Founded amid the COVID-19 pandemic, the WHO Hub for Epidemic and Pandemic Intelligence hopes to strengthen global surveillance but faces substantial challenges. By Udani Samarasekera.

This study provides a comprehensive global picture of HPV genotype-specific AFs in ICC, before the influence of HPV vaccination. These data can inform HPV genotype-specific vaccination and screening strategies to reduce the burden of ICC.

Nemolizumab plus TCS–TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved.

Children are not born equal in their likelihood of survival. The risk of mortality is highest during and shortly after birth. In the immediate postnatal period and beyond, perinatal events, nutrition, infections, family and environmental exposures, and health services largely determine the risk of death. We argue that current public health programmes do not fully acknowledge this spectrum of risk or respond accordingly. As a result, opportunities to improve the care, survival, and development of children in resource-poor settings are overlooked.

Science, Volume 385, Issue 6708, Page 479-480, August 2024.

Science, Volume 385, Issue 6708, Page 478-479, August 2024.

Abstract Interactions between eukaryotic hosts and their bacterial symbionts drive key ecological and evolutionary processes, from regulating ecosystems to the evolution of complex molecular machines and processes. Over time, endosymbionts generally evolve reduced genomes, and their relationship with their host tends to stabilize. However, host-bacteria relationships may be heavily influenced by environmental changes. Here, we review these effects on one of the most ancient and diverse endosymbiotic groups, formed by - among others - Legionellales, Francisellaceae, and Piscirickettsiaceae. This group is referred to as Deep-branching Intracellular Gammaproteobacteria (DIG), whose last common ancestor presumably emerged about 2 Ga ago. We show that DIGs are globally distributed, but generally very lowly abundant, and are mainly identified in aquatic biomes. Most DIGs harbor a type IVB secretion system, critical for host-adaptation, but its structure and composition vary. Finally, we review the different types of microbial interactions that can occur in diverse environments, with direct or indirect effects on DIG populations. The increased use of omics technologies on environmental samples will allow a better understanding of host-bacterial interactions and help unravel the definition of DIG as a group from an ecological, molecular and evolutionary perspective.

Tropical Medicine &International Health, Volume 29, Issue 8, Page i-iv, August 2024.

Treatment with either dose of fosravuconazole was not superior to itraconazole, and the two doses had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug–drug interactions compared with the relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery are warranted.

by Miguel Ángel González-Block, Emilio Gutiérrez-Calderón, Blanca Estela Pelcastre-Villafuerte, Juan Arroyo-Laguna, Yamila Comes, Pedro Crocco, Andréa Fachel-Leal, Laura Noboa, Daniela Riva-Knauth, Berenice Rodríguez-Zea, Mónica Ruoti, Elsa Sarti, Esteban Puentes-Rosas …

by Edward Mullins, Ruth McCabe, Sheila M. Bird, Paul Randell, Marcus J. Pond, Lesley Regan, Eleanor Parker, Myra McClure, Christl A. Donnelly …

by Shuchuan Miao, Xiaoyan Wang, Lu Ma, Chao You Background Current evidence linking sedentary behavior (SB), physical activity (PA), and inflammation raises questions about their causal relationships, prompting concerns about potential residual confounding or reverse causation. Methods A bidirectional Mendelian randomization (MR) analysis was conducted. SB data (n = 408,815) from “computer use,” “television watching,” and “driving” were included. The PA data encompassed nine types of PA (n = 460,376) over the last four weeks and included data on the frequency of vigorous PA (n = 440,512) and moderate PA (n = 440,266) for over 10 min. Additionally, three genome-wide association study datasets (n = 64,949) on light, moderate, and vigorous exercise were included to minimize potential bias from changes in exercise intensity. Inflammation data included levels of C-reactive protein (CRP) (n = 575,531), glycoprotein acetyl (GlycA) (n = 115,082), interleukin (IL)-8, IL-6, IL-6 receptor (IL-6R), and soluble IL-6R (sIL-6R) (n = 35,278). All datasets represented participants of European ancestry. Results Television watching as an SB showed significant positive causal effects on GlycA and CRP (inverse variance weighted (IVW), odds ratios (OR): 1.34, 95% confidence intervals (CI): 1.25–1.44, p = 3.570 × 10−17; IVW, OR: 1.21, 95% CI: 1.16–1.26, p = 1.500 × 10−19, respectively), with more robust evidence for GlycA. In the direction from inflammation to PA, a negative causal relationship between CRP and“number of days/week of moderate PA 10+ minutes”was observed (IVW, OR: 0.92, 95% CI: 0.89–0.96, p = 3.260 × 10−5). Sensitivity analyses were used to verify the robustness and reliability of the results. However, other initially observed associations ceased to be significant after controlling for obesity-related confounders. Conclusion Our MR analysis suggested a potential causal relationship between television watching and chronic low-grade inflammation, with more substantial evidence for GlycA. Additionally, different types of SB may have varying effects on inflammation. Obesity-related traits could partly or entirely influence the relationship between SB, PA, and inflammatory markers. Furthermore, Our findings indicate that SB is an independent risk factor for inflammation, separate from PA, and highlight the different mechanisms by which SB and PA affect disease. …

