Surveillance Study Research Articles

Association of antenatal or neonatal SARS-COV-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study

Perinatal exposure to SARS-CoV-2 may affect neurodevelopment before 12 months of age, but longer-term outcomes remain unknown. We examined whether antenatal or neonatal SARS-CoV-2 exposure compared with non-exposure is associated with neurodevelopment, respiratory symptoms, and health care usage in early childhood. This prospective national population-based cohort study was conducted in England and Wales, United Kingdom. We enrolled term-born children (≥37 weeks' gestation) with and without antenatal or neonatal exposure to SARS-CoV-2 infection by approaching parents of eligible children who were cared for in 87 NHS hospitals. Potential participants were identified through the national active surveillance studies of pregnant women and newborn infants hospitalised with confirmed SARS-CoV-2 infection conducted through the UK Obstetric Surveillance System and the British Paediatric Surveillance Unit. We defined antenatal and neonatal SARS-CoV-2 exposure as infants born to mothers hospitalised with confirmed SARS-CoV-2 infection between 14+0 and 36+6 weeks gestation and infants admitted to hospital with confirmed SARS-CoV-2 infection within the first 28 days after birth. Children born preterm or with major congenital anomaly or who were not residing in the UK were excluded. We assessed children's development (Ages and Stages Questionnaire 3rd Edition (ASQ-3); Ages and Stages Questionnaire Social-Emotional 2nd Edition (ASQ:SE-2)), respiratory symptoms (Liverpool Respiratory Symptom Questionnaire (LRSQ)) and health care usage (parent-completed questionnaire) at 21-32 months of age. Primary outcome: total ASQ-3 score, converted to z-scores. Secondary outcomes: ASQ:SE-2 z-scores; risk of delay in ASQ-3 domains; total LRSQ scores, converted to z-scores. Analyses were adjusted for children's age, sex, maternal ethnicity, parental education, and index of multiple deprivation. Between October 20, 2021 and January 27, 2023, we approached 668 and 1877 families out of 712 and 1917 potentially eligible participants in the exposed and comparison cohort. Of the 125 and 306 participants who were enrolled to the exposed and comparison cohort 121 and 301 participants completed the questionnaires and 96 and 243 participants were included in the analysis. In the age adjusted analysis, the mean total ASQ-3 z-score was lower in the exposed than the comparison cohort (-0.3, 95% CI:-0.6 to-0.05), however, when adjusted for sex, parental education, ethnicity and IMD quintile, there was no significant difference (difference in mean z-score=-0.2 95% CI:-0.5 to 0.03). SARS-CoV-2 exposure was associated with increased risk of delayed personal-social skills (odds ratio=3.81; 95% CI: 1.07-13.66), higher ASQ:SE-2 total z-scores (difference in mean z-score=0.4; 95% CI: 0.2-0.6) and increased risk of delayed social-emotional development (OR=3.58, 95% CI: 1.30-9.83), after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. The exposed cohort had a higher mean total LRSQ z-score than the comparison cohort (0.3 95% CI: 0-0.6) and higher inpatient (38% vs. 21%, p=0.0001), outpatient (38% vs. 30%, p=0.0090), and General Practitioner appointments (60% vs. 50%, p=0.021) than the comparison cohort, after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. No differences in other secondary outcomes between the exposed and comparison cohorts were found. Although the exposed cohort did not differ from the comparison cohort on the primary outcome, total ASQ-3 score, the exposed cohort were at greater risk of delayed social-emotional development, had a greater prevalence of respiratory symptoms and increased health care usage relative to the comparison cohort. The study is limited by the smaller sample size due to the low response rate and lack of clinical developmental assessments. Given the association of poor social-emotional development with antenatal or neonatal SARS-CoV-2 exposure, developmental screening, and follow-up of children with confirmed antenatal or neonatal SARS-CoV-2 infection may be warranted to identify those in need of early intervention. Action Medical Research for Children.

Ethyl Acetate in E-liquids: Implications for Breath Testing.

Electronic cigarette liquids (e-liquids) can contain a variety of chemicals to impart flavors, smells, and pharmacological effects. Surveillance studies have identified hundreds of chemicals used in e-liquids which have known health and safety implications. Ethyl acetate has been identified as a common constituent of e-liquids. Ethyl acetate is rapidly hydrolyzed to ethanol in vivo. Animal studies have demonstrated that inhaling >2000 mg/L ethyl acetate can lead to accumulation of ethanol in the blood at concentrations greater than 1000 mg/L, or 0.10%. A "Heisenberg" e-liquid was submitted to the Laboratory for Forensic Toxicology Research for analysis after a random workplace drug test resulted in a breath test result of 0.019% for a safety-sensitive position employee. Analysis of this sample resulted in the detection of 1488 ± 6 mg/L ethyl acetate. The evaluation of several "Heisenberg" e-liquids determined that these products contain ethyl acetate. The identification of ethyl acetate in e-liquids demonstrates poor regulatory oversight and enforcement that potentially has consequences to preliminary breath ethanol testing and interpretations. The accumulation of ethanol in the breath from the ingestion/inhalation of ethyl acetate from an e-liquid used prior to a breath test may contribute to the detection of ethanol.

