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Journal of Chromatography. A Oct 2023Control of N-nitrosamines has been in the focus of health authorities in recent years because many of these compounds are probable human carcinogens. In July 2018 the...
Control of N-nitrosamines has been in the focus of health authorities in recent years because many of these compounds are probable human carcinogens. In July 2018 the U.S. Food and Drug Administration (FDA) announced a recall for valsartan-containing medicines due to contamination with the carcinogenic low molecular weight nitrosamine, N-nitrosodimethylamine (NDMA). It has become clear that the problem can not only exist in the case of sartans, but in any active pharmaceutical ingredient (API)/drug product in which secondary or tertiary amines are present (as API or as impurities) and a nitrosating agent is available. The decision was made by regulators, according to which manufacturers of pharmaceutical products are obliged to perform a risk assessment for the potential presence of nitrosamines in active pharmaceutical ingredients and drug products. This resulted in a high demand for validated analytical methods that are able to quantify N-nitrosamines at low ppb levels in pharmaceutical products. In this work we have developed and validated a generic fast GC-MS method suitable for the quantitative determination of a wide range of low molecular weight nitrosamines, which include N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitroso-diphenylamine (NDPh), N-nitrosodipropylamine (NDPA), N-nitrosomethylethylamine (NMEA), N-nitrosomorpholine (NMOR), N-nitrosopiperidine (NPIP), N-nitroso-ethylisopropylamine (EIPNA), N-nitroso-diisopropylamine (DIPNA), N-nitroso-N-methylaniline (NMPA), 1-Methyl-4-nitrosopiperazine (MeNP) and N-nitroso-pyrrolidine (NPYR). The advantage of the method is that it is possible to screen low molecular weight nitrosamines in low concentrations with a short analysis time in a wide range of APIs and drug products.
Topics: United States; Humans; Pharmaceutical Preparations; Dimethylnitrosamine; Gas Chromatography-Mass Spectrometry; Molecular Weight; Nitrosamines
PubMed: 37696123
DOI: 10.1016/j.chroma.2023.464323 -
Women's Health (London, England) 2024Adolescent girls face numerous challenges which hinder their ability to manage menstruation in a healthy and dignified manner.
BACKGROUND
Adolescent girls face numerous challenges which hinder their ability to manage menstruation in a healthy and dignified manner.
OBJECTIVES
To examine the menstrual hygiene practices of adolescent girls schooling in rural Anambra communities.
STUDY DESIGN
Cross-sectional descriptive study.
METHOD
Participants were selected using multistage stratified random sampling technique and interviewed using self-administered semi-structured questionnaire. Data were analysed using Statistical Package for Social Sciences version 22.0.
RESULTS
Mean age of all, pre-menarche and post-menarche girls were 14.7 ± 1.84, 12.8 ± 1.09 and 15.1 ± 1.73 years, respectively. About 46% of the pre-menarche girls had not received any information on menstruation. Common sources of initial menstruation information were mother (87.3%), school (52.2%) and peers (20.0%). Among the 1091 (85.0% (1091/1283)) post-menarche girls, last menstrual period, last menstrual period duration and cycle length could not be recalled by 53.9%, 34.4% and 39.3%, respectively. Majority (98.3%) who could recall last menstrual period had a cycle length of ⩽30 days and the mean duration of menses was 4.4 ± 0.84 days. Disposable sanitary pad was mostly (60%) cited as recommended product, but cloth/rags (40.6%) or tissue paper (32. 3%) were predominantly used. Majority (88.6%) took their bath ⩾twice/day, 50.9% changed sanitary product ⩽twice/day while 72.5% exhibited poor hand washing. Sanitary products were mostly discarded by burning (45.4%). Fifty-one percent could not change in school predominantly due to lack of functional toilets/changing rooms (84.2%) while 72.5% of those who changed did so in bushes or unused spaces. Challenges faced during menstruation include restriction from holy places (38.9%), waist pain (74.9%), blood stains (36.1%) and lack of money to buy pad (27.0%). Factors significantly associated with using commercial pads were age (p = 0.047), class (p = 0.006), mother's educational status (p < 0.001), social class (p < 0.001), ability to recall last menstrual period date (p = 0.029) or duration (p = 0.001).