by Kasem U. Salim, Francisco S. Álvarez, Alec M. Chan-Golston, Colleen C. Naughton, Ricardo Cisneros, Andrea Joyce Dengue fever is a mosquito-borne illness that infects 390 million people annually. Dengue outbreaks in Guatemala have been occurring more often and at increased rates since the first dengue outbreak in Guatemala in the 1970s. This study will examine environmental and socioeconomic factors associated with dengue in Guatemala at the municipality (county) level. Socioeconomic factors included population density, Mayan population, economic activity, and attending school. Environmental factors included average minimum annual temperature and annual precipitation. The relationship between environmental and socioeconomic variables and dengue fever incidence was initially evaluated through univariate zero-inflated negative binomial models, and then again through three zero-inflated multivariate negative binomial regression models. For all three models, elevation was considered a predictor of zero-inflation. In the combined model, there was a positive relationship between minimum temperature, economic activity and dengue fever incidence, and a negative relationship between population density, Mayan population and dengue fever. Predicted rates of dengue fever incidence and adjusted confidence intervals were calculated after increasing minimum yearly temperature by 1°C and 2°C. The three municipalities with the highest minimum yearly temperature (El Estor, Iztapa, and Panzós) and the municipality of Guatemala, all had an increase in the magnitude of the risk of dengue fever incidence following 1°C and 2°C increase in temperature. This research suggests that these socioeconomic and environmental factors are associated with risk of dengue in Guatemala. The predicted rates of dengue fever also highlight the potential effect that climate change in the form of increasing temperature can have on dengue in Guatemala.

by Elizabeth A. Miller, Rachel Amato, Julia B. Ponder, Irene Bueno Antimicrobial resistance is a global health concern. As such, there have been increased efforts to monitor and standardize antimicrobial prescribing practices in humans and domestic animals. In contrast, there is relatively little known about specific prescribing practices in wild animals despite the wide use of antimicrobials and other microbial interventions, such as probiotics to treat captive wildlife. Therefore, the goal of this study was to examine current antimicrobial and probiotic use from a cross-section of wildlife rehabilitation facilities in the United States. An anonymous electronic survey was sent to 105 United States permitted wildlife facilities to collect information about admissions, current antimicrobial and probiotic use practices, and current staff knowledge and attitudes surrounding antimicrobial resistance and probiotic effectiveness. Respondents from over 50% of facilities participated in the survey (54/105), including 45 facilities that treated birds. All facilities reported using antimicrobials, including some from groups considered critically important for human medicine, for a wide range of medical conditions and prophylaxis. Among antibiotics, enrofloxacin and amoxicillin-clavulanic acid were the most commonly used. Antifungals were not as widespread, but itraconazole was the most commonly used. Over 75% of respondents said that their facilities would benefit from having standardized antimicrobial guidelines in place. Probiotics were also used in more than 50% of facilities, but there was notable disparity in opinions regarding their efficacy. The results of this survey are a first step towards understanding antimicrobial and probiotic use practices in the treatment of captive wildlife and developing an antimicrobial stewardship program for wildlife rehabilitation.

by Nour M. Alkashef, Mohamed N. Seleem Cryptococcosis is a fungal infection that is becoming increasingly prevalent worldwide, particularly among individuals with compromised immune systems, such as HIV patients. Amphotericin B (AmB) is the first-line treatment mainly combined with flucytosine. The scarcity and the prohibitive cost of this regimen urge the use of fluconazole as an alternative, leading to increased rates of treatment failure and relapses. Therefore, there is a critical need for efficient and cost-effective therapy to enhance the efficacy of AmB. In this study, we evaluated the efficacy of the HIV protease inhibitors (PIs) to synergize the activity of AmB in the treatment of cryptococcosis. Five PIs (ritonavir, atazanavir, saquinavir, lopinavir, and nelfinavir) were found to synergistically potentiate the killing activity of AmB against Cryptococcus strains with ƩFICI ranging between 0.09 and 0.5 against 20 clinical isolates. This synergistic activity was further confirmed in a time-kill assay, where different AmB/PIs combinations exhibited fungicidal activity within 24 hrs. Additionally, PIs in combination with AmB exhibited an extended post-antifungal effect on treated cryptococcal cells for approximately 10 hrs compared to 4 hours with AmB alone. This promising activity against cryptococcal cells did not exhibit increased cytotoxicity towards treated kidney cells, ruling out the risk of drug combination-induced nephrotoxicity. Finally, we evaluated the efficacy of AmB/PIs combinations in the Caenorhabditis elegans model of cryptococcosis, where these combinations significantly reduced the fungal burden of the treated nematodes by approximately 2.44 Log10 CFU (92.4%) compared to the untreated worms and 1.40 Log10 ((39.4%) compared to AmB alone. The cost-effectiveness and accessibility of PIs in resource-limited geographical areas compared to other antifungal agents, such as flucytosine, make them an appealing choice for combination therapy.

by Sara D’Arcangelo, Paola Di Fermo, Firas Diban, Vincenzo Ferrone, Simonetta D’Ercole, Mara Di Giulio, Silvia Di Lodovico The imbalance in skin microbiota is characterized by an increased number of pathogens in respect to commensal microorganisms. Starting from a skin microbiota collection, the aim of this work was to evaluate the possible role of Pomegranate (Punica granatum L.) Peel Extract (PPE) in restoring the skin microbiota balance acting on Staphylococcus spp. PPE was extracted following green methodology by using n-butane and the Dimethyl Ether (DME) solvents and analyzed for phytochemical composition and antimicrobial activity. The PPE antimicrobial action was evaluated against Gram +, Gram − bacteria and yeast reference strains and the most effective extract was tested against the main skin microbiota isolated strains. PPE extracted with DME showed the best antimicrobial action with MICs ranging from 1 to 128 mg/mL; the main active compounds were Catechin, Quercetin, Vanillic acid and Gallic acid. The PPE in DME anti-adhesive effect was examined against S. epidermidis and S. aureus mono and dual-species biofilm formation by biomass quantification and CFU/mL determination. The extract toxicity was evaluated by using Galleria mellonella larvae in vivo model. The extract displayed a significant anti-adhesive activity with a remarkable species-specific action at 4 and 8 mg/mL against S. epidermidis and S. aureus mono and dual-species biofilms. PPE in DME could represent an eco-sustainable non-toxic strategy to affect the Staphylococcal skin colonization in a species-specific way. The innovation of this work is represented by the reuse of food waste to balance skin microbiota.

