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Associations between epileptic seizures in pregnancy and adverse pregnancy outcomes: A systematic review and meta-analysis
Get PDFBackground: Epileptic seizures during pregnancy may increase the risk of adverse pregnancy outcomes. Socioeconomic disparities in epilepsy incidence may extend to seizure control. We conducted a systematic review and meta-analysis to assess the association between epileptic seizures during pregnancy and adverse pregnancy outcomes. We also evaluated the association between socioeconomic and individual-level factors and seizure occurrence. Methods and findings: We searched MEDLINE, Embase, CINAHL, and PsycINFO databases from inception to May 2025 for observational studies on pregnant women with epileptic seizures. We compared maternal and foetal outcomes in pregnant women with and without seizures and assessed the association between seizure occurrence and socioeconomic or individual-level factors. We used the Newcastle–Ottawa Scale to assess the risk of bias of included studies. Meta-analyses using random effects model were performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs). From 13,381 identified publications, 25 studies (24,596 pregnancies) are included in this analysis. In pregnant women with epilepsy, women with seizures compared to those without had increased odds of caesarean birth (OR 1.62, 95% CI 1.14 to 2.30, p=0.007), peripartum depression (OR 2.20, 95% CI 1.04 to 4.65, p=0.04), and small for gestational age baby (OR 1.32, 95% CI 1.03 to 1.69, p=0.03). The odds of preterm birth (OR 1.66, 95% CI 1.29 to 2.15, p<0.001), low birthweight (OR 1.47, 95% CI 1.12 to 1.93, p=0.006), and small for gestational age baby (OR 1.44, 95% CI 1.19 to 1.74, p<0.001) were higher in women with seizures compared to women without epilepsy. The risk of seizures was greater in pregnant women with epilepsy with low income compared to those with higher income (OR 1.57, 95% CI 1.22 to 2.02, p<0.001), and in women with focal epilepsy compared to those with generalised epilepsy (OR 1.84, 95% CI 1.54 to 2.20, p<0.001). The number of studies for some outcomes was small, limiting subgroup analyses and detection of heterogeneity. Conclusion: Epileptic seizures are associated with increased risks of adverse maternal and foetal outcomes. Risk assessment to identify women with epilepsy at highest risk of seizures is needed to optimise care.</p
Efficacy and health economics of Bufei Yishen granules in patients with frequent exacerbator phenotype in the stable phase of chronic obstructive pulmonary disease: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial
Get PDFIntroduction: Patients with frequent exacerbator phenotype in chronic obstructive pulmonary disease (COPD) tend to experience a progressive decline in lung function, a gradual deterioration of the disease, and even a serious threat to their lives. However, current treatment measures still need further improvements to reduce the frequency of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, our team developed Bufei Yishen (BFYS) granules specifically for patients with frequent exacerbator phenotype in COPD and is conducting a randomized controlled trial (RCT) to validate their effectiveness. Methods: A multi-center, randomized, double-blind, placebo-controlled trial will be conducted. A total of 848 patients will participate in the study, with a treatment duration of 1 year. The participants will be randomly assigned to the experimental group and the control group in a 1:1 ratio. Both groups will receive health education and conventional drugs. In addition, the experimental group will receive BFYS granules, while the control group will be given the corresponding BFYS placebo. The primary outcome is the frequency of AECOPD. The secondary outcomes include the frequency of AECOPD leading to hospitalization, the mortality rate, lung function, six-minute walk distance (6MWD), clinical symptoms and signs scores, and quality of life. Safety outcomes include vital signs and laboratory tests. Statistical analysis will be conducted using SPSS software (version 25.0). Furthermore, the health economics evaluation of the BFYS granules will use cost-effectiveness analysis methods.Ethics and dissemination: The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Henan University of Chinese Medicine (No. 2024HL-043-01). Written informed consent will be obtained from all participants. The results will be published in a peer-reviewed journal after the end of the study. The data of this trial will be disseminated publicly through conferences and publications. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT06326658.</p
Plasmodium falciparum Subtilisin-like Domain-Containing Protein (PfSDP), a Cross-Stage Antigen, Elicits Short-Lived Antibody Response Following Natural Infection with Plasmodium falciparum
