Volume 13, Issue 1, December 2024 .

by Karen-Helene Støverud, David Bouget, André Pedersen, Håkon Olav Leira, Tore Amundsen, Thomas Langø, Erlend Fagertun Hofstad To improve the prognosis of patients suffering from pulmonary diseases, such as lung cancer, early diagnosis and treatment are crucial. The analysis of CT images is invaluable for diagnosis, whereas high quality segmentation of the airway tree are required for intervention planning and live guidance during bronchoscopy. Recently, the Multi-domain Airway Tree Modeling (ATM’22) challenge released a large dataset, both enabling training of deep-learning based models and bringing substantial improvement of the state-of-the-art for the airway segmentation task. The ATM’22 dataset includes a large group of COVID’19 patients and a range of other lung diseases, however, relatively few patients with severe pathologies affecting the airway tree anatomy was found. In this study, we introduce a new public benchmark dataset (AeroPath), consisting of 27 CT images from patients with pathologies ranging from emphysema to large tumors, with corresponding trachea and bronchi annotations. Second, we present a multiscale fusion design for automatic airway segmentation. Models were trained on the ATM’22 dataset, tested on the AeroPath dataset, and further evaluated against competitive open-source methods. The same performance metrics as used in the ATM’22 challenge were used to benchmark the different considered approaches. Lastly, an open web application is developed, to easily test the proposed model on new data. The results demonstrated that our proposed architecture predicted topologically correct segmentations for all the patients included in the AeroPath dataset. The proposed method is robust and able to handle various anomalies, down to at least the fifth airway generation. In addition, the AeroPath dataset, featuring patients with challenging pathologies, will contribute to development of new state-of-the-art methods. The AeroPath dataset and the web application are made openly available.

by Yuanying Pang, Ankita Singh, Shayok Chakraborty, Neil Charness, Walter R. Boot, Zhe He Background and objectives This study aims to develop a machine learning-based approach to predict adherence to gamified cognitive training using a variety of baseline measures (demographic, attitudinal, and cognitive abilities) as well as game performance data. We aimed to: (1) identify the cognitive games with the strongest adherence prediction and their key performance indicators; (2) compare baseline characteristics and game performance indicators for adherence prediction, and (3) test ensemble models that use baseline characteristics and game performance data to predict adherence over ten weeks. Research design and method Using machine learning algorithms including logistic regression, ridge regression, support vector machines, classification trees, and random forests, we predicted adherence from weeks 3 to 12. Predictors included game performance metrics in the first two weeks and baseline measures. These models’ robustness and generalizability were tested through five-fold cross-validation. Results The findings indicated that game performance measures were superior to baseline characteristics in predicting adherence. Notably, the games “Supply Run,” “Ante Up,” and “Sentry Duty” emerged as significant adherence predictors. Key performance indicators included the highest level achieved, total game sessions played, and overall gameplay proportion. A notable finding was the negative correlation between initial high achievement levels and sustained adherence, suggesting that maintaining a balanced difficulty level is crucial for long-term engagement. Conversely, a positive correlation between the number of sessions played and adherence highlighted the importance of early active involvement. Discussion and implications The insights from this research inform just-in-time strategies to promote adherence to cognitive training programs, catering to the needs and abilities of the aging population. It also underscores the potential of tailored, gamified interventions to foster long-term adherence to cognitive training. …

by Taher Mohammadizad, Kamran Taherpour, Hossein Ali Ghasemi, Hassan Shirzadi, Fatemeh Tavakolinasab, Mohammad Hassan Nazaran Organic sources of trace minerals (TM) in broiler diets are more bioavailable and stable than inorganic sources, making them particularly beneficial during challenging periods such as heat stress (HS) conditions. A 42-d study investigated the effects of using advanced chelate technology-based TM (ACTM) or adding varying amounts of ACTM to broiler diets during HS conditions. The study involved 672 male broiler chickens in 7 treatment groups, including a thermoneutral control (TNC) group and six HS treatments. There were 8 replicate pens per treatment and 12 birds per replicate. The six HS treatments included birds exposed to a cyclic HS environment (34°C) for 8 h and were as follows: HSC, which consisted of the same basal diet with the recommended ITM levels; ACTM50 and ACTM100, which replaced the basal diet with 50% and 100% ACTM instead of ITM; ITM+ACTM12.5 and ITM+ACTM25, which involved adding extra ACTM to the ITM basal diet at 12.5% and 25%, respectively; and ITM125, which used 125% of the recommended levels of ITM in the basal diet. Compared with the HSC treatment, the TNC, ACTM100, and ITM+ACTM25 treatments resulted in increased (P < 0.05) body weight; tibia weight; tibia ash, phosphorus, iron, and manganese contents; secondary antibody titers; and serum TAC and SOD values but decreased (P < 0.05) serum MDA concentrations and the expression levels of the hepatic genes IL-1β, IL-6, and INF-γ. The TNC and ACTM100 groups also showed greater (P < 0.05) feed efficiency, tibia length, tibia zinc content, and hepatic SOD1 expression but exhibited reduced (P < 0.05) hepatic NF-kB expression. Significant increases (P < 0.05) in primary anti-NDV titers, serum GPx1 activity, and Nrf2 and GPx1 gene expression levels were also detected in the ACTM100, ITM+ACTM12.5, and ITM+ACTM25 groups. In conclusion, the findings suggest that replacing ITM with ACTM or adding ACTM to ITM diets, especially at a 25% higher dose, can effectively protect broilers from heat stress by promoting growth, reducing inflammation, and increasing the expression of antioxidant proteins.

