttle, Heijerman, Clements, Prat Aymerich, Goossens, Bonten, Bielicki, Atkinson, van Werkhoven, Simitsopoulou, Pantzartzi, Zarras, Ftergioti, Kitsou, Karypiadou, Lampada, Charisi, Savvidou, Tsiatsiou, Chorafa, Michailidou, Roilides, Iosifidis, Stiegler, Junk, Kiesel, Belschner, Seyfried, Schmauder, Peter, Walter, Imort, Behret, Renk, Berger, Pfeiffer, Früh, Robinson, Marten, Werner, Gijon, Calderon, Machin, Cabello, Seoane, Mesa, Oviedo, Baron, Hernandez, Rojo, Gardiner, Capozzi, Ross, Hemeson, Nyirenda Nyangwa, Brock, Hultin, Hill, Severi Conti, Gualco, Vanoni
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
IntroductionSyndromic panel assays, that is, using one test to simultaneously target multiple pathogens with overlapping signs and symptoms, have been integrated into routine paediatric care over the past decade, mainly for more severely ill and hospitalised patients. Their wider availability and short turnaround times open the possibility to apply them to non-hospitalised patients as well. In this context, it is important to trial how clinicians make use of pathogen detection data and if their early availability influences management decisions, particularly antibiotic use and hospitalisation. Methods and analysisAdvanced Diagnostics for Enhanced QUality of Antibiotic prescription in respiratory Tract infections in Emergency rooms is an individually randomised, controlled, open-label effectiveness trial comparing the impact of a respiratory pathogen panel assay (BIOFIRE Respiratory Panel 2.1plus) used as a rapid syndromic test on nasopharyngeal swabs in addition to the standard of care versus standard of care alone. The trial will 1:1 randomise 520 participants under the age of 18 at 7 paediatric emergency departments in 5 European countries. Inclusion criteria for the trial consist of two sets, with the first describing respiratory tract infections in paediatric patients and the second describing the situation of potential management uncertainty in which test results may immediately affect management decisions. Enrolment started in July 2021 and is expected to be completed in early 2024. We will perform a two-sample t-test assuming a pooled variance estimate to compare the log-transformed mean time on antibiotic treatment (in hours) and number of days alive out of the hospital within 14 days after study enrolment between the control and intervention arms. Ethics and disseminationThe trial protocol and materials were approved by research ethics committees in all participating countries. The respiratory pathogen panel assay is CE marked (assessed to meet European regulations) and FDA (United States Food and Drug Administration) cleared for diagnostic use. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate. Trial registration number NCT04781530.
Læs mere Tjek på PubMedMpirirwe, R., Segawa, I., Ojiambo, K. O., Kamacooko, O., Nangendo, J., Semitala, F. C., Kyambadde, P., Kalyango, J. N., Kiragga, A., Karamagi, C., Katahoire, A., Kamya, M., Mujugira, A.
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
ObjectiveTo evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA). DesignSystematic review and meta-analysis. Data sourcesWe searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022. Eligibility criteria for studiesRandomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA. Data extraction and synthesisSeven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention. ResultsOf 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26). ConclusionsA hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs. PROSPERO registration numberCRD42020219363.
Læs mere Tjek på PubMedSchöbi, N., Sanchez, C., Welzel, T., Bamford, A., Webb, K., Rojo, P., Tremoulet, A., Atkinson, A., Schlapbach, L. J., Bielicki, J. A., The Swissped-RECOVERY trial group, Andre, Bailey, Blanchard-Rohner, Buettcher, Grazioli, Koehler, Perez, Trück, Vanoni, Zimmermann
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
ObjectivesIn trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial. DesignThis is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial. Setting10 Swiss paediatric hospitals (secondary and tertiary care) participated. ParticipantsPaediatric patients hospitalised with PIMS-TS. InterventionsAll patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event. ResultsOf 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like). ConclusionThe masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future. Trial registration numbersSNCTP000004720 and NCT 04826588.
Læs mere Tjek på PubMedMarx, T., Moore, L., Talbot, D., Guertin, J. R., Lachapelle, P., Blais, S., Singbo, N., Simonyan, D., Lavallee, J., Zada, N., Shahrigharahkoshan, S., Huard, B., Olivier, P., Mallet, M., Letourneau, M., Lafreniere, M., Archambault, P., Berthelot, S., For the Network of Canadian Emergency Researchers
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
ObjectiveTo compare health outcomes and costs given in the emergency department (ED) and walk-in clinics for ambulatory children presenting with acute respiratory diseases. DesignA retrospective cohort study. SettingThis study was conducted from April 2016 to March 2017 in one ED and one walk-in clinic. The ED is a paediatric tertiary care centre, and the clinic has access to lab tests and X-rays. ParticipantsInclusion criteria were children: (1) aged from 2 to 17 years old and (2) discharged home with a diagnosis of upper respiratory tract infection (URTI), pneumonia or acute asthma. Main outcome measuresThe primary outcome measure was the proportion of patients returning to any ED or clinic within 3 and 7 days of the index visit. The secondary outcome measures were the mean cost of care estimated using time-driven activity-based costing and the incidence of antibiotic prescription for URTI patients. ResultsWe included 532 children seen in the ED and 201 seen in the walk-in clinic. The incidence of return visits at 3 and 7 days was 20.7% and 27.3% in the ED vs 6.5% and 11.4% in the clinic (adjusted relative risk at 3 days (aRR) (95% CI) 3.17 (1.77 to 5.66) and aRR at 7 days 2.24 (1.46 to 3.44)). The mean cost (95% CI) of care (CAD) at the index visit was $C96.68 (92.62 to 100.74) in the ED vs $C48.82 (45.47 to 52.16) in the clinic (mean difference (95% CI): 46.15 (41.29 to 51.02)). Antibiotic prescription for URTI was less common in the ED than in the clinic (1.5% vs 16.4%; aRR 0.10 (95% CI 0.03 to 0.32)). ConclusionsThe incidence of return visits and cost of care were significantly higher in the ED, while antibiotic use for URTI was more frequent in the walk-in clinic. These data may help determine which setting offers the highest value to ambulatory children with acute respiratory conditions.
Læs mere Tjek på PubMedIroh Tam, P.-Y., Twabi, H. H., Gondwe, M., O'Byrne, T., Lufesi, N., Desmond, N.
