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Elin Dahlén, Julius Collin, Jenny Hellman, Christer Norman, Pontus Nauclér, Anders Ternhag
International Journal of Infectious Diseases, 6.10.2022
Tilføjet 6.10.2022
The objective of this study was to compare the incidence rate for complications to upper respiratory tract infections, including acute bronchitis (URTI) and lower urinary tract infections (UTI) for untreated compared with those treated with antibiotics.
Læs mere Tjek på PubMedLizhen Cao, Lin He, Siyuan Wang, Lianjie Xu, Shifang Zhuang
International Journal of Infectious Diseases, 6.10.2022
Tilføjet 6.10.2022
Chlamydia are Gram-negative, obligate intracellular pathogens, which currently comprise 13 species and 3 candidate species (Bommana and Polkinghorne 2019). Most of them have significant impacts on the health of humans or animals. Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci are the major species that infect humans and can cause a variety of diseases (Elwell et al. 2016).
Læs mere Tjek på PubMedAna Belkin, Avshalom Leibowitz, Liat Shargian, Dafna Yahav
Clinical Microbiology and Infection, 6.10.2022
Tilføjet 6.10.2022
Patients with genetic and acquired humoral immunodeficiency present with an atypical COVID-19 course. Persistent viral shedding with multiple viral relapses continue in these patients for weeks. [1] Lymphopenia, recent anti-CD20 therapy, chimeric antigen receptor T cell therapy (CAR-T), hypogammaglobulinemia and hematopoietic stem cell transplantation are associated with virological persistence. [2] These patients have low seroconversion rates following SARS-CoV-2 vaccination, and are predisposed to SARS-CoV-2 infection and severe disease.
Læs mere Tjek på PubMedEric J. Rubin, Lindsey R. Baden, John N. Nkengasong, Stephen Morrissey
New England Journal of Medicine, 5.10.2022
Tilføjet 6.10.2022
Heba N. Altarawneh, Hiam Chemaitelly, Houssein H. Ayoub, Mohammad R. Hasan, Peter Coyle, Hadi M. Yassine, Hebah A. Al-Khatib, Maria K. Smatti, Zaina Al-Kanaani, Einas Al-Kuwari, Andrew Jeremijenko, Anvar H. Kaleeckal, Ali N. Latif, Riyazuddin M. Shaik, Hanan F. Abdul-Rahim, Gheyath K. Nasrallah, Mohamed G. Al-Kuwari, Adeel A. Butt, Hamad E. Al-Romaihi, Mohamed H. Al-Thani, Abdullatif Al-Khal, Roberto Bertollini, Patrick Tang, Laith J. Abu-Raddad
New England Journal of Medicine, 5.10.2022
Tilføjet 6.10.2022
Guillaume Mestrallet
Frontiers in Immunology, 26.10.2022
Tilføjet 6.10.2022
Dendritic cells (DCs) play a key role to modulate anti-cancer immunity in the tumor microenvironment (TME). They link innate to adaptive immunity by processing and presenting tumor antigens to T cells thereby initiating an anti-tumor response. However, subsets of DCs also induce immune-tolerance, leading to tumor immune escape. In this regard, the TME plays a major role in adversely affecting DC function. Better understanding of DC impairment mechanisms in the TME will lead to more efficient DC-targeting immunotherapy. Here, we review the different subtypes and functions of DCs in the TME, including conventional DCs, plasmacytoid DC and the newly proposed subset, mregDC. We further focus on how cancer cells modulate DCs to escape from the host’s immune-surveillance. Immune checkpoint expression, small molecule mediators, metabolites, deprivation of pro-immunogenic and release of pro-tumorigenic cytokine secretion by tumors and tumor-attracted immuno-suppressive cells inhibit DC differentiation and function. Finally, we discuss the impact of established therapies on DCs, such as immune checkpoint blockade. Creative DC-targeted therapeutic strategies will be highlighted, including cancer vaccines and cell-based therapies.
Læs mere Tjek på PubMedTsukushi Kamiya, Douglas G. Paton, Flaminia Catteruccia, Sarah E. Reece
Trends in Parasitology, 5.10.2022
Tilføjet 6.10.2022
Proof-of-concept studies demonstrate that antimalarial drugs designed for human treatment can also be applied to mosquitoes to interrupt malaria transmission. Deploying a new control tool is ideally undertaken within a stewardship programme that maximises a drug's lifespan by minimising the risk of resistance evolution and slowing its spread once emerged. We ask: what are the epidemiological and evolutionary consequences of targeting parasites within mosquitoes? Our synthesis argues that targeting parasites inside mosquitoes (i) can be modelled by readily expanding existing epidemiological frameworks; (ii) provides a functionally novel control method that has potential to be more robust to resistance evolution than targeting parasites in humans; and (iii) could extend the lifespan and clinical benefit of antimalarials used exclusively to treat humans.