by Dinaol Bedada Dibaba, Bezatu Mengistie Alemu, Sisay Abebe Debela The Water, Sanitation, and Hygiene (WASH) interventions have been acknowledged for their role in the public health and educational outcomes. While there are strong evidences that reveal that WASH facilities do reduce the prevalence of infectious diseases and improve the learning environment, data remain thin and equivocal on the differential impacts of WASH facilities on education by gender. The literature reviewed does not, in most cases; go to the extent of investigating if indeed both men and women students have unique needs especially in underprivileged areas. This is the point from which the present systematic review and meta-analysis intend to fill this gap by assessing the global evidence on the effect of WASH interventions on educational outcomes with due consideration given to gender. This systematic review will include international databases used for the search, such as PubMed, Google Scholar, Web of Science, Europe PubMed Central, and Scopus. Study eligibility will include cross-sectional studies published in English on the impact of WASH interventions on school attendance and academic performance, stratifying gender-specific outcomes. Data extracted will be analyzed using the STATA software version 17. The percentage of heterogeneity will be quantified through the I2 statistics to show the variability between the included studies. Based on the observed results, diversity will be checked among the outcomes of the study and based on that random-effect model will be used to estimate the pooled effect size. I will, therefore, make use of the Egger and Begg tests for checking statistical asymmetry. Publication bias will be assessed with funnel plots. These will ensure the methodologies used provide comprehensive and rigorous data analysis, which will give strong insights into the impacts of the WASH intervention on educational outcomes.Prospero registration number: Systematic review and Meta-analysis registration number: PROSPERO CRD42024536477.

by Kennedy O. Ogolla, Douglas N. Anyona, Judith K. Chemuliti, Winnie W. Kimani, Francisca M. King’oo, Kennedy M. Waweru, Dalmas O. Omia, Isaac K. Nyamongo, Salome A. Bukachi In the absence of effective drugs, vaccines constitute the cornerstone for the prevention of Newcastle disease (ND). Different strategies have been implemented to increase vaccination, but uptake remains low, underscoring the need for novel vaccine delivery methods. We designed and assessed the effectiveness of a community-centered ND vaccine delivery model in southeastern Kenya. Under the model, we sensitized smallholder chicken farmers (SCFs) through structured training on chicken husbandry, biosecurity, ND, and its vaccination, among other aspects. We subsequently engaged trained community vaccinators (CVs) to deliver vaccines and/or provide vaccination services to SCFs at a cost on one hand and, at no cost on the other, in selected sites to address challenges of inadequate service providers, vaccine unavailability, and inaccessibility. We tested this model under paid and free vaccination frameworks over one year and assessed the model’s effect on vaccine uptake, ND-related deaths, and vaccine accessibility, among other aspects. Overall, we vaccinated more chickens at free sites compared to paid sites. However, we vaccinated a significantly higher mean number of chickens per household at paid (49.4±38.5) compared to free (28.4±25.9) sites (t = 8.4, p…

by Rong Chen, Qiaoling Bao, Xiaofeng Ma Background Inflammatory cytokines play a major role in the pathogenesis of myocardial infarction (MI). Although information on the importance of interleukin 13 (IL13) in human MI is limited, it has been well documented in the mouse model. Genetic variation in the IL13 gene has been associated with the structure and expression of the IL13. In the present study, we hypothesized that IL13 common genetic variants would be associated with a predisposition to the development of MI. Materials and methods The present study enrolled 305 MI patients and 310 matched healthy controls. Common genetic polymorphisms in the IL13 gene (rs20541, rs1881457, and rs1800925) were genotyped using the TaqMan SNP genotyping method. Plasma levels of IL13 were measured using an enzyme-linked immunosorbent assay (ELISA). Results In MI patients, minor alleles of the IL13 rs1881457 and rs1800925 polymorphisms were less common than in healthy controls [rs1881457: AC (P = 0.004, OR = 0.61), C (P = 0.001, OR = 0.66); rs1800925: CT (P = 0.006, OR = 0.59)]. Further haplotype analysis of three studied SNPs revealed a significant association with predisposition to MI. Interestingly, IL13 rs1881457 and rs1800925 were linked to plasma levels of IL13: the reference genotype had higher levels, heterozygotes were intermediate, and the alternate genotype had the lowest levels. Conclusions In the Chinese population, IL13 (rs1881457 and rs180092) variants are associated with different plasma IL13 levels and offer protection against MI development. However, additional research is required to validate our findings in different populations, including descent samples. …