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
ObjectivesWe aimed to assess the prevalence, presentation and referral patterns of children with acute illness attending primary health centres (PHCs) in a low-resource setting. Design, setting and participantsWe conducted a secondary analysis of ASPIRE. Children presenting at eight PHCs in urban Blantyre district in southern Malawi with both recorded clinician and mHealth (non-clinician) triage data were included, and patient records from different data collection points along the patient healthcare seeking pathway were consolidated and analysed. ResultsBetween April 2017 and September 2018, a total of 204 924 children were triaged, of whom 155 931 had both recorded clinician and mHealth triage data. The most common presenting symptoms at PHCs were fever (0.3%), cough (0.2%) and difficulty breathing (0.2%). The most common signs associated with referral for under-5 children were trauma (26.7%) and temperature (7.4%). The proportion of emergency and priority clinician triage were highest among young infants
Læs mere Tjek på PubMedAmbrosio, L., Faulkner, J., Morris, J. H., Stuart, B., Lambrick, D., Compton, E., Portillo, M. C.
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
ObjectiveTo understand the physical activity and mental health of individuals living with long-term conditions during the COVID-19 pandemic. DesignA sequential explanatory mixed-methods study with two phases: phase 1: quantitative survey and phase 2: qualitative follow-up interviews. SettingFor the quantitative phase, an online survey was launched in March 2021, using Microsoft Forms. For the qualitative phase, in-depth semistructured interviews were conducted via online. Participants368 adults over 18 years old living in the UK with at least one long-term condition completed the survey. Interviews were conducted in a subsample of participants from the previous quantitative phase, with 26 people. Data were analysed using thematic analysis. ResultsResponses from the survey showed that people with one long-term condition were significantly more physically active and spent less time sitting, than those with two or more conditions, presenting with significantly higher well-being (p
Læs mere Tjek på PubMedHagel, S., Brillinger, N., Decker, S., Deja, M., Ertmer, C., Fiedler, S., Franken, P., Heim, M., Weigand, M. A., Zarbock, A., Pletz, M. W., SepNet Critical Care Trials Group, Ehler, Bloos, Bauer, Brenner, Meybohm, Kluge, Vogt, Lahmer, Fortenbach, John, Berger, Ling, Dutzmann, Nierhaus, Güldner, Bach, Nierhaus, Jung, Bruno, Zoller, Frank, Müller, Bercker, Feussner, Groesdonk, Putensen, Münster, Rosenberger, Häberle, Frey, Wischermann, Otto, Lindner, Heyckendorf, Reuchsel, Reichmann, Weis
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
IntroductionHerpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome. Methods and analysisProspective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥105 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial. Ethics and disseminationThe trial was approved by the responsible ethics committee and by Germany’s Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany’s Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers. Trial registration number NCT06134492.
Læs mere Tjek på PubMedBergmann, J., Egger, M., Müller, F., Jahn, K.
BMJ Open, 26.04.2024
Tilføjet 26.04.2024
IntroductionCritical illness polyneuropathy and myopathy (CIP/CIM) are frequent complications in the intensive care unit (ICU) with major consequences for the progress and outcome of subjects. CIP/CIM delays the weaning process, prolongs the hospital stay and increases the mortality rate. Additionally, it may have long-term consequences beyond the hospitalisation phase with prolonged disability. Even though there is growing interest in CIP/CIM, research about the clinical and post-clinical course as well as the middle-term and long-term outcomes of subjects with CIP/CIM is scarce. A large prospective study of critically ill subjects is needed with accurate diagnosis during the acute stage and comprehensive assessment during long-term follow-up. Methods and analysisThis prospective observational cohort study aims to compare the clinical and post-clinical course of chronically critically ill subjects with and without the diagnosis of CIP/CIM and to determine predictors for the middle-term and long-term outcomes of subjects with CIP/CIM. In addition, the influence of the preclinical health status and the preclinical frailty on the long-term outcome of subjects with CIP/CIM will be investigated. This single-centre study will include 250 critically ill patients who were invasively ventilated for at least 5 days at the ICU and show reduced motor strength. At five study visits at admission and discharge to neurological rehabilitation, and 12, 18 and 24 months after disease onset, a comprehensive test battery will be applied including assessments of functioning and impairment, independence, health-related quality of life, activity and participation, cognition, gait and balance, fatigue, mental health and frailty. Secondary objectives are the documentation of therapy goals, therapy content and achieved milestones during the rehabilitation, to evaluate the clinimetric properties of the Mini-BESTest in critically ill patients, and to evaluate the time course and outcome of subjects with CIP/CIM after SARS-CoV-2 infection. Ethics and disseminationThe study was approved by the ethical committee of the Ludwig-Maximilians University Munich. Participants will be included in the study after having signed informed consent. Results will be published in scientific, peer-reviewed journals and at national and international conferences. Trial registration numberGerman Clinical Trial Register (DRKS00021753).
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
Abstract Background In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. Methods Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. Results Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value:
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
Abstract The present study aimed to explore the pathogenic spectrum and risk factors of peritoneal dialysis-associated peritonitis (Peritoneal dialysis associated peritonitis, PDAP) in Yongzhou, Hunan, China. The clinical and epidemiological data on regular peritoneal dialysis (Peritoneal dialysis, PD) between January 2016 and December 2020 in Yongzhou were collected for retrospective analysis. The related factors of peritonitis were evaluated by single-factor analysis, while risk factors of refractory PDAP were evaluated by multivariate logistic regression analysis.172/331 172 (51.9%) patients developed peritonitis. The risk factors of PDAP in PD patients included high C-reactive protein (C-reactive protein, CRP), low albumin(Albumin, ALB), low hemoglobin (Hemoglobin, Hb), low educational level (junior high school or lower), preference of spicy food, irregular diet, low annual household income, unfavorable fluid exchange conditions, unstable employment (including working as a farmer), and unfavorable humidity conditions (P
Læs mere Tjek på PubMedWeiyi Tan, Hai Nian, Lam-Son Phan Tran, Jing Jin, Tengxiang Lian
Trends in Microbiology, 26.04.2024
Tilføjet 26.04.2024
The crucial role of rhizosphere microbes in plant growth and their resilience to environmental stresses underscores the intricate communication between microbes and plants. Plants are equipped with a diverse set of signaling molecules that facilitate communication across different biological kingdoms, although our comprehension of these mechanisms is still evolving. Small peptides produced by plants (SPPs) and microbes (SPMs) play a pivotal role in intracellular signaling and are essential in orchestrating various plant development stages. In this review, we posit that SPPs and SPMs serve as crucial signaling agents for the bidirectional cross-kingdom communication between plants and rhizosphere microbes. We explore several potential mechanistic pathways through which this communication occurs. Additionally, we propose that leveraging small peptides, inspired by plant–rhizosphere microbe interactions, represents an innovative approach in the field of holobiont engineering.
Læs mere Tjek på PubMedPaul Adepoju
Lancet, 26.04.2024
Tilføjet 26.04.2024
Moderna\'s decision has been criticised by the Africa CDC, with experts urging countries to invest domestically. Paul Adepoju reports.
