The development of new drug modalities has been facilitated recently by the introduction of boron as a component of organic compounds, and specifically within a benzoxaborale scaffold. This has enabled exploration of new chemical space and the development of effective compounds targeting a broad range of morbidities, including infections by protozoa, fungi, worms, and bacteria. Most notable is the recent demonstration of a single oral dose cure using acoziborole against African trypanosomiasis. Common and species-/structure-specific interactions between benzoxaboroles and parasite species have emerged and provide vital insights into the mechanisms of cidality, as well as potential challenges in terms of resistance and/or side effects. Here, we discuss the literature specific to benzoxaborole studies in parasitic protists and consider unanswered questions concerning this important new drug class.

A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus.

by The PLOS ONE Editors …

by Sabrina Sultana Rimi, Md. Nahid Ashraf, Sanzila Hossain Sigma, Md. Tanjir Ahammed, Mahbubul Pratik Siddique, Mohammad Ali Zinnah, Md. Tanvir Rahman, Md. Shafiqul Islam Biofilm development significantly enhances the virulence of methicillin-resistant Staphylococcus aureus (MRSA), leading to severe infections and decreased susceptibility to antibiotics, especially in strains associated with hospital environments. This study examined the occurrence of MRSA, their ability to form biofilms, agr typing, and the antibiotic resistance profiles of biofilm-forming MRSA strains isolated from environmental surfaces at Mymensingh Medical College Hospital (MMCH). From 120 swab samples, 86 (71.67%) tested positive for S. aureus. MRSA was identified in 86 isolates using the disk diffusion technique, and by polymerase chain reaction (PCR), 56 (65.1%) isolates were confirmed to carry the mecA gene. The Crystal Violet Microtiter Plate (CVMP) test revealed that 80.35% (45 isolates) were biofilm-forming and 19.6% (11 isolates) were non-biofilm-forming. Out of 45 biofilm producer isolates 37.5% and 42.9% isolates exhibited strong and intermediate biofilm-forming characteristics, respectively. Molecular analysis revealed that 17.78% of MRSA isolates carried at least one gene related to biofilm formation, specifically icaA, icaB, and icaD genes were discovered in 13.33%, 8.89%, 6.67% of the MRSA isolates, respectively. In agr typing, the most prevalent group was agr I (71.11%), followed by group III (17.78%) and group II (11.11%). Group IV was not detected. The distribution of agr gene groups showed a significant difference among biofilm-forming isolates (p < 0.05). In agr group I, 18.75% of isolates carried the icaA gene, 12.5% carried the icaB gene, and 9.37% carried the icaD gene. Biofilm-forming genes were not detected in any of the isolates from agr groups II or III. There are no statistically significant differences between agr groups and the presence of these genes (p > 0.05). Antibiotic resistance varied significantly among agr groups, with agr group I displaying the highest resistance, agr group II, and agr group III exhibiting the least resistance (p < 0.05). Seventy-three (73.3%) of the isolates were multi-drug resistant, with agr group I displaying nineteen MDR patterns. The occurrence of MRSA in hospital environments and their capacity to form biofilm raises concerns for public health. These findings support the importance of further research focused on agr quorum sensing systems as a basis for developing novel antibacterial agents.

by Muhammad Azeem, Ghulam Mustafa, Sibtain Ahmed, Amna Mushtaq, Muhammad Arshad, Muhammad Usama, Muhammad Farooq Viral diseases pose a serious global health threat due to their rapid transmission and widespread impact. The RNA-dependent RNA polymerase (RdRp) participates in the synthesis, transcription, and replication of viral RNA in host. The current study investigates the antiviral potential of secondary metabolites particularly those derived from bacteria, fungi, and plants to develop novel medicines. Using a virtual screening approach that combines molecular docking and molecular dynamics (MD) simulations, we aimed to discover compounds with strong interactions with RdRp of five different retroviruses. The top five compounds were selected for each viral RdRp based on their docking scores, binding patterns, molecular interactions, and drug-likeness properties. The molecular docking study uncovered several metabolites with antiviral activity against RdRp. For instance, cytochalasin Z8 had the lowest docking score of –8.9 (kcal/mol) against RdRp of SARS-CoV-2, aspulvinone D (–9.2 kcal/mol) against HIV-1, talaromyolide D (–9.9 kcal/mol) for hepatitis C, aspulvinone D (–9.9 kcal/mol) against Ebola and talaromyolide D also maintained the lowest docking score of –9.2 kcal/mol against RdRp enzyme of dengue virus. These compounds showed remarkable antiviral potential comparable to standard drug (remdesivir –7.4 kcal/mol) approved to target RdRp and possess no significant toxicity. The molecular dynamics simulation confirmed that the best selected ligands were firmly bound to their respective target proteins for a simulation time of 200 ns. The identified lead compounds possess distinctive pharmacological characteristics, making them potential candidates for repurposing as antiviral drugs against SARS-CoV-2. Further experimental evaluation and investigation are recommended to ascertain their efficacy and potential.