Get PDFWith the increasing detection of artemisinin resistance to front-line antimalarials in Africa and notwithstanding the planned roll-out of RTS’S and R21 in Africa, the search for new vaccines with high efficacy remains an imperative. Towards this endeavour, we performed in silico screening to identify Plasmodium falciparum gametocyte stage genes that could be targets of protection or diagnosis. Through the analysis we identified a gene, Pf3D7_1105800, coding for a Plasmodium falciparum subtilisin-like domain-containing protein (PfSDP) and thus dubbed the gene Pfsdp. Genetic diversity assessment revealed the Pfsdp gene to be relatively conserved across continents with signs of directional selection. Using RT qPCR and Western blots, we observed that Pfsdp is expressed in all developmental stages of the parasite both at the transcript and protein level. Immunofluorescence assays found PfSDP protein co-localizing with PfMSP-1 and partially with Pfs48/45 at the asexual and sexual stages, respectively. Further, we demonstrated that anti-PfSDP peptide-specific antibodies inhibited erythrocyte invasion by 20–60% in a dose-dependent manner, suggesting that PfSDP protein might play a role in merozoite invasion. We also discovered that PfSDP protein is immunogenic in children from different endemic areas with antibody levels increasing from acute infection to day 7 post-treatment, followed by a gradual decay. The limited effect of antibodies on erythrocyte invasion could imply that it might be more involved in other processes in the development of the parasite.</p
Co-occurrence of native and invasive malaria vectors in anthropogenic habitats in Metehara, Ethiopia: Opportunities for urban malaria control
Get PDFLocal data are essential to understand the threat posed by invasive Anopheles stephensi and native malaria vectors on urban malaria transmission. This study investigated key bioecological features of invasive and native malaria vectors in Metehara town, Ethiopia. In parallel with a case-control study assessing the impact of An. stephensi on urban malaria transmission, a bioecological assessment was conducted between November 2023 and October 2024. All potential larval breeding habitats were mapped, followed by bimonthly collections of immature and adult mosquitoes from randomly selected locations. Immatures were collected using standard dippers, and adults with CDC light traps, BG Pro traps, and Prokopack aspirators. Adult Anopheles were identified morphologically, while species identification of immatures, adult blood-meal analysis, and sporozoite detection were performed via PCR. Of 767 potential larval breeding habitats, 98.3% (n = 754) were anthropogenic, with the majority (95.2%, n = 730) accessible for oviposition, either fully (73.1%, n = 551) or partially (23.7%, n = 179). More than half were water storage containers for human consumption (37.3%, n = 281) or associated with construction (20.8%, n = 157), while abandoned containers, including discarded tyres, accounted for 22.3% (n = 168). Among anthropogenic habitats positive for Anopheles immatures (55.3%, n = 417), one-third contained both An. stephensi and An. arabiensis. Habitat positivity for An. arabiensis showed significant seasonal variation (likelihood ratio, LR = 46.96, P < 0.01), whereas An. stephensi remained stable (LR = 13.06, P = 0.11). Of 2078 adult catches, An. arabiensis was the most abundant species (63.7%, n = 1323), followed by An. pharoensis (26.4%, n = 549). The human blood index was highest in An. arabiensis (21.8%), compared with An. pharoensis (8.3%) and An. stephensi (1.9%). Sporozoite rate was highest in An. pharoensis (4.2%, 23/548), followed by An. arabiensis (0.4%, 5/1321), while no An. stephensi tested positive (0/173). In conclusion, most breeding habitats were anthropogenic, supporting both native and invasive vectors. Anopheles arabiensis exhibited seasonal variation, whereas An. stephensi remained stable. Integrated vector control targeting anthropogenic larval habitats is recommended. Identification of An. pharoensis from larval pools, given its high sporozoite rate, is critical to guide urban malaria control.</p
Distribution of Rotavirus alphagastroenteritidis Strains in Blantyre, Malawi, During and After the COVID-19 Pandemic