Læs mere Tjek på PubMedKwaku Poku Asante, Don P Mathanga, Paul Milligan, Samuel Akech, Abraham Oduro, Victor Mwapasa, Kerryn A Moore, Titus K Kwambai, Mary J Hamel, Thomas Gyan, Nelli Westercamp, Atupele Kapito-Tembo, Patricia Njuguna, Daniel Ansong, Simon Kariuki, Tisungane Mvalo, Paul Snell, David Schellenberg, Paul Welega, Lucas Otieno, Alfred Chimala, Edwin A Afari, Philip Bejon, Kenneth Maleta, Tsiri Agbenyega, Robert W Snow, Madaliso Zulu, Jobiba Chinkhumba, Aaron M Samuels, Malaria Vaccine Programme Evaluation Partners
Lancet, 26.04.2024
Tilføjet 26.04.2024
In the first 2 years of implementation of RTS,S, the three primary doses were effectively deployed through national immunisation programmes. There was no evidence of the safety signals that had been observed in the phase 3 trial, and introduction of the vaccine was associated with substantial reductions in hospital admission with severe malaria. Evaluation continues to assess the impact of four doses of RTS,S.
Læs mere Tjek på PubMedMorgan K Walker, Guoqing Diao, Sarah Warner, Ahmed Babiker, Maniraj Neupane, Jeffrey R Strich, Christina Yek, Sameer S Kadri, National Institutes of Health Antimicrobial Resistance Outcomes Research Initiative (NIH–ARORI)
Lancet Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
High carbapenem use in targeting non-severe ECR Enterobacterales infections in US hospitals predates 2020 IDSA guidance and has persisted thereafter. Efforts to increase awareness and implementation of recommendations among clinicians to use carbapenem-sparing alternatives in ECR Enterobacterales infections might decrease global carbapenem selective pressure.
Læs mere Tjek på PubMedKirsten E Lyke, Joel V Chua, Michael Koren, Heather Friberg, Gregory D Gromowski, Rekha R Rapaka, Adam T Waickman, Sudhaunshu Joshi, Kathleen Strauss, Michael K McCracken, Hernando Gutierrez-Barbosa, Biraj Shrestha, Christopher Culbertson, Paula Bernal, Rafael A De La Barrera, Jeffrey R Currier, Richard G Jarman, Robert Edelman
Lancet Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
Participants who had tetravalent dengue purified inactivated vaccine prime and live-attenuated vaccine boost were unprotected against dengue virus-1 infection and further showed increased clinical, immunological, and transcriptomic evidence for inflammation potentially mediated by pre-existing infection-enhancing antibodies. This study highlights the impact of small cohort, human challenge models studying dengue pathogenesis and downstream vaccine development.
Læs mere Tjek på PubMedClinical Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
Abstract Background Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999—2020.Methods Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time.Results Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period.Conclusion Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.
Læs mere Tjek på PubMedLyle G. Best, Esther Erdei, Karin Haack, Jack W. Kent Jr., Kimberly M. Malloy, Deborah E. Newman, Marcia O’Leary, Rae A. O’Leary, Quan Sun, Ana Navas-Acien, Nora Franceschini, Shelley A. Cole
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Lyle G. Best, Esther Erdei, Karin Haack, Jack W. Kent Jr., Kimberly M. Malloy, Deborah E. Newman, Marcia O’Leary, Rae A. O’Leary, Quan Sun, Ana Navas-Acien, Nora Franceschini, Shelley A. Cole Background Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205. Methodology/Principal findings The Strong Heart and Strong Heart Family studies have accumulated detailed genetic, cardiovascular risk and event data in geographically dispersed American Indian communities since 1988. Genotypic data and 91 COVID-19 adjudicated deaths or hospitalizations from 2/1/20 through 3/1/23 were identified among 3,780 participants in two subsets. Among 21 candidate variants including genes in the interferon response pathway, APOE, TMPRSS2, TLR3, the HLA complex and the ABO blood group, only rs1205, a 3’ untranslated region variant in the CRP gene, showed nominally significant association in T-dominant model analyses (odds ratio 1.859, 95%CI 1.001–3.453, p = 0.049) after adjustment for age, sex, center, body mass index, and a history of cardiovascular disease. Within the younger subset, association with the rs1205 T-Dom genotype was stronger, both in the same adjusted logistic model and in the SOLAR analysis also adjusting for other genetic relatedness. Conclusion A T-dominant genotype of rs1205 in the CRP gene is associated with COVID-19 death or hospitalization, even after adjustment for relevant clinical factors and potential participant relatedness. Additional study of other populations and genetic variants of this gene are warranted.
Læs mere Tjek på PubMedGermán Ricardo Magaña-Ávila, Erika Moreno, Consuelo Plata, Héctor Carbajal-Contreras, Adrian Rafael Murillo-de-Ozores, Kevin García-Ávila, Norma Vázquez, Maria Syed, Jan Wysocki, Daniel Batlle, Gerardo Gamba, María Castañeda-Bueno
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Germán Ricardo Magaña-Ávila, Erika Moreno, Consuelo Plata, Héctor Carbajal-Contreras, Adrian Rafael Murillo-de-Ozores, Kevin García-Ávila, Norma Vázquez, Maria Syed, Jan Wysocki, Daniel Batlle, Gerardo Gamba, María Castañeda-Bueno Severe cases of COVID-19 are characterized by development of acute respiratory distress syndrome (ARDS). Water accumulation in the lungs is thought to occur as consequence of an exaggerated inflammatory response. A possible mechanism could involve decreased activity of the epithelial Na+ channel, ENaC, expressed in type II pneumocytes. Reduced transepithelial Na+ reabsorption could contribute to lung edema due to reduced alveolar fluid clearance. This hypothesis is based on the observation of the presence of a novel furin cleavage site in the S protein of SARS-CoV-2 that is identical to the furin cleavage site present in the alpha subunit of ENaC. Proteolytic processing of αENaC by furin-like proteases is essential for channel activity. Thus, competition between S protein and αENaC for furin-mediated cleavage in SARS-CoV-2-infected cells may negatively affect channel activity. Here we present experimental evidence showing that coexpression of the S protein with ENaC in a cellular model reduces channel activity. In addition, we show that bidirectional competition for cleavage by furin-like proteases occurs between 〈ENaC and S protein. In transgenic mice sensitive to lethal SARS-CoV-2, however, a significant decrease in gamma ENaC expression was not observed by immunostaining of lungs infected as shown by SARS-CoV2 nucleoprotein staining.