Læs mere Tjek på PubMedChristian V. Forst, Laura Martin-Sancho, Shashank Tripathi, Guojun Wang, Luiz Gustavo Dos Anjos Borges, Minghui Wang, Adam Geber, Lauren Lashua, Tao Ding, Xianxiao Zhou, Chalise E. Carter, Giorgi Metreveli, Ariel Rodriguez-Frandsen, Matthew D. Urbanowski, Kris M. White, David A. Stein, Hong Moulton, Sumit K. Chanda, Lars Pache, Megan L. Shaw, Ted M. Ross, Elodie Ghedin, Adolfo García-Sastre, Bin Zhang
Science Advances, 5.10.2022
Tilføjet 6.10.2022
Michael Bonadonna, Sandro Altamura, Elisabeth Tybl, Gael Palais, Maria Qatato, Maria Polycarpou-Schwarz, Martin Schneider, Christina Kalk, Wibke Rüdiger, Alina Ertl, Natasha Anstee, Ruzhica Bogeska, Dominic Helm, Michael D. Milsom, Bruno Galy
Science Advances, 5.10.2022
Tilføjet 6.10.2022
Joe N. Frost, Sarah K. Wideman, Alexandra E. Preston, Megan R. Teh, Zhichao Ai, Lihui Wang, Amy Cross, Natasha White, Yavuz Yazicioglu, Michael Bonadonna, Alexander J. Clarke, Andrew E. Armitage, Bruno Galy, Irina A. Udalova, Hal Drakesmith
Science Advances, 5.10.2022
Tilføjet 6.10.2022
Sanjeev Kumar, Anamika Patel, Lilin Lai, Chennareddy Chakravarthy, Rajesh Valanparambil, Elluri Seetharami Reddy, Kamalvishnu Gottimukkala, Meredith E. Davis-Gardner, Venkata Viswanadh Edara, Susanne Linderman, Kaustuv Nayak, Kritika Dixit, Pragati Sharma, Prashant Bajpai, Vanshika Singh, Filipp Frank, Narayanaiah Cheedarla, Hans P. Verkerke, Andrew S. Neish, John D. Roback, Grace Mantus, Pawan Kumar Goel, Manju Rahi, Carl W. Davis, Jens Wrammert, Sucheta Godbole, Amy R. Henry, Daniel C. Douek, Mehul S. Suthar, Rafi Ahmed, Eric Ortlund, Amit Sharma, Kaja Murali-Krishna, Anmol Chandele
Science Advances, 5.10.2022
Tilføjet 6.10.2022
Fiorino, Cassandra; Liu, Yiling; Henao, Ricardo; Ko, Emily R.; Burke, Thomas W.; Ginsburg, Geoffrey S.; McClain, Micah T.; Woods, Christopher W.; Tsalik, Ephraim L.
Critical Care Medicine, 26.10.2022
Tilføjet 6.10.2022
Objectives:
Sepsis causes significant mortality. However, most patients who die of sepsis do not present with severe infection, hampering efforts to deliver early, aggressive therapy. It is also known that the host gene expression response to infection precedes clinical illness. This study seeks to develop transcriptomic models to predict progression to sepsis or shock within 72 hours of hospitalization and to validate previously identified transcriptomic signatures in the prediction of 28-day mortality.
Design:
Retrospective differential gene expression analysis and predictive modeling using RNA sequencing data.
Patients:
Two-hundred seventy-seven patients enrolled at four large academic medical centers; all with clinically adjudicated infection were considered for inclusion in this study.
Measurements and Main Results:
Sepsis progression was defined as an increase in Sepsis 3 category within 72 hours. Transcriptomic data were generated using RNAseq of whole blood. Least absolute shrinkage and selection operator modeling was used to identify predictive signatures for various measures of disease progression. Four previously identified gene signatures were tested for their ability to predict 28-day mortality. There were no significant differentially expressed genes in 136 subjects with worsened Sepsis 3 category compared with 141 nonprogressor controls. There were 1,178 differentially expressed genes identified when sepsis progression was defined as ICU admission or 28-day mortality. A model based on these genes predicted progression with an area under the curve of 0.71. Validation of previously identified gene signatures to predict sepsis mortality revealed area under the receiver operating characteristic values of 0.70–0.75 and no significant difference between signatures.
Conclusions:
Host gene expression was unable to predict sepsis progression when defined by an increase in Sepsis-3 category, suggesting this definition is not a useful framework for transcriptomic prediction methods. However, there was a differential response when progression was defined as ICU admission or death. Validation of previously described signatures predicted 28-day mortality with insufficient accuracy to offer meaningful clinical utility.
Læs mere Tjek på PubMedGouel-Cheron, Aurelie; Swihart, Bruce J.; Warner, Sarah; Mathew, Lauren; Strich, Jeffrey R.; Mancera, Alex; Follmann, Dean; Kadri, Sameer S.
Critical Care Medicine, 26.10.2022
Tilføjet 6.10.2022
Objectives:
Bloodstream infections (BSIs) acquired in the ICU represent a detrimental yet potentially preventable condition. We determined the prevalence of BSI acquired in the ICU (ICU-onset BSI), pathogen profile, and associated risk factors.
Design:
Retrospective cohort study.
DATA SOURCES:
Eighty-five U.S. hospitals in the Cerner Healthfacts Database.
PATIENT SELECTION:
Adult hospitalizations between January 2009 and December 2015 including a (≥ 3 d) ICU stay.
DATA EXTRACTION AND DATA SYNTHESIS:
Prevalence of ICU-onset BSI (between ICU Day 3 and ICU discharge) and associated pathogen and antibiotic resistance distributions were compared with BSI present on (ICU) admission (ICU-BSIPOA); and BSI present on ICU admission day or Day 2. Cox models identified risk factors for ICU-onset BSI among host, care setting, and treatment-related factors. Among 150,948 ICU patients, 5,600 (3.7%) had ICU-BSIPOA and 1,306 (0.9%) had ICU-onset BSI. Of those with ICU-BSIPOA, 4,359 (77.8%) were admitted to ICU at hospital admission day. Patients with ICU-onset BSI (vs ICU-BSIPOA) displayed higher crude mortality of 37.9% (vs 20.4%) (p < 0.001) and longer median (interquartile range) length of stay of 13 days (8–23 d) (vs 5 d [3–8 d]) (p < 0.001) (considering all ICU stay). Compared with ICU-BSIPOA, ICU-onset BSI displayed more Pseudomonas, Acinetobacter, Enterococcus, Candida, and Coagulase-negative Staphylococcus species, and more methicillin-resistant staphylococci, vancomycin-resistant enterococci, ceftriaxone-resistant Enterobacter, and carbapenem-resistant Enterobacterales and Acinetobacter species, respectively. Being younger, male, Black, Hispanic, having greater comorbidity burden, sepsis, trauma, acute pulmonary or gastrointestinal presentations, and pre-ICU exposure to antibacterial and antifungal agents was associated with greater ICU-onset BSI risk after adjusted analysis. Mixed ICUs (vs medical or surgical ICUs) and urban and small/medium rural hospitals were also associated with greater ICU-onset BSI risk. The associated risk of acquiring ICU-onset BSI manifested with any duration of mechanical ventilation and 7 days after insertion of central venous or arterial catheters.
Conclusions:
ICU-onset BSI is a serious condition that displays a unique pathogen and resistance profile compared with ICU-BSIPOA. Further scrutiny of modifiable risk factors for ICU-onset BSI may inform control strategies.