by Zeynep Clulow, David Reiner Distrust in science has been linked to scepticism over vaccines and climate change. Using data from nationally representative surveys administered in eight key countries for global efforts to mitigate climate change and COVID-19 (Australia, Brazil, China, India, Japan, South Africa, the UK and US), we find that distrust in scientists was an important predictor variable for most sceptics, who were sceptical of one issue but not both, in February 2021, when most countries had experienced their first wave of the pandemic. However, the association was significantly weaker among the segment of hardcore sceptics who were both climate sceptics and antivaxxers. We demonstrate that these individuals tended to possess many of the typical sceptic characteristics such as high distrust in social institutions and rightward political orientation, which are (collectively) suggestive of an underlying sceptic mindset rather than a specific distrust of scientists. Our results suggest that different types of sceptics necessitate different strategies to dispel scepticism.

by Barun Kumar Singh, Shiva Raj Mishra, Resham B. Khatri Background Understanding the clustering of two or more risk factors of non-communicable disease, such as smoking, overweight/obesity, and hypertension, among women of reproductive age could facilitate the design and implementation of strategies for prevention and control measures. This study examined the factors associated with smoking, overweight/obesity, and hypertension among Nepalese women of reproductive age (15–49 years). Methods This study used the Nepal Demographic and Health Surveys (NDHS) 2016 (6,079 women for smoking and overweight/obesity, 6076 for hypertension) and 2022 (6,957 women for overweight/obesity and smoking status and 3,749 women for hypertension) for comparison of trends of NCD risk factors among women aged 15–49 years. Additionally, for each participant, risk factors score (range of 0 to 3) was created by summing individual risk factors. We assessed the determinants of risk factor clustering using multivariable Poisson regression models with robust sandwich variance estimator to calculate adjusted prevalence ratios using NDHS 2022. Results The national prevalence of overweight/obesity increased from 22.2% in 2016 to 29.2% in 2022 among women of reproductive age. In 2022, the prevalence for smoking, overweight/obesity, and hypertension were 3.8%, 29.2%, and 9.6%, respectively. More than one in four women (28.7%) had one NCD risk factor, while 6.5% had two such risk factors. Higher aged women (40–49 years) were more likely to have multiple NCD risk factors than those aged 15–29 years (APR: 3.19; 95% CI: 2.68–3.80). Those in the richest wealth quintile (APR: 1.52; 95% CI: 1.24–1.85), as well as married (APR: 3.02; 95% CI: 2.43–3.76) and widowed/divorced (APR: 2.85; 95% CI: 2.14–3.80) were more likely to have multiple NCD risk factors. Women from Koshi province (APR: 1.74; 95% CI: 1.41–2.15) had more NCD risk factors than those from the Sudurpaschim province. Working women also had a higher prevalence of NCD risk factors compared to non-working women (APR: 1.23; 95% CI: 1.06–1.43). Additionally, Hill Janajatis (APR: 1.44; 95% CI: 1.21–1.72) and Dalits (APR: 1.42; 95% CI: 1.15–1.75) women were more likely to have NCD risk factors compared to women of Brahmin hill origin. Conclusions Clustering of two or more NCD risk factors was higher among women aged ≥30 years, those who are currently married or widowed/divorced/separated, working women, and individuals from the wealthiest socioeconomic groups. A higher burden of risk factors underscores the importance of targeted public health interventions, particularly among women from advantaged socio-economic groups, those of affluent regions, and in the workplace. …

by Rebecca M. Cantu, Sara C. Sanders, Grace A. Turner, Jessica N. Snowden, Ashton Ingold, Susanna Hartzell, Suzanne House, Dana Frederick, Uday K. Chalwadi, Eric R. Siegel, Joshua L. Kennedy Purpose To identify characteristics of SARS-CoV-2 infection that are associated with hospitalization in children initially evaluated in a Pediatric Emergency Department (ED). Methods We identified cases of SARS-CoV-2 positive patients seen in the Arkansas Children’s Hospital (ACH) ED or hospitalized between May 27, 2020, and April 28, 2022, using ICD-10 codes within the Pediatric Hospital Information System (PHIS) Database. We compared infection waves for differences in patient characteristics and used logistic regressions to examine which features led to a higher chance of hospitalization. Findings We included 681 pre-Delta cases, 673 Delta cases, and 970 Omicron cases. Almost 17% of patients were admitted to the hospital. Compared to Omicron-infected children, pre-Delta and Delta-infected children were twice as likely hospitalized (OR = 2.2 and 2.0, respectively; p3 times as likely to be hospitalized than children ages 5–14 years regardless of wave (OR = 3.42; 95%CI = 2.36–4.94). Rural children were almost three times as likely than urban children to be hospitalized across all waves (OR = 2.73; 95%CI = 1.97–3.78). Finally, those with a complex condition had nearly a 15-fold increase in odds of admission (OR = 14.6; 95%CI = 10.6–20.0). Conclusions Children diagnosed during the pre-Delta or Delta waves were more likely to be hospitalized than those diagnosed during the Omicron wave. Younger and rural patients were more likely to be hospitalized regardless of the wave. We suspect lower vaccination rates and larger distances from medical care influenced higher hospitalization rates. …