by Jinxi Li, Ting Xiang, Xinyun Chen, Ping Fu Introduction The neutrophil-percentage-to-albumin ratio (NPAR), a novel inflammatory biomarker, has been used to predict the prognosis of patients with cancer and cardiovascular disease. However, the relationship between NPAR and chronic kidney disease (CKD) remains unknown. The purpose of this study was to investigate the possible association between NPAR and CKD. Methods The cross-sectional study included participants with complete information on NPAR, serum creatinine (Scr), or urinary albumin-to-creatinine ratio (UACR) from the 2009–2018 National Health and Nutrition Examination Survey (NHANES). CKD was defined as the presence of either low estimated glomerular filtration rate (eGFR) or albuminuria. Univariate and multivariate logistic regression and restricted cubic spline regression were used to assess the linear and nonlinear associations between NPAR and renal function. Subgroup and interactive analyses were performed to explore potential interactive effects of covariates. Missing values were imputed using random forest. Results A total of 25,236 participants were enrolled in the study, of whom 4518 (17.9%) were diagnosed with CKD. After adjustment for covariates, the odds ratios (ORs) for prevalent CKD were 1.19 (95% CI = 1.07–1.31, p…

by Fabiola Moreno Echevarria, Mathew Caputo, Daniel Camp, Susheel Reddy, Chad J. Achenbach Background SARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and findings A retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 –June 30, 2022; Period 2: July 1 –December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08–1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26–1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51–1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19. …

Abstract Purpose Asymptomatic pharyngeal gonorrhoea could play an important role in transmission and should be screened for in persons at risk. We investigated the sensitivity of oral gargle samples to detect N. gonorrhoea and describe the frequency of infection by anatomical site. Methods From June 2021 to July 2022 persons diagnosed with gonorrhoea in the STI/HIV department were asked to provide self-collected specimens for single-site testing by NAAT from throat (by gargling and swabbing), anorectum, and first-void urine. Results 104 episodes of gonorrhoea were analysed in 88 individuals. The median age was 33 years, 85 persons (96.5%) were male. The pharynx was the most common site of infection (71 cases, 68.2%); in 26 persons (25.0%) it was the only site of infection. Anorectal infection was detected in 65 cases (62.5%) and urogenital infection in 25 cases (24.0%). In 46 cases (44.2%) infection was detected in more than one anatomical site. Gargling was less sensitive than throat swabbing to detect pharyngeal infection (85.9% versus 97.2%, p = .038), but was preferred by patients. Only 4 of 71 pharyngeal infections (5.6%) were symptomatic; anorectal and urogenital infections were symptomatic in 12.3% and 76.0% of cases, respectively. Culture recovery of N.gonorrhoeae was only possible in 15.8% of throat swabs, but was successful in 61.9% of anorectal and 84.2% of urogenital samples. Conclusions Asymptomatic pharyngeal gonorrhoea is common. Gargle samples should be used only as alternative specimens with inferior sensitivity compared to throat swab samples. …

Abstract Objective Recent guidelines indicated that, in addition to antibiotics, nonantibiotic interventions serve as available preventive options for urinary tract infections (UTIs). This study aimed to compare the efficacy and safety of various nonantibiotic interventions in preventing UTIs. Methods The authors systematically searched databases for eligible studies. The inclusion criteria encompassed randomized controlled trials (RCTs) focusing on one or more nonantibiotic interventions for UTI prevention, with the incidence of UTIs being a key outcome measure. Subgroup analyses were performed according to age, sex, and follow-up. Results 50 RCTs comprising 10,495 subjects and investigating 14 interventions, were included. Nearly 80% of the RCTs utilized double-blind or triple-blind designs. In the whole group, D-mannose (risk ratio [RR] 0.34, 0.21 to 0.56), vaccine (RR 0.65, 0.52 to 0.82), probiotics (RR 0.69, 0.50 to 0.94), cranberry (RR 0.72, 0.60 to 0.87), and triple therapy (cranberry plus probiotics plus vitamin A) (RR 0.27, 0.09 to 0.87), exhibited a significant reduction in UTI incidence compared to the placebo. Probiotics (RR 0.50, 0.28 to 0.89) were the most effective in the nonadult group, while vitamin D (RR 0.46, 0.27 to 0.81) showed the highest efficacy in the long follow-up group (≥ 1 year). There was no significant difference in the incidence of adverse events between the interventions and the placebo group. Conclusions D-mannose, triple therapy, vaccine, probiotics, and cranberry serve as potential nonantibiotic intervention options for clinical UTI prevention. …