Læs mere Tjek på PubMedHazem Aqel, Husni Farah
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Hazem Aqel, Husni Farah Seriphidium herba-alba (Asso), a plant celebrated for its therapeutic qualities, is widely used in traditional medicinal practices throughout the Middle East and North Africa. In a detailed study of Seriphidium herba-alba (Asso), essential oils and extracts were analyzed for their chemical composition and antimicrobial properties. The essential oil, characterized using mass spectrometry and retention index methods, revealed a complex blend of 52 compounds, with santolina alcohol, α-thujone, β-thujone, and chrysanthenone as major constituents. Extraction yields varied significantly, depending on the plant part and method used; notably, methanol soaking of aerial parts yielded the most extract at 17.75%. The antimicrobial analysis showed that the extracts had selective antibacterial activity, particularly against Staphylococcus aureus, and broad-spectrum antifungal activity against organisms such as Candida albicans and Aspergillus spp. The methanol-soaked extract demonstrated the strongest antimicrobial properties, indicating its potential as a natural antimicrobial source. This study not only underscores the therapeutic potential of Seriphidium herba-alba (Asso) in pharmaceutical applications but also sets a foundation for future research focused on isolating specific bioactive compounds and in vivo testing.
Læs mere Tjek på PubMedSeyma S. Celina, Jiří Černý
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Seyma S. Celina, Jiří Černý Crimean-Congo haemorrhagic fever orthonairovirus (CCHFV) is a negative-sense, single-stranded RNA virus with a segmented genome and the causative agent of a severe Crimean-Congo haemorrhagic fever (CCHF) disease. The virus is transmitted mainly by tick species in Hyalomma genus but other ticks such as representatives of genera Dermacentor and Rhipicephalus may also be involved in virus life cycle. To improve our understanding of CCHFV adaptation to its tick species, we compared nucleotide composition and codon usage patterns among the all CCHFV strains i) which sequences and other metadata as locality of collection and date of isolation are available in GenBank and ii) which were isolated from in-field collected tick species. These criteria fulfilled 70 sequences (24 coding for S, 23 for M, and 23 for L segment) of virus isolates originating from different representatives of Hyalomma and Rhipicephalus genera. Phylogenetic analyses confirmed that Hyalomma- and Rhipicephalus-originating CCHFV isolates belong to phylogenetically distinct CCHFV clades. Analyses of nucleotide composition among the Hyalomma- and Rhipicephalus-originating CCHFV isolates also showed significant differences, mainly in nucleotides located at the 3rd codon positions indicating changes in codon usage among these lineages. Analyses of codon adaptation index (CAI), effective number of codons (ENC), and other codon usage statistics revealed significant differences between Hyalomma- and Rhipicephalus-isolated CCHFV strains. Despite both sets of strains displayed a higher adaptation to use codons that are preferred by Hyalomma ticks than Rhipicephalus ticks, there were distinct codon usage preferences observed between the two tick species. These findings suggest that over the course of its long co-evolution with tick vectors, CCHFV has optimized its codon usage to efficiently utilize translational resources of Hyalomma species.
Læs mere Tjek på PubMedTadesse Tarik Tamir, Soliyana Adisu Gezhegn, Dejen Tegegne Dagnew, Abebe Tilahun Mekonenne, Genetu Tadese Aweke, Ayenew Molla Lakew
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Tadesse Tarik Tamir, Soliyana Adisu Gezhegn, Dejen Tegegne Dagnew, Abebe Tilahun Mekonenne, Genetu Tadese Aweke, Ayenew Molla Lakew Introduction Undernutrition poses a significant global public health challenge, adversely affecting childhood cognitive and physical development while increasing the risk of disease and mortality. Stunting, characterized by impaired growth and development in children due to insufficient psychological stimulation, frequent infections, and inadequate nutrition, remains a critical issue. Although economic growth alone cannot fully address the prevalence of stunting, there exists a robust correlation between a country’s income level and childhood stunting rates. Countries with higher incomes tend to have lower rates of childhood stunting. Notably, while childhood stunting is declining worldwide, it remains persistent in Africa. Consequently, this study aims to assess the prevalence of childhood stunting and its determinants in low- and lower-middle-income African countries Method This study conducted a secondary analysis of standard demographic and health surveys in low- and lower-middle-income African countries spanning the period from 2010 to 2022. The analysis included a total sample of 204,214 weighted children under the age of five years. To identify the determinants of stunting, we employed a multilevel mixed-effect model, considering the three levels of variables. The measures of association (fixed effect) were determined using the adjusted odds ratio at a 95% confidence interval. Significance was declared when the association between the outcome variable and the explanatory variable had a p-value less than 0.05. Result In low and lower-middle-income African countries, 31.28% of children under five years old experience stunting, with a 95% confidence interval ranging from 31.08% to 31.48%. The results from a multilevel mixed-effect analysis revealed that 24 months or more of age of child, male gender, low and high birth weight, low and high maternal BMI, no and low maternal education, low household wealth index, multiple (twin or triplet) births, rural residence, and low income of countries were significantly associated with childhood stunting. Conclusion Stunting among children under five years of age in low- and lower-middle-income African countries was relatively high. Individual, community, and country-level factors were statistically associated with childhood stunting. Equally importantly, with child, maternal, and community factors of stunting, the income of countries needs to be considered in providing nutritional interventions to mitigate childhood stunting in Africa.
Læs mere Tjek på PubMedYang Cao, Jingzheng Luan
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Yang Cao, Jingzheng Luan Differential Evolution (DE) is widely recognized as a highly effective evolutionary algorithm for global optimization. It has proven its efficacy in tackling diverse problems across various fields and real-world applications. DE boasts several advantages, such as ease of implementation, reliability, speed, and adaptability. However, DE does have certain limitations, such as suboptimal solution exploitation and challenging parameter tuning. To address these challenges, this research paper introduces a novel algorithm called Enhanced Binary JADE (EBJADE), which combines differential evolution with multi-population and elites regeneration. The primary innovation of this paper lies in the introduction of strategy with enhanced exploitation capabilities. This strategy is based on utilizing the sorting of three vectors from the current generation to perturb the target vector. By introducing directional differences, guiding the search towards improved solutions. Additionally, this study adopts a multi-population method with a rewarding subpopulation to dynamically adjust the allocation of two different mutation strategies. Finally, the paper incorporates the sampling concept of elite individuals from the Estimation of Distribution Algorithm (EDA) to regenerate new solutions through the selection process in DE. Experimental results, using the CEC2014 benchmark tests, demonstrate the strong competitiveness and superior performance of the proposed algorithm.