Læs mere Tjek på PubMedAnh Quan Truong, Xuan Co Dao, Dinh Hoa Vu, Hoang Anh Nguyen, Thi Hong Gam Do, Nhan Thang Tran, Nhat Minh Tran, Ngan Binh Vu, Hong Nhung Pham, Van Cuong Bui, The Anh Trinh, Quoc Tuan Dang, Gia Binh Nguyen, Jeffrey Lipman, Menino O. Cotta, Jason A. Roberts aNational Drug Information and Adverse Drug Reaction Monitoring Centre, Hanoi University of Pharmacygrid.444951.9, Hanoi, Vietnam bIntensive Care Unit, Bach Mai Hospital, Hanoi, Vietnam cDepartment of Pharmacy, Bach Mai Hospital, Hanoi, Vietnam dDepartment of Analytical Chemistry and Toxicology, Hanoi University of Pharmacygrid.444951.9, Hanoi, Vietnam eDepartment of Microbiology, Bach Mai Hospital, Hanoi, Vietnam fUniversity of Queenslandgrid.1003.2 Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia gDepartment of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia hDivision of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France iPharmacy Department, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
Antimicrobial Agents And Chemotherapy, 5.10.2022
Tilføjet 5.10.2022
Sebastian G. Wicha, Annabelle Walz, Mohammed H. Cherkaoui-Rbati, Nils Bundgaard, Karsten Kuritz, Christin Gumpp, Nathalie Gobeau, Jörg Möhrle, Matthias Rottmann, Claudia Demarta-Gatsi aDepartment of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany bDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil, Switzerland cUniversity of Basel, Basel, Switzerland dMedicines for Malaria Venturegrid.452605.0, Geneva, Switzerland eIntiQuan GmbH, Basel, Switzerland
Antimicrobial Agents And Chemotherapy, 5.10.2022
Tilføjet 5.10.2022
Carlynn G. Winters, Ram M. Basnet, Paige E. Faasuamalie, Shamira J. Shallom, Adrian M. Zelazny, Shashank Gupta, Kenneth N. Olivier aLaboratory of Chronic Airway Infection, Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA bDepartment of Laboratory Medicine, Clinical Center, National Institutes of Healthgrid.94365.3d, Bethesda, Maryland, USA
Antimicrobial Agents And Chemotherapy, 5.10.2022
Tilføjet 5.10.2022
Eirik Amundsen, Åse Haugstvedt, Vegard Skogen, Rigmor C. Berg
PLoS One Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
by Eirik Amundsen, Åse Haugstvedt, Vegard Skogen, Rigmor C. Berg
Background Chemsex typically involves drugs such as GHB/GBL, crystal meth and mephedrone, and is increasingly common among MSM. The behaviour has been found to be associated with sexually transmitted infections (STIs) and mental health problems. We aimed to assess the extent of chemsex engagement and associations with different aspects of health, among MSM attending a free specialist walk-in clinic for STIs in Oslo, Norway. Methods Anonymous cross-sectional survey data was collected from June to October 2016. Differences in STI health (chlamydia, gonorrhoea, syphilis, HIV diagnoses), mental health (depression/anxiety) and internalised homonegativity between MSM using and not using GHB/GBL, crystal meth, mephedrone, cocaine or ketamine with sex in the last year were assessed descriptively and in a multivariate logistic regression model. The predictors were number of self-reported chlamydia, gonorrhoea or syphilis diagnoses, HIV diagnosis, depression/anxiety, and degree of internalised homonegativity. We adjusted for age, education level and having lived abroad. Results Of the 518 MSM respondents, 17% reported sexualised use of either GHB/GBL, crystal meth, mephedrone, cocaine or ketamine in the last year (chemsex). We found significant positive associations between chemsex and self-reported HIV diagnoses (adjusted odds ratio [aOR] = 3.26, 95%CI = 1.37–7.76), number of reported chlamydia, gonorrhoea or syphilis diagnoses in the last year (aOR = 1.63, 95%CI = 1.18–2.12), having lived more than one year abroad (aOR = 2.10, 95%CI = 1.20–3.65), but no significant association with depression/anxiety (aOR = 1.02, 95%CI = 0.53–1.93), nor internalised homonegativity (aOR = 0.62, 95%CI = 0.33–1.19). Conclusion Chemsex engagement in Norway is relatively low compared to findings from STI clinics in other European countries, and GHB/GBL and cocaine the two most commonly used drugs with sex. Chemsex was more common among MSM having lived more than one year abroad, reporting HIV diagnoses and a higher number of either chlamydia, gonorrhoea or syphilis diagnoses in the last year. Health care providers need to be made aware of chemsex as a behavioural phenomenon among MSM, and special care should be afforded to MSM living with HIV and being diagnosed with STIs.
Læs mere Tjek på PubMedPéter Gyula, Tamás Tóth, Teréz Gorcsa, Tünde Nyikó, Anita Sós-Hegedűs, György Szittya
PLoS One Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
by Péter Gyula, Tamás Tóth, Teréz Gorcsa, Tünde Nyikó, Anita Sós-Hegedűs, György Szittya
Arabidopsis thaliana is one of the most studied model organisms of plant biology with hundreds of geographical variants called ecotypes. One might expect that this enormous genetic variety could result in differential response to pathogens. Indeed, we observed previously that the Bur ecotype develops much more severe symptoms (upward curling leaves and wavy leaf margins) upon infection with two positive-strand RNA viruses of different families (turnip vein-clearing virus, TVCV, and turnip mosaic virus, TuMV). To find the genes potentially responsible for the ecotype-specific response, we performed a differential expression analysis of the mRNA and sRNA pools of TVCV and TuMV-infected Bur and Col plants along with the corresponding mock controls. We focused on the genes and sRNAs that showed an induced or reduced expression selectively in the Bur virus samples in both virus series. We found that the two ecotypes respond to the viral infection differently, yet both viruses selectively block the production of the TAS3-derived small RNA specimen called tasiARF only in the virus-infected Bur plants. The tasiARF normally forms a gradient through the adaxial and abaxial parts of the leaf (being more abundant in the adaxial part) and post-transcriptionally regulates ARF4, a major leaf polarity determinant in plants. The lack of tasiARF-mediated silencing could lead to an ectopically expressed ARF4 in the adaxial part of the leaf where the misregulation of auxin-dependent signaling would result in an irregular growth of the leaf blade manifesting as upward curling leaf and wavy leaf margin. QTL mapping using Recombinant Inbred Lines (RILs) suggests that the observed symptoms are the result of a multigenic interaction that allows the symptoms to develop only in the Bur ecotype. The particular nature of genetic differences leading to the ecotype-specific symptoms remains obscure and needs further study.
