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47 ud af 47 tidsskrifter valgt, ingen søgeord valgt, emner højest 7 dage gamle, sorteret efter nyeste først.
194 emner vises.
Amy Fabritius, Anabel Alonso, Andrew Wood, Shaheen Sulthana, Mark Winey
PLoS One Infectious Diseases, 27.03.2024
Tilføjet 27.03.2024
by Amy Fabritius, Anabel Alonso, Andrew Wood, Shaheen Sulthana, Mark Winey There is an ongoing need for antifungal agents to treat humans. Identification of new antifungal agents can be based on screening compounds using whole cell assays. Screening compounds that target a particular molecule is possible in budding yeast wherein sophisticated strain engineering allows for controlled expression of endogenous or heterologous genes. We have considered the yeast Mps1 protein kinase as a reasonable target for antifungal agents because mutant or druggable forms of the protein, upon inactivation, cause rapid loss of cell viability. Furthermore, extensive analysis of the Mps1 in budding yeast has offered potential tactics for identifying inhibitors of its enzymatic activity. One such tactic is based on the finding that overexpression of Mps1 leads to cell cycle arrest via activation of the spindle assembly checkpoint. We have endeavored to adapt this assay to be based on the overexpression of Mps1 orthologs from pathogenic yeast in hopes of having a whole-cell assay system to test the activity of these orthologs. Mps1 orthologous genes from seven pathogenic yeast or other pathogenic fungal species were isolated and expressed in budding yeast. Two orthologs clearly produced phenotypes similar to those produced by the overexpression of budding yeast Mps1, indicating that this system for heterologous Mps1 expression has potential as a platform for identifying prospective antifungal agents.
Læs mere Tjek på PubMedCornelius Osei-Owusu, Satveer Dhillon, Isaac Luginaah
PLoS One Infectious Diseases, 27.03.2024
Tilføjet 27.03.2024
by Cornelius Osei-Owusu, Satveer Dhillon, Isaac Luginaah Over the past few years, food insecurity has been increasing globally due to the COVID-19 pandemic, climate change, economic downturns and conflict and a number of other intersecting factors. Older adults residing in low- and middle-income countries are more vulnerable to food insecurity. While the impacts of food insecurity on physical health outcomes have been thoroughly researched, the effect on mental health outcomes remains under-researched, especially among older adults. Hence, this systematic review aims to investigate existing literature to assess how food insecurity impacts the mental health of older persons residing in LMICs. A systematic search of six databases and Google for studies was conducted. The search was limited to studies written in English and published between 2000 to the present. We identified 725 studies, out of which 40 studies were selected for a full-text review and 12 studies were included for a final analysis. The significant finding in all the included studies was that food insecurity is associated with the worsening mental health of older adults. We also found a complex interplay of factors such as gender, age, rural/urban and health conditions associated with the aggravation of several mental health outcomes. The findings of this study illuminate the need for improved food programs to improve food security and, consequently, mental health among older adults.
Læs mere Tjek på PubMedMohsen Ahmadi, Danial Javaheri, Matin Khajavi, Kasra Danesh, Junbeom Hur
PLoS One Infectious Diseases, 27.03.2024
Tilføjet 27.03.2024
by Mohsen Ahmadi, Danial Javaheri, Matin Khajavi, Kasra Danesh, Junbeom Hur Alzheimer’s disease is the most prevalent form of dementia, which is a gradual condition that begins with mild memory loss and progresses to difficulties communicating and responding to the environment. Recent advancements in neuroimaging techniques have resulted in large-scale multimodal neuroimaging data, leading to an increased interest in using deep learning for the early diagnosis and automated classification of Alzheimer’s disease. This study uses machine learning (ML) methods to determine the severity level of Alzheimer’s disease using MRI images, where the dataset consists of four levels of severity. A hybrid of 12 feature extraction methods is used to diagnose Alzheimer’s disease severity, and six traditional machine learning methods are applied, including decision tree, K-nearest neighbor, linear discrimination analysis, Naïve Bayes, support vector machine, and ensemble learning methods. During training, optimization is performed to obtain the best solution for each classifier. Additionally, a CNN model is trained using a machine learning system algorithm to identify specific patterns. The accuracy of the Naïve Bayes, Support Vector Machines, K-nearest neighbor, Linear discrimination classifier, Decision tree, Ensembled learning, and presented CNN architecture are 67.5%, 72.3%, 74.5%, 65.6%, 62.4%, 73.8% and, 95.3%, respectively. Based on the results, the presented CNN approach outperforms other traditional machine learning methods to find Alzheimer severity.
Læs mere Tjek på PubMedMalaria Journal, 27.03.2024
Tilføjet 27.03.2024
Abstract Background The degree to which Anopheles mosquitoes prefer biting humans over other vertebrate hosts, i.e. the human blood index (HBI), is a crucial parameter for assessing malaria transmission risk. However, existing techniques for identifying mosquito blood meals are demanding in terms of time and effort, involve costly reagents, and are prone to inaccuracies due to factors such as cross-reactivity with other antigens or partially digested blood meals in the mosquito gut. This study demonstrates the first field application of mid-infrared spectroscopy and machine learning (MIRS-ML), to rapidly assess the blood-feeding histories of malaria vectors, with direct comparison to PCR assays. Methods and results Female Anopheles funestus mosquitoes (N = 1854) were collected from rural Tanzania and desiccated then scanned with an attenuated total reflectance Fourier-transform Infrared (ATR-FTIR) spectrometer. Blood meals were confirmed by PCR, establishing the ‘ground truth’ for machine learning algorithms. Logistic regression and multi-layer perceptron classifiers were employed to identify blood meal sources, achieving accuracies of 88%–90%, respectively, as well as HBI estimates aligning well with the PCR-based standard HBI. Conclusions This research provides evidence of MIRS-ML effectiveness in classifying blood meals in wild Anopheles funestus, as a potential complementary surveillance tool in settings where conventional molecular techniques are impractical. The cost-effectiveness, simplicity, and scalability of MIRS-ML, along with its generalizability, outweigh minor gaps in HBI estimation. Since this approach has already been demonstrated for measuring other entomological and parasitological indicators of malaria, the validation in this study broadens its range of use cases, positioning it as an integrated system for estimating pathogen transmission risk and evaluating the impact of interventions.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract Purpose This study aims to evaluate the effectiveness of mitigation strategies and analyze the impact of human behavior on the transmission of Mpox. The results can provide guidance to public health authorities on comprehensive prevention and control for the new Mpox virus strain in the Democratic Republic of Congo as of December 2023. Methods We develop a two-layer Watts-Strogatz network model. The basic reproduction number is calculated using the next-generation matrix approach. Markov chain Monte Carlo (MCMC) optimization algorithm is used to fit Mpox cases in Canada into the network model. Numerical simulations are used to assess the impact of mitigation strategies and human behavior on the final epidemic size. Results Our results show that the contact transmission rate of low-risk groups and susceptible humans increases when the contact transmission rate of high-risk groups and susceptible humans is controlled as the Mpox epidemic spreads. The contact transmission rate of high-risk groups after May 18, 2022, is approximately 20% lower than that before May 18, 2022. Our findings indicate a positive correlation between the basic reproduction number and the level of heterogeneity in human contacts, with the basic reproduction number estimated at 2.3475 (95% CI: 0.0749–6.9084). Reducing the average number of sexual contacts to two per week effectively reduces the reproduction number to below one. Conclusion We need to pay attention to the re-emergence of the epidemics caused by low-risk groups when an outbreak dominated by high-risk groups is under control. Numerical simulations show that reducing the average number of sexual contacts to two per week is effective in slowing down the rapid spread of the epidemic. Our findings offer guidance for the public health authorities of the Democratic Republic of Congo in developing effective mitigation strategies.