Abstract Purpose It is unknown whether social distancing impacts frequency of presentation and severity of childhood bone and joint infection (BJI). In New Zealand, the COVID-19 disease elimination strategy involved strict social isolation policies spanning March 2020-September 2022. Examination of this period may provide insight around risk factors for BJI. Methods A retrospective review of all patients 

Abstract Background Currently, there are hundreds of hematological parameters used for rapid diagnosis of neonatal sepsis, but there is no network meta-analysis to compare the diagnostic efficacy of these parameters. Methods We searched for literature on the diagnostic neonatal sepsis and selected 20 of the most common parameters to compare their diagnostic efficacy. We used Bayesian network meta-analysis, Frequentist network meta-analysis, and individual traditional diagnostic meta-analysis to analyze the data and verify the stability of the results. Based on the above analysis, we ranked the diagnostic efficacy of 20 parameters and searched for the optimal indicator. We also conducted subgroup analysis based on different designs. GRADE was used to evaluate the quality of evidence. Results 311 articles were included in the analysis, of which 206 articles were included in the network meta-analysis. Bayesian models fond the top three of the advantage index were P-SEP, SAA, and CD64. In Individual model, P-SEP, SAA, and CD64 had the best sensitivity; ABC, SAA, and P-SEP had the best specificity. Frequentist model showed that CD64, P-SEP, and IL-10 ranked in the top three for sensitivity, while P-SEP, ABC, and I/M in specificity. Overall, P-SEP, SAA, CD64, and PCT have good sensitivity and specificity among all the three methods. The results of subgroup analysis were consistent with the overall analysis. All evidence was mostly of moderate or low quality. Conclusions P-SEP, SAA, CD64, and PCT have good diagnostic efficacy for neonatal sepsis. However, further studies are required to confirm these findings. …

Abstract Purpose COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021. Methods The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded. Results We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p 

The pathogen of community-acquired pneumonia (CAP) in children is typically uncertain during initial treatment, leading to systematic empiric antibiotic use. This study investigates if having rapid multiplex PCR results in the emergency department (ED) improves empiric treatment.

Meropenem is commonly used against Pseudomonas aeruginosa. Traditionally, the time unbound antibiotic concentration exceeds the MIC (fT>MIC) is used to select carbapenem regimens. We aimed to characterize the effects of different baseline resistance mechanisms on bacterial killing and resistance emergence; evaluate whether fT>MIC can predict these effects; and, develop a novel Quantitative and Systems Pharmacology (QSP) model to describe the effects of baseline resistance mechanisms on the time-course of bacterial response.

Bacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licenced phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis.

Abstract Cellular phenotype and function are altered in different microenvironments. For targeted therapies it is important to understand site-specific cellular adaptations. Juvenile Idiopathic Arthritis (JIA) is characterised by autoimmune joint inflammation, with frequent inadequate treatment responses. To comprehensively assess the inflammatory immune landscape, we designed a 37-parameter spectral flow cytometry panel delineating mononuclear cells from JIA synovial fluid (SF) of autoimmune inflamed joints, compared to JIA and healthy control blood. Synovial monocytes and NK cells (CD56bright) lack Fc-receptor CD16, suggesting antibody-mediated targeting may be ineffective. B cells and DCs, both in small frequencies in SF, undergo maturation with high 4-1BB, CD71, CD39 expression, supporting T cell activation. SF effector and regulatory T cells were highly active with newly described co-receptor combinations that may alter function, and suggestion of metabolic reprogramming via CD71, TNFR2 and PD-1. Most SF effector phenotypes, as well as an identified CD4-Foxp3+ T cell population, were restricted to the inflamed joint, yet specific SF-predominant CD4+Foxp3+ Treg subpopulations were increased in blood of active but not inactive JIA, suggesting possible recirculation and loss of immunoregulation at distal sites. This first comprehensive dataset of the site-specific inflammatory landscape at protein level will inform functional studies and the development of targeted therapeutics to restore immunoregulatory balance and achieve remission in JIA…

Tropical Medicine &International Health, EarlyView.