CONCLUSION
Menstrual hygiene management was unsatisfactory among studied adolescents. Continuous education of adolescent girls on menstrual hygiene management and advocacy for adequate menstrual hygiene management support are imperative.
Topics: Female; Adolescent; Humans; Menstruation; Hygiene; Cross-Sectional Studies; Health Knowledge, Attitudes, Practice; Schools
PubMed: 38318680
DOI: 10.1177/17455057241228204 -
Journal of Family Medicine and Primary... Sep 2023Chronic gastritis is one of the most prevalent disorders affecting individuals, which affects hundreds of millions of people in different ways around the world. The...
INTRODUCTION
Chronic gastritis is one of the most prevalent disorders affecting individuals, which affects hundreds of millions of people in different ways around the world. The significant incidence of poor dietary quality and diet-related illnesses may be addressed by orienting customers toward healthier food options. The objective of the study was to estimate the knowledge of front-of-package labels (FoPLs) and food group-based dietary intake of nutrients among patients with chronic gastritis.
MATERIALS AND METHODS
The study design was a hospital-based cross-sectional study that was done in Guntur district of Andhra Pradesh. The study population included 208 chronic gastritis patients between 20 to 60 years of age selected by systematic sampling. Detailed information on sociodemographic and lifestyle factors was collected using a questionnaire and 24-h dietary recall was done. The objective assessment of Knowledge of FoPLs was assessed mock package images representing a fictional brand to prevent other factors from interfering with product evaluation.
RESULTS
A total of 208 patients were studied with a near-equal proportion of males and females. Among participants, more than half (57.2%) can interpret FoPL, more than three-fourths (77.4%) have a belief that they eat a healthy diet mostly and only half (52.4%) of participants are somewhat knowledgeable about nutrition, and finally almost half (46.6%) of participants are not seeing the FoP label during food purchase. The mean score of knowledge of FoP labeling was 0.92 ± 1.135. Knowledge of FOPL was positively associated with the age of study participants OR 0.178 (95% CI: 0.178 to 0.856) with P value = 0.02. Grains have the maximum intake among all the food groups with a mean intake of 123.21 g/day.
CONCLUSION
The majority of participants do not know the food labeling, thus methods of education that focus on dietary interventions are urgently needed to raise awareness among the people.
PubMed: 38024917
DOI: 10.4103/jfmpc.jfmpc_322_23 -
Sensors (Basel, Switzerland) Jul 2023Moving target detection (MTD) is a crucial task in computer vision applications. In this paper, we investigate the problem of detecting moving targets in infrared (IR)...
Moving target detection (MTD) is a crucial task in computer vision applications. In this paper, we investigate the problem of detecting moving targets in infrared (IR) surveillance video sequences captured using a steady camera in a maritime setting. For this purpose, we employ robust principal component analysis (RPCA), which is an improvement of principal component analysis (PCA) that separates an input matrix into the following two matrices: a low-rank matrix that is representative, in our case study, of the slowly changing background, and a sparse matrix that is representative of the foreground. RPCA is usually implemented in a non-causal batch form. To pursue a real-time application, we tested an online implementation, which, unfortunately, was affected by the presence of the target in the scene during the initialization phase. Therefore, we improved the robustness by implementing a saliency-based strategy. The advantages offered by the resulting technique, which we called "saliency-aided online moving window RPCA" (S-OMW-RPCA) are the following: RPCA is implemented online; along with the temporal features exploited by RPCA, the spatial features are also taken into consideration by using a saliency filter; the results are robust against the condition of the scene during the initialization. Finally, we compare the performance of the proposed technique in terms of precision, recall, and execution time with that of an online RPCA, thus, showing the effectiveness of the saliency-based approach.
PubMed: 37514626
DOI: 10.3390/s23146334 -
Heliyon Jun 2024The aim of this study was to investigate the effects of temporal instability and possible heterogeneity on pedestrian accident severity, 48786 accident data from 2018 to...
The aim of this study was to investigate the effects of temporal instability and possible heterogeneity on pedestrian accident severity, 48786 accident data from 2018 to 2021 in the UK STATS database were used as the study object, and accident severity was used as the dependent variable, and 49 accident characteristics were selected as independent variables from 6 characteristics of accident pedestrian, driver, vehicle, road, environment and time to construct the pedestrian accident mean heterogeneity random-parameter logit model and examined its temporal stability. The results of model estimation and likelihood ratio tests indicate that the variables affecting pedestrian injury severity are highly variable and not stable over the years. And further demonstrates the potential of models that address unobserved heterogeneity for significant relationships in pedestrian accident severity analyses.