by Elisa Villa-Martínez, Amelia Rios, Roxana Gutiérrez-Vidal, Bruno Escalante Nitric oxide (NO) regulates vascular homeostasis and plays a key role in revascularization and angiogenesis. The endothelial nitric oxide synthase (eNOS) enzyme catalyzes NO production in endothelial cells. Overexpression of the eNOS gene has been implicated in pathologies with dysfunctional angiogenic processes, such as cancer. Therefore, modulating eNOS gene expression using small interfering RNAs (siRNAs) represents a viable strategy for antitumor therapy. siRNAs are highly specific to the target gene, thus reducing off-target effects. Given the widespread distribution of endothelium and the crucial physiological role of eNOS, localized delivery of nucleic acid to the affected area is essential. Therefore, the development of an efficient eNOS-siRNA delivery carrier capable of controlled release is imperative for targeting specific vascular regions, particularly those associated with tumor vascular growth. Thus, this study aims to utilize ultrasound-mediated microbubble destruction (UMMD) technology with cationic microbubbles loaded with eNOS-siRNA to enhance transfection efficiency and improve siRNA delivery, thereby preventing sprouting angiogenesis. The efficiency of eNOS-siRNA transfection facilitated by UMMD was assessed using bEnd.3 cells. Synthesis of nitric oxide and eNOS protein expression were also evaluated. The silencing of eNOS gene in a model of angiogenesis was assayed using the rat aortic ring assay. The results showed that from 6 to 24 h, the transfection of fluorescent siRNA with UMMD was twice as high as that of lipofection. Moreover, transfection of eNOS-siRNA with UMMD enhanced the knockdown level (65.40 ± 4.50%) compared to lipofectamine (40 ± 1.70%). Silencing of eNOS gene with UMMD required less amount of eNOS-siRNA (42 ng) to decrease the level of eNOS protein expression (52.30 ± 0.08%) to the same extent as 79 ng of eNOS-siRNA using lipofectamine (56.30 ± 0.10%). NO production assisted by UMMD was reduced by 81% compared to 67% reduction transfecting with lipofectamine. This diminished NO production led to higher attenuation of aortic ring outgrowth. Three-fold reduction compared to lipofectamine transfection. In conclusion, we propose the combination of eNOS-siRNA and UMMD as an efficient, safe, non-viral nucleic acid transfection strategy for inhibition of tumor progression.

Abstract Background Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. Methods Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. Results Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5–14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p 

Abstract Background Plasmodium falciparum, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-based combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs, such as lumefantrine, mefloquine, and amodiaquine. However, the urgency for new treatments has risen due to the parasite\'s growing resistance to existing therapies. In this study, a common characteristic of the P. falciparum proteome—stretches of poly-lysine residues, such as those found in proteins related to adhesion and pathogenicity—is investigated for its potential to treat infected erythrocytes. Methods This study utilizes in vitro culturing of intra-erythrocytic P. falciparum to assess the ability of poly-lysine peptides to inhibit the parasite’s growth, measured via flow cytometry of acridine orange-stained infected erythrocytes. The inhibitory effect of many poly-lysine lengths and modifications were tested this way. Affinity pull-downs and mass spectrometry were performed to identify the proteins interacting with these poly-lysines. Results A single dose of these poly-basic peptides can successfully diminish parasitemia in human erythrocytes in vitro with minimal toxicity. The effectiveness of the treatment correlates with the length of the poly-lysine peptide, with 30 lysine peptides supporting the eradication of erythrocytic parasites within 72 h. PEG-ylation of the poly-lysine peptides or utilizing poly-lysine dendrimers and polymers retains or increases parasite clearance efficiency and bolsters the stability of these potential new therapeutics. Lastly, affinity pull-downs and mass-spectrometry identify P. falciparum’s outer membrane proteins as likely targets for polybasic peptide medications. Conclusion Since poly-lysine dendrimers are already FDA-approved for drug delivery and this study displays their potency against intraerythrocytic P. falciparum, their adaptation as anti-malarial drugs presents a promising new therapeutic strategy for malaria. …

Abstract Background Spatial repellents can provide personal and household protection against biting vector mosquitoes by volatizing repellents into the air within a given area. Mosquito Shield™ is a transfluthrin passive emanator undergoing evaluation for malaria control. Studies evaluating its entomological impact against different local malaria vector populations would help guide its deployment in endemic countries. Methods A two-arm single-blinded small-scale household randomised entomological trial was conducted to assess the impact of Mosquito Shield™ on the human landing rate of wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) vector mosquitoes in houses in the Ganhoua village of the Zakpota District of central Benin. From a total of 30 houses, 15 were randomly allocated to receive Mosquito Shield™, while the remainder received a placebo product. The trial lasted through the life of the Mosquito Shield™ product (32 days). Mosquito sampling was performed by human landing catches at baseline and at 6 timepoints post-intervention (days 0–1, 7–8, 14–15, 21–22, 28–29 and 31–32). Collections were performed for 2 nights at each sampling time point. WHO cylinder bioassays were conducted during the trial with F1 An. gambiae s.l. mosquitoes that emerged from larvae from the study area to assess the intensity of resistance to pyrethroids in the wild vector population. Results The vector population in the study area showed a high intensity of resistance to pyrethroids. Baseline An. gambiae s.l. human landing rates were similar in houses in both study arms before product application (11.53/person/night vs 11.67/person/night, p > 0.05). A total of 5736 mosquitoes were collected in the placebo control arm and 3862 in the Mosquito Shield™ arm post-intervention. Overall An. gambiae s.l. post-intervention human landing rates were significantly lower in houses in the Mosquito Shield™ arm (18.13/person/night) compared to the houses in the placebo control arm (26.84/person/night, IRR = 0.658, p 