Læs mere Tjek på PubMedRon Blonder, Yael Feldman-Maggor, Shelley Rap
PLoS One Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
by Ron Blonder, Yael Feldman-Maggor, Shelley Rap
The experience of graduate degree lecturers in the natural sciences when they switched to online teaching during the Covid-19 pandemic is described. The shift to online teaching throughout the pandemic provided an opportunity to evaluate how lecturers integrate technology into their teaching and what they need to improve their remote teaching. This study used a twofold perspective of TPACK (Technological Pedagogical Content Knowledge) and self-efficacy in online education. Its data were derived from pre-and post-questionnaires, comprising closed and open-ended questions, given at the start and end of the semester. We found that lecturers focused on learning and applying technological and techno-pedagogical knowledge but paid less attention to the integration of three components: technology, pedagogy, and scientific content. Although no statistically significant differences in lecturers’ perceived self-efficacy was found between the start and the end of the semester, at the end of the semester we found a statistically significant correlation between the variables involved in building self-efficacy in online teaching: (1) satisfaction with online teaching and the belief that (2) technology promotes teaching, student interactions, participation, and engagement. Our results enabled us to identify the knowledge aspects that lecturers implemented initiatively and to better understand what aspects required more professional development training. In addition, the results emphasized the importance of developing the lecturers’ self-efficacy for online teaching. These insights can help to improve and enhance online teaching in higher education.
Læs mere Tjek på PubMedSonia Ijaz Haider, Farhatulain Ahmed, Hassan Pasha, Hadia Pasha, Nudrat Farheen, Muhammad Talha Zahid
PLoS One Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
by Sonia Ijaz Haider, Farhatulain Ahmed, Hassan Pasha, Hadia Pasha, Nudrat Farheen, Muhammad Talha Zahid
Purpose Life satisfaction influences well-being. Medical students often experience more stress as compared to their counterparts in other disciplines as they are required to meet the demands of both academic workload and clinical responsibilities. However, during the current pandemic, in addition to academic changes, inability to complete clinical placements, loss of peer interaction and social connectedness and, deployment to areas in times of crisis could exacerbate their stress. This would impact their ability to cope with stress and eventually influence their life satisfaction. Students approach these challenges in various ways, either positively, religiously, or by avoiding. This study aimed to explore the association between resilience, coping mechanisms and life satisfaction in medical students during the pandemic. Methods A cross-sectional web-based survey was conducted from undergraduate medical students from year 1 to year 5. Three instruments were used to measure life satisfaction, resilience, and coping, namely The Brief Resilience Scale, The Satisfaction with Life Scale and the COPE inventory. Mean and standard deviation were calculated for all continuous variables. Robust linear regression model was used for analysis. Hierarchical (forward) stepwise model building technique was used for final model. Alpha cut off was kept at 0.05. Results A total of 351 students (out of 500 students) completed the questionnaires. A moderately negative, slightly linear correlation between life satisfaction and avoidant coping was reported. Life satisfaction showed moderately positive, slightly linear correlation with resilience score. Three variables stayed significant in the final model: Resilience, avoidant coping, and religion coping. Conclusion Life satisfaction can be improved among medical students by focusing on strategies which enhance resilience. Religion is identified as a significant coping strategy among medical students. Students coping mechanism can vary and more research is needed to assess which types of coping strategies could contribute positively to the quality of their personal and professional lives
Læs mere Tjek på PubMedMatteo Guardiani, Philipp Frank, Andrija Kostić, Gordian Edenhofer, Jakob Roth, Berit Uhlmann, Torsten Enßlin
PLoS One Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
by Matteo Guardiani, Philipp Frank, Andrija Kostić, Gordian Edenhofer, Jakob Roth, Berit Uhlmann, Torsten Enßlin
The viral load of patients infected with SARS-CoV-2 varies on logarithmic scales and possibly with age. Controversial claims have been made in the literature regarding whether the viral load distribution actually depends on the age of the patients. Such a dependence would have implications for the COVID-19 spreading mechanism, the age-dependent immune system reaction, and thus for policymaking. We hereby develop a method to analyze viral-load distribution data as a function of the patients’ age within a flexible, non-parametric, hierarchical, Bayesian, and causal model. The causal nature of the developed reconstruction additionally allows to test for bias in the data. This could be due to, e.g., bias in patient-testing and data collection or systematic errors in the measurement of the viral load. We perform these tests by calculating the Bayesian evidence for each implied possible causal direction. The possibility of testing for bias in data collection and identifying causal directions can be very useful in other contexts as well. For this reason we make our model freely available. When applied to publicly available age and SARS-CoV-2 viral load data, we find a statistically significant increase in the viral load with age, but only for one of the two analyzed datasets. If we consider this dataset, and based on the current understanding of viral load’s impact on patients’ infectivity, we expect a non-negligible difference in the infectivity of different age groups. This difference is nonetheless too small to justify considering any age group as noninfectious.