Safety of sarilumab in a Japanese population with rheumatoid arthritis by age group: Data from an interim analysis of a post-marketing surveillance study.

Using data from a post-marketing surveillance, this interim subgroup analysis investigated the safety of sarilumab in younger (<65 years) and older patients (≥65 and ≥75 years) with rheumatoid arthritis. During this interim analysis, patients who were treated with sarilumab in Japan were enrolled between June 2018-2021. Data collected by 12 January 2022 were analysed, with adverse drug events monitored over 52 weeks. Of 972 patients with available data, proportion of patients aged <65 years, ≥65 years and ≥75 years were 40.8%, 59.2% and 27.8%, respectively. Most patients (95.5%) received the standard 200 mg dose of sarilumab as the initial dose. Adverse drug reactions were reported in 24.6% of patients, with serious events accounting for 6.4% of cases. No malignancy and low incidences of adverse drug reactions of special interest were reported across all age groups (<65 years, 7.8%; ≥65 years, 8.2%; ≥75 years, 8.5%). When stratified by absolute neutrophil count above and below the lower limit of normal, there were no numerical differences in incidences of serious and non-serious infections between age groups. Regardless of age, sarilumab therapy was well tolerated by patients with rheumatoid arthritis, with no new safety signals reported in this study.

Surveillance and phylogenetic analysis of a pathogenic bacterium candidate in nasal discharge from children.

"The infectious organism lurking in human airways (IOLA)" is a candidate pathogenic bacterium detected in bronchoalveolar lavage fluid specimens derived from adult patients with chronic lower respiratory tract infections. Genomic analyses of IOLA have revealed that it possesses the smallest and most AT-rich genome among human-derived bacteria. However, its biological properties remain unclear because no culture method has been established for IOLA. Here, we conducted a large-scale IOLA surveillance study of nasal discharge specimens from children in Japan and investigated the correlation between IOLA detection frequency and patient characteristics. We detected IOLA in 5.4% (103 of 1,920) of pediatric nasal discharge samples. No significant differences were observed in the frequency of detection based on the patient's background. However, with respect to age, the frequency of detection tended to be significantly high at 2-3 and 6 years old. Phylogenetic analysis revealed five phylotypes in the IOLA 16S rRNA gene sequences, and the sequences detected in adult patients with respiratory infections in a previous study belonged to one of the five phylotypes. The involvement of IOLA in the symptoms is not clear, but IOLA is detected at a relatively high frequency in pediatric nasal discharge. Many subjects with detected IOLA were not always IOLA positive, and IOLA was detected transiently. Our findings suggest that IOLA is horizontally transmitted through groups in nursery and elementary schools, and there are differences in biological characteristics among the IOLA phylotypes.IMPORTANCE"The infectious organism lurking in human airways (IOLA)" is a candidate pathogenic bacterium strongly suspected to be infectious to the respiratory tracts of humans and animals. However, a culture method for IOLA has not been established yet, and its properties remain unclear. In this study, IOLA was detected at a relatively high frequency in the nasal discharge of children, and five phylotypes of IOLA were identified. One of these phylotypes was found in the bronchoalveolar lavage fluid from adult patients, suggesting lineage-specific differences in the pathogenicity of IOLA. Moreover, it was suggested that IOLA is horizontally transmitted when children gather in groups such as nursery and elementary schools. These findings strongly indicate that IOLAs have been clinically undetected so far but are spreading among children, with one lineage being involved in respiratory diseases in adults. Examining the presence of IOLA in clinical specimens may help to understand the etiology of respiratory diseases with unknown causes.

Demographic characteristics, perinatal smoking patterns, and risk for neonatal health complications among pregnant smokers in the United States who begin using electronic cigarettes during pregnancy: A descriptive study using population-based surveillance data.

Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (a) characteristics of smokers who begin using ECs during pregnancy, (b) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (c) risk for neonatal health complications among smokers who initiate ECs during pregnancy. Pregnant women using CCs exclusively pre-pregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified as dual users (used both ECs and CCs) or EC replacers (used ECs exclusively). Of 29,505 pregnant smokers, 1.5% reported using ECs during the last 3 pregnancy months. Among them, 29.7% became EC-exclusive users. EC initiators were disproportionately non-Hispanic White. Relative to quitters, EC initiators had lower income, were less likely to be married, have intended pregnancies, receive first-trimester prenatal care, and participate in a federal assistance program. Compared to CC-exclusive users, EC initiators overall, and dual users specifically, were more likely to reduce pre- and post-natal CC usage relative to pre-pregnancy levels. EC initiators' risk for neonatal health complications fell between quitters and CC-exclusive users, though differences were not statistically significant. Although EC initiators reduced CC use more than CC-exclusive users, only 29.7% reported complete CC cessation, and there was insufficient evidence of reduction in neonatal health complications relative to CC-exclusive users. Currently, ECs should not be considered a viable gestational smoking cessation strategy. Health agencies have identified a critical need for research evaluating the use of e-cigarettes in supporting prenatal smoking cessation. Using the US Pregnancy Risk Assessment Monitoring System surveillance study data, we provide real-world evidence that prenatal e-cigarette initiation as a smoking cessation tool is used infrequently among pregnant combustible cigarettes smokers. Most using e-cigarettes in the last three months of pregnancy also used combustible cigarettes.

#636 A phase 4, open label, multicenter prospective study of the safety and efficacy of agalsidase beta in Chinese patients with Fabry disease

Abstract Background and Aims Fabry disease (FD) is a rare inherited lysosomal storage disease caused by pathogenic GLA gene variants which result in a deficiency of the enzymatic activity of α-galactosidase A. Enzyme replacement therapy (ERT) is the mainstay of FD-specific treatment, but there are currently no reported clinical trials of ERT for FD in the Chinese population. This is the first phase 4 study to evaluate the safety and efficacy of ERT for FD in China since the approval of agalsidase beta in China in 2019. Method A 54-week, phase 4, open label, single arm, prospective, post-marketing surveillance (PMS) study of agalsidase beta (NCT05054387) was performed at 6 sites in China. Twenty-two Chinese ERT-naïve FD participants (≥8 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 were enrolled and received infusions of agalsidase beta (Fabrazyme®, Sanofi) at a dose of 1.0 mg/kg every 2 weeks for up to 48 weeks. The primary endpoint was safety and tolerability of agalsidase beta. The endpoints of clinical efficacy included the changes of plasma globotriaosylceramide (GL-3), globotriaosylsphingosine (Lyso-GL-3), FD symptoms (including angiokeratoma, hypohidrosis, anhidrosis, abdominal pain, headache, tinnitus, heat tolerance, and activity tolerance), and eGFR from baseline to week 48. A post-hoc subgroup analysis was conducted to explore the differences in ERT efficacy between two subgroups of different ages (&amp;lt;30 years and ≥30 years). Results All 22 patients completed the study intervention. There were 18 males (81.8%) and the mean age of ERT initiation was 29.0 ± 13.5 years. Treatment-related adverse events (AEs) and infusion-associated reactions (IARs) were reported in 8 participants (36.4%), which was less than ∼60% as previously reported for IARs. Most AEs were mild or moderate and no AE caused permanent treatment discontinuation or death. The mean plasma GL-3 and Lyso-GL-3 levels decreased remarkably at week 6 and remained stable throughout the trial, with the mean percentage reduction from baseline to week 6 through week 48 ranged from −34.6% ± 27.4% to ­41.9% ± 14.9% and −58.8% ± 20.2% to ­64.9% ± 12.7%, respectively (Fig. 1a and b). The reduction was more remarkable for the classic male patients (n = 18; GL-3: 7.99 ± 2.19 ug/mL at baseline and 4.31 ± 1.71 ug/mL at week 48, −46.0% ± 18.4%; Lyso-GL-3: 83.11 ± 25.69 ng/mL at baseline and 25.89 ± 13.43 ng/mL at week 48, −67.8% ± 17.6%). Thirteen (59.1%) participants experienced improved FD symptoms at week 48, with no cases of worsening symptoms. The mean eGFR was 115.6 ± 37.3 mL/min/1.73 m2 at baseline and 118.4 ± 42.9 mL/min/1.73 m2 at week 48, with a change of 0.0 ± 12.4 mL/min/1.73 m2 from baseline to week 48 (Fig. 1c). In the subgroup analysis, participants were divided into the younger group with age &amp;lt;30 years (n = 11) and the older group with age ≥30 years (n = 11) according to their age of ERT initiation. At week 48, the reduction of mean plasma GL-3 (−47.1% ± 23.6% vs −22.0% ± 26.0%) and Lyso-GL-3 levels (−72.4 ± 17.3% vs −48.2% ± 19.8%), the stabilization of renal function (the mean change of eGFR from baseline to week 48: 5.2 ± 7.9 mL/min/1.73 m2 vs −5.2 ± 14.1 mL/min/1.73 m2) and the percentage of symptom improvement (81.8% vs. 36.4%) were generally more remarkable in the younger group than in the older group (Table 1). Conclusion This first phase 4 study of ERT for Fabry disease in China demonstrates that agalsidase beta is safe and well tolerated with a relatively low IAR rate, and effective in reducing plasma GL-3 and Lyso-GL-3, improving symptoms, and stabilizing renal function in Chinese patients with FD. Furthermore, the present study implies that patients who initiate ERT at a younger age benefit more from the therapy. Funding: Commercial support - Sanofi Pharmaceuticals.