Læs mere Tjek på PubMedAiden E. Juge, Reinaldo F. Cooke, Guadalupe Ceja, Morgan Matt, Courtney L. Daigle
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Aiden E. Juge, Reinaldo F. Cooke, Guadalupe Ceja, Morgan Matt, Courtney L. Daigle Clinical illness (CI) scoring using visual observation is the most widely applied method of detecting respiratory disease in cattle but has limited effectiveness in practice. In contrast, body-mounted sensor technology effectively facilitates disease detection. To evaluate whether a combination of movement behavior and CI scoring is effective for disease detection, cattle were vaccinated to induce a temporary inflammatory immune response. Cattle were evaluated before and after vaccination to identify the CI variables that are most indicative of sick cattle. Respiratory rate (H2 = 43.08, P < 0.0001), nasal discharge (H2 = 8.35, P = 0.015), and ocular discharge (H2 = 16.38, P = 0.0003) increased after vaccination, and rumen fill decreased (H2 = 20.10, P < 0.0001). Locomotor activity was measured via leg-mounted sensors for the four days preceding and seven days following vaccination. A statistical model that included temperature, steps, lying time, respiratory rate, rumen fill, head position, and excess saliva was developed to distinguish between scores from before and after vaccination with a sensitivity of 0.898 and specificity of 0.915. Several clinical illness signs were difficult to measure in practice. Binoculars were required for scoring respiratory rate and eye-related metrics, and cattle had to be fitted with colored collars for individual identification. Scoring each animal took up to three minutes in a small research pen; therefore, technologies that can automate both behavior monitoring and identification of clinical illness signs are key to improving capacity for BRD detection and treatment.
Læs mere Tjek på PubMedPeng Qin, Manying Bai
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Peng Qin, Manying Bai This study investigates the impact of oil market uncertainty on the volatility of Chinese sector indexes. We utilize commonly used realized volatility of WTI and Brent oil price along with the CBOE crude oil volatility index (OVX) to embody the oil market uncertainty. Based on the sample span from Mar 16, 2011 to Dec 31, 2019, this study utilizes vector autoregression (VAR) model to derive the impacts of the three different uncertainty indicators on Chinese stock volatilities. The empirical results show, for all sectors, the impact of OVX on sectors volatilities are more economically and statistically significant than that of realized volatility of both WTI and Brent oil prices, especially after the Chinese refined oil pricing reform of March 27, 2013. That implies OVX is more informative than traditional WTI and Brent oil prices with respect to volatility spillover from oil market to Chinese stock market. This study could provide some important implications for the participants in Chinese stock market.
Læs mere Tjek på PubMedYuying Jiang, Xiaorong Bao
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Yuying Jiang, Xiaorong Bao Background The purpose of this study was to look at the relationship between the Systemic Immune Inflammatory Index (SII) and bone mineral density (BMD) in the pelvis, left upper and lower limbs, lumbar spine, thoracic spine, and trunk in a chronic kidney disease (CKD) population in the United States. Methods The National Health and Nutrition Examination Survey (2011–2016) yielded 2302 people with CKD aged >18 years. CKD was defined as eGFR less than 90 ml/min/1.73 m2 or eGFR greater than 90 ml/min/1.73 m2 with urine ACR greater than 30 mg/L.SII was calculated as PC * (NC / LC) from platelet count (PC), neutrophil count (NC), and lymphocyte count (LC). Multiple logistic regression was used to examine the relationship between BMD and SII at different sites in CKD patients, smoothed curve-fitting and generalized weighting models were used to investigate non-linear relationships, and a two-tailed linear regression model was used to find potential inflection points in the model. Results We discovered a negative correlation between SII and pelvic BMD among 2302 participants after controlling for gender, age, and race [β = -0.008; 95% confidence value -0.008; 95% confidence interval (CI) -0.014, -0.002]. Lower PEBMD was related to increasing SII (trend p = 0.01125). After additional correction, only pelvic BMD remained adversely linked with SII [value -0.006; 95% CI -0.012, -0.000, p = 0.03368]. Smoothed curve fitting revealed a consistent inverse relationship between SII and pelvic BMD. Further stratified analyses revealed a substantial positive negative connection between SII and pelvic BMD in individuals who did not have hypertension, diabetes, a BMI of more than 30 kg/m2, or stage 2 CKD. The connection between SII and PEBMD in people without diabetes revealed a strong inverted U-shaped curve. Conclusion In individuals with CKD in the United States, there was a negative connection between the systemic immunoinflammatory index (SII) and pelvic BMD. The SII might be a low-cost and simple test for CKD-related BMD loss.
Læs mere Tjek på PubMedManjula Karpurapu, Kavita Kumari Kakarala, Sangwoon Chung, Yunjuan Nie, Amritendu Koley, Patrick Dougherty, John W. Christman
PLoS One Infectious Diseases, 26.04.2024
Tilføjet 26.04.2024
by Manjula Karpurapu, Kavita Kumari Kakarala, Sangwoon Chung, Yunjuan Nie, Amritendu Koley, Patrick Dougherty, John W. Christman Our previous research demonstrated that PU.1 regulates expression of the genes involved in inflammation in macrophages. Selective knockdown of PU.1 in macrophages ameliorated LPS-induced acute lung injury (ALI) in bone marrow chimera mice. Inhibitors that block the transcriptional activity of PU.1 in macrophages have the potential to mitigate the pathophysiology of LPS-induced ALI. However, complete inactivation of PU.1 gene disrupts normal myelopoiesis. Although the green tea polyphenol Epigallocatechin gallate (EGCG) has been shown to regulate inflammatory genes in various cell types, it is not known if EGCG alters the transcriptional activity of PU.1 protein. Using Schrodinger Glide docking, we have identified that EGCG binds with PU.1 protein, altering its DNA-binding and self-dimerization activity. In silico analysis shows that EGCG forms Hydrogen bonds with Glutamic Acid 209, Leucine 250 in DNA binding and Lysine 196, Tryptophan 193, and Leucine 182 in the self-dimerization domain of the PU.1 protein. Experimental validation using mouse bone marrow-derived macrophages (BMDM) confirmed that EGCG inhibits both DNA binding by PU.1 and self-dimerization. Importantly, EGCG had no impact on expression of the total PU.1 protein levels but significantly reduced expression of various inflammatory genes and generation of ROS. In summary, we report that EGCG acts as an inhibitor of the PU.1 transcription factor in macrophages.