Get PDFRotavirus alphagastroenteritidis remains the leading cause of severe gastroenteritis in children under five years, despite widespread vaccine use. The COVID-19 pandemic disrupted healthcare and vaccination delivery, while non-pharmacological interventions may have influenced R. alphagastroenteritidis transmission. We conducted hospital-based surveillance of R. alphagastroenteritidis gastroenteritis at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, from October 2019 to October 2024. Children under five presenting with acute gastroenteritis were enrolled; 99.1% of vaccine-eligible participants had received at least one R. alphagastroenteritidis vaccine dose. Stool samples were tested for R. alphagastroenteritidis by enzyme immunoassay (EIA) and genotyped using RT-PCR. Among 1135 enrolled children, 29.1% (330/1135) were R. alphagastroenteritidis-positive. Cases occurred year-round except for December 2020–January 2021, when no R. alphagastroenteritidis infections were detected, and February–March 2023, when no samples were collected. The prevalence varied significantly by age group between children greater than 23 months of age to the rest of the age groups (<6 months, 6–11 months, and 12–22 months) (p = 0.0046). The most common R. alphagastroenteritidis G-genotypes were G3 (38.7%), G2 (25.4%), and G12 (17.2%), with G2 emerging as the predominant strain from June 2023. G3P[8] was the most frequent G–P combination (25%). Its overall prevalence did not change during the pandemic; however, genotype distribution shifted compared to pre-COVID-19 patterns. Sustained surveillance and genomic analyses are essential to monitor evolving strain dynamics and inform vaccine policy.</p
A single mutation G454A in the P450 CYP9K1 drives pyrethroid resistance in the major malaria vector Anopheles funestus reducing bed net efficacy
Get PDFMetabolic mechanisms conferring pyrethroid resistance in malaria vectors are jeopardizing the effectiveness of insecticide-based interventions, and identification of their markers is a key requirement for robust resistance management. Here, using a field-lab-field approach, we demonstrated that a single mutation G454A in the P450 CYP9K1 is driving pyrethroid resistance in the major malaria vector Anopheles funestus in East and Central Africa. Drastic reduction in CYP9K1 diversity was observed in Ugandan samples collected in 2014, with selection of a predominant haplotype (G454A mutation at 90%), which was completely absent in the other African regions. However, six years later (2020) the Ugandan 454A-CYP9K1 haplotype was found predominant in Cameroon (84.6%), but absent in Malawi (Southern Africa) and Ghana (West Africa). Comparative in vitro heterologous expression and metabolism assays revealed that the mutant 454A-CYP9K1 (R) allele significantly metabolises more type II pyrethroid (deltamethrin) compared with the wild G454-CYP9K1 (S) allele. Transgenic Drosophila melanogaster flies expressing 454A-CYP9K1 (R) allele exhibited significantly higher type I and II pyrethroids resistance compared to flies expressing the wild G454-CYP9K1 (S) allele. Furthermore, laboratory testing and field experimental hut trials in Cameroon demonstrated that mosquitoes harbouring the resistant 454A-CYP9K1 allele significantly survived to pyrethroids exposure (Odds ratio = 567, p &lt; 0.0001). This study highlights the rapid spread of pyrethroid resistant CYP9K1 allele, under directional selection in East and Central Africa, contributing to reduced bed net efficacy. The newly designed DNA-based assay here will add to the toolbox of resistance monitoring and improving its management strategies.</p
Optimized methods for the targeted surveillance of extended-spectrum beta-lactamase-producing Escherichia coli in human stool
Get PDFUnderstanding transmission pathways of important opportunistic, drug-resistant pathogens, such as extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, is essential to implementing targeted prevention strategies to interrupt transmission and reduce the number of infections. To link transmission of ESBL-producing E. coli (ESBL-EC) between two sources, single-nucleotide resolution of E. coli strains, as well as E. coli diversity within and between samples, is required. However, the microbiological methods to best track these pathogens are unclear. Here, we compared different steps in the microbiological workflow to determine the impact different pre-enrichment broths, pre-enrichment incubation times, selection in pre-enrichment, selective plating, and DNA extraction methods had on recovering ESBL-EC from human stool samples, with the aim to acquire high-quality DNA for sequencing and genomic epidemiology. We demonstrate that using a 4-h pre-enrichment in Buffered Peptone Water, plating on cefotaxime-supplemented MacConkey agar and extracting DNA using Lucigen MasterPure DNA Purification kit improves the recovery of ESBL-EC from human stool and produced high-quality DNA for whole-genome sequencing. We conclude that our optimized workflow can be applied for single-nucleotide variant analysis of an ESBL-EC from stool.</p
Cluster-based subgroups of prediabetes and its association with prediabetes progression and regression: a prospective cohort study.