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

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

Background: South Africa has a high HIV incidence and oral pre-exposure prophylaxis (PrEP) is available as public-sector standard of care. Access to alternative prevention methods for women may further reduce HIV acquisition. Setting: South African public-sector. Methods: We performed a systematic search for high-quality up-to-date guidelines recommending dapivirine ring as PrEP using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-Adolopment process. We appraised the systematic review and randomised controlled trial (RCT) evidence underpinning the selected guideline’s recommendations and conducted a cost-effectiveness analysis. The GRADE Evidence-to-Decision framework guided the adaptation of source guideline recommendations, according to our local context. Results: We identified the 2021 World Health Organization PrEP Guidelines, informed by two placebo-controlled RCTs, which were included in a contemporaneous systematic review. There were 23 fewer HIV acquisitions per 1000 clients with dapivirine ring versus placebo (95% confidence interval 10-34), with no increase in adverse events (moderate certainty evidence). We found no RCTs comparing dapivirine to oral PrEP, or amongst adolescent/pregnant/breastfeeding clients. Dapivirine is less cost-effective than oral PrEP at $14.59/ring, at the current price. Conclusion: The source guideline recommendation was adapted for the local context. Dapivirine ring appears to be less efficacious than oral PrEP, although comparative studies are lacking. Data in adolescents and pregnancy are also lacking, currently limiting the use of dapivirine as an alternative for women unable to take oral PrEP. At the current price, dapivirine is not cost-effective and unaffordable for inclusion in the South African Essential Medicines List. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Abstract Background This study aimed to investigate existing evidence regarding the associations of obesity and diabetes with Plasmodium infection and severe malaria in adults.Methods We comprehensively searched relevant studies using EMBASE, MEDLINE, Global Health, and CINAHL. The primary exposures were obesity and diabetes. The primary outcomes were Plasmodium infection and severe malaria. We performed meta-analyses to pool unadjusted and adjusted odds ratios (ORs) using a random-effects model.Results We found 9 studies that met our inclusion criteria; all these studies were eligible for meta-analyses. None of the 9 studies investigated the potential link between obesity and Plasmodium infection. The meta-analysis results showed that there was no statistically significant relationship between obesity and severe malaria (two studies), diabetes and Plasmodium infection (five studies), or diabetes and severe malaria (three studies).Conclusion Our study findings showed that obesity was not associated with severe malaria, and diabetes was not associated with neither Plasmodium infection nor severe malaria. Additional epidemiological studies should be conducted to elucidate the relationships between obesity, diabetes, and Plasmodium infection.

Abstract Malaria elimination relies on detection of Plasmodium falciparum Histidine-Rich Proteins 2/3 (HRP2/3) through rapid diagnostic tests (RDTs) and treatment with artemisinin-combination therapies (ACTs). Data from the Horn of Africa suggest increasing hrp2/3 gene deletions and ACT partial resistance kelch13 (k13) mutations. To assess this, 233 samples collected during a national survey from 7 regions of Ethiopia were studied for hrp2/3 deletions by droplet digital dPCR and k13 mutations by DNA sequencing. Approximately 22% of the study population harbored complete hrp2/3 deletions by ddPCR. Thirty-two of 42 of k13 SNPs identified were R622I associated with ACT partial resistance. Both hrp2/3 deletions and k13 mutations associated with ACT partial resistance appear to be co-occurring especially in Northwest Ethiopia. Ongoing national surveillance relying on accurate laboratory methods are required to fully elaborate the genetic diversity of P. falciparum to inform public health policy makers.

Abdala COVID-19 vaccine is an alum adjuvanted recombinant protein subunit vaccine based on the receptor binding domain (RBD) of the spike protein of SARS-CoV-2 [1]. It was developed by the Center for Genetic Engineering and Biotechnology in Habana, Cuba in early 2021, and has been widely deployed in Cuba since July 2021 [1, 2]. The primary series consists of three doses administered intramuscularly on days 0, 14 and 28.

ObjectiveThis meta-analysis aimed to estimate the national prevalence of postpartum depression (PPD) in Uganda and identify predictors in both pre-COVID-19 and post-COVID-19 eras. DesignUsed a systematic review and meta-analysis methodology. Data sourcesReviewed papers were sourced from Medline/PubMed, PsycINFO, CINAHL/EBSCOhost, Google Scholar, ScienceDirect and African Journals Online. Eligibility criteria for selected studiesThe review encompassed observational studies published on PPD in Uganda from 1 January 2000 to 30 November 2023. Results11 studies (involving 7564 participants) published from 1 January 2000 to 30 November 2023 were reviewed. The pooled prevalence of PPD in Uganda was 29% (95% CI 21% to 37%, I2=98.32%). Subgroup analysis indicated a similar prevalence before (29%, 95% CI 20% to 39%) and during (28%, 95% CI 22% to 32%) the COVID-19 period. Special groups exhibited a higher prevalence (32%, 95% CI 16% to 47%) than general postpartum women (28%, 95% CI 19% to 37%). Factors associated with PPD included poor social support (OR 1.19, 95% CI 1.17 to 1.22, I2=96.8%), maternal illness (OR 1.22, 95% CI 1.19 to 1.26, I2=96.9%), poor socioeconomic status (OR 1.43, 95% CI 1.40 to 1.46, I2=99.5%) and undergoing caesarean section (OR 1.15, 95% CI 1.12 to 1.17, I2=80.6%). Surprisingly, there was a marginal decrease in PPD during the COVID-19 period. Subgroup analysis highlighted a higher prevalence among mothers with HIV. ConclusionThis study underscores the significant prevalence of PPD in Uganda, with sociodemographic factors increasing risk. Despite a slight decrease during the COVID-19 period, the importance of prioritising maternal mental health is emphasised, considering sociodemographic factors and pandemic challenges, to improve maternal and child health outcomes and overall well-being. …