Abstract Background We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds.Methods This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed.Results Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06–1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups.Conclusions Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine.Clinical Trials Registration NCT05568797…

Abstract Background The adjuvanted respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50–59 years without or with increased risk for RSV disease due to specific chronic medical conditions.Methods This observer-blind, phase 3, noninferiority trial included adults aged 50–59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50–59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed.Results The exposed population included 1152 participants aged 50–59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50–59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups.Conclusions RSVPreF3 OA was immunologically noninferior in 50–59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50–59-year-olds was consistent with that in ≥60-year-olds.Clinical Trial Registration ClinicalTrials.gov: NCT05590403.

respiratory syncytial virusvaccinesolder and high-risk adults…

Abstract Background Ghana is a malaria-endemic country with the entire population at risk. The Northern region of the country recorded the highest malaria case fatality rate (CFR) for two consecutive years: 1.11% in 2013 and 1.07% in 2014. Even though the National Malaria Elimination Programme (NMEP) has achieved a reduction in malaria mortality, the existence of high case fatality in the Northern region was alarming. This study, therefore, aimed to determine the factors associated with malaria mortality in the northern region of Ghana to institute control measures. Methods An unmatched case control study was conducted from July 2015 to August 2015. The study population consisted of patients admitted to health facilities for severe malaria in the Northern region of Ghana. A case was defined as a patient diagnosed with severe malaria at an eligible health facility who died as a result of malaria. A control was a patient diagnosed with severe malaria admitted to an eligible health facility who did not die. Health facilities that recorded CFRs of 1.0% and above were randomly sampled for this study, after which, 10 cases and 20 controls were recruited from each health facility. Information on cases and controls was then abstracted from hospital records using an electronically deployed abstraction tool. Continuous variables were expressed as means and medians, and categorical variables as frequencies and proportions. Multivariable logistic regression was used to assess the strength of the association between malaria mortality and factors predictive of malaria mortality. A p-value of 

Abstract Background The government of Lao PDR has increased efforts to control malaria transmission in order to reach its national elimination goal by 2030. Weather can influence malaria transmission dynamics and should be considered when assessing the impact of elimination interventions but this relationship has not been well characterized in Lao PDR. This study examined the space–time association between climate variables and Plasmodium falciparum and Plasmodium vivax malaria incidence from 2010 to 2022. Methods Spatiotemporal Bayesian modelling was used to investigate the monthly relationship, and model selection criteria were used to evaluate the performance of the models and weather variable specifications. As the malaria control and elimination situation was spatially and temporally dynamic during the study period, the association was examined annually at the provincial level. Results Malaria incidence decreased from 2010 to 2022 and was concentrated in the southern regions for both P. falciparum and P. vivax. Rainfall and maximum humidity were identified as most strongly associated with malaria during the study period. Rainfall was associated with P. falciparum incidence in the north and central regions during 2010–2011, and with P. vivax incidence in the north and central regions during 2012–2015. Maximum humidity was persistently associated with P. falciparum and P. vivax incidence in the south. Conclusions Malaria remains prevalent in Lao PDR, particularly in the south, and the relationship with weather varies between regions but was strongest for rainfall and maximum humidity for both species. During peak periods with suitable weather conditions, vector control activities and raising public health awareness on the proper usage of intervention measures, such as indoor residual spraying and personal protection, should be prioritized. …

Burkholderia cepacia complex (BCC), aerobic gram-negative rods, comprises at least 24 phylogenetically related bacterial species that are widely distributed in soil and plants [1]. The clinical manifestations of BCC vary extensively, ranging from asymptomatic to severe lower respiratory infections, such as cystic fibrosis (CF) and chronic granulomatous disease, or bloodstream infection in immunocompromised patients [1,2]; however, central nervous system (CNS) infections caused by BCC are rare. We present a case of choroid plexitis due to refractory BCC following coronavirus disease 2019 (COVID-19) that was successfully treated with a long-term, multiantibiotic regimen.

ObjectivesThe COVID-19 pandemic and related lockdown measures disrupted global healthcare provision, including opioid prescribing. In North America, opioid sales declined while opioid-related deaths increased. In Europe, the effect of the pandemic on prescribing is not yet known. Given the ongoing increase in opioid-related harm and mortality, it is crucial to analyse the impact of the COVID-19 crisis and lockdown measures on opioid prescribing. Therefore, the objective of this study was to characterise opioid prescribing in the Netherlands during the COVID-19 pandemic. DesignA nationwide register-based study characterising opioid prescribing using aggregated insurance reimbursement data. SettingDutch healthcare during the first 2 years of the COVID lockdown. ParticipantsThe whole Dutch population. Primary and secondary outcome measuresComparing the number of opioid prescriptions during the pandemic with a prepandemic period using a risk ratio (RR), with separate analysis on the prescription type (first-time or repeat prescription), patients’ sex, age and socioeconomic status. We also explored lockdown effects. ResultsDuring the first lockdown, the total number of new opioid prescriptions and prescriptions to young patients (briefly) decreased (RR 0.88, 95% CI 0.88 to 0.89 and RR 0.73, 95% CI 0.70 to 0.75, respectively), but the overall number of opioid prescriptions remained stable throughout the pandemic compared with prepandemic. Women, older patients and patients living in lower socioeconomic areas received more opioids per capita, but the pandemic did not amplify these differences. ConclusionsThe pandemic appears to have had a limited impact on opioid prescribing in the Netherlands. Yet, chronic use of opioids remains an important public health issue. …