No full textBackgroundCluster analysis provides an effective approach in stratifying prediabetes into different subgroups; however, the association of the cluster-based subgroups with prediabetes progression and regression has not been investigated. We aimed to address this issue in a Chinese population.MethodsA total of 4,128 participants with prediabetes were included to generate cluster-based subgroups of prediabetes based on age, body mass index (BMI), triglyceride-and-glucose (TyG) index, and hemoglobin A1c (HbA1c), using a k-means clustering model. Among them, 1,554 participants were followed-up for about three years to ascertain prediabetes progression and regression. Their association with the cluster-based subgroups of prediabetes was assessed using multinomial logistic regression analyses.ResultsThree clusters of prediabetes were identified among the 4,128 participants, with cluster 0, 1 and 2 accounting for 28.0%, 31.4% and 40.6%, respectively. Participants with prediabetes were featured by the youngest age and the lowest HbA1c in cluster 0, the highest BMI and TyG index in cluster 1, and the oldest age and the lowest BMI in cluster 2. After multivariable-adjustment, both cluster 1 [odds ratio (OR) 3.31, 95% confidence interval (CI): 2.01–5.44] and cluster 2 (OR 2.58, 95% CI: 1.60–4.18) were associated with increased odds of progression to diabetes when compared with cluster 0. They were also associated with decreased odds of regression to normoglycemia (OR 0.54, and 0.56, respectively).ConclusionsPrediabetes participants featured by older age, higher degree of insulin resistance, higher BMI and worse glycemic condition had higher probability of progression to diabetes but lower chance of regression to normoglycemia.</p
Interventions to Reduce Self-Stigma Among People Living With HIV: A Systematic Review
Get PDFOver 4 decades into the global HIV pandemic, HIV-related self-stigma—a mindset of negative beliefs, thoughts, and behaviors a person holds about themselves—remains a major barrier to HIV treatment, management, and care. HIV-related self-stigma is a persistent public health threat and leads to depression and other mental health problems, lowers adherence to antiretroviral medication, and acts as a barrier to health services. Not enough is known about what interventions work and how they work to reduce self-stigma. We conducted a systematic review of existing interventions that address self-stigma among people living with HIV to address this gap. We searched PubMed, Embase, and Web of Science; used Covidence review software; dual-screened the results; extracted data from each included study; analyzed the data using Cochrane guidelines and the Template for Intervention Description and Replication Framework; and categorized the content based on emerging themes around the intervention/program. We included 35 studies in the review, with the majority (32/35, 91%) showing promise to reduce HIV self-stigma or components of self-stigma. Intervention approaches included working on thoughts, feelings, and beliefs through a range of cognitive-based, inquiry-based, and mindful-based techniques, often with a forward-looking goal-setting focus. However, comparison of studies was difficult with different definitions and understandings of self-stigma and different measurement scales. Many studies were small-scale and lacked sufficient in-depth descriptions. This study makes an important contribution to the field of HIV more broadly and HIV-related stigma, specifically, in proposing a common definition of self-stigma and providing in-depth descriptions of interventions in terms of content, type, level, and effectiveness.</p
Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial
Get PDFBACKGROUND:Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.METHODS:This multicenter, participant-blinded, blinded end point, randomized controlled clinical trial included 558 patients with acute ischemic stroke who underwent IVT in 18 hospitals from August 2021 to May 2023. After IVT, patients were randomized 1:1 to the RIC (unilateral upper limb; cuff pressure, 200 mm Hg, twice daily for 7 days) or sham RIC groups (the same procedure; cuff pressure, 60 mm Hg). The primary efficacy outcome was an excellent functional outcome (modified Rankin Scale score, 0–1) at 90 days after IVT.RESULTS:In total, 558 eligible patients were randomized, and 11 (2.0%) were excluded because they did not receive an RIC or sham RIC. Thus, 547 patients (RIC, n=274; sham RIC, n=273) were included in the modified intention-to-treat analysis, of whom 15 patients were lost to follow-up and 532 (95.3%) completed the trial. At 90 days, 62.7% of patients in the RIC group and 56.8% in the sham RIC group had an excellent functional outcome (unadjusted risk ratio, 1.10 [95% CI, 0.96–1.27]; P=0.169). The proportion of patients with any adverse events was 11.2% in the RIC group and 8.1% in the sham RIC group, with no significant difference (P=0.221).CONCLUSIONS:RIC was safe in patients with acute ischemic stroke who received IVT. However, it did not significantly improve excellent functional outcome.</p