ObjectiveThis meta-analysis aimed to estimate the national prevalence of postpartum depression (PPD) in Uganda and identify predictors in both pre-COVID-19 and post-COVID-19 eras. DesignUsed a systematic review and meta-analysis methodology. Data sourcesReviewed papers were sourced from Medline/PubMed, PsycINFO, CINAHL/EBSCOhost, Google Scholar, ScienceDirect and African Journals Online. Eligibility criteria for selected studiesThe review encompassed observational studies published on PPD in Uganda from 1 January 2000 to 30 November 2023. Results11 studies (involving 7564 participants) published from 1 January 2000 to 30 November 2023 were reviewed. The pooled prevalence of PPD in Uganda was 29% (95% CI 21% to 37%, I2=98.32%). Subgroup analysis indicated a similar prevalence before (29%, 95% CI 20% to 39%) and during (28%, 95% CI 22% to 32%) the COVID-19 period. Special groups exhibited a higher prevalence (32%, 95% CI 16% to 47%) than general postpartum women (28%, 95% CI 19% to 37%). Factors associated with PPD included poor social support (OR 1.19, 95% CI 1.17 to 1.22, I2=96.8%), maternal illness (OR 1.22, 95% CI 1.19 to 1.26, I2=96.9%), poor socioeconomic status (OR 1.43, 95% CI 1.40 to 1.46, I2=99.5%) and undergoing caesarean section (OR 1.15, 95% CI 1.12 to 1.17, I2=80.6%). Surprisingly, there was a marginal decrease in PPD during the COVID-19 period. Subgroup analysis highlighted a higher prevalence among mothers with HIV. ConclusionThis study underscores the significant prevalence of PPD in Uganda, with sociodemographic factors increasing risk. Despite a slight decrease during the COVID-19 period, the importance of prioritising maternal mental health is emphasised, considering sociodemographic factors and pandemic challenges, to improve maternal and child health outcomes and overall well-being. …

ObjectiveThis meta-analysis aimed to estimate the national prevalence of postpartum depression (PPD) in Uganda and identify predictors in both pre-COVID-19 and post-COVID-19 eras. DesignUsed a systematic review and meta-analysis methodology. Data sourcesReviewed papers were sourced from Medline/PubMed, PsycINFO, CINAHL/EBSCOhost, Google Scholar, ScienceDirect and African Journals Online. Eligibility criteria for selected studiesThe review encompassed observational studies published on PPD in Uganda from 1 January 2000 to 30 November 2023. Results11 studies (involving 7564 participants) published from 1 January 2000 to 30 November 2023 were reviewed. The pooled prevalence of PPD in Uganda was 29% (95% CI 21% to 37%, I2=98.32%). Subgroup analysis indicated a similar prevalence before (29%, 95% CI 20% to 39%) and during (28%, 95% CI 22% to 32%) the COVID-19 period. Special groups exhibited a higher prevalence (32%, 95% CI 16% to 47%) than general postpartum women (28%, 95% CI 19% to 37%). Factors associated with PPD included poor social support (OR 1.19, 95% CI 1.17 to 1.22, I2=96.8%), maternal illness (OR 1.22, 95% CI 1.19 to 1.26, I2=96.9%), poor socioeconomic status (OR 1.43, 95% CI 1.40 to 1.46, I2=99.5%) and undergoing caesarean section (OR 1.15, 95% CI 1.12 to 1.17, I2=80.6%). Surprisingly, there was a marginal decrease in PPD during the COVID-19 period. Subgroup analysis highlighted a higher prevalence among mothers with HIV. ConclusionThis study underscores the significant prevalence of PPD in Uganda, with sociodemographic factors increasing risk. Despite a slight decrease during the COVID-19 period, the importance of prioritising maternal mental health is emphasised, considering sociodemographic factors and pandemic challenges, to improve maternal and child health outcomes and overall well-being. …

BackgroundLoss to follow-up (LTFU) among paediatric patients living with HIV presents a significant challenge to the global scale-up of life-saving antiretroviral therapy (ART). ObjectivesThis study aims to estimate LTFU incidence and its determinants among children with HIV on ART in Shashemene town public health institutions, Oromia, Ethiopia. DesignA retrospective cohort study from 1 January 2015 to 30 December 2020. SettingThis study was conducted in Shashemene town, Oromia, Ethiopia. ParticipantsMedical records of 269 children receiving ART at health facilities in Shashemene town were included. MethodsData from patients’ medical records were collected using a standardised checklist. EpiData V.3.1 was employed for data entry, while Statistical Package for the Social Sciences (SPSS) V.25 facilitated analysis. The Kaplan-Meier survival curve was used for estimation of survival time. To measure association, adjusted HRs (AHRs) with 95% CIs were calculated. Both bivariable and multivariable Cox proportional hazards regression models were employed to identify predictors of LTFU. ResultsOf the 269 children living with HIV included in the final analysis, 43 (16%) were lost to follow-up. The overall incidence rate of LTFU was 3.3 (95% CI 2.4 to 4.4) per 100 child-years of observation. Age less than 5 years (AHR 0.03, 95% CI 0.00 to 0.36), non-orphan status of the child (AHR 0.13, 95% CI 0.05 to 0.34), < 30 min distance to health facility (AHR 0.24, 95% CI 0.08 to 0.73), disclosed HIV status (AHR 0. 32, 95% CI 0.13 to 0.80), history of opportunistic infection (AHR 3.54, 95% CI 1.15 to 10.87) and low CD4 count (AHR 5.17, 95% CI 2.08 to 12.85) were significant predictors of LTFU. ConclusionThe incidence rate of LTFU was lower compared with other studies in Ethiopia. This result indicated that age less than 5 years, non-orphans, low CD4, disclosed HIV status and distance from health facility were predictors of LTFU. …