Early impact of nirsevimab on ambulatory all-cause bronchiolitis: a prospective multicentric surveillance study in France.

After implementation of nirsevimab in 2023 in France as compared with 2022-2023, we found a 52.7%, 95% CI [46.4-58.9]) decrease in all-cause bronchiolitis in children <3 months with the lowest number of bronchiolitis cases in this population since 2017.

Safety and effectiveness of apremilast in Japanese patients with psoriatic disease: Results of a post-marketing surveillance study.

The safety and efficacy of apremilast in psoriatic disease has been demonstrated in clinical trials, including in Japanese patients. This post-marketing surveillance study was conducted after approval of apremalast in Japan in 2016 to evaluate the safety and effectiveness of the drug in Japanese patients with plaque psoriasis (PsO) and psoriatic arthritis (PsA) in routine clinical practice. Patients (enrolled between September 1, 2017, and August 31, 2019), were observed for 12 months after apremilast treatment initiation or until discontinuation or withdrawal. Safety was assessed by evaluating adverse reactions (ARs) and serious ARs. Effectiveness measures in PsO included the proportion of patients who achieved global improvement and Physician's Global Assessment (PGA) scores of 0/1 and the change from baseline in the Dermatology Life Quality Index (DLQI) after 6 and 12 months treatment. The safety analysis set included 1063 patients (PsO, n = 992; PsA, n = 127). ARs and serious ARs were reported in 29.4% and 0.7% of patients, respectively; most occurred <1 month after apremilast initiation. There were no reports of fatal ARs, serious infections, hypersensitivity, or vasculitis. No new safety signals were identified. Among the key survey items, gastrointestinal disorders were the most common ARs (21.3%). In patients with PsO, after 6 and 12 months of treatment, effectiveness rates of achieving highly effective or effective global improvement of were 90.9% and 93.8%; PGA 0/1 was achieved by 42.7% and 58.1% of patients; mean decrease from baseline in total DLQI score was 4.2 (p < 0.0001) and 5.7 (p < 0.0001), respectively. Effectiveness was evaluated in a small number of patients with PsA for some measures; after 6 and 12 months of treatment, improvements were observed in global improvement effectiveness rates, Disease Activity Score in 28 Joints score, Visual Analog Scale score, and DLQI score. We conclude that orally administered apremilast was well tolerated and effective in Japanese patients with PsO and/or PsA enrolled in this post-marketing surveillance study.

Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

Genetic diversity and distribution of noroviruses among all age groups of patients with diarrhea in Amhara National Regional State, Ethiopia.

Norovirus (NoV) is the leading cause of diarrheal disease worldwide and the impact is high in developing countries, including Ethiopia. Moreover, there is a significant and fluctuating global genetic diversity that varies across diverse environments over time. Nevertheless, there is a scarcity of data on the genetic diversity of NoV in Ethiopia. This study was aimed to assess the genetic diversity and distribution of NoVs circulating in the Amhara National Regional State, Ethiopia, by considering all age groups. A total of 519 fecal samples were collected from diarrheal patients from May 01/2021 to November 30/ 2021. The fecal samples were screened for the presence of NoVs using real-time RT-PCR by targeting a portion of the major capsid protein coding region. The positive samples were further amplified using conventional RT-PCR, and sequenced. The positivity rate of NoV was (8.9%; 46/519). The detection rate of NoV genogroup II (GII) and genogroup I (GI) was 38 (82.6%) and 8 (17.4%), respectively. Overall, five distinct GII (GII.3, GII.6, GII.10, GII.17, and GII.21) and two GI (GI.3 and GI.5) genotypes were detected. Within the GII types, GII.3 was the predominant (34.2%) followed by GII.21 (15.8%), GII.17 (10.5%), GII.6 and GII.10 each (2.6%). Norovirus GII.21 is reported for the first time in Ethiopia. The genetic diversity and distribution of NoVs were significantly different across the four sampling sits and age groups. The phylogenetic analysis revealed close relatedness of the current strains with published strains from Ethiopia and elsewhere. The distribution and genetic diversity of NoV was considerably high, with predominance of non-GII.4 genotypes. The GII.21 genotype is a new add on the growing evidences on the genetic diversity of NoVs in Ethiopia. Future nationwide surveillance studies are necessary to gain comprehensive data in Ethiopia.