Læs mere Tjek på PubMedMalaria Journal, 26.04.2024
Tilføjet 26.04.2024
Malaria Journal, 26.04.2024
Tilføjet 26.04.2024
Abstract Background There are giant steps taken in the introduction of the novel malaria vaccine poised towards reducing mortality and morbidity associated with malaria. Objectives This study aimed to determine the knowledge of malaria vaccine and factors militating against willingness to accept the vaccine among mothers presenting in nine hospitals in Enugu metropolis. Methods This was a cross-sectional study carried out among 491 mothers who presented with their children in nine hospitals in Enugu metropolis, South-East Nigeria. A pre-tested and interviewer-administered questionnaire was used in this study. Results A majority of the respondents, 72.1% were aware of malaria vaccine. A majority of the respondents, 83.1% were willing to receive malaria vaccine. Similarly, a majority of the mothers, 92.9%, were willing to vaccinate baby with the malaria vaccine, while 81.1% were willing to vaccinate self and baby with the malaria vaccine. The subjects who belong to the low socio-economic class were five times less likely to vaccinate self and baby with malaria vaccine when compared with those who were in the high socio-economic class (AOR = 0.2, 95% CI 0.1–0.5). Mothers who had good knowledge of malaria vaccination were 3.3 times more likely to vaccinate self and baby with malaria vaccine when compared with those who had poor knowledge of malaria vaccination (AOR = 3.3, 95% CI 1–6–6.8). Conclusion Although the study documented a high vaccine acceptance among the mothers, there exists a poor knowledge of the malaria vaccine among them.
Læs mere Tjek på PubMedMalaria Journal, 26.04.2024
Tilføjet 26.04.2024
Abstract Background Pregnancy Associated Malaria (PAM) include malaria in pregnancy (MiP), placental malaria (PM), and congenital malaria (CM). The evidence available in Colombia on PAM focuses on one of the presentations (MiP, PM or CM), and no study longitudinally analyses the infection from the pregnant woman, passing through the placenta, until culminating in the newborn. This study determined the frequency of MiP, PM, and CM caused by Plasmodium vivax, Plasmodium falciparum, or mixed infections, according to Thick Blood Smear (TBS) and quantitative Polymerase Chain Reaction (qPCR). Identifying associated factors of PAM and clinical-epidemiological outcomes in northwestern Colombia. Methods Prospective study of 431 pregnant women, their placenta, and newborns registered in the data bank of the research Group “Salud y Comunidad César Uribe Piedrahíta” which collected information between 2014 and 2020 in endemic municipalities of the departments of Córdoba and Antioquia. The frequency of infection was determined with 95% confidence intervals. Comparisons were made with the Chi-square test, Student t-test, prevalence ratios, and control for confounding variables by log-binomial regression. Results The frequency of MiP was 22.3% (4.6% using TBS), PM 24.8% (1.4% using TBS), and CM 11.8% (0% using TBS). Using TBS predominated P. vivax. Using qPCR the proportions of P. vivax and P. falciparum were similar for MiP and PM, but P. falciparum predominated in CM. The frequency was higher in nulliparous, and women with previous malaria. The main clinical effects of PAM were anaemia, low birth weight, and abnormal APGAR score. Conclusions The magnitude of infections was not detected with TBS because most cases were submicroscopic (TBS-negative, qPCR-positive). This confirmed the importance of improving the molecular detection of cases. PAM continue being underestimated in the country due to that in Colombia the control programme is based on TBS, despite its outcomes on maternal, and congenital health.
Læs mere Tjek på PubMedMalaria Journal, 26.04.2024
Tilføjet 26.04.2024
Abstract Background The residual activity of a clothianidin + deltamethrin mixture and clothianidin alone in IRS covered more than the period of malaria transmission in northern Benin. The aim of this study was to show whether the prolonged residual efficacy of clothianidin-based products resulted in a greater reduction in vector populations and subsequent malaria transmission compared with the shorter residual efficacy of pirimiphos-methyl. Methods Human bait mosquito collections by local volunteers and pyrethrum spray collections were used in 6 communes under IRS monitoring and evaluation from 2019 to 2021. ELISA/CSP and species PCR tests were performed on Anopheles gambiae sensu lato (s.l.) to determine the infectivity rate and subspecies by commune and year. The decrease in biting rate, entomological inoculation rate, incidence, inhibition of blood feeding, resting density of An. gambiae s.l. were studied and compared between insecticides per commune. Results The An. gambiae complex was the major vector throughout the study area, acounting for 98.71% (19,660/19,917) of all Anopheles mosquitoes collected. Anopheles gambiae s.l. collected was lower inside treated houses (45.19%: 4,630/10,245) than outside (54.73%: 5,607/10,245) after IRS (p
Læs mere Tjek på PubMedInfection, 26.04.2024
Tilføjet 26.04.2024
Abstract Background This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality. Patients and methods The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%). Results Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30 mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3–9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84–8.2, p
Læs mere Tjek på PubMedInfection, 26.04.2024
Tilføjet 26.04.2024
Abstract Purpose Antibodies against SARS-CoV-2 spike (anti-S) may confer protection against symptomatic COVID-19. Whether their level predicts progression among those with COVID-19 pneumonia remains unclear. Methods We conducted a retrospective cohort study to assess predictors of anti-S levels and whether anti-S titer is associated with death or mechanical ventilation (MV). Adults hospitalized for COVID-19 pneumonia between July 2021 and July 2022 were enrolled if anti-S had been measured within 72 h of admission. Predictors of anti-S level were explored using multivariable quantile regression. The association between anti-S levels and 30-day death/MV was investigated via multivariable logistic regression. Analyses were stratified by vaccine status. Results The median anti-S level was 1370 BAU/ml in 328 vaccinated and 15.5 BAU/ml in 206 unvaccinated individuals. Among the vaccinated, shorter symptom duration (p = 0.001), hematological malignancies (p = 0.002), and immunosuppressive therapy (p = 0.004) were associated with lower anti-S levels. In the unvaccinated group, symptom duration was the only predictor of anti-S levels (p
Læs mere Tjek på PubMedInfection, 26.04.2024
Tilføjet 26.04.2024
Abstract Purpose A German multicentre study BLOOMY was the first to use machine learning approach to develop mortality prediction scores for bloodstream infection (BSI) patients, but the scores have not been assessed in other cohorts. Our aim was to assess how the BLOOMY 14-day and 6-month scores estimate mortality in our cohort of 497 cases with BSI. Methods Clinical data, laboratory data, and patient outcome were gathered retrospectively from patient records. The scores were calculated as presented in the BLOOMY study with the exception in the day of the evaluation. Results In our cohort, BLOOMY 14-day score estimated death by day 14 with an area under curve (AUC) of 0.87 (95% Confidence Interval 0.80–0.94). Using ≥ 6 points as a cutoff, sensitivity was 68.8%, specificity 88.1%, positive predictive value (PPV) 39.3%, and negative predictive value (NPV) 96.2%. These results were similar in the original BLOOMY cohort and outweighed both quick Sepsis-Related Organ Failure Assessment (AUC 0.76) and Pitt Bacteraemia Score (AUC 0.79) in our cohort. BLOOMY 6-month score to estimate 6-month mortality had an AUC of 0.79 (0.73–0.85). Using ≥ 6 points as a cutoff, sensitivity was 98.3%, specificity 10.7%, PPV 25.7%, and NPV 95.2%. AUCs of 6-month score to estimate 1-year and 5-year mortality were 0.80 (0.74–0.85) and 0.77 (0.73–0.82), respectively. Conclusion The BLOOMY 14-day and 6-month scores performed well in the estimations of mortality in our cohort and exceeded some established scores, but their adoption in clinical work remains to be seen.