BackgroundLoss to follow-up (LTFU) among paediatric patients living with HIV presents a significant challenge to the global scale-up of life-saving antiretroviral therapy (ART). ObjectivesThis study aims to estimate LTFU incidence and its determinants among children with HIV on ART in Shashemene town public health institutions, Oromia, Ethiopia. DesignA retrospective cohort study from 1 January 2015 to 30 December 2020. SettingThis study was conducted in Shashemene town, Oromia, Ethiopia. ParticipantsMedical records of 269 children receiving ART at health facilities in Shashemene town were included. MethodsData from patients’ medical records were collected using a standardised checklist. EpiData V.3.1 was employed for data entry, while Statistical Package for the Social Sciences (SPSS) V.25 facilitated analysis. The Kaplan-Meier survival curve was used for estimation of survival time. To measure association, adjusted HRs (AHRs) with 95% CIs were calculated. Both bivariable and multivariable Cox proportional hazards regression models were employed to identify predictors of LTFU. ResultsOf the 269 children living with HIV included in the final analysis, 43 (16%) were lost to follow-up. The overall incidence rate of LTFU was 3.3 (95% CI 2.4 to 4.4) per 100 child-years of observation. Age less than 5 years (AHR 0.03, 95% CI 0.00 to 0.36), non-orphan status of the child (AHR 0.13, 95% CI 0.05 to 0.34), < 30 min distance to health facility (AHR 0.24, 95% CI 0.08 to 0.73), disclosed HIV status (AHR 0. 32, 95% CI 0.13 to 0.80), history of opportunistic infection (AHR 3.54, 95% CI 1.15 to 10.87) and low CD4 count (AHR 5.17, 95% CI 2.08 to 12.85) were significant predictors of LTFU. ConclusionThe incidence rate of LTFU was lower compared with other studies in Ethiopia. This result indicated that age less than 5 years, non-orphans, low CD4, disclosed HIV status and distance from health facility were predictors of LTFU. …

BackgroundLoss to follow-up (LTFU) among paediatric patients living with HIV presents a significant challenge to the global scale-up of life-saving antiretroviral therapy (ART). ObjectivesThis study aims to estimate LTFU incidence and its determinants among children with HIV on ART in Shashemene town public health institutions, Oromia, Ethiopia. DesignA retrospective cohort study from 1 January 2015 to 30 December 2020. SettingThis study was conducted in Shashemene town, Oromia, Ethiopia. ParticipantsMedical records of 269 children receiving ART at health facilities in Shashemene town were included. MethodsData from patients’ medical records were collected using a standardised checklist. EpiData V.3.1 was employed for data entry, while Statistical Package for the Social Sciences (SPSS) V.25 facilitated analysis. The Kaplan-Meier survival curve was used for estimation of survival time. To measure association, adjusted HRs (AHRs) with 95% CIs were calculated. Both bivariable and multivariable Cox proportional hazards regression models were employed to identify predictors of LTFU. ResultsOf the 269 children living with HIV included in the final analysis, 43 (16%) were lost to follow-up. The overall incidence rate of LTFU was 3.3 (95% CI 2.4 to 4.4) per 100 child-years of observation. Age less than 5 years (AHR 0.03, 95% CI 0.00 to 0.36), non-orphan status of the child (AHR 0.13, 95% CI 0.05 to 0.34), < 30 min distance to health facility (AHR 0.24, 95% CI 0.08 to 0.73), disclosed HIV status (AHR 0. 32, 95% CI 0.13 to 0.80), history of opportunistic infection (AHR 3.54, 95% CI 1.15 to 10.87) and low CD4 count (AHR 5.17, 95% CI 2.08 to 12.85) were significant predictors of LTFU. ConclusionThe incidence rate of LTFU was lower compared with other studies in Ethiopia. This result indicated that age less than 5 years, non-orphans, low CD4, disclosed HIV status and distance from health facility were predictors of LTFU. …

ObjectiveThere is limited information regarding the incidence of treatment-related adverse events (AE) following antiretroviral therapy (ART) in women. So, this review aimed to describe the incidence of AE of ART in women living with HIV/AIDS. DesignSystematic review and meta-analysis. Data sourcesMedline, Embase, Cochrane Library, Epistemonikos, Lilacs and Who Index, from inception to 9 April 2023. Eligibility criteriaWe included randomised controlled trials with at least 12 weeks of follow-up and evaluated AE of ART in women at any age living with HIV/AIDS, without restrictions on status, year or language of publication. We excluded post hoc or secondary analyses and open-label extensions without comparator, and trials involving pregnant or breastfeeding women or with a focus on coinfection with tuberculosis, hepatitis B or C. The primary outcomes were the incidence rate of participants with any clinical and/or laboratory AE related or not to ART and treatment discontinuation. Data extraction and synthesisTwo independent reviewers extracted data and assessed the risk of bias using Cochrane’s risk of bias tool 2. We used Bayesian random-effects meta-analysis to summarise event rates. Results were presented as event rates per 1000 person-years (95% credibility intervals, 95% CrI). The pooled incidence rate per 1000 person-years adjusted for duration and loss to follow-up was estimated. We assessed the certainty of the evidence using Grading of Recommendations, Assessment, Development and Evaluation. ResultsA total of 24 339 studies were identified for screening, of which 10 studies (2871 women) met the eligibility criteria, with 11 different antiretrovirals (ARVs) regimens. Seven studies included exclusively women, while in the remaining three, the proportion of women ranged from 11% to 46%. Nine studies received industry funding. The pooled analysis showed a mean incidence rate of ART-related clinical and laboratory AE of 341.60 events per 1000 person-years (95% CrI 133.60–862.70), treatment discontinuation of 20.78 events per 1000 person-years (95% CrI 5.58–57.31) and ART-related discontinuation of 4.31 per 1000 person-years (95% CrI 0.13–54.72). Summary estimates were subject to significant uncertainty due to the limited number of studies and sparse data. The certainty of the evidence was graded as very low for all outcomes assessed. ConclusionExisting randomised trials do not provide sufficient evidence on the incidence rates of safety outcomes from antiretroviral treatment in women living with HIV/AIDS. Large comparative studies in well-characterised populations are needed to provide a more comprehensive landscape of the safety profile of these ARV therapies in women with HIV/AIDS. PROSPERO registration numberCRD42021251051. …