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract Introduction Skin diseases such as impetigo pose a significant public health challenge in low resource settings. Despite this, there is a dearth of epidemiological data on the prevalence of this condition in Ghana. Methods We conducted a cross sectional study in three settings in Ghana: community members in East Mamprusi district in the North East region, a secondary school in Sekyere East district, and inmates of the Kumasi central prisons both in the Ashanti region. Following a period of training, we performed a standardised skin examination on each participant to assess for scabies and impetigo. We calculated the prevalence of each skin condition and investigated determinants of impetigo. Results/ findings Of the 1327 participants [males 64.1% and median age 22 (16–29) years], 746 (56.2%) had scabies and 186 (14%) had impetigo which was usually very mild or mild in severity. Most participants with impetigo also had scabies (161/186, 86.6%). Having an itch [RR 6.05 (95% CI 2.53–14.47)], presence of scabies burrows [RR 1.99 (95% CI 1.54–2.59)], clinical scabies [RR 3.15 (2.11–4.72)] or being in preschool [RR 4.56 (1.78–11.67)] increased the risk for impetigo. A combination of the presence of clinical scabies, age, sex and itch most accurately predicted the odds of having impetigo. Conclusions There is substantial burden of impetigo and scabies in Ghana. There is a need to institute measures to improve detection and control of these common dermatoses as part of Universal Health Coverage package to reduce the scourge of the diseases in this setting.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract Introduction Leprosy is a chronic granulomatous infectious disease, mainly affecting the skin and peripheral nerves, caused by the obligate intracellular bacteria Mycobacterium leprae. The disease has been discussed in several review articles in recent research, but as far as we know, only a few have addressed the effects of leprosy on nails, especially those who examine the dermoscopic features of nails in leprosy patients. Purposes We aimed to document nail changes in leprosy patients and identify any particular findings through dermoscopic examination. Method This was an observational study conducted in the Dermatology and Venereology Clinic of Hasan Sadikin Hospital, West Java, Indonesia, from March 2023 through May 2023. All patients have established cases of leprosy, and the diagnosis is based on clinical and bacteriological examinations. Recruitment was done through total sampling. Dermoscopic examination of all fingernails and toenails was performed at 10x magnification using a handheld dermatoscope (Heine DELTA 20 T Dermatoscope) in polarized mode without the linkage fluid to document the dermoscopic features. Result Of a total of 19 patients, 15 had nail changes due to leprosy. Out of 15 patients, 13 patients were male. Patients below 25 years old had more nail changes. Most of the patients had a duration of disease greater than two years. Both fingers and toes were involved in nine patients. In this study, the most common dermoscopic feature found was the longitudinal ridge. Other dermoscopic features found in this study were transverse lines, onycholysis, longitudinal melanonychia, leukonychia, subungual hemorrhage, subungual hyperkeratosis, anonychia, and onychorrexis. Conclusion Nail changes are found in leprosy patients and have a wide variety of clinical appearances. A dermoscopy should be performed to assess nail changes in leprosy.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract Background Timely and accurate identification of pathogens is crucial for appropriate treatment and prognosis of infectious diseases. As an increasingly popular pathogen detection method, the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens in febrile patients with suspected infection requires further exploration. Methods This study included 368 febrile patients with suspected infections who were admitted to the Infectious Disease Department of Qilu Hospital, Shandong University between January 5, 2021 and April 14, 2023. Both mNGS testing and conventional culture were performed in all patients. Clinical data of enrolled patients were collected, and the diagnostic performances of mNGS and culture were compared. Results Of the 368 enrolled patients, 231 were finally diagnosed with infection and 137 were with diseases other than infection. The sensitivity (58.01% vs. 21.65%, p
Læs mere Tjek på PubMedRam KumarHimanshu KambojShweta DhandaAssim VermaYogesh ChanderKuldeep NehraAdrish BhatiRamesh Kumar DedarDeepak Kumar SharmaSanjay BaruaBhupendra N. TripathiShalini SharmaNaveen Kumara National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, Indiab Livestock Research Station, Rajasthan University of Veterinary and Animal Sciences, Nohar, Rajasthan, Indiac Dadhich Cattle Farm, Nohar, Indiad Department of Veterinary Microbiology, Rajasthan University of Veterinary and Animal Sciences, Udaipur, India
Virulence, 26.03.2024
Tilføjet 26.03.2024
Hannah E. Ledvina, Aaron T. Whiteley
Nat Rev Microbiol, 26.03.2024
Tilføjet 26.03.2024
Clinical Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract Background Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described.Methods In this controlled case-ascertained household transmission study, we recruited asymptomatic children
Læs mere Tjek på PubMedClinical Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract In a retrospective multicenter study of 575 patients with bloodstream infections or pneumonia due to wild-type AmpC β-lactamase-producing Enterobacterales, species with low in-vitro mutation rates for AmpC derepression were associated to fewer treatment failures due to AmpC overproduction (aHR 0.5, 95%CI 0.2-0.9). However, compared to cefepime/carbapenems using 3GC as definitive therapy remained associated with this adverse outcome (15% vs. 1%).
Læs mere Tjek på PubMedClinical Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract Background Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here, we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).Methods Through comprehensive examination of data from nearly 4,000 participants enrolled in six registrational trials for HABP/VABP submitted to the FDA between 2005-2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator.Results DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Though infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar.Conclusions Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design.
Læs mere Tjek på PubMedClinical Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract Background Streptococcal bacteremia is associated with high mortality. The study aims to identify predictors of mortality among patients with streptococcal bacteremia.Methods This retrospective study was conducted at the Lausanne University Hospital, Switzerland and included episodes of streptococcal bacteremia among adult patients from 2015 to 2023.Results During the study period, 861 episodes of streptococcal bacteremia were included. The majority of episodes were categorized in the Mitis group (348 episodes; 40%), followed by the Pyogenic group (215; 25%). Endocarditis was the most common source of bacteremia (164; 19%). The overall 14-day mortality rate was 8% (65 episodes). The results from the Cox multivariable regression model showed that a Charlson comorbidity index >4 (P 0.001; HR 2.87, CI 1.58-5.22), S. pyogenes (P 0.011; HR 2.54, CI 1.24-5.21), sepsis (P
Læs mere Tjek på PubMedJournal of Medical Virology, 26.03.2024
Tilføjet 26.03.2024
Marta Albanell-Fernández, Fernando Salazar González, Olalla Montero Pérez, Victoria Aniyar, Francisco-Javier Carrera Hueso, Alex Soriano, Carolina García-Vidal, Pedro Puerta-Alcalde, José Antonio Martínez, Pedro Vázquez Ferreiro
International Journal of Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Fungal infections are a significant cause of morbidity and mortality in hospitalised patients, leading to rising healthcare costs. Global data indicates a growing prevalence of invasive candidiasis and candidemia (IC/C). Large studies report incidence rates of 3–5 per 100,000 people in the general population, 1–2% of all ICU admissions, and an estimated 750,000 cases worldwide annually [1–3]. Candidemia morbidity and mortality rates range from 20 to 49% [4,5].
Læs mere Tjek på PubMedMohamed, S. F., Kisia, L., Mashiashi, I., Mair, F., Wisdom, J. P., Bunn, C., Gray, C., Kibe, P. M., Sanya, R. E., Karugu, C. H., Mtenga, S. M., Binyaruka, P., Asiki, G.