Læs mere Tjek på PubMedViki Bockstal, Georgi Shukarev, Chelsea McLean, Neil Goldstein, Stephan Bart, Auguste Gaddah, Dickson Anumenden, Jeroen N. Stoop, Anne Marit de Groot, Maria G. Pau, Jenny Hendriks, Stephen C. De Rosa, Kristen W. Cohen, M. Juliana McElrath, Benoit Callendret, Kerstin Luhn, Macaya Douoguih, Cynthia Robinson
PLoS One Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
by Viki Bockstal, Georgi Shukarev, Chelsea McLean, Neil Goldstein, Stephan Bart, Auguste Gaddah, Dickson Anumenden, Jeroen N. Stoop, Anne Marit de Groot, Maria G. Pau, Jenny Hendriks, Stephen C. De Rosa, Kristen W. Cohen, M. Juliana McElrath, Benoit Callendret, Kerstin Luhn, Macaya Douoguih, Cynthia Robinson
Background Though clinically similar, Ebola virus disease and Marburg virus disease are caused by different viruses. Of the 30 documented outbreaks of these diseases in sub-Saharan Africa, eight were major outbreaks (≥200 cases; five caused by Zaire ebolavirus [EBOV], two by Sudan ebolavirus [SUDV], and one by Marburg virus [MARV]). Our purpose is to develop a multivalent vaccine regimen protecting against each of these filoviruses. This first-in-human study assessed the safety and immunogenicity of several multivalent two-dose vaccine regimens that contain Ad26.Filo and MVA-BN-Filo. Methods Ad26.Filo combines three vaccines encoding the glycoprotein (GP) of EBOV, SUDV, and MARV. MVA-BN-Filo is a multivalent vector encoding EBOV, SUDV, and MARV GPs, and Taï Forest nucleoprotein. This Phase 1, randomized, double-blind, placebo-controlled study enrolled healthy adults (18–50 years) into four groups, randomized 5:1 (active:placebo), to assess different Ad26.Filo and MVA-BN-Filo vaccine directionality and administration intervals. The primary endpoint was safety; immune responses against EBOV, SUDV, and MARV GPs were also assessed. Results Seventy-two participants were randomized, and 60 (83.3%) completed the study. All regimens were well tolerated with no deaths or vaccine-related serious adverse events (AEs). The most frequently reported solicited local AE was injection site pain/tenderness. Solicited systemic AEs most frequently reported were headache, fatigue, chills, and myalgia; most solicited AEs were Grade 1–2. Solicited/unsolicited AE profiles were similar between regimens. Twenty-one days post-dose 2, 100% of participants on active regimen responded to vaccination and exhibited binding antibodies against EBOV, SUDV, and MARV GPs; neutralizing antibody responses were robust against EBOV (85.7–100%), but lower against SUDV (35.7–100%) and MARV (0–57.1%) GPs. An Ad26.Filo booster induced a rapid further increase in humoral responses. Conclusion This study demonstrates that heterologous two-dose vaccine regimens with Ad26.Filo and MVA-BN-Filo are well tolerated and immunogenic in healthy adults. ClinicalTrials.gov NCT02860650.
Læs mere Tjek på PubMedRandi Jessen, Line Nielsen, Nicolai Balle Larsen, Arieh Sierra Cohen, Vithiagaran Gunalan, Ellinor Marving, Alonzo Alfaro-Núñez, Charlotta Polacek, The Danish COVID-19 Genome Consortium (DCGC), Anders Fomsgaard, Katja Spiess
PLoS One Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
by Randi Jessen, Line Nielsen, Nicolai Balle Larsen, Arieh Sierra Cohen, Vithiagaran Gunalan, Ellinor Marving, Alonzo Alfaro-Núñez, Charlotta Polacek, The Danish COVID-19 Genome Consortium (DCGC) , Anders Fomsgaard, Katja Spiess
Fast surveillance strategies are needed to control the spread of new emerging SARS-CoV-2 variants and gain time for evaluation of their pathogenic potential. This was essential for the Omicron variant (B.1.1.529) that replaced the Delta variant (B.1.617.2) and is currently the dominant SARS-CoV-2 variant circulating worldwide. RT-qPCR strategies complement whole genome sequencing, especially in resource lean countries, but mutations in the targeting primer and probe sequences of new emerging variants can lead to a failure of the existing RT-qPCRs. Here, we introduced an RT-qPCR platform for detecting the Delta- and the Omicron variant simultaneously using a degenerate probe targeting the key ΔH69/V70 mutation in the spike protein. By inclusion of the L452R mutation into the RT-qPCR platform, we could detect not only the Delta and the Omicron variants, but also the Omicron sub-lineages BA.1, BA.2 and BA.4/BA.5. The RT-qPCR platform was validated in small- and large-scale. It can easily be incorporated for continued monitoring of Omicron sub-lineages, and offers a fast adaption strategy of existing RT-qPCRs to detect new emerging SARS-CoV-2 variants using degenerate probes.
Læs mere Tjek på PubMedMalaria Journal, 5.10.2022
Tilføjet 5.10.2022
Abstract
Background
Quantifying disease costs is critical for policymakers to set priorities, allocate resources, select control and prevention strategies, and evaluate the cost-effectiveness of interventions. Although malaria carries a very large disease burden, the availability of comprehensive and comparable estimates of malaria costs across endemic countries is scarce.
Methods
A literature review to summarize methodologies utilized to estimate malaria treatment costs was conducted to identify gaps in knowledge.
Results
Only 45 publications met the inclusion criteria. They utilize different methods, include distinct cost components, have varied geographical coverage (a country vs a city), include different periods in the analysis, and focus on specific parasite types or population groups (e.g., pregnant women).
Conclusions
Cost estimates currently available are not comparable, hindering broad statements on the costs of malaria, and constraining advocacy efforts towards investment in malaria control and elimination, particularly with the finance and development sectors of the government.
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BMC Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
Abstract
Background
Neonatal bacterial meningitis is a common neonatal disease with high morbidity, and can cause serious sequelae when left untreated. Escherichia coli is the common pathogen, and its endotoxin, lipopolysaccharide (LPS) can damage the endothelial cells, increasing the permeability of the blood-brain barrier (BBB), leading to intracranial inflammation. However, the specific mechanism of bacterial meningitis induced by LPS damaging BBB remains unclear. In this study, the mouse brain microvascular endothelial (bEND.3) cells were used as a research object to investigate whether LPS damage BBB through the PI3K/Akt pathway.
Methods
The bEND.3 cells were stimulated with different concentrations of LPS for 12 h, and the expression of tight junction proteins (ZO-1, claudin-5, occludin) was detected using western blotting. The cells were challenged with the same concentration of LPS (1ug/ml) across different timepoints (0, 2 h, 4 h, 6 h, 12 h, 24 h). Expression of TJ proteins and signal pathway molecules (PI3K, p-PI3K, Akt, p-Akt) were detected. The distribution of ZO-1 in bEND.3 cells were detected by immunofluorescence staining.