ObjectiveThere is limited information regarding the incidence of treatment-related adverse events (AE) following antiretroviral therapy (ART) in women. So, this review aimed to describe the incidence of AE of ART in women living with HIV/AIDS. DesignSystematic review and meta-analysis. Data sourcesMedline, Embase, Cochrane Library, Epistemonikos, Lilacs and Who Index, from inception to 9 April 2023. Eligibility criteriaWe included randomised controlled trials with at least 12 weeks of follow-up and evaluated AE of ART in women at any age living with HIV/AIDS, without restrictions on status, year or language of publication. We excluded post hoc or secondary analyses and open-label extensions without comparator, and trials involving pregnant or breastfeeding women or with a focus on coinfection with tuberculosis, hepatitis B or C. The primary outcomes were the incidence rate of participants with any clinical and/or laboratory AE related or not to ART and treatment discontinuation. Data extraction and synthesisTwo independent reviewers extracted data and assessed the risk of bias using Cochrane’s risk of bias tool 2. We used Bayesian random-effects meta-analysis to summarise event rates. Results were presented as event rates per 1000 person-years (95% credibility intervals, 95% CrI). The pooled incidence rate per 1000 person-years adjusted for duration and loss to follow-up was estimated. We assessed the certainty of the evidence using Grading of Recommendations, Assessment, Development and Evaluation. ResultsA total of 24 339 studies were identified for screening, of which 10 studies (2871 women) met the eligibility criteria, with 11 different antiretrovirals (ARVs) regimens. Seven studies included exclusively women, while in the remaining three, the proportion of women ranged from 11% to 46%. Nine studies received industry funding. The pooled analysis showed a mean incidence rate of ART-related clinical and laboratory AE of 341.60 events per 1000 person-years (95% CrI 133.60–862.70), treatment discontinuation of 20.78 events per 1000 person-years (95% CrI 5.58–57.31) and ART-related discontinuation of 4.31 per 1000 person-years (95% CrI 0.13–54.72). Summary estimates were subject to significant uncertainty due to the limited number of studies and sparse data. The certainty of the evidence was graded as very low for all outcomes assessed. ConclusionExisting randomised trials do not provide sufficient evidence on the incidence rates of safety outcomes from antiretroviral treatment in women living with HIV/AIDS. Large comparative studies in well-characterised populations are needed to provide a more comprehensive landscape of the safety profile of these ARV therapies in women with HIV/AIDS. PROSPERO registration numberCRD42021251051. …

ObjectiveThere is limited information regarding the incidence of treatment-related adverse events (AE) following antiretroviral therapy (ART) in women. So, this review aimed to describe the incidence of AE of ART in women living with HIV/AIDS. DesignSystematic review and meta-analysis. Data sourcesMedline, Embase, Cochrane Library, Epistemonikos, Lilacs and Who Index, from inception to 9 April 2023. Eligibility criteriaWe included randomised controlled trials with at least 12 weeks of follow-up and evaluated AE of ART in women at any age living with HIV/AIDS, without restrictions on status, year or language of publication. We excluded post hoc or secondary analyses and open-label extensions without comparator, and trials involving pregnant or breastfeeding women or with a focus on coinfection with tuberculosis, hepatitis B or C. The primary outcomes were the incidence rate of participants with any clinical and/or laboratory AE related or not to ART and treatment discontinuation. Data extraction and synthesisTwo independent reviewers extracted data and assessed the risk of bias using Cochrane’s risk of bias tool 2. We used Bayesian random-effects meta-analysis to summarise event rates. Results were presented as event rates per 1000 person-years (95% credibility intervals, 95% CrI). The pooled incidence rate per 1000 person-years adjusted for duration and loss to follow-up was estimated. We assessed the certainty of the evidence using Grading of Recommendations, Assessment, Development and Evaluation. ResultsA total of 24 339 studies were identified for screening, of which 10 studies (2871 women) met the eligibility criteria, with 11 different antiretrovirals (ARVs) regimens. Seven studies included exclusively women, while in the remaining three, the proportion of women ranged from 11% to 46%. Nine studies received industry funding. The pooled analysis showed a mean incidence rate of ART-related clinical and laboratory AE of 341.60 events per 1000 person-years (95% CrI 133.60–862.70), treatment discontinuation of 20.78 events per 1000 person-years (95% CrI 5.58–57.31) and ART-related discontinuation of 4.31 per 1000 person-years (95% CrI 0.13–54.72). Summary estimates were subject to significant uncertainty due to the limited number of studies and sparse data. The certainty of the evidence was graded as very low for all outcomes assessed. ConclusionExisting randomised trials do not provide sufficient evidence on the incidence rates of safety outcomes from antiretroviral treatment in women living with HIV/AIDS. Large comparative studies in well-characterised populations are needed to provide a more comprehensive landscape of the safety profile of these ARV therapies in women with HIV/AIDS. PROSPERO registration numberCRD42021251051. …

IntroductionThe absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional ‘step-up’ therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis. Methods and analysisNORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure. Ethics and disseminationEthical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences. Trial registration numberNCT05180175; Pre-results. EudraCT number: 2019-002942-19. …

IntroductionThe absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional ‘step-up’ therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis. Methods and analysisNORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure. Ethics and disseminationEthical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences. Trial registration numberNCT05180175; Pre-results. EudraCT number: 2019-002942-19. …

IntroductionThe absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional ‘step-up’ therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis. Methods and analysisNORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure. Ethics and disseminationEthical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences. Trial registration numberNCT05180175; Pre-results. EudraCT number: 2019-002942-19. …

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 3, Page 252-253, August 1, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 3, Page 257-259, August 1, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 3, Page 343-351, August 1, 2024.

Abstract Background HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. Methods Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. Results A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p