BMJ Open, 26.03.2024
Tilføjet 26.03.2024
BackgroundThe COVID-19 pandemic caused disruptions in care that adversely affected the management of non-communicable diseases (NCDs) globally. Countries have responded in various ways to support people with NCDs during the pandemic. This study aimed to identify policy gaps, if any, in the management of NCDs, particularly diabetes, during COVID-19 in Kenya and Tanzania to inform recommendations for priority actions for NCD management during any future similar crises. MethodsWe undertook a desk review of pre-existing and newly developed national frameworks, policy models and guidelines for addressing NCDs including type 2 diabetes. This was followed by 13 key informant interviews with stakeholders involved in NCD decision-making: six in Kenya and seven in Tanzania. Thematic analysis was used to analyse the documents. ResultsSeventeen guidance documents were identified (Kenya=10; Tanzania=7). These included pre-existing and/or updated policies/strategic plans, guidelines, a letter, a policy brief and a report. Neither country had comprehensive policies/guidelines to ensure continuity of NCD care before the COVID-19 pandemic. However, efforts were made to update pre-existing documents and several more were developed during the pandemic to guide NCD care. Some measures were put in place during the COVID-19 period to ensure continuity of care for patients with NCDs such as longer supply of medicines. Inadequate attention was given to monitoring and evaluation and implementation issues. ConclusionKenya and Tanzania developed and updated some policies/guidelines to include continuity of care in emergencies. However, there were gaps in the documents and between policy/guideline documents and practice. Health systems need to establish disaster preparedness plans that integrate attention to NCD care to enable them to better handle severe disruptions caused by emergencies such as pandemics. Such guidance needs to include contingency planning to enable adequate resources for NCD care and must also address evaluation of implementation effectiveness.
Læs mere Tjek på PubMedAdsul, N., Tyagi, J., Bhaumik, S.
BMJ Open, 26.03.2024
Tilføjet 26.03.2024
IntroductionCOVID-19 exposed the fragility of health systems, where even the most basic health services in high-income and low-income and middle-income nations could not withstand the health systems shock due to the pandemic. Community health workers (CHWs) can contribute to improving the resilience of health systems, specifically to withstand shocks and emergencies and to avoid disruptions of routine service delivery. We aim to explore and understand the ‘individual’ and ‘systems-level’ resilience factors that shaped the involvement of CHWs in the COVID-19 response. Methods and analysisWe will search five electronic databases (PubMed, Cochrane Library, EMBASE, CINAHL and SciELO (Spanish)) and conduct citation screening to identify studies on CHWs’ response during the COVID-19 pandemic. Two review authors will independently screen the studies for inclusion and to extract data. The software Rayyan will be used to assist in screening the relevant literature. A thematic analysis approach will be followed to analyse and synthesise the qualitative evidence. The quality of the included studies will be critically assessed using the Critical Skills Appraisal Programme Tool. We will use the GRADE CERQual(Grading of Recommendations, Assessment, Development, and Evaluations - Confidence in the Evidence from Reviews of Qualitative Research) approach to assess certainty in the synthesised findings of the qualitative evidence. Ethics and disseminationThis study will be conducted on published evidence, with no living participants; thus, no ethical approval is required. The final review will be submitted and published in a peer-reviewed journal. We will also develop a policy brief to communicate the review findings to the stakeholders.
Læs mere Tjek på PubMedLiu, J., Wang, R., Qiu, J., Su, T.
BMJ Open, 26.03.2024
Tilføjet 26.03.2024
IntroductionAcute kidney injury (AKI) is a critical condition with a complex aetiology and different outcomes, where haemodynamic dysfunction, renal hypoperfusion and inflammation serve as key contributors to its development and progression. Early and accurate diagnosis is vital for initiating targeted treatments like fluid resuscitation, vasoactive agents or steroid therapy, which are essential for improving patient outcomes. Intravoxel incoherent motion (IVIM) MRI assesses both capillary perfusion and tissue water diffusion, while arterial spin labelling (ASL) MRI measures renal blood flow without the need for contrast. Research on combined use of IVIM and ASL MRI in patients with AKI is rare. This study aims to investigate the MRI characteristics of IVIM and ASL in patients with tubulointerstitial nephritis (TIN) and to explore their relationship with pathological findings and renal recovery. Methods and analysisSingle-centre, prospective, observational cohort study of 30 patients with biopsy-proven TIN. Participants will undergo renal IVIM and ASL MRI within 7 days post-biopsy. The pathological assessments of active and chronic tubulointerstitial injuries will be semiscored using modified Banff criteria. The estimated glomerular filtration rate (eGFR) during follow-up and prevalence of chronic kidney disease at 3 and 6 months will be reported. An eGFR below 45 mL/min is considered a poor renal outcome. Ethics and disseminationThe study has been reviewed and approved by the Ethics Committee of Peking University First Hospital and written informed consent will be obtained from all participants (2022Y503). The study results will be disseminated through publication in a relevant peer-reviewed journal and presentation at academic meetings to increase awareness and share findings with the scientific community.
Læs mere Tjek på PubMedMcDonough, J. H., Rhodes, K., Procter, N.
BMJ Open, 26.03.2024
Tilføjet 26.03.2024
IntroductionMental health nurses work in potentially unpredictable, stressful and complex environments that can lead to burn-out and high staff turnover. Clinical supervision is a formal and professional agreement between two or more people that aims to strengthen individuals’ competencies and organisational strengths. Effective clinical supervision has been noted as a method of reducing workplace issues within mental health nursing, but there is not currently a synthesis of evidence in this area. The key objective of this scoping review is to identify, map and analyse the available evidence reporting on the impact of clinical supervision on workforce outcomes for mental health nurses. MethodsA scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension method will be conducted exploring clinical supervision for mental health nurses. A search for academic literature from Medline, CINAHL, Embase and PsycINFO will be combined with grey literature sourced through Google to identify potentially relevant studies. Studies identified by the search strategy will be managed using Covidence, and two authors will screen all identified articles. Reference lists of included studies will be handsearched to identify any potentially relevant studies missed by the search strategy. AnalysisA summary tool including predefined categories (such as author, date published, workforce outcome measured) will be used to summarise the included studies in this scoping review. Additionally, a narrative synthesis approach will be used to report the outcomes of included studies and provide further analysis. Ethics and disseminationThis scoping review protocol described research that will use secondary analysis of publicly available information, and therefore, does not require ethics approval. The findings of this research will be disseminated through publication in a peer-reviewed academic journal and relevant conference presentations.
Læs mere Tjek på PubMedAlbert Tell i Puig, Dominique Soldati-Favre
Trends in Parasitology, 26.03.2024
Tilføjet 26.03.2024
Microtubules (MTs) play a vital role as key components of the eukaryotic cytoskeleton. The phylum Apicomplexa comprises eukaryotic unicellular parasitic organisms defined by the presence of an apical complex which consists of specialized secretory organelles and tubulin-based cytoskeletal elements. One apicomplexan parasite, Toxoplasma gondii, is an omnipresent opportunistic pathogen with significant medical and veterinary implications. To ensure successful infection and widespread dissemination, T. gondii heavily relies on the tubulin structures present in the apical complex. Recent advances in high-resolution imaging, coupled with reverse genetics, have offered deeper insights into the composition, functionality, and dynamics of these tubulin-based structures. The apicomplexan tubulins differ from those of their mammalian hosts, endowing them with unique attributes and susceptibility to specific classes of inhibitory compounds.
Læs mere Tjek på PubMedRagnhild Reehorst Lereim, Petra Nytrova, Astrid Guldbrandsen, Eva Kubala Havrdova, Kjell-Morten Myhr, Harald Barsnes, Frode S. Berven
PLoS One Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
by Ragnhild Reehorst Lereim, Petra Nytrova, Astrid Guldbrandsen, Eva Kubala Havrdova, Kjell-Morten Myhr, Harald Barsnes, Frode S. Berven Background Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system leading to demyelination and axonal loss. Relapsing-remitting multiple sclerosis (RRMS) is commonly treated by anti-inflammatory drugs, where one of the most effective drugs to date is the monoclonal antibody natalizumab. Methods The cerebrospinal fluid (CSF) proteome was analyzed in 56 patients with RRMS before and after natalizumab treatment, using label-free mass spectrometry and a subset of the changed proteins were verified by parallel reaction monitoring in a new cohort of 20 patients, confirming the majority of observed changes. Results A total of 287 differentially abundant proteins were detected including (i) the decrease of proteins with roles in immunity, such as immunoglobulin heavy constant mu, chitinase-3-like protein 1 and chitotriosidase, (ii) an increase of proteins involved in metabolism, such as lactate dehydrogenase A and B and malate-dehydrogenase cytoplasmic, and (iii) an increase of proteins associated with the central nervous system, including lactadherin and amyloid precursor protein. Comparison with the CSF-PR database provided evidence that natalizumab counters protein changes commonly observed in RRMS. Furthermore, vitamin-D binding protein and apolipoprotein 1 and 2 were unchanged during treatment with natalizumab, implying that these may be involved in disease activity unaffected by natalizumab. Conclusions Our study revealed that some of the previously suggested biomarkers for MS were affected by the natalizumab treatment while others were not. Proteins not previously suggested as biomarkers were also found affected by the treatment. In sum, the results provide new information on how the natalizumab treatment impacts the CSF proteome of MS patients, and points towards processes affected by the treatment. These findings ought to be explored further to disclose potential novel disease mechanisms and predict treatment responses.