IntroductionPoverty, HIV and perinatal depression represent a triple threat to public health in sub-Saharan Africa because of their combined negative effects on parenting and child development. In the resource-constrained context of low-income and middle-income countries, a lay-counsellor-delivered intervention that combines a psychological and parenting intervention could offer the potential to mitigate the consequences of perinatal depression while also optimising scarce resources for healthcare. Measuring the cost-effectiveness of such a novel intervention will help decision-makers to better understand the relative costs and effects associated with replicating the intervention, thereby supporting evidence-based decision-making. This protocol sets out the methodological framework for analysing the cost-effectiveness of a cluster randomised controlled trial (RCT) that compares a combined intervention to enhanced standard of care when treating depressed, HIV-positive pregnant women and their infants in rural South Africa. Methods and analysisThis cost-effectiveness analysis (CEA) protocol complies with the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. A societal perspective will be chosen. The proposed methods will determine the cost and efficiency of implementing the intervention as per the randomised control trial protocol, as well as the cost of replicating the intervention in a non-research setting. The costs will be calculated using an appropriately adjusted version of the Standardised Early Childhood Development Costing Tool. Primary health outcomes will be used in combination with costs to determine the cost per improvement in maternal perinatal depression at 12 months postnatal and the cost per improvement in child cognitive development at 24 months of age. To facilitate priority setting, the incremental cost-effectiveness ratios for improvements in child cognitive development will be ranked against six other child cognitive-development interventions according to Verguet et al’s methodology (2022). A combination of activity-based and ingredient-based costing approaches will be used to identify, measure and value activities and inputs for all alternatives. Outcomes data will be sourced from the RCT team. Ethics and disseminationThe University of Oxford is the sponsor of the CEA. Ethics approval has been obtained from the Human Sciences Research Council (HSRC, #REC 5/23/08/17), South Africa and the Oxford Tropical Research Ethics Committee (OxTREC #31–17), UK. Consent for publication is not applicable since no participant data are used in this protocol. We plan to disseminate the CEA results to key policymakers and researchers in the form of a policy brief, meetings and academic papers. Trial registration detailsISRCTN registry #11 284 870 (14/11/2017) and SANCTR DOH-27-102020-9097 (17/11/2017). …

ObjectiveTo assess antibiotics prescribing and use patterns for inpatients at Benjamin Mkapa Zonal Referral Hospital (BMH) using the WHO-Point Prevalence Survey (WHO-PPS). DesignA cross-sectional survey. SettingThe Benjamin Mkapa Zonal Referral Hospital, Dodoma, Tanzania. ParticipantsInpatient prescriptions, regardless of whether antibiotics were prescribed (n=286) on the day of PPS. Outcome measuresOur study analysed the prevalence of antibiotic use at BMH for inpatients, the type of antibiotics used, the indications for use and the proportion of oral and parenteral antibiotics. We also assessed prescription-prescribed antibiotics after a positive antimicrobial susceptibility testing (AST) result. ResultsA survey was conducted on 286 prescriptions, which revealed that 30.07% of them included antibiotics. On average, each prescription contained at least 1.6 antibiotics. All prescriptions that included antibiotics were written in generic names, and 77.91% (67/86) of them followed the Standard Treatment Guidelines. Of the prescriptions that included antibiotics, 58.14% (50/86) had a single antibiotic, 20.93% (18/86) had parenteral antibiotics and 79.07% (68/86) had oral antibiotics. Based on AWaRe’s (Access, Watch and Reserve) categorisation of antibiotics, 50% (8/16) were in the Access group, 31.25% (5/16) were in the Watch group, 12.50% (2/16) were in the Reserve group and 6.25% (1/16) were not recommended antimicrobial combinations. Out of 86 prescriptions included antibiotics, only 4.65% showed positive culture growth. However, antibiotics were still prescribed in 29.07% of prescriptions where there was no growth of bacteria, and in 66.28% of prescriptions, antibiotics were prescribed empirically without any requesting of bacteria culture and AST. ConclusionBMH has reduced inpatient Antibiotic Use by half compared with the 2019 WHO-PPS. Adherence to National Treatment Guidelines is suboptimal. Clinicians should use AST results to guide antibiotic prescribing. …