Results
A negative correlation is observed between ZO-1 and LPS concentration. Moreover, a reduced expression of ZO-1 was most significant under 1 ug/ml of LPS, and the difference was statistically significant (P < 0.05). Additionally, there is a negative correlation between ZO-1 and LPS stimulation time. Meanwhile, the expression of claudin-5 and occludin did not change significantly with the stimulation of LPS concentration and time. The immunofluorescence assay showed that the amount of ZO-1 on the surface of bEND.3 cells stimulated with LPS was significantly lower than that of the control group. After LPS stimulation, p-Akt protein increased at 2 h and peaked at 4 h. The titer of p-PI3K did not change significantly with time.
Conclusion
LPS can downregulate the expression of ZO-1; however, its effect on claudin-5 and occludin is minimal. Akt signal pathway may be involved in the regulation of ZO-1 expression induced by LPS in bEND.3 cells.
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BMC Infectious Diseases, 5.10.2022
Tilføjet 5.10.2022
Abstract
Background
Inappropriate empiric antimicrobial treatment (IET) contributes to worsened outcomes. While IET’s differential impact across types of nosocomial pneumonia (NP: non-ventilated [nvHABP], ventilated [vHABP] hospital-acquired and ventilator-associated [VABP] bacterial pneumonia) is established, its potential interaction with the bacterial etiology is less clear.
Methods
We conducted a multicenter retrospective cohort study in the Premier Healthcare Database using an administrative algorithm to identify NP. We paired respective pathogens with empiric treatments. Antimicrobial coverage was appropriate if a drug administered within 2 days of infection onset covered the recovered organism(s). All other treatment was IET.
Results
Among 17,819 patients with NP, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Gram-negative (GN) organisms accounted for > 50% of all infections. GN pathogens were ~ 2 × as likely (7.4% vHABP to 10.7% nvHABP) to engender IET than Gram-positive (GP, 2.9% vHABP to 4.9% nvHABP) pathogens. Although rare (5.6% nvHABP to 8.3% VABP), GN + GP infections had the highest rates of IET (6.7% vHABP to 12.9% nvHABP). Carbapenem-resistant GNs were highly likely to receive IET (33.8% nvHABP to 40.2% VABP). Hospital mortality trended higher in the IET group, reaching statistical significance in GN + GP vHABP (47.8% IET vs. 29.3% non-IET, p = 0.016). 30-day readmission was more common with IET (16.0%) than non-IET (12.6%, p = 0.024) in GN VABP. Generally post-infection onset hospital length of stay and costs were higher with IET than non-IET.
Conclusions
IET is ~ 2 × more common in GN than GP infections. Although the magnitude of its impact varies by NP type, IET contributes to worsened clinical and economic outcomes.
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BMC Infectious Diseases, 4.10.2022
Tilføjet 5.10.2022
Abstract
Background
The clinical presentation of hospital-acquired pneumonia (HAP) in older patients is often complex and non-specific, posing a diagnostic challenge. This study evaluates the value of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and heparin-binding protein (HBP) in combination with traditional inflammatory markers procalcitonin (PCT) and C-reactive protein (CRP) in diagnosing HAP in older patients.
Methods
Thirty-eight elderly male patients with HAP (≥ 80 years old) and 46 age-matched controls, who were hospitalized for other reasons than HAP, were enrolled. The serum sTREM-1, HBP, PCT and CRP levels were measured by ELISA on the first day after enrollment. In addition, routine blood test, blood gas, sputum analysis, clinical pulmonary infection score (CPIS) assessment, and chest X-ray were performed, and the correlations with HAP were analyzed.
Results
The serum sTREM-1 (n = 38, 170.75 ± 158.33 pg/ml), HBP (2.08 ± 0.50), PCT (9.44 ± 17.73) and CRP (79.63 ± 71.37) were all significantly higher in the HAP group, when compared to the control group (P < 0.05). Furthermore, the values were positively correlated with the CPIS. The ROC curve analysis revealed that the AUC for sTREM-1 (0.667) and HBP (0.711) were lower, when compared to that for PCT (AUC = 0.839) and CRP (AUC = 0.840). The combination of PCT and CRP with sTREM-1 (AUC = 0.927) or HBP (AUC = 0.930) had the highest AUC values.
Conclusion
Serum sTREM-1, HBP, PCT and CRP can all be used as diagnostic markers for HAP in the elderly. The combination of traditional inflammatory markers PCT and CRP with novel inflammatory marker sTREM-1 or HBP further improves the diagnostic performance.
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Part, C., Filippi, V., Cresswell, J. A., Ganaba, R., Hajat, S., Nakstad, B., Roos, N., Kadio, K., Chersich, M., Lusambili, A., Kouanda, S., Kovats, S.
BMJ Open, 5.10.2022
Tilføjet 5.10.2022
Objective
To examine the effects of high ambient temperature on infant feeding practices and childcare.
Design
Secondary analysis of quantitative data from a prospective cohort study.
Setting
Community-based interviews in the commune of Bobo-Dioulasso, Burkina Faso. Exclusive breastfeeding is not widely practised in Burkina Faso.
Participants
866 women (1:1 urban:rural) were interviewed over 12 months. Participants were interviewed at three time points: cohort entry (when between 20 weeks’ gestation and 22 weeks’ postpartum), three and nine months thereafter. Retention at nine-month follow-up was 90%. Our secondary analysis focused on postpartum women (n=857).
Exposure
Daily mean temperature (°C) measured at one weather station in Bobo-Dioulasso. Meteorological data were obtained from publicly available archives (TuTiempo.net).
Primary outcome measures
Self-reported time spent breastfeeding (minutes/day), exclusive breastfeeding of infants under 6 months (no fluids other than breast milk provided in past 24 hours), supplementary feeding of infants aged 6–12 months (any fluid other than breast milk provided in past 24 hours), time spent caring for children (minutes/day).
Results
The population experienced year-round high temperatures (daily mean temperature range=22.6°C–33.7°C). Breastfeeding decreased by 2.3 minutes/day (95% CI -4.6 to 0.04, p=0.05), and childcare increased by 0.6 minutes/day (0.06 to 1.2, p=0.03), per 1°C increase in same-day mean temperature. Temperature interacted with infant age to affect breastfeeding duration (p=0.02), with a stronger (negative) association between temperature and breastfeeding as infants aged (0–57 weeks). Odds of exclusive breastfeeding very young infants (0–3 months) tended to decrease as temperature increased (OR=0.88, 0.75 to 1.02, p=0.09). There was no association between temperature and exclusive breastfeeding at 3–6 months or supplementary feeding (6–12 months).