Læs mere Tjek på PubMedGizachew Tadele Tiruneh, Nebreed Fesseha, Dessalew Emaway, Wuleta Betemariam, Tsinuel Girma Nigatu, Hema Magge, Lisa Ruth Hirschhorn
PLoS One Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
by Gizachew Tadele Tiruneh, Nebreed Fesseha, Dessalew Emaway, Wuleta Betemariam, Tsinuel Girma Nigatu, Hema Magge, Lisa Ruth Hirschhorn Background In Ethiopia, neonatal mortality is persistently high. The country has been implementing community-based treatment of possible serious bacterial infection (PSBI) in young infants when referral to a hospital is not feasible since 2012. However, access to and quality of PSBI services remained low and were worsened by COVID-19. From November 2020 to June 2022, we conducted implementation research to mitigate the impact of COVID-19 and improve PSBI management implementation uptake and delivery in two woredas in Ethiopia. Methods In April-May 2021, guided by implementation research frameworks, we conducted formative research to understand the PSBI management implementation challenges, including those due to the COVID-19 pandemic. Through a participatory process engaging stakeholders, we designed adaptive implementation strategies to bridge identified gaps using mechanism mapping to achieve implementation outcomes. Strategies included training and coaching, supportive supervision and mentorship, technical support units, improved supply of essential commodities, and community awareness creation about PSBI and COVID-19. We conducted cross-sectional household surveys in the two woredas before (April 2021) and after the implementation of strategies (June 2022) to measure changes in targeted outcomes. Results We interviewed 4,262 and 4,082 women who gave live birth 2–14 months before data collection and identified 374 and 264 PSBI cases in April 2021 and June 2022, respectively. The prevalence of PSBI significantly decreased (p-value = 0.018) from 8.7% in April 2021 to 6.4% while the mothers’ care-seeking behavior from medical care for their sick newborns increased significantly from 56% to 91% (p-value
Læs mere Tjek på PubMedWei Ma, Yunyun Hou, Mingyu Jin, Pengpeng Jian
PLoS One Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
by Wei Ma, Yunyun Hou, Mingyu Jin, Pengpeng Jian Multi-stage attacks are one of the most critical security threats in the current cyberspace. To accurately identify multi-stage attacks, this paper proposes an anomaly-based multi-stage attack detection method. It constructs a Multi-Stage Profile (MSP) by modeling the stable system’s normal state to detect attack behaviors. Initially, the method employs Doc2Vec to vectorize alert messages generated by the intrusion detection systems (IDS), extracting profound inter-message correlations. Subsequently, Hidden Markov Models (HMM) are employed to model the normal system state, constructing an MSP, with relevant HMM parameters dynamically acquired via clustering algorithms. Finally, the detection of attacks is achieved by determining the anomaly threshold through the generation probability (GP). To evaluate the performance of the proposed method, experiments were conducted using three public datasets and compared with three advanced multi-stage attack detection methods. The experimental results demonstrate that our method achieves an accuracy of over 99% and precision of 100% in multi-stage attack detection. This confirms the effectiveness of our method in adapting to different attack scenarios and ultimately completing attack detection.
Læs mere Tjek på PubMedHana Kim, Jang-Hoon Jo, Hong-Gu Lee, Woncheoul Park, Hak-Kyo Lee, Jong-Eun Park, Donghyun Shin
PLoS One Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
by Hana Kim, Jang-Hoon Jo, Hong-Gu Lee, Woncheoul Park, Hak-Kyo Lee, Jong-Eun Park, Donghyun Shin Climate change increases global temperatures, which is lethal to both livestock and humans. Heat stress is known as one of the various livestock stresses, and dairy cows react sensitively to high-temperature stress. We aimed to better understand the effects of heat stress on the health of dairy cows and observing biological changes. Individual cows were divided into normal (21–22 °C, 50–60% humidity) and high temperature (31–32 °C, 80–95% humidity), respectively, for 7-days. We performed metabolomic and transcriptome analyses of the blood and gut microbiomes of feces. In the high-temperature group, nine metabolites including linoleic acid and fructose were downregulated, and 154 upregulated and 72 downregulated DEGs (Differentially Expressed Genes) were identified, and eighteen microbes including Intestinimonas and Pseudoflavonifractor in genus level were significantly different from normal group. Linoleic acid and fructose have confirmed that associated with various stresses, and functional analysis of DEG and microorganisms showing significant differences confirmed that high-temperature stress is related to the inflammatory response, immune system, cellular energy mechanism, and microbial butyrate production. These biological changes were likely to withstand high-temperature stress. Immune and inflammatory responses are known to be induced by heat stress, which has been identified to maintain homeostasis through modulation at metabolome, transcriptome and microbiome levels. In these findings, heat stress condition can trigger alteration of immune system and cellular energy metabolism, which is shown as reduced metabolites, pathway enrichment and differential microbes. As results of this study did not include direct phenotypic data, we believe that additional validation is required in the future. In conclusion, high-temperature stress contributed to the reduction of metabolites, changes in gene expression patterns and composition of gut microbiota, which are thought to support dairy cows in withstanding high-temperature stress via modulating immune-related genes, and cellular energy metabolism to maintain homeostasis.
Læs mere Tjek på PubMedJu-Bin Kang, Hyun-Kyoung Son, Murad-Ali Shah, Phil-Ok Koh
PLoS One Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
by Ju-Bin Kang, Hyun-Kyoung Son, Murad-Ali Shah, Phil-Ok Koh Stroke is a leading cause of death and long-term disability which can cause oxidative damage and inflammation of the neuronal cells. Retinoic acid is an active metabolite of vitamin A that has various beneficial effects including antioxidant and anti-inflammatory effects. In this study, we investigated whether retinoic acid modulates oxidative stress and inflammatory factors in a stroke animal model. A middle cerebral artery occlusion (MCAO) was performed on adult male rats to induce focal cerebral ischemia. Retinoic acid (5 mg/kg) or vehicle was injected into the peritoneal cavity for four days before MCAO surgery. The neurobehavioral tests were carried out 24 h after MCAO and cerebral cortex tissues were collected. The cortical damage was assessed by hematoxylin-eosin staining and reactive oxygen species assay. In addition, Western blot and immunohistochemical staining were performed to investigate the activation of glial cells and inflammatory cytokines in MCAO animals. Ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) were used as markers of microglial and astrocyte activation, respectively. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were used as representative pro-inflammatory cytokines. Results showed that MCAO damage caused neurobehavioral defects and histopathological changes in the ischemic region and increased oxidative stress. Retinoic acid treatment reduced these changes caused by MCAO damage. We detected increases in Iba-1 and GFAP in MCAO animals treated with vehicle. However, retinoic acid alleviated increases in Iba-1 and GFAP caused by MCAO damage. Moreover, MCAO increased levels of nuclear factor-κB and pro-inflammatory cytokines, including TNF-α and IL-1β. Retinoic acid alleviated the expression of these inflammatory proteins. These findings elucidate that retinoic acid regulates microglia and astrocyte activation and modulates pro-inflammatory cytokines. Therefore, this study suggests that retinoic acid exhibits strong antioxidant and anti-inflammatory properties by reducing oxidative stress, inhibiting neuroglia cell activation, and preventing the increase of pro-inflammatory cytokines in a cerebral ischemia.