IntroductionDental caries among children is a major global health problem and is a particular public health challenge in Saudi Arabia. Dental caries cause pain, infection and negatively impact quality of life. As part of population oral health improvement efforts in Saudi Arabia, this project aims to evaluate the effectiveness of a supervised toothbrushing programme in kindergartens. Methods and analysisThis study is a cluster randomised controlled trial. Enrolment began in September 2022, for two academic years (2022–2024) on 20 randomly selected kindergartens in Riyadh. The data collection phase will be completed in September 2024. Ten kindergartens are randomly allocated to supervised toothbrushing and 10 to treatment as usual, which is an annual oral health awareness visit. The primary endpoint will be the worsening of obvious decay experience as measured by decayed (into dentine), missing and filled teeth (d3mft) from baseline to the second year of follow-up. The secondary endpoint will be the increase in the number of teeth affected. A priori subgroups of the region of Riyadh, school type (public, private), child sex and presence/absence of prior decay at baseline, will be analysed. We require 244 evaluable endpoints using a power of 80% to meet the sample size requirement. In addition, questionnaires on behaviours, quality of life, process monitoring and cost analysis are being deployed. Ethics and disseminationEthics approval for this study was given by the King Fahad Medical City Institutional Review Board in the Saudi Ministry of Health (22-083E/March 2022). The data analysis has been approved by the University of Glasgow Medical Veterinary and Life Sciences Research Ethical Committee (200220194/March 2023). The results of this study will be disseminated through presentations at scientific conferences and in scientific journals. Trial registration numberNCT05512156. …

ObjectivesThe purpose of this study was to systematically summarise the empirical evidence on the prevalence of HIV among long-distance truck drivers (LDTDs) from all parts of the world. DesignA systematic review and meta-analysis were conducted. Data sourcesWe searched PubMed, ProQuest Central, PubMed Central, Cumulated Index to Nursing and Allied Health Literature and Global Index Medicus to identify relevant information published from 1989 to 16 May 2023. Eligibility criteriaPeer-reviewed publications of English language reporting on the prevalence of HIV among LDTDs were included. Non-empirical studies like literature reviews were excluded. Data extraction and synthesisUsing a standardised data abstraction form, we extracted information on study characteristics and HIV prevalence levels. Crude prevalence estimates per 100 participants were computed and later transformed using logit transformation to have them follow a normal distribution. A meta-analysis of prevalences using the random effects model was performed. The I2 statistic was used to quantify the degree of heterogeneity across studies. A subgroup analysis using meta-regression was performed to investigate factors that could explain variability across studies. The Joanna Briggs Institute tools and Newcastle-Ottawa Scale were used to assess the quality of the included studies. To assess the certainty of evidence, the Grading of Recommendations Assessment, Development, and Evaluation approach was used. ResultsOf the 1787 articles identified, 42 were included. Most of the included studies were conducted in sub-Saharan Africa (45.23%, n=19) and Asia and the Pacific (35.71%, n=15). The pooled prevalence of HIV was 3.86%, 95% CI (2.22% to 6.64%). The burden of HIV was highest in sub-Saharan Africa at 14.34%, 95% CI (9.94% to 20.26%), followed by Asia and the Pacific at 2.12%, 95 CI (0.94% to 4.7%) and lastly Western, Central Europe and North America at 0.17%, 95% CI (0.03% to 0.82%). The overall heterogeneity score was (I2=98.2%, p

IntroductionThe United Nations Convention on the Rights of Persons with Disabilities asserts that all persons with disabilities have the right to receive the support they require to participate in decisions that affect them. Yet, persons with dementia continue to be excluded from decisions on issues that matter to them. Our planned scoping review seeks to address this gap by documenting the current knowledge on supported decision-making for persons with dementia and informing the next steps for research and practice. Methods and analysisWe will use Arksey and O’Malley’s (2005) six-stage framework to guide our review of the English scientific literature (2005 onwards), searching the following databases: MEDLINE, PsycINFO, CINAHL, AgeLine and the Social Science Abstracts. Our review will focus on primary studies examining supported decision-making for persons with dementia, including the voices of those with dementia. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews, we will identify (1) domains of supported decision-making discussed in the empirical literature and (2) practices/factors that facilitate or inhibit supported decision-making. Consultations with persons with dementia and their care partners will provide insights into lived experiences, helping identify gaps between research literature and lived realities. The preliminary title and abstract search for eligible articles were conducted between August and October 2023 and updated in June 2024, yielding 56 eligible articles for review. Ethics and disseminationThis scoping review will be conducted following the standards of the Tri-Council Policy Statement for Ethical Conduct for Research Involving Humans (1998 with 2000, 2002 and 2005 amendments). The procedures for eliciting feedback from persons with dementia and their care partners were approved by the Office of Research Ethics Board at McGill University (Reference # 23-08-048). Dissemination of review findings to persons with dementia and care partners will occur during ongoing community consultations. Visual aids and brief lay summaries will be used to facilitate input and dialogue. Dissemination to the broader practice and research communities will include workshops conducted in collaboration with study partners and presentations and publications in peer-reviewed forums. …