Læs mere Tjek på PubMedInfection, 26.04.2024
Tilføjet 26.04.2024
Abstract Purpose Physicians may administer Nirmatrelvir-ritonavir to patients who have been symptomatic for more than 5 days. There is currently no clear evidence to support this approach. Methods A real-world study was conducted to investigate the potential relationship between the administration of Nirmatrelvir-ritonavir and the rates of intubation or in-hospital mortality among COVID-19 patients who experienced symptoms for more than 5 days. The end point was a composite event of intubation or in-hospital mortality. The outcomes between those patients who received Nirmatrelvir-ritonavir and those who did not were compared. Results A total of 847 patients were included in the analysis. Among them, 312 patients (36.84%) received Nirmatrelvir-ritonavir. Within the entire population, 86 patients (10.15%) experienced intubation or in-hospital mortality. The main analysis indicated that there was a significant association between the application of Nirmatrelvir-ritonavir and intubation or in-hospital mortality, with an odds ratio of 0.50 (95% confidence interval, 0.28 to 0.87; P = 0.0153) using inverse probability of treatment weighting. The finding was consistent with multiple sensitivity analyses. Conclusions The application of Nirmatrelvir-ritonavir was associated with a significantly reduced risk of intubation or death in hospitalized COVID-19 patients who experienced symptoms for more than 5 days as compared to those who did not receive the treatment.
Læs mere Tjek på PubMedInfection, 26.04.2024
Tilføjet 26.04.2024
Abstract Background Sepsis is a recognized global health challenge that places a considerable disease burden on countries. Although there has been some progress in the study of sepsis, the mortality rate of sepsis remains high. The relationship between serum osmolality and the prognosis of patients with sepsis is unclear. Method Patients with sepsis who met the criteria in the Medical Information Mart for Intensive Care IV database were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using multivariable Cox regression. The relationship between serum osmolality and the 28-day mortality risk in patients with sepsis was investigated using curve fitting, and inflection points were calculated. Results A total of 13,219 patients with sepsis were enrolled in the study; the mean age was 65.1 years, 56.9 % were male, and the 28-day mortality rate was 18.8 %. After adjusting for covariates, the risk of 28-day mortality was elevated by 99% (HR 1.99, 95%CI 1.74-2.28) in the highest quintile of serum osmolality (Q5 >303.21) and by 59% (HR 1.59, 95%CI 1.39-1.83) in the lowest quintile (Q1 ≤285.80), as compared to the reference quintile (Q3 291.38-296.29). The results of the curve fitting showed a U-shaped relationship between serum osmolality and the risk of 28-day mortality, with an inflection point of 286.9 mmol/L. Conclusion There is a U-shaped relationship between serum osmolality and the 28-day mortality risk in patients with sepsis. Higher or lower serum osmolality is associated with an increased risk of mortality in patients with sepsis. Patients with sepsis have a lower risk of mortality when their osmolality is 285.80-296.29 mmol/L.
Læs mere Tjek på PubMedInfection, 26.04.2024
Tilføjet 26.04.2024
Abstract Background Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, often harboring resistance-associated mutations to azithromycin (AZM). Global surveillance has been mandated to tackle the burden caused by MG, yet no data are available for Austria. Thus, we aimed to investigate the prevalence of MG, disease characteristics, and treatment outcomes at the largest Austrian HIV—and STI clinic. Methods All MG test results at the Medical University of Vienna from 02/2019 to 03/2022 were evaluated. Azithromycin resistance testing was implemented in 03/2021. Results Among 2671 MG tests, 199 distinct and mostly asymptomatic (68%; 135/199) MG infections were identified, affecting 10% (178/1775) of all individuals. This study included 83% (1479/1775) men, 53% (940/1775) men who have sex with men (MSM), 31% (540/1754) HIV+, and 15% (267/1775) who were using HIV pre-exposure prophylaxis (PrEP). In logistic regression analysis, ‘MSM’ (aOR 2.55 (95% CI 1.65–3.92)), ‘use of PrEP’ (aOR 2.29 (95% CI 1.58–3.32)), and ‘history of syphilis’ (aOR 1.57 (95% CI 1.01–2.24) were independent predictors for MG infections. Eighty-nine percent (178/199) received treatment: 11% (21/178) doxycycline (2 weeks), 52% (92/178) AZM (5 days), and 37% ( 65/178) moxifloxacin (7–10 days) and 60% (106/178) had follow-up data available showing negative tests in 63% (5/8), 76% (44/58) and 85% (34/40), respectively. AZM resistance analysis was available for 57% (114/199)) and detected in 68% (78/114). Resistance-guided therapy achieved a cure in 87% (53/61), yet, empiric AZM-treatment (prior to 03/2021) cleared 68% (26/38). Conclusions Mycoplasma genitalium was readily detected in this Austrian observational study, affected predominantly MSM and often presented as asymptomatic disease. We observed a worryingly high prevalence of AZM resistance mutations; however, empiric AZM treatment cleared twice as many MG infections as expected.