Læs mere Tjek på PubMedSaranyoo Prasitwuttisak, Nattapon Chantarapanich, Komsan Apinyauppatham, Kopchai Poomparnich, Samroeng Inglam
PLoS One Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
by Saranyoo Prasitwuttisak, Nattapon Chantarapanich, Komsan Apinyauppatham, Kopchai Poomparnich, Samroeng Inglam This study evaluated the biomechanical performance of narrow-diameter implant (NDI) treatment in atrophic maxillary posterior teeth in aging patients by finite element analysis. The upper left posterior bone segment with first and second premolar teeth missing obtained from a patient’s cone beam computed tomography data was simulated with cortical bone thicknesses of 0.5 and 1.0 mm. Three model groups were analyzed. The Regimen group had NDIs of 3.3 × 10 mm in length with non-splinted crowns. Experimental-1 group had NDIs of 3.0 × 10 mm in length with non-splinted crowns and Experimental-2 group had NDIs of 3.0 × 10 mm in length with splinted crowns. The applied load was 56.9 N in three directions: axial (along the implant axis), oblique at 30° (30° to the bucco-palatal plane compared to the vertical axis of the tooth), and lateral load at 90° (90° in the bucco-palatal plane compared to the vertical axis of the tooth). The results of the von Mises stress on the implant fixture, the elastic strain, and principal value of stress on the crestal marginal bone were analyzed. The axial load direction was comparable in the von Mises stress values in all groups, which indicated it was not necessary to use splinted crowns. The elastic strain values in the axial and oblique directions were within the limits of Frost’s mechanostat theory. The principal value of stress in all groups were under the threshold of the compressive stress and tensile strength of cortical bone. In the oblique and lateral directions, the splinted crown showed better results for both the von Mises stress, elastic strain, and principal value of stress than the non-splinted crown. In conclusion, category 2 NDIs can be used in the upper premolar region of aging patients in the case of insufficient bone for category 3 NDI restorations.
Læs mere Tjek på PubMedBenjamin P. DarwitzChristopher J. GenitoLance R. Thurlow1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA2Division of Oral and Craniofacial Health Sciences, University of North Carolina at Chapel Hill Adams School of Dentistry, Chapel Hill, North Carolina, USA, Anthony R. Richardson
Infection and Immunity, 26.03.2024
Tilføjet 26.03.2024
Journal of Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract In 2011, in Germany, Escherichia coli O104:H4 caused the enterohemorrhagic E. coli (EHEC) outbreak with the highest incidence rate of hemolytic uremic syndrome. This pathogen carries an exceptionally potent combination of EHEC- and enteroaggregative E. coli (EAEC)-specific virulence factors. Here, we identified an E. coli O104:H4 isolate that carried a single nucleotide polymorphism (SNP) in the start codon (ATG > ATA) of rpoS, encoding the alternative sigma factor S. The rpoS ATG > ATA SNP was associated with enhanced EAEC-specific virulence gene expression. Deletion of rpoS in E. coli O104:H4 Δstx2 and typical EAEC resulted in a similar effect. Both rpoS ATG > ATA and ΔrpoS strains exhibited stronger virulence-related phenotypes in comparison to wild type. Using promoter-reporter gene fusions, we demonstrated that wild-type RpoS repressed aggR, encoding the main regulator of EAEC virulence. In summary, our work demonstrates that RpoS acts as a global repressor of E. coli O104:H4 virulence, primarily through an AggR-dependent mechanism.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract Background The role of ribonucleases in tuberculosis (TB) among people with HIV (PWH) is unknown. We explored ribonuclease activity in plasma from PWH with and without TB.Methods Participants were identified from a cohort of treatment-naïve PWH in Ethiopia who had been classified for TB disease (HIV+/TB + or HIV+/TB-). Ribonuclease activity in plasma was investigated by quantification of synthetic spike-in RNAs using sequencing and qPCR, and by a specific ribonuclease activity assay. Quantification of ribonuclease 1, 2, 3, 6, 7 and T2 proteins was performed by ELISA. Ribonuclease activity and protein concentrations were correlated with markers of TB and HIV disease severity and with concentrations of inflammatory mediators.Results Ribonuclease activity was significantly higher in plasma of HIV+/TB + (n = 51) compared to HIV+/TB- (n = 78), causing reduced stability of synthetic spike-in RNAs. concentrations of ribonucleases 2, 3 and T2 were also significantly increased in HIV+/TB + compared to HIV+/TB-. Ribonuclease activity was correlated with HIV viral load, and inversely correlated with CD4 count, mid-upper arm circumference and body mass index. Moreover, ribonuclease activity correlated with concentrations of interleukin-27, kynurenine/tryptophan ratio and procalcitonin.Conclusion PWH with TB disease have elevated plasma ribonuclease activity, which is also associated with HIV severity and systemic inflammation.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 26.03.2024
Tilføjet 26.03.2024
Abstract There is an urgent need for vaccines against Neisseria gonorrhoeae (Ng), the causative agent of gonorrhea. Vaccination with an outer-membrane vesicle (OMV)-based Neisseria meningitidis (Nm) vaccine provides some protection from Ng; however, the mechanisms underlying this cross-protection are unknown. To address this need, we developed multiplexed bead-based assays for the relative quantification of human and mouse IgG and IgA against Ng antigens. The assays were evaluated for analyte independence, dilutional linearity, specificity, sensitivity, intra- and inter-assay variability, and robustness to sample storage conditions. The assay was then used to test samples from mice and humans immunized with an Nm-OMV vaccine.