Abstract Background Dissemination and outcome reporting biases are a significant problem in clinical research, with far-reaching implications for both scientific understanding and clinical decision-making. This study investigates the prevalence of dissemination- and outcome reporting biases in registered interventional malaria research. Methods All malaria interventional trials registered on ClinicalTrials.gov from 2010 to 2020 were identified. Subsequently, publications that matched the registration were searched. The primary outcome measures were the percentage of registered studies that resulted in subsequent publication of study results, the concordance between registered outcomes, and reported outcomes. Secondary outcomes were compliance with WHO standards for timely publication (issued in 2017) of summary study results in the respective trial registry (within 12 months of study completion) or peer-reviewed publication (within 24 months of study completion) was evaluated. Results A total of 579 trials were identified on ClinicalTrials.gov, of which 544 met the inclusion criteria. Notably, almost 36.6% of these trials (199/544) were registered retrospectively, with 129 (23.7%) registered after the first patient enrolment and 70 (12.9%) following study completion. Publications were identified for 351 out of 544 registered trials (64.5%), involving 1,526,081 study participants. Conversely, publications were not found for 193 of the 544 registrations (35.5%), which aimed to enrol 417,922 study participants. Among these 544 registrations, 444 (81.6%) did not meet the WHO standard to post summary results within 12 months of primary study completion (the last visit of the last subject for collection of data on the primary outcome), while 386 out of 544 registrations (71.0%) failed to publish their results in a peer-reviewed journal within 24 months of primary study completion. Discrepancies were noted in the reported primary outcomes compared to the registered primary outcomes in 47.6% (222/466) of the published trials, and an even higher discordance rate of 73.2% (341/466 publications) for secondary outcomes. Conclusions Non-dissemination remains a significant issue in interventional malaria research, with most trials failing to meet WHO standards for timely dissemination of summary results and peer-reviewed journal publications. Additionally, outcome reporting bias is highly prevalent across malaria publications. To address these challenges, it is crucial to implement strategies that enhance the timely reporting of research findings and reduce both non-dissemination and outcome reporting bias. …

Abstract Background Malaria is a major disease burden in Ethiopia. Migration can influence malaria transmission dynamics, with individuals relocating from malaria-free highland regions to malarious lowlands potentially facing elevated risks of contracting malaria. Migrants may find it difficult to protect themselves against malaria and have limited access to diagnosis or treatment. Settlers in gold mining sites are one type of migrant and are often neglected in malaria research yet may have particularly high malaria risk. This study was a malaria prevalence survey among settlers in a new gold mining settlement in the highly malarious Gambella Region, Ethiopia. Methods n = 590 people were surveyed for demographic information and their knowledge and practices of malaria. Participants were tested for malaria using rapid diagnostic tests and microscopy. Using logistic regressions, the influence of demographic characteristics on malaria infections and bed net access were analysed. A sub-sample of participants was interviewed to comprehend settlement living conditions and healthcare accessibility. Results The overall prevalence of Plasmodium falciparum was 37.5% (CI 32.4–42.3%). Young children were most likely to have malaria, with individuals aged 15–24 having 67% lower odds (aOR: 0.33; CI 0.13–0.86) of infection compared to those aged 1–4 years old. Meanwhile, those age 25-plus had 75% decreased odds of malaria infection (aOR 0.25; CI 0.10–0.65). Individuals with bed nets had ~ 50% decreased odds of testing positive for falciparum malaria than those reporting having no bed net (aOR: 0.47; CI 0.22–0.97). Individuals who relocated from low elevation with high malaria test positivity rate areas were more prone to testing positive for malaria, as were those residing in densely populated households with multiple malaria cases. Conversely, individuals from higher elevations with low malaria test positivity rates, and those living in households with 5–10 occupants and 

Abstract Background Compared to intensive care unit patients with SARS-CoV-2 negative acute respiratory tract infections, patients with SARS-CoV-2 are supposed to develop more frequently and more severely neurologic sequelae. Delirium and subsequent neurocognitive deficits (NCD) have implications for patients’ morbidity and mortality. However, the extent of brain injury during acute COVID-19 and subsequent NCD still remain largely unexplored. Body-fluid biomarkers may offer valuable insights into the quantification of acute delirium, brain injury and may help to predict subsequent NCD following COVID-19. Methods In a multicenter, observational case-control study, conducted across four German University Hospitals, hospitalized adult and pediatric patients with an acute COVID-19 and SARS-CoV-2 negative controls presenting with acute respiratory tract infections were included. Study procedures comprised the assessment of pre-existing neurocognitive function, daily screening for delirium, neurological examination and blood sampling. Fourteen biomarkers indicative of neuroaxonal, glial, neurovascular injury and inflammation were analyzed. Neurocognitive functions were re-evaluated after three months. Results We enrolled 118 participants (90 adults, 28 children). The incidence of delirium [85 out of 90 patients (94.4%) were assessable for delirium) was comparable between patients with COVID-19 [16 out of 61 patients (26.2%)] and SARS-CoV-2 negative controls [8 out of 24 patients (33.3%); p > 0.05] across adults and children. No differences in outcomes as measured by the modified Rankin Scale, the Short-Blessed Test, the Informant Questionnaire on Cognitive Decline in the Elderly, and the pediatrics cerebral performance category scale were observed after three months. Levels of body-fluid biomarkers were generally elevated in both adult and pediatric cohorts, without significant differences between SARS-CoV-2 negative controls and COVID-19. In COVID-19 patients experiencing delirium, levels of GFAP and MMP-9 were significantly higher compared to those without delirium. Conclusions Delirium and subsequent NCD are not more frequent in COVID-19 as compared to SARS-CoV-2 negative patients with acute respiratory tract infections. Consistently, biomarker levels of brain injury indicated no differences between COVID-19 cases and SARS-CoV-2 negative controls. Our data suggest that delirium in COVID-19 does not distinctly trigger substantial and persistent subsequent NCD compared to patients with other acute respiratory tract infections. Trial registration ClinicalTrials.gov: NCT04359914; date of registration 24-APR 2020. …