PubMed: 38867994
DOI: 10.1016/j.heliyon.2024.e32013 -
Nucleic Acids Research Jan 2024One challenge in the development of novel drugs is their interaction with potential off-targets, which can cause unintended side-effects, that can lead to the subsequent...
One challenge in the development of novel drugs is their interaction with potential off-targets, which can cause unintended side-effects, that can lead to the subsequent withdrawal of approved drugs. At the same time, these off-targets may also present a chance for the repositioning of withdrawn drugs for new indications, which are potentially rare or more severe than the original indication and where certain adverse reactions may be avoidable or tolerable. To enable further insights into this topic, we updated our database Withdrawn by adding pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS), as well as mechanism of action and human disease pathway prediction features for drugs that are or were temporarily withdrawn or discontinued in at least one country. As withdrawal data are still spread over dozens of national websites, we are continuously updating our lists of discontinued or withdrawn drugs and related (off-)targets. Furthermore, new systematic entry points for browsing the data, such as an ATC tree, were added, increasing the accessibility of the database in a user-friendly way. Withdrawn 2.0 is publicly available without the need for registration or login at https://bioinformatics.charite.de/withdrawn_3/index.php.
Topics: Humans; Drug-Related Side Effects and Adverse Reactions; Pharmacovigilance; Safety-Based Drug Withdrawals; Databases, Pharmaceutical
PubMed: 37971295
DOI: 10.1093/nar/gkad1017 -
The Lancet. Infectious Diseases Apr 2024There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a...
An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial.
BACKGROUND
There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a clinical trial administering CTH522, a recombinant version of the C trachomatis major outer membrane molecule, in different dose concentrations with and without adjuvant, to establish its safety and immunogenicity when administered intramuscularly, intradermally, and topically into the eye, in prime-boost regimens.
METHODS
CHLM-02 was a phase 1, double-blind, randomised, placebo-controlled trial at the National Institute for Health Research Imperial Clinical Research Facility, London, UK. Participants were healthy men and non-pregnant women aged 18-45 years, without pre-existing C trachomatis genital infection. Participants were assigned into six groups by the electronic database in a pre-prepared randomisation list (A-F). Participants were randomly assigned (1:1:1:1:1) to each of the groups A-E (12 participants each) and 6 were randomly assigned to group F. Investigators were masked to treatment allocation. Groups A-E received investigational medicinal product and group F received placebo only. Two liposomal adjuvants were compared, CAF01 and CAF09b. The groups were intramuscular 85 μg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 μg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 μg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F). The primary outcome was safety; the secondary outcome (humoral immunogenicity) was the percentage of trial participants achieving anti-CTH522 IgG seroconversion, defined as four-fold and ten-fold increase over baseline concentrations. Analyses were done as intention to treat and as per protocol. The trial is registered with ClinicalTrials.gov, NCT03926728, and is complete.
FINDINGS
Between Feb 17, 2020 and Feb 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 years). No serious adverse events occurred but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal product doses. Study procedures were otherwise well tolerated; the majority of adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (severe). There was 100% four-fold seroconversion rate by day 42 in the active groups (A-E) and no seroconversion in the placebo group. Serum IgG anti-CTH522 titres were higher after 85 μg CTH522-CAF01 than 15 μg, although not significantly (intention-to-treat median IgG titre ratio groups A-C:D=5·6; p=0·062), with no difference after three injections of 85 μg CTH522-CAF01 compared with CTH522-CAF09b (group E). Intradermal CTH522 (group C) induced high titres of serum IgG anti-CTH522 neutralising antibodies against serovars B (trachoma) and D (urogenital). Topical ocular CTH522 (group B) at day 28 and 112 induced higher total ocular IgA compared with baseline (p<0·001). Participants in all active vaccine groups, particularly groups B and E, developed cell mediated immune responses against CTH522.
INTERPRETATION
CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 μg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials.
FUNDING
The EU Horizon Program TRACVAC.