Employing digital PCR for enhanced detection of perinatal Toxoplasma gondii infection: A cross-sectional surveillance and maternal-infant outcomes study in El Salvador.

Toxoplasma gondii is a parasitic infection that can be transmitted in utero, resulting in fetal chorioretinitis and other long-term neurological outcomes. If diagnosed early, pregnancy-safe chemotherapeutics can prevent vertical transmission. Unfortunately, diagnosis of acute, primary infection among pregnant women remains neglected, particularly in low-and-middle-income countries. Clinically actionable diagnosis is complex due to the commonality of infection during childhood and early adulthood which spawn long-last antibody titers and historically unreliable direct molecular diagnostics. The current study employed a cross-sectional T. gondii perinatal surveillance study using digital PCR, a next generation molecular diagnostic platform, and a maternal-fetal outcomes survey to ascertain the risk of vertical toxoplasmosis transmission in the Western Region of El Salvador. Of 198 enrolled mothers at the time of childbirth, 6.6% had evidence of recent T. gondii infection-85% of these cases were identified using digital PCR. Neonates born to these acutely infected mothers were significantly more likely to meconium aspiration syndrome and mothers were more likely to experience labor and delivery complications. Multivariable logistic regression found higher maternal T. gondii infection odds were associated with the presence of pet cats, the definitive T. gondii host. In closing, this study provides evidence of maternal T. gondii infection, vertical transmission and deleterious fetal outcomes in a vulnerable population near the El Salvador-Guatemala border. Further, this is the first published study to show clinical utility potential of digital PCR for accurate diagnosis of congenital toxoplasmosis cases.

The complete coding sequence of Influenza A/Unknown/Chelyabinsk/206/H7N4.

An influenza virus strain was obtained during a bird surveillance study in 2023 near Lake Chebarkul in the Chelyabinsk region, Russia. This complete coding genome sequence of the virus sampled from the Ural region significantly expands the knowledge about the spread of the H7N4 subtype of the influenza A virus.

Relationship between Anaplastic Lymphoma Kinase (ALK) Inhibitors and Epileptic Seizure Disorder: A Post-Marketing Surveillance Study.

ALK has been to be involved in the uptake and regulation of D2R, a G protein-coupled receptor expressed in various brain regions. Therefore, it is crucial to understand the relationship between ALK inhibitors and seizures is an important issue. This study investigated the relationship between ALK inhibitors and seizures. This study investigated the relationship between ALK inhibitors and seizures through a disproportionality analysis using the FAERS. The target drugs were the ALK inhibitors crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The seizures covered were defined HLGT: ''Seizures (incl subtype)'' including HLT: ''Seizures and seizure disorders NEC.'' This study used the IC, a signal score, as a Bayesian statistical method for disproportionality analysis. The signal scores of ''Seizures and seizure disorders NEC'' for each ALK inhibitor were crizotinib (IC: -0.00052, 95%CrI: -0.38-0.27), ceritinib (IC: 1.18, 95%CrI: 0.68-1.54), alectinib (IC: 0.68, 95%CrI: 0.19-1.02), brigatinib (IC: 1.04, 95%CrI: 0.32-1.54), and lorlatinib (IC: 0.82, 95%CrI: 0.11-1.32). On the other hand, ''Generalized tonic-clonic seizures'', ''partial simple seizures NEC, '' ''Absence seizures,'' and ''partial complex seizures'' had no or few reported cases, and no signal was detected. To our knowledge, this is the first report to evaluate the relationship between ALK inhibitors and seizures using post-marketing surveillance data. These results suggest that ceritinib, alectinib, brigatinib, and lorlatinib, which are highly brain-migrating drugs, are associated with seizures.