Abstract Purpose This study aimed to present an evidence-based conclusion through a systematic meta-analysis to distinguish clinical signs and symptoms associated with the presence of group A beta-hemolytic streptococcus, as confirmed by throat culture or rapid test, from those in cases without culture confirmation. Methods The study protocol has been published in PROSPERO (CRD42023450854). Studies published between January 1, 2013 and August 15, 2023 were scanned in seven databases. The methodological quality of the articles was assessed using The Joanna Briggs Institution (JBI) Cross-Sectional Studies and Cohort Studies checklist. Effect size calculations were made using fixed effects and random effects models. Results A total of 22 articles were included in the systematic review, with 14 included in the meta-analysis. The prevalence of streptococcal pharyngitis in these studies ranged from 7.3 to 44.1%. According to the meta-analysis results, a significant association was observed between GAS test positivity and the presence of tonsillar exudate, palatal petechiae, tonsillar hypertrophy, dysphagia, fever, and cervical lymphadenopathy (p  0.05). Conclusion The findings of the meta-analysis suggest that, in addition to the Centor criteria, palatal petechiae, dysphagia, and tonsillar hypertrophy are noteworthy indicators of GAS infection. Contrary to previous studies, our meta-analysis indicates that symptoms such as headache, sore throat, cough, absence of cough, hoarseness, scarlatiniform rash, tonsillar erythema, vomiting, rhinorrhea, and abdominal pain may not be associated with streptococcal infection. Further research is needed to elucidate these findings. …

Abstract Purpose Opisthorchis felineus is a trematode causing a foodborne infection transmitted by raw freshwater fish belonging to Cyprinidae family. Human outbreaks in Italy dated back to 2003–2011 and involved lakes of Central Italy. The aim of this study is to report epidemiological and clinical characteristics of the human opisthorchiasis outbreak occurred in Central Italy in 2022 comparing it with previous events. Methods We report cases diagnosed from June to December 2022 in Perugia hospital thanks to serological and molecular tests and direct examination of feces. Results Sixty-seven individuals were traced back by epidemiological investigation. Forty-seven received a diagnosis of opisthorchiasis, of which 45 were confirmed cases and two were considered as probable cases. These 47 individuals attended a Trasimeno lakeshore restaurant in May 2022. All but 20 presented symptoms, mostly fever. Sixteen (15 confirmed and 1 probable) cases required hospitalization. Feces examination revealed Opisthorchis spp. eggs in 35/45 (78%) confirmed cases. Thirty individuals underwent to serology and molecular stool test: 5 (16.7%) results positive to the former, 1 (3.3%) to the latter while 4 (13.3%) to both. Laboratory tests, available in 28 patients, showed eosinophilia in 82.1%, increase of alanine aminotransferase, gamma-glutamyl transferase and alkaline phosphatase in 64.3%, 75% and 67.9%, respectively. Because of pharmacy shortage of praziquantel, 22 patients were treated with albendazole, of which 13 failed clearing the parasite. Conclusion Opisthorchiasis still represents a challenging diagnosis, in particular for asymptomatic patients. Albendazole may lead to treatment failure. Control measures in known endemic areas should be implemented. Trial registration number 27,498/23/ON, approved by Ethical Committee of Umbrian Region in 09.13.2023. …

Abstract Introduction Dalbavancin is an antibiotic characterized by an extended half-life and efficacy against methicillin-resistant Staphylococci. Currently, there are only narrative reviews summarizing the evidence about the use of dalbavancin for infective endocarditis (IE), many of which are focused primarily on its use as consolidation therapy. For this reason, we conducted a systematic review to describe the clinical efficacy and the safety of dalbavancin in IE treatment. Methods We searched for available evidence using the MEDLINE (PubMed), Embase, Scopus, Cochrane Library and Web of Science libraries, with no restrictions regarding the publication year. The risk of bias was performed using the Cochrane ROBINS-I tool for the comparative studies and the Newcastle-Ottawa Scale for descriptive studies. Results Nine studies were included. All of them were observational. Native valve endocarditis was the most common kind of IE found in the studies’ populations (128/263, 48.7%), followed by prosthetic valve endocarditis, and cardiovascular implantable electronic device-related endocarditis. Coagulase-negative Staphylococci were the most common pathogens isolated (83/269, 30.1%), followed by S. aureus, Enterococci spp and Streptococci spp. Five out of nine studies documented a clinical failure rate of less than 10%. Dalbavancin showed a favourable safety profile. Dalbavancin appears to be a promising option for the consolidation therapy of IE. However, further studies comparing dalbavancin with standard of care are needed. PROSPERO registration number CRD42023430032. …