PubMed: 38615673
DOI: 10.1016/S1473-3099(24)00147-6 -
European Journal of Immunology Nov 2023To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for...
To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4 T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4 T-cell recall responses. Therapeutically, CD4 T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4 T cells with CaEno1 modulated host CD4 T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4 T-cell responses.
Topics: Humans; Candida albicans; T-Lymphocytes; CD4-Positive T-Lymphocytes; Phosphopyruvate Hydratase; Antibodies, Monoclonal
PubMed: 37503840
DOI: 10.1002/eji.202250284 -
Journal of Clinical Anesthesia Sep 2023Performing hip or knee arthroplasty as an outpatient surgery has been shown to be operationally and financially beneficial for selected patients. By applying machine...
STUDY OBJECTIVE
Performing hip or knee arthroplasty as an outpatient surgery has been shown to be operationally and financially beneficial for selected patients. By applying machine learning models to predict patients suitable for outpatient arthroplasty, health care systems can better utilize resources efficiently. The goal of this study was to develop predictive models for identifying patients likely to be discharged same-day following hip or knee arthroplasty.
DESIGN
Model performance was assessed with 10-fold stratified cross-validation, evaluated over baseline determined by the proportion of eligible outpatient arthroplasty over sample size. The models used for classification were logistic regression, support vector classifier, balanced random forest, balanced bagging XGBoost classifier, and balanced bagging LightGBM classifier.
SETTING
The patient records were sampled from arthroplasty procedures at a single institution from October 2013 to November 2021.
PATIENTS
The electronic intake records of 7322 knee and hip arthroplasty patients were sampled for the dataset. After data processing, 5523 records were kept for model training and validation.
INTERVENTIONS
None.
MEASUREMENTS
The primary measures for the models were the F1-score, area under the receiver operating characteristic curve (ROCAUC), and area under the precision-recall curve. To measure feature importance, the SHapley Additive exPlanations value (SHAP) were reported from the model with the highest F1-score.
RESULTS
The best performing classifier (balanced random forest classifier) achieved an F1-score of 0.347: an improvement of 0.174 over baseline and 0.031 over logistic regression. The ROCAUC for this model was 0.734. Using SHAP, the top determinant features of the model included patient sex, surgical approach, surgery type, and body mass index.
CONCLUSIONS
Machine learning models may utilize electronic health records to screen arthroplasty procedures for outpatient eligibility. Tree-based models demonstrated superior performance in this study.
Topics: Humans; Outpatients; Arthroplasty, Replacement, Hip; Benchmarking; Arthroplasty, Replacement, Knee; Machine Learning; Lower Extremity
PubMed: 37201387
DOI: 10.1016/j.jclinane.2023.111147 -
Drug Safety Oct 2023Substandard medicines can lead to serious safety issues affecting public health; however, the nature of such issues can be widely heterogeneous. Health product...
BACKGROUND AND OBJECTIVE
Substandard medicines can lead to serious safety issues affecting public health; however, the nature of such issues can be widely heterogeneous. Health product regulators seek to prioritise critical product quality defects for review to ensure that prompt risk mitigation measures are taken. This study aims to classify the nature of issues for substandard medicines using machine learning to augment a risk-based and timely review of cases.
METHODS
A combined machine learning algorithm with a keyword-based model was developed to classify quality issues using text relating to substandard medicines (CISTERM). The nature of issues for product defect cases were classified based on Medical Dictionary for Regulatory Activities-Health Sciences Authority (MedDRA-HSA) lowest-level terms.
RESULTS
Product defect cases received from January 2010 to December 2021 were used for training (n = 11,082) and for testing (n = 2771). The machine learning model achieved a good recall (precision) of 92% (96%) for 'Product adulterated and/or contains prohibited substance', 86% (90%) for 'Out of specification or out of trend test result' and 90% (91%) for 'Manufacturing non-compliance'.
CONCLUSION
Post-market surveillance of substandard medicines remains a key activity for drug regulatory authorities. A combined machine learning algorithm with keyword-based model can help to prioritise the review of product quality defect issues in a timely manner.
Topics: Humans; Substandard Drugs; Machine Learning; Algorithms; Drug Contamination; Public Health
PubMed: 37776421
DOI: 10.1007/s40264-023-01339-8