Determination of 13 potential anti-obesity agents in hair by dispersive liquid-liquid microextraction-assisted UHPLC-MS/MS

As the adulteration of dietary supplements with synthetic drugs remains a prevalent issue, the inclusion of anti-obesity agents may pose health risks, potentially leading to central nervous system or cardiovascular diseases. However, surveillance studies on the use of anti-obesity agents by the Chinese population are limited. This study aims to establish an efficient and rapid hair pretreatment method using dispersive liquid-liquid microextraction (DLLME) combined with high-speed grinding and develop a sensitive and accurate analytical method employing ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for detecting 13 potential anti-obesity agents in hair samples. Herein, hair samples were washed sequentially with 0.1% sodium dodecyl sulfate (SDS), water and acetone, and then ground at high speed using 1 mL of an extraction solution (internal standard solution-n-butanol-1.2 mol/L Na2HPO4, pH10.0, 100:400:500, v/v/v for procaterol; internal standard solution-ethyl acetate-1.2 mol/L Na2HPO4, pH8.0, 100:300:600, v/v/v for other 12 anti-obesity agents) while simultaneously performing DLLME. The developed method successfully detected 13 anti-obesity agents within 11 min, including bambuterol, clenbuterol, ractopamine, clorprenaline, formoterol, salbutamol, terbutaline, procaterol, phentermine, bupropion, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine, which improved the screening efficiency. The calibration curves exhibited good linearity of 0.025–5 ng/mg, achieving correlation coefficients of r ≥ 0.99. The lower limits of quantification (LLOQs) for the analytes were 0.025 ng/mg, demonstrating acceptable levels of accuracy and precision. Recovery rates ranged between 73.30% and 107.47% across the three concentrations of 0.075, 0.375, and 3.75 ng/mg. The validated method was successfully applied to 369 real cases and detected six analytes, including bambuterol, salbutamol, terbutaline, sibutramine, desmethyl sibutramine, and N,N-didesmethyl sibutramine. This method offers several advantages, including simple pretreatment, high extraction efficiency, rapid extraction, solvent economy, and pollution mitigation, making it highly suitable for large-scale surveillance of usage of added anti-obesity agents.

Drug Utilization Evaluation of Antidepressant Prescribing Practice in a Psychiatric Outpatient Hospital: A Prospective Cross-Sectional Study

Background: One of the main causes of morbidity is psychiatric disorders, which are becoming a burden to public health. The therapeutic choices are influenced by several factors, including treatment paradigms, safety, and costs that determine outcomes. Aim: We carried out the drug utilization evaluation (DUE) of antidepressants in patients visiting the psychiatry outpatient department. Study Design: An observational, prospective, and cross-sectional study. Place and Duration of Study: Department of Psychiatry, Jaya Krishna Hospital, Hanamkonda, TS, between September 2021 to April 2022. Methodology: We included patients who visited the psychiatric outpatient hospital, were clinically diagnosed, and received any antidepressants for the long term. The relevant data collected from the information resources was systematically analyzed for DUE. Results: Among 417 patients, the majority were in the age group of 31-40 (33.3%) years, and the most affected were female (57.3%), married (73.4%), and housewives (29.5%). Depression (37.6%) was the most commonly diagnosed psychiatric disorder. Of these prescriptions, 5.3% were monotherapy, the remaining was polytherapy (94.7%), and the majority of them had three drugs (36.2%). The average number of drugs per encounter was 3.4, drugs prescribed by generic names were 41.4%, injectable drugs prescribed were 2.6%, and drugs listed in the National List of Essential Medicines were 61.3%. Of all, 88.7% of prescriptions had at least one antidepressant, predominantly SSRIs, and fluoxetine (23.0%) was the most commonly prescribed. Benzodiazepines (59.7%) were the most frequently prescribed concomitant drug class and clonazepam (50.6%) was the most widely prescribed. Suicidal thoughts (5.8%) were the most commonly observed ADR. Conclusion: The study observed a pattern of polytherapy, mainly antidepressants from the SSRIs, notably fluoxetine mostly prescribed, and suicidal thoughts were the frequent ADR. Drug use surveillance studies, rationalizing therapeutic choices, and proper patient counseling would improve therapeutic outcomes by minimizing side effects and ADRs.