Abstract Purpose This study aimed to conduct a comprehensive molecular epidemiology study of major HIV-1 subtypes in developed Eastern China (Zhejiang Province). Methods Plasma samples and epidemiological information were collected from 4180 newly diagnosed HIV-1 positive patients in Zhejiang Province in 2021. Pol sequences were obtained to determine the subtypes via multiple analytical tools. HIV-1 molecular networks were constructed on the basis of genetic distances to analyze transmission patterns among major subtypes. Furthermore, the birth-death skyline (BDSKY) model was utilized to estimate the transmission risks associated with large clusters (LCs). Results In 4180 patients, 3699 (88.49%) pol sequences were successfully obtained and classified into four subtype groups. In the networks under an optimal genetic distance of 0.01 substitutions/site, the majority of links (74.52%, 1383/1856) involved individuals within the same city, highlighting the predominant role of local transmission in driving the HIV-1 epidemic. In the CRF07_BC, CRF01_AE, and others/URFs networks, men who have sex with men (MSM) were the primary sexual transmission population, with the younger MSM group (

Abstract Background Respiratory syncytial virus (RSV) is a common cause for severe lower respiratory tract infections (LRTI) in children 

Abstract Background Lyme borreliosis is one of the most prevalent tick-borne diseases in Europe. Studies on seroprevalence of Borrelia burgdorferi IgG antibodies in children are rare. The aim of this study was to determine the seroprevalence of B. burgdorferi IgG antibodies in children and adolescents residing in North-Western Switzerland and neighbouring countries. Methods Prospective cross-sectional observational single-centre study using left-over plasma of asymptomatic paediatric patients. Included were children aged 1–17 years living in North-Western Switzerland and bordering areas of France and Germany. Excluded were children with symptoms of Lyme borreliosis or a chronic disease possibly affecting plasma antibodies (immunodeficiency syndrome, systemic lupus erythematosus) or with such medication (e.g., intravenous immunoglobuline treatment, allogenic stem cell transplantation, immunosuppressive treatment) as well as refugees seeking asylum. IgG antibodies against B. burgdorferi were measured by ELISA and positive or borderline results by line blot. Positivity was defined as scenario 1: ELISA positive/line blot positive or borderline OR ELISA borderline/line blot positive. Scenario 2: ELISA positive or borderline/line blot positive. A multivariable logistic regression model for seropositivity was applied. Results 962 children were included (mean age 9.63 years, standard deviation 5.01, 54.5% males). Seroprevalence for scenario 1 was 13.3% (95% CI: 11.2–15.6) and for scenario 2 11.2% (95% CI: 9.3–13.4). Seroprevalence (scenario 1) was comparable for age groups, sex and rural versus urban residence. Conclusion This study shows an increased seroprevalence for B. burgdorferi in the paediatric age compared to previous childhood studies. We also found an increased risk for B. burgdorferi infection at young age. …

Journal of Medical Virology, Volume 96, Issue 10, October 2024.

Journal of Medical Virology, Volume 96, Issue 10, October 2024.

Journal of Medical Virology, Volume 96, Issue 10, October 2024.

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal disease. Droplet digital polymerase chain reaction (ddPCR) presents unparalleled sensitivity and enables absolute quantification of viral load. In this prospective study, we enrolled 111 patients with SFTS and collected 259 continuous samples. Our findings unveil a robust reverse transcription (RT)–ddPCR method for SFTS with a limit of detection of 2.46 copies/µL (95% CI, 1.50–11.05), surpassing the sensitivity of RT–quantitative polymerase chain reaction at 103.29 copies/µL (95% CI, 79.69–216.35). Longitudinal cohort analysis revealed significantly higher RT-ddPCR detection rates at days 10 to 11, 13 to 14, and ≥15 of the disease course as compared with RT–quantitative polymerase chain reaction (P < .05). Positive RT-ddPCR results were associated with declined platelet and elevated aspartate aminotransferase and lactate dehydrogenase on the same day vs negative RT-ddPCR samples. RT-ddPCR exhibits commendable diagnostic efficacy in SFTS, and it remains detectable in blood samples from patients with an extended disease course. Furthermore, RT-ddPCR correlates with clinical laboratory tests, furnishing valuable reference data for clinical diagnosis.

Abstract Background Patients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. Management of these infections is increasingly challenging due to decreased antimicrobial susceptibility to beta-lactam antibiotics. The pharmacokinetics of these agents are inadequately characterized in patients with CF.Methods One hundred fifty-five pediatric and adult participants with CF receiving cefepime (n=82), meropenem (n=42), or piperacillin-tazobactam (n=31) were enrolled. Opportunistic blood samples were obtained during hospitalization. Population PK analysis was conducted using nonlinear mixed-effects modeling. Clinical and demographic characteristics were evaluated as potential covariates. Monte Carlo simulations were performed to evaluate probability of target attainment (PTA) for different dosing regimens.Results Estimated creatinine clearance, and total or lean body weight, affected the pharmacokinetics of cefepime and meropenem. No covariates were identified for piperacillin and tazobactam. In the cefepime group, a 3-h infusion achieved higher PTA than a 0.5-h infusion for all participants. Estimated breakpoints (the respective minimum inhibitory concentration (MIC) up to which ≥90% of patients are predicted to reach a PK/PD target) were two- to four-fold higher in pediatric participants receiving a 3-h vs. 0.5-h infusion. In the meropenem group, increased creatinine clearance led to reduced PTA. In the piperacillin-tazobactam group, total daily dose and mode of administration were principal drivers of PTA.Conclusions Standard dosing regimens fail to achieve specific MIC targets in patients with CF. Therefore, clinicians should incorporate local antibiograms and PK models to determine optimal dosing. Further PK optimization to account for interindividual differences could be achieved by real-time beta-lactam therapeutic drug monitoring.