Conclusions
Women spent considerably less time breastfeeding (~25 minutes/day) during the hottest, compared with coolest, times of the year. Climate change adaptation plans for health should include advice to breastfeeding mothers during periods of high temperature.
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Havelaar, A. H., Brhane, M., Ahmed, I. A., Kedir, J., Chen, D., Deblais, L., French, N., Gebreyes, W. A., Hassen, J. Y., Li, X., Manary, M. J., Mekuria, Z., Ibrahim, A. M., Mummed, B., Ojeda, A., Rajashekara, G., Roba, K. T., Saleem, C., Singh, N., Usmane, I. A., Yang, Y., Yimer, G., McKune, S.
BMJ Open, 5.10.2022
Tilføjet 5.10.2022
Introduction
Undernutrition is an underlying cause of mortality in children under five (CU5) years of age. Animal-source foods have been shown to decrease malnutrition in CU5. Livestock are important reservoirs for Campylobacter bacteria, which are recognised as risk factors for child malnutrition. Increasing livestock production may be beneficial for improving nutrition of children but these benefits may be negated by increased exposure to Campylobacter and research is needed to evaluate the complex pathways of Campylobacter exposure and infection applicable to low-income and middle-income countries. We aim to identify reservoirs of infection with Campylobacter spp. of infants in rural Eastern Ethiopia and evaluate interactions with child health (environmental enteric dysfunction and stunting) in the context of their sociodemographic environment.
Methods and analysis
This longitudinal study involves 115 infants who are followed from birth to 12 months of age and are selected randomly from 10 kebeles of Haramaya woreda, East Hararghe zone, Oromia region, Ethiopia. Questionnaire-based information is obtained on demographics, livelihoods, wealth, health, nutrition and women empowerment; animal ownership/management and diseases; and water, sanitation and hygiene. Faecal samples are collected from infants, mothers, siblings and livestock, drinking water and soil. These samples are analysed by a range of phenotypic and genotypic microbiological methods to characterise the genetic structure of the Campylobacter population in each of these reservoirs, which will support inference about the main sources of exposure for infants.
Ethics and dissemination
Ethical approval was obtained from the University of Florida Internal Review Board (IRB201903141), the Haramaya University Institutional Health Research Ethics Committee (COHMS/1010/3796/20) and the Ethiopia National Research Ethics Review Committee (SM/14.1/1059/20). Written informed consent is obtained from all participating households. Research findings will be disseminated to stakeholders through conferences and peer-reviewed journals and through the Feed the Future Innovation Lab for Livestock Systems.
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Debellut, F., Tang, K., Clark, A., Pecenka, C., Assao, B., Guindo, O., Grais, R. F., Isanaka, S.
BMJ Open, 5.10.2022
Tilføjet 5.10.2022
Objectives
To evaluate the cost-effectiveness of alternative rotavirus vaccines in Niger, using UNIVAC, a proportionate outcomes model.
Setting
The study leverages global, regional and local data to inform cost-effectiveness modelling. Local data were collected as part of a clinical trial taking place in the Madarounfa district, Maradi region, Niger.
Participants
The study models impact of infants vaccination on rotavirus gastroenteritis in children under 5 years of age.
Interventions
We compared the use of ROTARIX (GlaxoSmithKline, Belgium), ROTAVAC (Bharat Biotech, India) and ROTASIIL (Serum Institute, India) to no vaccination and to each other over a 10-year period starting in 2021.
Results
We estimated that ROTARIX, ROTAVAC and ROTASIIL would each prevent 13 million cases and 20 000 deaths of children under 5 years over a 10-year period in Niger. Compared with no vaccination, the cost to avert a disability-adjusted life-year was US$146 with ROTARIX, US$107 with ROTASIIL and US$76 with ROTAVAC from the government perspective. ROTAVAC dominated ROTARIX and ROTASIIL (eg, provided similar or higher benefits at a lower cost) and had 90% chance to be cost-effective at a US$100 willingness-to-pay threshold.
Conclusions
This study can inform decision-making around rotavirus vaccination policy in Niger, demonstrating that ROTAVAC is likely the most cost-effective option. Alternative products (ROTASIIL and ROTARIX) may also be considered by decision-makers if they are priced more competitively, or if their cold chain requirements could bring additional economic benefits.
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Sakr, F., Toufaili, Z., Akiki, Z., Akel, M., Malaeb, D., Dabbous, M., Salameh, P.
BMJ Open, 5.10.2022
Tilføjet 5.10.2022
Objectives
This study investigated parental knowledge, attitudes and practices towards fever in preschool children to help address gaps in public health and provide information with the aim of supporting clinical reports for parental education.
Design
A cross-sectional study design was used to explore parental experiences with fever.
Setting
Participants were recruited randomly from schools all over Lebanon targeting the preschool divisions.
Participants
Parents of children aged 5 years or less.
Interventions
An electronic self-administered questionnaire was sent to the parents through the schools’ emails and e-learning mobile applications.
Primary and secondary outcomes
The primary outcome measure was to assess parental knowledge about the precise definition of fever, correct use of medications and to evaluate the impact of sociodemographic factors on this knowledge. The secondary outcome measures were to assess parental attitudes and practices of fever management, sources of information and reasons to seek primary medical attention.
Results
A total of 733 parents were included in the study. Only 44% identified fever correctly according to the recognised definition by international guidelines. A significant association between parents’ knowledge of antibiotics and years of parenting experience was found (adjusted OR, ORa=4.23, 95% CI 1.41 to 12.68, p=0.01). Other sociodemographic factors that were significantly associated with parents’ knowledge of antibiotics were age (ORa=3.42, 95% CI 1.09 to 10.73, p=0.036) and education level (ORa=7.99, 95% CI 3.71 to 17.23, p<0.001). Greater than 75% usually give their children antipyretics without consulting a doctor. Approximately one-quarter of parents (26.3%) consulted different doctors at the same time, of which more than half (58.4%) had received different medical information.