Læs mere Tjek på PubMedXiao-Jian ZhouJason LickliterMaureen MontrondLaura IshakKeith PietropaoloDayle JamesBruce BelangerArantxa HorgaJanet Hammond1Atea Pharmaceuticals Inc, Boston, Massachusetts, USA2Nucleus Network, Melbourne, Australia, Miguel Angel Martinez
Antimicrobial Agents And Chemotherapy, 26.03.2024
Tilføjet 26.03.2024
Sabrina MühlenAnn Kathrin HerovenBettina ElxnatSilke KahlDietmar H. PieperPetra Dersch1Department of Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany2Institute of Infectiology, University of Münster, Münster, Germany3German Centre for Infection Research (DZIF), partner site HZI, Braunschweig, and associated site University of Münster, Münster, Germany4Department of Molecular Immunology, Ruhr-University Bochum, Bochum, Germany5Microbial Interactions and Processes, Helmholtz Centre for Infection Research, Braunschweig, Germany, Anne-Catrin Uhlemann
Antimicrobial Agents And Chemotherapy, 26.03.2024
Tilføjet 26.03.2024
Jeffrey B. LockeChris M. PillarMariana CastanheiraCecilia G. CarvalhaesDavid AndesJalal A. AramChristina AndrzejewskiKen BartizalAnita F. DasTaylor SandisonGeorge R. ThompsonPeter G. Pappas1Cidara Therapeutics, Inc., San Diego, California, USA2Science and Operations, Microbiologics, Kalamazoo, Michigan, USA3JMI Laboratories, North Liberty, Iowa, USA4Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA5Medical Affairs, Melinta Therapeutics, LLC, Parsippany, New Jersey, USA6Division of Infectious Diseases, Department of Internal Medicine and Department of Medical Microbiology and Immunology, University of California Davis Medical Center, Sacramento, California, USA7Division of Infectious Diseases, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA, Andreas H. Groll
Antimicrobial Agents And Chemotherapy, 26.03.2024
Tilføjet 26.03.2024
Mariam RimaSaoussen OueslatiGarance CotelonElodie CretonRémy A. BonninLaurent DortetBogdan I. IorgaThierry Naas1Team ReSIST, INSERM U1184, School of Medicine Université Paris-Saclay, LabEx LERMIT, Le Kremlin-Bicêtre, France2Bacteriology-Hygiene Unit, Assistance Publique/Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France3French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacterales, Le Kremlin-Bicêtre, France4Université Paris-Saclay, CNRS UPR 2301, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France, Alessandra Carattoli
Antimicrobial Agents And Chemotherapy, 26.03.2024
Tilføjet 26.03.2024
BMC Infectious Diseases, 25.03.2024
Tilføjet 25.03.2024
Abstract Background Pakistan witnessed five waves of COVID-19 infections during the pandemic. Punjab, the largest province of Pakistan, remained the epicentre due to a high infection rate. Administrative data for five waves of the pandemic was analyzed to determine the rate of infections and the significance of pharmacological and non-pharmacological interventions on the severity and duration of infection. Methodology COVID-19 data from March 2020 to May 2023 was obtained from the Provincial Public Health Reference Laboratory (PPHRL), Punjab AIDS Control Program, Lahore. The data included samples from index cases, contacts, and recovered patients. A total of 36,252,48 cases were screened for COVID-19, and 90,923 (2.50%) were detected positive by RT-PCR, accounting for 5.69% of the cases reported positive throughout the country. Results Among the positive cases, 50.86% (n = 46,244) cases were new cases (registered for the first time), 40.41% (n = 36751) were the contact cases traced from the newly identified cases and 8.62% (n = 7842) repeated cases. The positivity rates among index cases were reported to be 2.37%, 2.34%, 4.61%, 2.09%, and 1.19%, respectively, for the five respective COVID-19 pandemic waves. Distribution by gender indicated that 64% of males and 35% of females were infected during the pandemic. The age factor demonstrated the most susceptibility to infection in women aged 19-29 years, whereas most males between the ages of 29-39 had an infection. Susceptibility to COVID-19 infection was observed to be equally likely between males and females; however, clinical outcomes indicated that infections in males were more severe and often resulted in fatalities as compared to those in females. This trend was also reflected in the viral titer as measured by the Ct values, where 40% of males had Ct values < 25 (an indicator of high viral titers) compared to 30% of females with Ct values < 25. Conclusion Overall, our data indicated that infection rates remained stable throughout the pandemic except for 3rd wave, which showed a higher incidence of infection rate of 4%. Additionally, data showed a positive impact of masking, social distancing, and immunization, as indicated by the shorter window of high infection rates.
Læs mere Tjek på PubMedClinical Infectious Diseases, 25.03.2024
Tilføjet 25.03.2024
Abstract Background In 2019, the South African tuberculosis program replaced ethionamide with linezolid as a part of an all-oral 9-month regimen. We evaluated treatment outcomes for patients assigned to regimens including linezolid in 2019 and ethionamide in 2017.Method This retrospective cohort study included patients treated for multi-drug resistant/rifampicin-resistant tuberculosis throughout South Africa between 1 Jan to 31 Dec 2017 and from 1 Jan to 31 Dec 2019. The cohort treated with a 9-month regimen containing ethionamide for four months, was compared with a cohort treated with a 9-month regimen containing linezolid for two months. The regimens were otherwise identical. Inverse probability weighting of propensity scores was used to adjust for potential confounding. A log-binomial regression model was used to estimate adjusted relative risk (aRR) comparing 24-month outcomes between cohorts including treatment success, death, loss to follow up, and treatment failure. Adverse event data were available for the linezolid cohort.Findings 817 patients were included in the cohort receiving ethionamide and 4244 in the cohort receiving linezolid. No evidence for a difference was observed between linezolid and ethionamide regimens for treatment success (aRR = 0·96, 95%CI 0·91-1·01), death (aRR = 1·01, 95%CI 0·87-1·17) or treatment failure (aRR = 0·87, 95%CI 0·44-1·75). Loss to follow up was more common in the linezolid group, although estimates were imprecise (aRR = 1·22, 95%CI 0·99-1·50).Interpretation No significant differences in treatment success and survival were observed with substitution of linezolid for ethionamide as a part of an all-oral 9-month regimen. Linezolid is an acceptable alternative to ethionamide in this shorter regimen for treatment of multi-drug resistant/rifampicin resistant tuberculosis.
Læs mere Tjek på PubMedClinical Infectious Diseases, 25.03.2024
Tilføjet 25.03.2024
Abstract A case of a male with human immunodeficiency virus with plasma genotyping detecting no resistance and a CRF02_AG subtype had a controlled HIV RNA on antiretroviral therapy since 2010. We introduced intramuscular therapy with cabotegravir and rilpivirine. One month later, his HIV RNA was 1500 copies/mL; genotyping found a subtype B with many mutations.
Læs mere Tjek på PubMedClinical Infectious Diseases, 25.03.2024
Tilføjet 25.03.2024
Clinical Infectious Diseases, 25.03.2024
Tilføjet 25.03.2024
Abstract Background A barrier to hepatitis C virus (HCV) cure is conventional testing. The aim of this study was to evaluate the effect of HCV antibody and RNA point-of-care-testing (POCT) on testing rates, linkage to care, treatment and acceptability of testing in three priority settings in Australia.Methods Participants were enrolled in an interventional cohort study at a reception prison, inpatient mental health service (MHS), and inpatient alcohol and other drug (AOD) unit—between October 2020 and December 2021. HCV POCT was performed using SD Bioline HCV antibody fingerstick test and a reflexive Xpert® HCV Viral Load Fingerstick test using capillary blood samples. A retrospective audit of HCV testing and treatment data was performed at each site for the preceding 12-month period to generate a historical control.Results 1,549 participants received a HCV antibody test with 17% (264/1,549) receiving a positive result, of which 21% (55/264) tested HCV RNA positive. Across all settings the rate of testing per year significantly increased between the historical controls and the study intervention period by three-fold (RR:2.57 95% CI: 2.32, 2.85) for HCV antibody testing and four-fold (RR:1.62; 95% CI:1.31, 2.01) for RNA testing. Treatment uptake was higher during the POCT intervention (86%, 47/55; P=0.010) compared to the historical controls (61%, 27/44).Conclusions This study demonstrated across three settings that the use of HCV antibody and RNA POCT increased testing rates, treatment uptake linkage to care. The testing model was highly acceptable for most participants.Clinical Trial Registration ACTRN-12621001578897
Læs mere Tjek på PubMedMartin Strnad, Nobuo Koizumi, Shuichi Nakamura, Marie Vancová, Ryan O.M. Rego
Trends in Parasitology, 24.03.2024
Tilføjet 24.03.2024
Pathogenic spirochetes cause a range of serious human diseases such as Lyme disease (LD), syphilis, leptospirosis, relapsing fever (RF), and periodontal disease. Motility is a critical virulence factor for spirochetes. From the mechanical perspective of the infection, it has been widely believed that flagella are the sole key players governing the migration and dissemination of these pathogens in the host. Here, we highlight the important contribution of spirochetal surface-exposed adhesive molecules and their dynamic interactions with host molecules in the process of infection, specifically in spirochetal swimming and crawling migration. We believe that these recent findings overturn the prevailing view depicting the spirochetal body to be just an inert elastic bag, which does not affect spirochetal cell locomotion.
Læs mere Tjek på PubMedRijk, M. H., Platteel, T. N., van den Berg, T. M. C., Geersing, G.-J., Little, P., Rutten, F. H., van Smeden, M., Venekamp, R. P.