Læs mere Tjek på PubMedJulie E. RaabDesmond J. HamiltonTucker B. HarjuThao N. HuynhBrian C. Russo1Department of Immunology and Microbiology, School of Medicine, University of Colorado—Anschutz Medical Campus, Denver, Colorado, USA, Anthony R. Richardson
Infection and Immunity, 26.04.2024
Tilføjet 26.04.2024
Clinical & Experimental Immunology, 26.04.2024
Tilføjet 26.04.2024
Abstract Cerebral aneurysm (CA) represent a significant clinical challenge, characterized by pathological dilation of cerebral arteries. Recent evidence underscores the crucial involvement of immune cells in CA pathogenesis. This study aims to explore the complex interplay between immune cells and CA formation. We analyzed single-cell RNA sequencing data from the GSE193533 dataset, focusing on unruptured CA and their controls. Comprehensive cell-type identification and pseudotime trajectory analyses were conducted to delineate the dynamic shifts in immune cell populations. Additionally, a two-sample Mendelian Randomization (MR) approach was employed to investigate the causal influence of various immunophenotypes on CA susceptibility and the reciprocal effect of CA formation on immune phenotypes. Single-cell transcriptomic analysis revealed a progressive loss of vascular smooth muscle cells (VSMCs) and an increase in monocytes/macrophages (Mo/MΦ) and other immune cells, signifying a shift from a structural to an inflammatory milieu in CA evolution. MR analysis identified some vital immunophenotypes, such as CD64 on CD14+ CD16+ monocytes (OR: 1.236, 95% CI: 1.064 to 1.435, p=0.006), as potential risk factors for CA development, while others, like CD28- CD8br %CD8br (OR: 0.883, 95% CI: 0.789 to 0.988, p=0.030), appeared protective. Reverse MR analysis demonstrated that CA formation could modulate specific immunophenotypic expressions, highlighting a complex bidirectional interaction between CA pathology and immune response. This study underscores the pivotal role of immune cells in this process through the integration of single-cell transcriptomics with MR analysis, offering a comprehensive perspective on CA pathogenesis, potentially guiding future therapeutic strategies targeting specific immune pathways.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 26.04.2024
Tilføjet 26.04.2024
SUMMARY CD8 T cells are crucial adaptive immune cells with cytotoxicity to fight against pathogens or abnormal self-cells via major histocompatibility complex class I-dependent priming pathways. The composition of the memory CD8 T cell pool is influenced by various factors. Physiological aging, chronic viral infection, and autoimmune diseases promote the accumulation of CD8 T cells with highly differentiated memory phenotypes. Accumulating studies have shown that some of these memory CD8 T cells also exhibit innate-like cytotoxicity and upregulate the expression of receptors associated with natural killer (NK) cells. Further analysis shows that these NK-like CD8 T cells have transcriptional profiles of both NK and CD8 T cells, suggesting the transformation of CD8 T cells into NK cells. However, the specific induction mechanism underlying NK-like transformation and the implications of this process for CD8 T cells are still unclear. This review aimed to deduce the possible differentiation model of NK-like CD8 T cells, summarize the functions of major NK cell receptors expressed on these cells and provide a new perspective for exploring the role of these CD8 T cells in health and disease.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 26.04.2024
Tilføjet 26.04.2024
Abstract Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multi-center study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations.WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in one patient, respectively. In 3 patients (18.7%) no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD.
Læs mere Tjek på PubMedEvangelos Giampazolias, Mariana Pereira da Costa, Khiem C. Lam, Kok Haw Jonathan Lim, Ana Cardoso, Cécile Piot, Probir Chakravarty, Sonja Blasche, Swara Patel, Adi Biram, Tomas Castro-Dopico, Michael D. Buck, Richard R. Rodrigues, Gry Juul Poulsen, Susana A. Palma-Duran, Neil C. Rogers, Maria A. Koufaki, Carlos M. Minutti, Pengbo Wang, Alexander Vdovin, Bruno Frederico, Eleanor Childs, Sonia Lee, Ben Simpson, Andrea Iseppon, Sara Omenetti, Gavin Kelly, Robert Goldstone, Emma Nye, Alejandro Suárez-Bonnet, Simon L. Priestnall, James I. MacRae, Santiago Zelenay, Kiran Raosaheb Patil, Kevin Litchfield, James C. Lee, Tine Jess, Romina S. Goldszmid, Caetano Reis e Sousa
Science, 25.04.2024
Tilføjet 25.04.2024
Deus S. Ishengoma, Roly Gosling, Rosario Martinez-Vega, Khalid B. Beshir, Jeffrey A. Bailey, John Chimumbwa, Colin Sutherland, Melissa D. Conrad, Fitsum G. Tadesse, Jonathan J. Juliano, Moses R. Kamya, Wilfred F. Mbacham, Didier Ménard, Philip J. Rosenthal, Jaishree Raman, Allison Tatarsky, Sofonias K. Tessema, David A. Fidock, Abdoulaye A. Djimde
Nature, 25.04.2024
Tilføjet 25.04.2024
Marília Antônia Oliveira da Trindade, Álvaro Luan Santana Fonseca, Isabelle Helena Lima Dias, Sergei Rodrigo Magalhães de Sousa, Martin Johannes Enk, Karla Valéria Batista Lima, Ricardo Jose de Paula Souza e Guimarães
Tropical Medicine & International Health, 25.04.2024
Tilføjet 25.04.2024
Clinical Infectious Diseases, 25.04.2024
Tilføjet 25.04.2024
Abstract We report identification of 5 patients with infections caused by NDM-5-producing E. coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management.
Læs mere Tjek på PubMedNew England Journal of Medicine, 25.04.2024
Tilføjet 25.04.2024
New England Journal of Medicine, Volume 390, Issue 16, Page 1532-1533, April 25, 2024.
Læs mere Tjek på PubMedNew England Journal of Medicine, 25.04.2024
Tilføjet 25.04.2024
New England Journal of Medicine, Volume 390, Issue 16, Page 1533-1535, April 25, 2024.
Læs mere Tjek på PubMedAlan Y. Hsu, Chun‐Ju Lin, Ning‐Yi Hsia, Yu‐Hsun Wang, Jing‐Xing Li, Huan‐Sheng Chen, James Cheng‐Chung Wei, Yi‐Yu Tsai
Journal of Medical Virology, 25.04.2024
Tilføjet 25.04.2024
Guilherme S. Lira, Victor A. Ota, Mariana Q. S. Melo, Anna C. P. Castiñeiras, Isabela C. Leitão, Bianca O. Silva, Diana Mariani, Cássia C. A. Gonçalves, Liane J. Ribeiro, Marcia Halpern, Thalita F. Abreu, Fabiana A. Carneiro, Helena T. Scheid, Leonardo A. V. Souza, Débora G. M. Rodrigues, Nádia V. G. Cruz, Andrea Cony, Silvia Carvalho, Loyze P. O. de Lima, Vincent L. Viala, Lucio A. Caldas, Wanderley de Souza, Luiza M. Higa, Carolina M. Voloch, Orlando C. Ferreira Jr., Clarissa R. Damaso, Rafael M. Galliez, Débora S. Faffe, Amilcar Tanuri, Terezinha M. P. P. Castiñeiras
Journal of Medical Virology, 25.04.2024
Tilføjet 25.04.2024
Charlotte Hewel, Hanno Schmidt, Stefan Runkel, Wolfgang Kohnen, Susann Schweiger‐Seemann, André Michel, Sven‐Ernö Bikar, Bettina Lieb, Bodo Plachter, Thomas Hankeln, Matthias Linke, Susanne Gerber
Journal of Medical Virology, 25.04.2024
Tilføjet 25.04.2024