ObjectiveTo evaluate the use of antigen-based rapid diagnostic tests (Ag-RDTs) alongside a digital tool to deliver household-level COVID-19 testing by community health workers (CHWs), in line with Rwanda’s ambition to decentralise COVID-19 testing. DesignThis was an operational pilot study to evaluate the impact and operational characteristics of using the digital e-ASCov tool combined with Ag-RDTs to support COVID-19 symptom screening and rapid testing by CHWs across eight districts in Rwanda. A total of 800 CHWs selected from both rural and urban areas were trained in delivering Ag-RDTs for COVID-19 testing and using the e-ASCOV application for data capture on a smartphone. Laboratory technicians repeated a subset of Ag-RDTs to assess the concordance of results obtained by CHWs. The study also assessed CHWs’ experience of the intervention using a mixed-methods approach. SettingEight rural, urban and semiurban districts in Rwanda. ParticipantsA total of 19 544 individuals were enrolled and screened for signs and symptoms of COVID-19. InterventionsCommunity-based screening for COVID-19 by CHWs using the digital tool e-ASCov combined with rapid testing using Ag-RDTs. Main outcome measuresNumber of participants screened and tested; concordance of Ag-RDT results between CHWs and laboratory technicians; feasibility of study procedures by CHWs and CHWs perceptions of the digital tool and Ag-RDT testing. ResultsFrom February to May 2022, CHWs screened 19 544 participants, of whom 4575 (23.4%) had COVID-19-related symptoms or a history of exposure to the infection. Among them, 86 (1.9%) were positive on Ag-RDTs. Concordance of Ag-RDT results between CHWs and laboratory technicians was 100%. Of the 800 trained CHWs, 746 (93.3%) were independently able to conduct household-based COVID-19 screening, perform the Ag-RDTs and send data to the central server. Most CHWs (>80%) found Ag-RDTs and e-ASCOV easy to use. ConclusionsThis study demonstrated the feasibility of deploying a digital tool and Ag-RDTs for household-level SARS-CoV-2 detection in Rwanda. The findings support a broader roll-out of digitally supported rapid testing by CHWs to broaden access to testing for priority diseases. …

ObjectiveWe assessed the association of early statin initiation with inpatient mortality among hospitalised COVID-19 patients. Design, setting and participantsThis observational study emulated a hypothetical target trial using electronic health records data from Northwestern Medicine Health System, Illinois, 2020–2022. We included patients who were ≥40 years, admitted ≥48 hours for COVID-19 from March 2020 to August 2022 and had no evidence of statin use before admission. InterventionsIndividuals who initiated any statins within 48 hours of admission were compared with individuals who did not initiate statins during this period. Primary outcome measuresInpatient mortality at hospital days 7, 14, 21 and 28 were determined using hospital records. Risk differences between exposure groups were calculated using augmented inverse propensity weighting (AIPW) with SuperLearner. ResultsA total of 8893 individuals (24.5% early statin initiators) were included. Early initiators tended to be older, male and have higher comorbidity burdens. Unadjusted day 28 mortality was higher in early initiators (6.0% vs 3.6%). Adjusted analysis showed slightly higher inpatient mortality risk at days 7 (RD: 0.5%, 95% CI: 0.2 to 0.8) and 21 (RD: 0.6%, 95% CI: 0.04 to 1.1), but not days 14 (RD: 0.4%, 95% CI: –0.03 to 0.9) and 28 (RD: 0.4%, 95% CI: –0.2 to 1.1). Sensitivity analyses using alternative modelling approaches showed no difference between groups. ConclusionsEarly statin initiation was not associated with lower mortality contrasting with findings of previous observational studies. Trial emulation helped in identifying and addressing sources of bias incompletely addressed by previous work. Statin use may be indicated for other conditions but not COVID-19. …

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 7, Page 919-930, October 1, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 7, Page 945-948, October 1, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 7, Page P1-P2, October 1, 2024.

Abstract Background The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis. Methods In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models. Results A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02–1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00–1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings. Conclusion Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients. …

Abstract Mathematical models play a crucial role in assisting public health authorities in timely disease control decision-making. For vector-borne diseases, integrating host and vector dynamics into models can be highly complex, particularly due to limited data availability, making system validation challenging. In this study, two compartmental models akin to the SIR type were developed to characterize vector-borne infectious disease dynamics. Motivated by dengue fever epidemiology, the models varied in their treatment of vector dynamics, one with implicit vector dynamics and the other explicitly modeling mosquito-host contact. Both considered temporary immunity after primary infection and disease enhancement in secondary infection, analogous to the temporary cross-immunity and the Antibody-dependent enhancement biological processes observed in dengue epidemiology. Qualitative analysis using bifurcation theory and numerical experiments revealed that the immunity period and disease enhancement outweighed the impact of explicit vector dynamics. Both models demonstrated similar bifurcation structures, indicating that explicit vector dynamics are only justified when assessing the effects of vector control methods. Otherwise, the extra equations are irrelevant, as both systems display similar dynamics scenarios. The study underscores the importance of using simple models for mathematical analysis, initiating crucial discussions among the modeling community in vector-borne diseases. …