BMJ Open, 24.03.2024
Tilføjet 24.03.2024
ObjectiveTo identify and synthesise relevant existing prognostic factors (PF) and prediction models (PM) for hospitalisation and all-cause mortality within 90 days in primary care patients with acute lower respiratory tract infections (LRTI). DesignSystematic review. MethodsSystematic searches of MEDLINE, Embase and the Cochrane Library were performed. All PF and PM studies on the risk of hospitalisation or all-cause mortality within 90 days in adult primary care LRTI patients were included. The risk of bias was assessed using the Quality in Prognostic Studies tool and Prediction Model Risk Of Bias Assessment Tool tools for PF and PM studies, respectively. The results of included PF and PM studies were descriptively summarised. ResultsOf 2799 unique records identified, 16 were included: 9 PF studies, 6 PM studies and 1 combination of both. The risk of bias was judged high for all studies, mainly due to limitations in the analysis domain. Based on reported multivariable associations in PF studies, increasing age, sex, current smoking, diabetes, a history of stroke, cancer or heart failure, previous hospitalisation, influenza vaccination (negative association), current use of systemic corticosteroids, recent antibiotic use, respiratory rate ≥25/min and diagnosis of pneumonia were identified as most promising candidate predictors. One newly developed PM was externally validated (c statistic 0.74, 95% CI 0.71 to 0.78) whereas the previously hospital-derived CRB-65 was externally validated in primary care in five studies (c statistic ranging from 0.72 (95% CI 0.63 to 0.81) to 0.79 (95% CI 0.65 to 0.92)). None of the PM studies reported measures of model calibration. ConclusionsImplementation of existing models for individualised risk prediction of 90-day hospitalisation or mortality in primary care LRTI patients in everyday practice is hampered by incomplete assessment of model performance. The identified candidate predictors provide useful information for clinicians and warrant consideration when developing or updating PMs using state-of-the-art development and validation techniques. PROSPERO registration numberCRD42022341233.
Læs mere Tjek på PubMedChimoyi, L., Ndini, P., Oladimeji, M., Seatlholo, N., Mawokomatanda, K., Charalambous, S., Setswe, G.
BMJ Open, 24.03.2024
Tilføjet 24.03.2024
ObjectiveTo explore the syndemic interaction between social, environmental, and structural contexts and HIV infection in peri-mining areas in South Africa. DesignMixed qualitative methods consisting of in-depth interviews (IDIs) and focus group discussions (FGDs) exploring the interaction between HIV infection and the social, environmental and structural factors affecting people living in the peri-mining areas of South Africa. Themes were analysed following the syndemic theoretical framework. SettingParticipants were recruited from three mining companies and locations in the peri-mining communities surrounding the mining companies in Limpopo, Mpumalanga, and Northern Cape provinces. ParticipantsInclusion criteria included mineworkers, healthcare workers, female sex workers (FSWs), injection drug users (IDUs), and other community members, ≥18 years, living in the peri-mining area at the time of participation. Three FGDs were conducted (n=30): 13 men and 17 women aged 18–55 years. IDIs were conducted with 45 participants: mineworkers (n=10), healthcare workers (n=11), FSWs (n=15), truck drivers (n=4) and IDUs (n=5). ResultsThe findings from this study indicate that a syndemic of four socio-behavioural factors is associated with HIV acquisition in peri-mining areas. These are migrancy, accessibility to alcohol and substance use, commercial and transactional sex, and uptake of HIV prevention services. ConclusionsOur findings have implications for HIV prevention programmes in mining companies, which rely on male condom usage promotion. More emphasis on better education about HIV prevalence, transmission and up-to-date prevention alternatives, such as pre-exposure prophylaxis for mineworkers is recommended. Furthermore, collaboration with community-based organisations is recommended to wholly address the syndemic factors influencing HIV transmission in peri-mining communities.
Læs mere Tjek på PubMedBurke, A., Davoren, M. P., Arensman, E., Harrington, J. M.
BMJ Open, 24.03.2024
Tilføjet 24.03.2024
ObjectivePsychoeducation is increasingly recognised for its value in facilitating adaption to a chronic disease diagnosis. This study aimed to synthesise available literature on the psychoeducation interventions available to adults living with chronic communicable disease. MethodsPubMed, CINAHL, Embase, SocINDEX, PsycINFO and PsycArticles were systematically searched up to May 2023. Peer-reviewed studies, published in English, investigating the impact of psychoeducational interventions on adults living with chronic communicable disease were included, across a range of outcome measures. Narrative synthesis was performed. The Effective Public Health Practice Project tool and Critical Appraisal Skills Programme tool were used to assess risk of bias. ResultsIn total, 22 studies were included in the review. The majority (n=16) of study populations focused on people living with HIV, followed by hepatitis C (n=5) and genital herpes (n=1). Interventions were delivered online (n=2), via telephone (n=1) and in-person (n=19). The majority of interventions were delivered in group sessions (n=16) and studies emphasised the value of group cohesion for social support, encouraging participants to share their own knowledge in addition to standard didactic presentations. Four studies facilitated peer-led delivery of the psychoeducation. Studies aiming to improve psychological well-being were beneficial in reducing depressive symptoms and/or emotional distress or showed improvement in the participant group overall. There was some evidence to suggest psychoeducation can improve readiness to attend treatment and medication adherence. ConclusionThe findings of this review highlight potential benefits of psychoeducation but indicate more robust clinical trials will be required to examine their effectiveness and elucidate the mechanisms by which they best operate. Future interventions incorporating a broader focus on resilience enhancement and coping skills specific to stigmatisation could more comprehensively serve the needs of adults living with chronic communicable disease, particularly with HIV. The role of peer support in group psychoeducation merits further exploration. PROSPERO registration numberCRD42021243058.
Læs mere Tjek på PubMedLiu, W., Wang, J., Wang, M., Ding, X., Wang, M., Liu, M.
BMJ Open, 24.03.2024
Tilføjet 24.03.2024
ObjectiveThis study aimed to systematically investigate the relationship between immune-inflammatory indexes with lower urinary tract symptoms (LUTSs). DesignCross-sectional study. SettingNational Health and Nutrition Examination Survey (NHANES) (2005–2008). ParticipantsA total of 2709 men with complete information for immune-inflammatory indexes and LUTSs were included from NHANES 2005–2008. Outcomes and analysesAutomated haematology analysing devices are used to measure blood cell counts, and LUTSs were presented by standard questionnaires. Non-linear and logistic regression analyses were used to estimate their association after adjustment for confounders. ResultsMultivariate logistic regression showed that pan-immune-inflammation value (OR (95% CI)=1.60 (1.14 to 2.23)), systemic inflammation response index (SIRI) (OR (95% CI)=1.82 (1.21 to 2.73)), neutrophil/lymphocyte ratio (NLR) (OR (95% CI)=1.81 (1.31 to 2.49)), derived NLR (dNLR) (OR (95% CI)=1.91 (1.35 to 2.70)) and C reactive protein (CRP) (OR (95% CI)=1.71 (1.05 to 2.79)) was positively associated with LUTS. Additionally, composite immune-inflammation markers exhibited a stronger association with LUTS than any single index, with the ORs for high SIRI+high CRP, high NLR+high CRP and high dNLR+high CRP being 2.26, 2.44 and 2.16, respectively (all p
Læs mere Tjek på PubMedZhang, M., Htun, N. S. N., Islam, S., Sen, A., Islam, A., Neogi, A. K., Tripura, R., Dysoley, L., Perrone, C., Chew, R., Batty, E. M., Thongpiam, W., Wongsantichon, J., Menggred, C., Zaman, S. I., Waithira, N., Blacksell, S., Liverani, M., Lee, S., Maude, R. J., Day, N. P. J., Lubell, Y., Peto, T. J.