Dolutegravir induces FOLR1 expression during brain organoid development

During the first month of pregnancy, the brain and spinal cord are formed through a process called neurulation. However, this process can be altered by low serum levels of folic acid, environmental factors, or genetic predispositions. In 2018, a surveillance study in Botswana, a country with a high incidence of human immunodeficiency virus (HIV) and lacking mandatory food folate fortification programs, found that newborns whose mothers were taking dolutegravir (DTG) during the first trimester of pregnancy had an increased risk of neural tube defects (NTDs). As a result, the World Health Organization and the U.S. Food and Drug Administration have issued guidelines emphasizing the potential risks associated with the use of DTG-based antiretroviral therapies during pregnancy. To elucidate the potential mechanisms underlying the DTG-induced NTDs, we sought to assess the potential neurotoxicity of DTG in stem cell-derived brain organoids. The gene expression of brain organoids developed in the presence of DTG was analyzed by RNA sequencing, Optical Coherence Tomography (OCT), Optical Coherence Elastography (OCE), and Brillouin microscopy. The sequencing data shows that DTG induces the expression of the folate receptor (FOLR1) and modifies the expression of genes required for neurogenesis. The Brillouin frequency shift observed at the surface of DTG-exposed brain organoids indicates an increase in superficial tissue stiffness. In contrast, reverberant OCE measurements indicate decreased organoid volumes and internal stiffness.

Prevalence of SARS-CoV-2 antibodies and associated factors in the adult population of Belgium: a general population cohort study between March 2021 and April 2022

BackgroundThis study assessed seroprevalence trends of SARS-CoV-2 antibodies in the Belgian adult population between March 2021 and April 2022, and explored factors associated with seropositivity and seroreversion among the vaccinated and unvaccinated population.MethodsA prospective longitudinal surveillance study was conducted within a random sample of the general population (18 + years) in Belgium, selected from the national register through a multistage sampling design. Participants provided a saliva sample and completed a survey questionnaire on three occasions: at baseline and in two follow-up waves. Outcome variables included (1) seropositivity, defined as the presence of SARS-CoV-2 antibodies, assessed with a semi-quantitative measure of anti-RBD (Receptor Binding Domain) IgG ELISA and (2) seroreversion, defined as passing from a positive to a negative antibody test between two measurements. Trends in SARS-CoV-2 antibody prevalence were assessed using binary logistic regression with contrasts applying post-stratification. Potential determinants of seropositivity were assessed through multilevel logistic regressions.ResultsIn total 6,178 valid observations were obtained from 2,768 individuals. SARS-CoV-2 antibody prevalence increased from 25.1% in the beginning of the study period to 92.3% at the end. Among the vaccinated population, factors significantly associated with higher seropositivity rates were being younger, having a bachelor diploma, living with others, having had a vaccine in the last 3 months and having received a nucleic-acid vaccine or a combination. Lower seropositivity rates were observed among vaccinated people with a neurological disease and transplant patients. Factors significantly associated with higher seropositivity rates among the unvaccinated population were having non-O blood type and being non-smoker. Among vaccinated people, the seroreversion rate was much lower (0.3%) in those who had received their latest vaccine in the last 3 months compared to those who had received their latest vaccine more than 3 months ago (2.7%) (OR 0.13; 95%CI 0.04–0.42).ConclusionsThe rapid increase in antibody seropositivity in the general adult population in Belgium during the study period was driven by the vaccination campaign which ran at full speed during this period. Among vaccinated people, seropositivity varied in function of the time since last vaccine, the type of vaccine, sociodemographic features and health status.

Prevalence and molecular epidemiology of carbapenemase-producing Enterobacterales isolated from dog and cat faeces submitted to veterinary laboratories in the USA.

To estimate the prevalence of carbapenemase-producing Enterobacterales (CPE) carriage among pets using faecal specimens submitted to veterinary diagnostic laboratories throughout the US. A secondary aim was to employ whole-genome sequencing (WGS) to characterize isolates of CPE from companion animals and compare them to publicly available CPE genomes. To estimate the prevalence of CPE in companion animals in the USA, a multicenter surveillance study including 8 different veterinary diagnostic laboratories from across the USA was conducted. Briefly, remnant faecal specimens from dogs and cats were screened using two selective agar plates (CHROMID Carba and MacConkey with 1 mg/L cefotaxime and 0.125 mg/L meropenem) and presumptive CPE isolates screened by the modified carbapenemase inactivation method for carbapenemase production. A total of 2393 specimens were screened and yielded 196 isolates for carbapenemase screening. A total of 5 isolates from 4 dogs and 1 cat at 3 different veterinary diagnostic laboratories were confirmed to produce a carbapenemase (0.21%). Whole-genome sequencing (WGS) revealed two E. coli (ST167) isolates that both produced an NDM-5 carbapenemase, two Enterobacter hormaechei (ST171) isolates that produced an NDM-5 carbapenemase and a KPC-4 carbapenemase respectively and one Klebsiella oxytoca (ST199) that produced an Oxa-48-type carbapenemase. Both E. coli isolates were found to be within at least 22 SNPs of previously characterized canine and human CPE isolates. This study demonstrates that the prevalence of CPE among companion animals is relatively low (0.21%) but that given the genetic relatedness of animal isolates to human isolates, additional surveillance is needed.