Conclusions
This research determines deficiencies in parents’ knowledge of fever with some malpractices in its management particularly regarding antipyretic use. It provides insight for healthcare providers to empower parental experiences by offering the necessary information to enhance general outcomes of febrile sickness.
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Seid, A. A., Aychiluhm, S. B., Mohammed, A. A.
BMJ Open, 5.10.2022
Tilføjet 5.10.2022
Objectives
To determine the pooled effectiveness and feasibility of telerehabilitation in patients with COVID-19.
Design
Systematic review and meta-analysis of randomised controlled trials (RCTs).
Data sources
PubMed, CINAHL, Science Direct, PEDro, Google Scholar and Cochrane Library databases were systematically searched to the end of March 2022.
Eligibility criteria and outcomes
RCTs investigating the effects of telerehabilitation in the management of patients with COVID-19 were included. The outcomes of interest were functional capacity, cardiopulmonary exercise tests, quality of life and other variables where data are available.
Data extraction and synthesis
Two reviewers screened, extracted data and performed methodological quality assessment independently. The revised Cochrane Risk of Bias tool was used to assess the risk of bias. Review Manager V.5.4 and Stata V.14.0 software were used for statistical analysis. Mean difference (MD) with 95% CI and the corresponding p value were used to determine the treatment effect between groups. A fixed-effect model was used for all variables as no significant heterogeneity was observed.
Results
Four studies with 334 patients with COVID-19 were included. The pooled result of telerehabilitation showed statistically significant improvement on 6-minute walking test (MD 75.50; 95% CI 54.69 to 96.30; p=0.48), 30-second sit-to-stand test (MD 1.76; 95% CI 1.47 to 2.04; p=0.30), Borg Scale (MD 2.49; 95% CI 2.16 to 2.83; p=0.28) and level of dyspnoea (MD 6.26; 95% CI 5.42 to 7.10; p=0.66). The overall treatment completion rate was 88.46%, and the most common reason for withdrawal after randomisation was lost to follow-up or uncooperativeness.
Conclusions
The findings showed that telerehabilitation interventions could improve functional capacity and exercise perception among patients affected by COVID-19 and can be implemented with a high completion rate and minimal adverse events. However, more studies are required to investigate the effects on cardiopulmonary function, quality of life, anxiety, depression and other variables.
PROSPERO registration number
CRD42021287975.
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Harrigan, S. P., Tsang, V. W. L., Yassi, A., Zungu, M., Spiegel, J. M.
BMJ Open, 5.10.2022
Tilføjet 5.10.2022
Objectives
To assess the extent to which protection of healthcare workers (HCWs) as COVID-19 emerged was associated with economic inequality among and within countries.
Design
Cross-sectional analysis of associations of perceptions of workplace risk acceptability and mitigation measure adequacy with indicators of respondents’ respective country’s economic income level (World Bank assessment) and degree of within-country inequality (Gini index).
Setting
A global self-administered online survey.
Participants
4977 HCWs and healthcare delivery stakeholders from 161 countries responded to health and safety risk questions and a subset of 4076 (81.2%) answered mitigation measure questions. The majority (65%) of study participants were female.
Results
While the levels of risk being experienced at the pandemic’s onset were consistently deemed as unacceptable across all groupings, participants from countries with less income inequality were somewhat less likely to report unacceptable levels of risk to HCWs regarding both workplace environment (OR=0.92, p=0.012) and workplace organisational factors (OR=0.93, p=0.017) compared with counterparts in more unequal national settings. In contrast, considerable variation existed in the degree to which mitigation measures were considered adequate. Adjusting for other influences through a logistic regression analysis, respondents from lower middle-income and low-income countries were comparatively much more likely to assess both occupational health and safety (OR=10.91, p≤0.001) and infection prevention and control (IPC) (OR=6.61, p=0.001) protection measures as inadequate, despite much higher COVID-19 rates in wealthier countries at the time of the survey. Greater within-country income inequality was also associated with perceptions of less adequate IPC measures (OR=0.94, p=0.025). These associations remained significant when accounting for country-level differences in occupational and gender composition of respondents, including specifically when only female care providers, our study’s largest and most at-risk subpopulation, were examined.
Conclusions
Economic inequality threatens resilience of health systems that rely on health workers working safely to provide needed care during emerging pandemics.
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Hailu Tesfaye, A., Alemayehu, M., Abere, G., Kabito, G. G.
BMJ Open, 5.10.2022
Tilføjet 5.10.2022
Objective
This study was conducted to assess the prevalence and risk factors of poor sleep quality (SQ) among the academic staff at the University of Gondar, Northwestern Ethiopia.
Design
An institution-based cross-sectional study was conducted from March to April 2021. A validated, self-administered, standardised Pittsburgh Sleep Quality Index (PSQI) was used to quantify the amount of self-reported poor SQ. The collected data were entered into EpiData V.4.6 and analysed using Stata V.14 software. Binary logistic regressions were computed to determine the association between variables. The association was determined using an adjusted OR (AOR) with a 95% CI at a p value of <0.05.
Setting
The study was conducted at the University of Gondar, Northwestern Ethiopia.
Participants
A total of 607 lecturers participated in this study.
Outcome measures
The primary outcome is the prevalence of poor SQ, which was measured using the PSQI.
Results
Overall response rate was 95.60% (N=607). The age of the participants ranges from 21 to 70 with a mean of 32.39 (SD±6.80) years. The magnitude of poor SQ during the COVID-19 pandemic in the last month was 60.30% (95% CI (56.28% to 64.21%)). Working greater than 10 hours per day (AOR=2.19, 95% CI (1.16 to 4.27)), electronic device use before bedtime (AOR=1.53, 95% CI (1.04 to 2.27)), high-risk perception of COVID-19 infections (AOR=1.60, 95% CI (1.04 to 2.46)) and perceived job stress (AOR=2.15 (95% CI (1.50 to 3.08)) were risk factors for poor SQ.
Conclusion
The study revealed that the prevalence of poor SQ was high during the COVID-19 pandemic. The finding highlights the importance of optimising the working hours per day, minimising electronic device use before bedtime, promoting risk perception toward COVID-19 infection and developing workplace coping strategies for stress, which play a substantial role in minimising poor SQ.
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