BMJ Open, 24.03.2024
Tilføjet 24.03.2024
IntroductionIn low-income and middle-income countries in Southeast Asia, the burden of diseases among rural population remains poorly understood, posing a challenge for effective healthcare prioritisation and resource allocation. Addressing this knowledge gap, the South and Southeast Asia Community-based Trials Network (SEACTN) will undertake a survey that aims to determine the prevalence of a wide range of non-communicable and communicable diseases, as one of the key initiatives of its first project—the Rural Febrile Illness project (RFI). This survey, alongside other RFI studies that explore fever aetiology, leading causes of mortality, and establishing village and health facility maps and profiles, will provide an updated epidemiological background of the rural areas where the network is operational. Methods and analysisDuring 2022–2023, a cross-sectional household survey will be conducted across three SEACTN sites in Bangladesh, Cambodia and Thailand. Using a two-stage cluster-sampling approach, we will employ a probability-proportional-to-size sample method for village, and a simple random sample for household, selection, enrolling all members from the selected households. Approximately 1500 participants will be enrolled per country. Participants will undergo questionnaire interview, physical examination and haemoglobin point-of-care testing. Blood samples will be collected and sent to central laboratories to test for chronic and acute infections, and biomarkers associated with cardiovascular disease, and diabetes. Prevalences will be presented as an overall estimate by country, and stratified and compared across sites and participants’ sociodemographic characteristics. Associations between disease status, risk factors and other characteristics will be explored. Ethics and disseminationThis study protocol has been approved by the Oxford Tropical Research Ethics Committee, National Research Ethics Committee of Bangladesh Medical Research Council, the Cambodian National Ethics Committee for Health Research, the Chiang Rai Provincial Public Health Research Ethical Committee. The results will be disseminated via the local health authorities and partners, peer-reviewed journals and conference presentations. Trial registration numberNCT05389540.
Læs mere Tjek på PubMedBMC Infectious Diseases, 24.03.2024
Tilføjet 24.03.2024
Abstract Background Men who have sex with men (MSM) are a key population group disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide. In Rwanda, the HIV epidemic remains a significant public health concern, and understanding the burden of HIV and hepatitis B and C coinfections among MSM is crucial for designing effective prevention and control strategies. This study aims to determine the prevalence of HIV, hepatitis B, and hepatitis C infections among MSM in Rwanda and identify correlates associated with HIV infection within this population. Methods We used respondent-driven sampling (RDS) to recruit participants between November and December 2021. A face-to-face, structured questionnaire was administered. Testing for HIV infection followed the national algorithm using two rapid tests: Alere Combo and STAT PAK as the first and second screening tests, respectively. Hepatitis B surface antigen (HBsAg) and anti-HCV tests were performed. All statistics were adjusted for RDS design, and a multivariable logistic regression model was constructed to identify factors associated with HIV infection. Results The prevalence of HIV among MSM was 6·9% (95% CI: 5·5–8·6), and among HIV-positive MSM, 12·9% (95% CI: 5·5–27·3) were recently infected. The prevalence of hepatitis B and C was 4·2% (95% CI: 3·0–5·7) and 0·7% (95% CI: 0·4–1·2), respectively. HIV and hepatitis B virus coinfection was 0·5% (95% CI: 0·2–1·1), whereas HIV and hepatitis C coinfection was 0·1% (95% CI: 0·0–0·5), and no coinfection for all three viruses was observed. MSM groups with an increased risk of HIV infection included those who ever suffered violence or abuse because of having sex with other men (AOR: 3·42; 95% CI: 1·87–6·25), those who refused to answer the question asking about ‘ever been paid money, goods, or services for sex’ (AOR: 10·4; 95% CI: 3·30–32·84), and those not consistently using condoms (AOR: 3·15; 95% CI: 1·31–7·60). Conclusion The findings suggest more targeted prevention and treatment approaches and underscore the importance of addressing structural and behavioral factors contributing to HIV vulnerability, setting interventions to reduce violence and abuse against MSM, promoting safe and consensual sexual practices, and expanding access to HIV prevention tools such as condoms and preexposure prophylaxis (PrEP).
Læs mere Tjek på PubMedBMC Infectious Diseases, 24.03.2024
Tilføjet 24.03.2024
Abstract Background This study explores regional variations in COVID-19 hospitalization rates, in-hospital mortality, and acute kidney injury (AKI) in England. We investigated the influence of population demographic characteristics, viral strain changes, and therapeutic advances on clinical outcomes. Methods Using hospital episode statistics, we conducted a retrospective cohort study with 749,844 admissions in 337,029 adult patients with laboratory-confirmed COVID-19 infection (March 1, 2020, to March 31, 2021). Multivariable logistic regression identified factors predicting AKI and mortality in COVID-19 hospitalized patients. Results London had the highest number of COVID-19 admissions (131,338, 18%), followed by the North-west region (122,683, 16%). The North-west had the highest population incidence of COVID-19 hospital admissions (21,167 per million population, pmp), while the South-west had the lowest (9,292 admissions pmp). Patients in London were relatively younger (67.0 ± 17.7 years) than those in the East of England (72.2 ± 16.8 years). The shortest length of stay was in the North-east (12.2 ± 14.9 days), while the longest was in the North-west (15.2 ± 17.9 days). All eight regions had higher odds of death compared to London, ranging from OR 1.04 (95% CI 1.00, 1.07) in the South-west to OR 1.24 (95% CI 1.21, 1.28) in the North-west. Older age, Asian ethnicity, emergency admission, transfers from other hospitals, AKI presence, ITU admission, social deprivation, and comorbidity were associated with higher odds of death. AKI incidence was 30.3%, and all regions had lower odds of developing AKI compared to London. Increasing age, mixed and black ethnicity, emergency admission, transfers from other providers, ITU care, and different levels of comorbidity were associated with higher odds of developing AKI. Conclusions London exhibited higher hospital admission numbers and AKI incidence, but lower odds of death compared to other regions in England. Trial registration Registered on National Library of Medicine website (www.clinicaltrials.gov) with registration number NCT04579562 on 8/10/2020.
Læs mere Tjek på PubMedBMC Infectious Diseases, 24.03.2024
Tilføjet 24.03.2024
Abstract Background Aspergillus spp liver abscess is a relatively rare entity and thus far no systematic review has been performed examining patients’ demographics, clinical manifestations, diagnosis, management, and outcome. Methods We performed a systematic review of the literature using MEDLINE and LILACS databases. We searched for articles published in the period from January 1990 to December 24, 2022, to identify patients who developed liver abscesses due to Aspergillus spp. Results Our search yielded 21 patients all of whom had invasive aspergillosis confirmed on liver biopsy. Of these patients 81% were adults, and 60% were males. The majority (86%) of patients were immunocompromised and 95% had symptomatic disease at the time of diagnosis. The most common symptoms were fever (79%), abdominal pain (47%), and constitutional symptoms (weight loss, chills, night sweats, fatigue) (38%). Liver enzymes were elevated in 50%, serum galactomannan was positive in 57%, and fungal blood cultures were positive in only 11%. Co-infection with other pathogens preceded development of apsergillosis in one-third of patients, and the majority of the abscesses (43%) were cryptogenic. In the remaining patients with known source, 28% of patients developed liver abscess through dissemination from the lungs, 19% through the portal vein system, and in 10% liver abscess developed through contiguous spread. The most common imaging modality was abdominal computerized tomography done in 86% of patients. Solitary abscess was present in 52% of patients while 48% had multiple abscesses. Inadequate initial empiric therapy was prescribed in 60% of patients and in 44% of patients definite treatment included combination therapy with two or more antifungal agents. Percutaneous drainage of the abscesses was done in 40% of patients, while 20% required liver resection for the treatment of the abscess. Overall mortality was very high at 38%. Conclusion Further studies are urgently needed for a better understanding of pathophysiology of liver aspergillosis and for developement of newer blood markers in order to expedite diagnosis and decrease mortality.
Læs mere Tjek på PubMedJinmei Chen, Leer Shen, Qingxin Guo, Siyuan Ma, Yi Zhang, Jie Chen, Lihong Qu, Soon Seng Ng, Xiaohua Chen
Journal of Medical Virology, 23.03.2024
Tilføjet 23.03.2024