Abstract Background Up to now several studies estimate the prevalence of HBV, HCV, and TB among people living with HIV (PLWH) in Iran; however, their results are inconsistent. This study aimed to estimate the overall prevalence of HBV, HVC, and TB among Iranian PLWH. Methods In this systematic review and meta-analysis six databases including Medline, Web of Science, Scopus, MagIran, Scientific Information Database (SID), and Barakat Knowledge network system were searched up to October 2023 with no language restriction. All studies estimated the prevalence of HBV, HCV, and TB among PLWH in Iran were included. The random-effects model was used to report the study estimates. Results were reported at a 95% confidence interval (CI). Results Out of 1050 retrieved references, 58 articles met the eligibility criteria. Overall among PLWH, HBV prevalence was 13.0% (95% CI: 11.0, 15.0), HCV prevalence was 54% (95% CI: 45.0, 64.0), and TB prevalence was 19% (95% CI: 13.0, 24.0). The results from multivariate meta-regression analysis showed no statistically significant association between HBV and TB prevalence with the year of study, quality of studies, age, gender, and persons who inject drugs (PWID). HCV prevalence was significantly associated with PWID. Conclusion We found HBV, HCV, and TB infections are common among PLWH in Iran and required to be screened and treated with effective and timely services. …

Abstract Background Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. Methods Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. Results Drug NPs are characterized by uniform particle size, stability, high drug loading, and − 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. Conclusion ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation. …

Abstract Background Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥ 5 cells/µL), to inform timely diagnosis and management of encephalitis.Methods This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis.Results Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-NMDAR encephalitis (37/59, 62.7%). Notably, the group without pleocytosis was comprised of similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; p>0.05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had absent pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs. 71.1% in patients with pleocytosis, p

Abstract Background Human parechovirus (HPeV) infection can result in severe disease in infants, including sepsis, seizures, brain injury, and death. In 2022, a resurgence of HPeV was noted in young infants. Spectrum of illness and outcomes remain to be fully described.Methods A multi-state retrospective cohort study was conducted to evaluate hospitalizations and outcomes of infants aged ≤6 months admitted in 2022 with laboratory-confirmed HPeV infection. Infants with severe disease were defined as having clinical seizures, or abnormalities on MRI or EEG during admission. Infants with severe vs non-severe disease were compared using descriptive statistics.Results 124 U.S. infants were identified with HPeV in 11 states. Cases of HPeV peaked in May and presented at a median of 25.8 days of life (0-194 d) with fever, fussiness, and poor feeding. Bacterial and other viral co-infections were rare. 33 (27%) of infants had severe neurologic disease, were more likely to present at an earlier age (13.9 vs 30 days of life, p

Publication date: Available online 2 August 2024 Source: Immunity Author(s): Zachary Even, Alexandre P. Meli, Antariksh Tyagi, Aurobind Vidyarthi, Neima Briggs, Dimitri A. de Kouchkovsky, Yong Kong, Yaqiu Wang, Daniel A. Waizman, Tyler A. Rice, Bony De Kumar, Xusheng Wang, Noah W. Palm, Joe Craft, Malay K. Basu, Sourav Ghosh, Carla V. Rothlin …

Abstract Objective Recent guidelines indicated that, in addition to antibiotics, nonantibiotic interventions serve as available preventive options for urinary tract infections (UTIs). This study aimed to compare the efficacy and safety of various nonantibiotic interventions in preventing UTIs. Methods The authors systematically searched databases for eligible studies. The inclusion criteria encompassed randomized controlled trials (RCTs) focusing on one or more nonantibiotic interventions for UTI prevention, with the incidence of UTIs being a key outcome measure. Subgroup analyses were performed according to age, sex, and follow-up. Results 50 RCTs comprising 10,495 subjects and investigating 14 interventions, were included. Nearly 80% of the RCTs utilized double-blind or triple-blind designs. In the whole group, D-mannose (risk ratio [RR] 0.34, 0.21 to 0.56), vaccine (RR 0.65, 0.52 to 0.82), probiotics (RR 0.69, 0.50 to 0.94), cranberry (RR 0.72, 0.60 to 0.87), and triple therapy (cranberry plus probiotics plus vitamin A) (RR 0.27, 0.09 to 0.87), exhibited a significant reduction in UTI incidence compared to the placebo. Probiotics (RR 0.50, 0.28 to 0.89) were the most effective in the nonadult group, while vitamin D (RR 0.46, 0.27 to 0.81) showed the highest efficacy in the long follow-up group (≥ 1 year). There was no significant difference in the incidence of adverse events between the interventions and the placebo group. Conclusions D-mannose, triple therapy, vaccine, probiotics, and cranberry serve as potential nonantibiotic intervention options for clinical UTI prevention. …