Abstract Background The severity of infectious disease outcomes is dependent on the virulence factors of the pathogen and the host immune response. CARD8 is a major regulator of the innate immune proinflammatory response and has been suggested to modulate the host response to common inflammatory diseases. In the present study, the C10X genetic polymorphism in the CARD8 gene was investigated in relation to bacterial meningitis. Methods A total of 400 clinically suspected meningitis patients hospitalized at the University of Gondar Hospital were enrolled in the study. Cerebrospinal fluid (CSF) and blood samples were collected for laboratory investigations. The collected CSF was cultured, and all the results obtained from the culture were confirmed using direct RT‒PCR. Genotyping of whole-blood samples was performed using a TaqMan assay. The results were compared with apparently healthy controls and with PCR-negative meningitis suspected patients. Results Of the included patients, 57% were men and the most common clinical signs and symptoms were fever (81%), headache (80%), neck stiffness (76%), nausea (68%), and vomiting (67%). Microbiology culture identified 7 patients with bacterial meningitis caused by Neisseria meningitidis (n = 4) and Streptococcus pneumoniae (n = 3). The RT-PCR revealed 39 positive samples for N. meningitidis (n = 10) and S. pneumoniae (n = 29). A total of 332 whole-blood samples were genotyped with the following results: 151 (45.5%) C10X heterozygotes, 59 (17.7%) C10X homozygotes and 122 (36.7%) wild genotypes. The polymorphic gene carriers among laboratory confirmed, clinically diagnosed meningitis and healthy controls were 23(46%), 246(40%), and 1526(39%), respectively with OR = 1.27 (0.7–2.3) and OR = 1.34 (0.76–2.4). The presence of the C10X polymorphism in the CARD8 gene was more prevalent in suspected meningitis patients than in healthy controls (OR 1.2; 1.00-1.5). Homozygote C10X polymorphic gene carriers were more susceptible to infectious disease. The presence of viable or active bacterial infection was found to be associated with the presence of heterozygous C10X carriers. Conclusions A greater proportion of C10X in the CARD8 gene in confirmed bacterial meningitis patients and clinically diagnosed meningitis patients than in healthy controls. Homozygote C10X polymorphic gene carriers were more susceptible to infectious disease than heterozygote gene carriers and healthy controls. …

Abstract Background Drug-resistant tuberculosis (DR-TB) remains a threat to public health. Shorter regimens have been proposed as potentially valuable treatments for multidrug or rifampicin resistant tuberculosis (MDR/RR-TB). We undertook a systematic review and network meta-analysis to evaluate the efficacy and safety of shorter MDR/RR-TB regimens. Methods We searched PubMed/MEDLINE, Cochrane Center for Clinical Trials (CENTRAL), Scopus, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, US Food and Drug Administration, and Chinese Clinical Trial Registry for primary articles published from 2013 to July 2023. Favorable (cured and treatment completed) and unfavorable (treatment failure, death, loss to follow-up, and culture conversion) outcomes were assessed as the main efficacy outcomes, while adverse events were assessed as the safety outcomes. The network meta-analysis was performed using R Studio version 4.3.1 and the Netmeta package. The study protocol adhered to the PRISMA-NMA guidelines and was registered in PROSPERO (CRD42023434050). Result We included 11 eligible studies (4 randomized control trials and 7 cohorts) that enrolled 3,548 patients with MDR/RR-TB. Treatment with a 6-month combination of BdqLzdLfxZTrd/Eto/H had two times more favorable outcomes [RR 2.2 (95% CI 1.22, 4.13), P = 0.0094], followed by a 9–11 month combination of km/CmMfx/LfxPtoCfzZEHh [RR1.67 (95% CI 1.45, 1.92), P 

Abstract Background The prevalence of Helicobacter pylori (H. pylori) infection and its potential relationship to various diseases is currently a focus of attention. The aim of this study is to investigate the association between current and past H. pylori infections and elevated levels of microalbuminuria in type 2 diabetic patients. Methods Two hundred patients with type 2 diabetes mellitus were tested for the presence of H. pylori infection. They were divided into three groups: 52 had a current H. pylori infection, 38 had a past H. pylori infection, and 110 had no H. pylori infection. All study participants underwent assessments of plasma glucose levels, glycated hemoglobin (HbA1c), albuminuria levels, inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), as well as other relevant investigations. Results The prevalence of H. pylori infection (current and past) was detected in 90 out of 200 diabetic patients (45%). There was no statistically significant difference between the three groups in terms of age, diabetes duration, family history of DM, family history of hypertension, residence, or dyspeptic symptoms, indicating that current or past infection with H. pylori has no association with these variables. The current H. pylori infection group showed the highest levels of inflammatory markers, ESR and CRP, which were significantly different from those in the non-infected group (p = 0.013 and p 

Summary Background Treatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT. Methods An analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT. Results In skin samples, the presence of foamy granuloma (OR = 7.36; 95%CI2.20-24.60; p = 0.0012) and histological bacillary index (hBI) ≥ 1+ (OR = 1.55; 95%CI1. 22-1.99; p = 0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD ± 2.02), while the control group exhibited a mean hBI of 1.8+ (SD ± 1.88). An hBI ≥ 3 + showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p = 0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p > 0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR = 1.4; 95%CI1.13-1.74; p = 0.0019). A mean EI of 4.48 (SD ± 2.80) was observed, with an EI ≥ 3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p = 0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI ≥ 1+, and EI ≥ 1 markedly increased the likelihood of TF by up to 95.41%. Conclusion Persistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF. …