Safety and effectiveness of guselkumab in Japanese patients with psoriasis: 20-week interim analysis of a postmarketing surveillance study.

A 52-week postmarketing surveillance study was initiated to evaluate the safety and effectiveness of guselkumab, a human anti-interleukin 23 subunit p19 monoclonal antibody, in Japanese patients with psoriasis vulgaris, psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis in real-world practice. Here, we report results of the 20-week interim analysis of the ongoing postmarketing surveillance study. Patients who received guselkumab between May 2018 (the date of commercial launch in Japan) and October 2020 were registered in this study. In total, 411 and 245 patients were included in the safety and effectiveness analysis sets, respectively. Adverse drug reactions (ADRs) occurred in 6.6% (27 of 411) and serious ADRs in 2.2% (nine of 411) of patients. The most frequent ADRs by System Organ Class were "Infections and infestations" (2.4%), with nasopharyngitis being the most frequently observed ADR (0.7%). The mean Psoriasis Area Severity Index score decreased from 11.6 at baseline to 6.5 at week 4 and 2.2 at week 20, with improvements achieving statistical significance at each time point. Clinical Global Impression, Dermatology Life Quality Index, and Nail Psoriasis Severity Index outcomesalso showed substantial improvements. Our findings demonstrate that guselkumab is well tolerated and effective in Japanese patients with psoriasis through 20 weeks of treatment in real-world clinical practice, showing significant effectiveness observed as early as 4 weeks. The study was officially registered with the University Hospital Medical Information Network Clinical Trials Registry with the identifier UMIN000032969.

DIARRHEA CAUSING ENTEROBACTERIACEAE AND THEIR ANTIBIOTIC RESISTANCE PATTERNS AMONG DIARRHEA PATIENTS FROM SANA’A CITY, YEMEN

Background and aims: The rise of antibiotic-resistant strains of the bacteria causing diarrhea remains a major worldwide health concern, especially in children under five. The purpose of this surveillance study was to ascertain the prevalence and antibiotic susceptibility profile of Enterobacteriaceae, which cause diarrhea. Materials and Methods: The National Center for Public Health Laboratories (NCPHL) in Sana'a city was the site of this cross-sectional investigation. Patient stool samples exhibiting diarrhea were gathered and cultivated using standard differential/selective medium. Standard biochemical assays and serological investigations were employed to identify the isolates. With the aid of Kirby-Bauer disk diffusion, the antibiogram was identified. Results: Enterobacteriaceae isolates were obtained from 972 stool samples collected; 15.3% (149/972) were diarrheagenic Enterobacteriaceae bacteria, including E. coli, Salmonella, and Shigella. There were 8.3% (81/972) Salmonella spp., 5.7% (56/972) Shigella spp., and 1.2% (12/972) E. coli. E. coli strains were grouped, with the most prominent being serogroups O153 (3, 2%) and O25 (2, 1.4%). Fifty-six (37.6%) Shigella species were identified as Shigella boydii type 2 and Shigella bodii type 17, which were the most common Shigella isolated (11, 8.1%, and 16, 10.7%, respectively). We detected high resistance of Salmonella isolates to tetracycline (29/81, 35.8%) but relatively low resistance to ciprofloxacin (7/81, 8.6%) and ceftriaxone (5/81, 6.3%). Conclusion: The many Enterobacteriaceae linked to instances of diarrhea in Sana'a, Yemen, were demonstrated in this study, along with the necessity of differential diagnosis for improved treatment results. Salmonella, Shigella, and Escherichia coli have all been linked to episodes of diarrhea in Sana'a city. To stop Yemen's antimicrobial resistance from spreading, regular antimicrobial susceptibility testing, efficient monitoring, and national surveillance of AMR bacteria should be put into place. Peer Review History: Received 3 February 2024; Revised 12 March 2024; Accepted 20 April; Available online 15 May 2024 Academic Editor: Dr. Gehan Fawzy Abdel Raoof Kandeel, Pharmacognosy Department, National Research Centre, Dokki, 12622, Giza, Egypt, gehankandeel9@yahoo.com Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Dr. George Zhu, Tehran University of Medical Sciences, Tehran, Iran, sansan4240732@163.com Dr. Esther Marguerite Chase DJANGA, Faculty of Medicine and Biomedical Sciences. Department of Public Health. University of Yaoundé I, Cameroon. e.djanga@yahoo.com