Abstract Purpose It is unknown whether social distancing impacts frequency of presentation and severity of childhood bone and joint infection (BJI). In New Zealand, the COVID-19 disease elimination strategy involved strict social isolation policies spanning March 2020-September 2022. Examination of this period may provide insight around risk factors for BJI. Methods A retrospective review of all patients 

Abstract Background Currently, there are hundreds of hematological parameters used for rapid diagnosis of neonatal sepsis, but there is no network meta-analysis to compare the diagnostic efficacy of these parameters. Methods We searched for literature on the diagnostic neonatal sepsis and selected 20 of the most common parameters to compare their diagnostic efficacy. We used Bayesian network meta-analysis, Frequentist network meta-analysis, and individual traditional diagnostic meta-analysis to analyze the data and verify the stability of the results. Based on the above analysis, we ranked the diagnostic efficacy of 20 parameters and searched for the optimal indicator. We also conducted subgroup analysis based on different designs. GRADE was used to evaluate the quality of evidence. Results 311 articles were included in the analysis, of which 206 articles were included in the network meta-analysis. Bayesian models fond the top three of the advantage index were P-SEP, SAA, and CD64. In Individual model, P-SEP, SAA, and CD64 had the best sensitivity; ABC, SAA, and P-SEP had the best specificity. Frequentist model showed that CD64, P-SEP, and IL-10 ranked in the top three for sensitivity, while P-SEP, ABC, and I/M in specificity. Overall, P-SEP, SAA, CD64, and PCT have good sensitivity and specificity among all the three methods. The results of subgroup analysis were consistent with the overall analysis. All evidence was mostly of moderate or low quality. Conclusions P-SEP, SAA, CD64, and PCT have good diagnostic efficacy for neonatal sepsis. However, further studies are required to confirm these findings. …

Journal of Medical Virology, Volume 96, Issue 8, August 2024.

Journal of Medical Virology, Volume 96, Issue 8, August 2024.

Journal of Medical Virology, Volume 96, Issue 8, August 2024.

Journal of Medical Virology, Volume 96, Issue 8, August 2024.

Journal of Medical Virology, Volume 96, Issue 8, August 2024.

Abstract Background Klebsiella pneumoniae invasive syndrome (KPIS) is characterized by primary pyogenic liver abscess associated with metastatic infections. Although rare, Klebsiella endocarditis carries a high mortality risk. Case presentation A 60-year-old lady with type II diabetes mellitus presented with fever, malaise, right hypochondriac pain and vomiting for two weeks. Ultrasound abdomen revealed a collection within liver, and distended gallbladder with echogenic debris within. 3 days after ultrasound guided pigtail drainage of gallbladder empyema, newly presence murmur detected. Pus, urine, and blood cultures obtained were positive for Klebsiella pneumonia. Echocardiogram exhibited oscillating mass attached to anterior mitral valve leaflet. After 6 weeks of intravenous ceftriaxone, follow-up echocardiogram and ultrasound showed complete resolution of mitral valve vegetation, hepatic and gallbladder collection. Conclusion Concomitant extrahepatic infective endocarditis (IE) should raise concerns in daily practice for patients with Klebsiella pneumoniae liver abscesses, despite the rarity of Klebsiella endocarditis. In the absence of diagnostic suspicion, antibiotic treatment regimens may be shortened, and adverse effects from IE infection may ensue. …

Abstract Background Klebsiella pneumoniae invasive syndrome (KPIS) is characterized by primary pyogenic liver abscess associated with metastatic infections. Although rare, Klebsiella endocarditis carries a high mortality risk. Case presentation A 60-year-old lady with type II diabetes mellitus presented with fever, malaise, right hypochondriac pain and vomiting for two weeks. Ultrasound abdomen revealed a collection within liver, and distended gallbladder with echogenic debris within. 3 days after ultrasound guided pigtail drainage of gallbladder empyema, newly presence murmur detected. Pus, urine, and blood cultures obtained were positive for Klebsiella pneumonia. Echocardiogram exhibited oscillating mass attached to anterior mitral valve leaflet. After 6 weeks of intravenous ceftriaxone, follow-up echocardiogram and ultrasound showed complete resolution of mitral valve vegetation, hepatic and gallbladder collection. Conclusion Concomitant extrahepatic infective endocarditis (IE) should raise concerns in daily practice for patients with Klebsiella pneumoniae liver abscesses, despite the rarity of Klebsiella endocarditis. In the absence of diagnostic suspicion, antibiotic treatment regimens may be shortened, and adverse effects from IE infection may ensue. …

Abstract Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH. …

Abstract Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH. …

Abstract Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH. …