Abstract Background The contribution of interspecies interactions between coinfecting pathogens to chronic refractory infection by affecting pathogenicity is well established. However, little is known about the impact of intraspecific interactions on infection relapse, despite the cross-talk of different strains within one species is more common in clinical infection. We reported a case of chronic refractory pulmonary infection relapse, caused by two methicillin-sensitive S. aureus (MSSA) strains (SA01 and SA02) and revealed a novel strategy for relapse via intraspecific cooperation. Methods The hemolytic ability, growth curve, biofilm formation, virulence genes and response of G. mellonella larvae to S. aureus infection were analysed to confirm this hypothesis. Results SA02 hemolytic activity was inhibited by SA01, along with the expression of hemolysin genes and the virulence factor Hla. Additionally, SA01 significantly enhanced the biofilm formation of SA02. AIP-RNAIII may be a possible pathway for this interaction. Compared with mono-infection, a worse outcome (decreased larval survival and increased microbial burden) of the two MSSA strains coinfected with G. mellonella confirmed that intraspecific interactions indeed enhanced bacterial survival in vivo. Conclusion The intraspecific interaction of S. aureus could lead to chronic refractory infection via pathogenicity changes. …

Abstract Background Long term respiratory complications of Corona Virus Disease-2019 (COVID-19) are of great concern. Many studies have reported altered respiratory patterns in COVID-19 recovered individuals and most of them were from severe to critically ill patients. The association of viral load at the time of infection with symptoms of long COVID-19 specifically on pulmonary functions after months of recovery is still not known. This study was aimed to assess the impact of SARS-CoV-2 viral load during mild-moderate COVID-19 disease on pulmonary functions in middle-aged population after 6–8 months of acute infection. Methods This study included 300 (102 healthy controls and 198 COVID-19 recovered) individuals between age 30–60 of either gender. Mild-moderate COVID-19 recovered individuals were recruited between a period of 6–8 months post-acute infection. Spirometry was performed with MIR-Spirolab-III. The association of spirometry pattern was compared with SARS-CoV-2 viral loads during acute infection. Results We observed up to 70% of the participants presented with either shortness of breath (11.5%), body aches (23.5%), recurrent cough (4.4%), recurrent respiratory infections (9.5%) and/or fatigue (33.3%) at follow up. In our study, 35.5% of COVID-19 recovered individuals had abnormal respiratory patterns (33.5% had restrictive and 2% had obstructive patterns). Viral load ≤ 20 CT value was associated with restrictive respiratory patterns (p = 0.004). No association was found between viral load and disease severity (p = 0.23). Conclusion In this study, we found one third of mild-moderate COVID-19 recovered individuals have restrictive respiratory patterns after 6–8 months of recovery. These findings had a strong association with SARS-CoV-2 viral loads during acute infection which has been reported for the first time in our study. Studying the relationship between viral load and pulmonary functions can contribute to identifying potential risk factors for long COVID and developing preventive measures to mitigate the long-term impact on lung health. Clinical trial number Not applicable. …

Abstract Background Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. Methods This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. Results A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P 

IMPORTANCE: Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. OBJECTIVES: We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included. MAIN OUTCOMES AND MEASURES: Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. RESULTS: Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%). CONCLUSIONS AND RELEVANCE: We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.

Proceedings of the National Academy of Sciences, Volume 121, Issue 40, October 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 40, October 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 40, October 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 40, October 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 40, October 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 41, October 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 41, October 2024.

Growing up in Amsterdam, The Netherlands, Louis Bont\'s father who worked at the Netherlands Cancer Institute (NKI), often said “doctors will never make good scientists”. This way, his father provided him with a challenge to become a clinician scientist, Bont realised only decades later. Today he is Department Head of Pediatrics at the Wilhelmina Children\'s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands, where his main area of research is respiratory syncytial virus (RSV). He has also been appointed an adjunct professor at Yale University (New Haven, CT, USA).

The data from PROMIS-I suggest a clinically important benefit of colistimethate sodium delivered via the I-neb adaptive aerosol delivery system in patients with bronchiectasis and P aeruginosa infection. These results were not replicated in PROMIS-II, which was affected by the COVID-19 pandemic and prematurely terminated.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI), hospital admission, and mortality in children worldwide. Early-life RSV LRTI has also been associated with subsequent long-term respiratory sequelae, including recurrent LRTI, recurrent wheezing, asthma, and lung function impairment, and these effects can persist into adulthood as chronic respiratory disease. New preventive measures (maternal vaccine or long-acting monoclonal antibodies) have been licensed to reduce the burden of acute RSV LRTI in infants and children at high risk through passive immunisation.

Respiratory syncytial virus (RSV), an RNA virus spread by droplet infection that affects all ages, is increasingly recognised as an important pathogen in adults, especially among older people living with comorbidities. Distinguishing RSV from other acute viral infections on clinical grounds alone, with sufficient precision to be clinically useful, is not possible. The reference standard diagnosis is by PCR: point-of-care tests perform less well with lower viral loads. Testing samples from a single respiratory tract site could result in underdetection.