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Journal of Chemical Information and... Feb 2024Virtual screening of large-scale chemical libraries has become increasingly useful for identifying high-quality candidates for drug discovery. While it is possible to...
Virtual screening of large-scale chemical libraries has become increasingly useful for identifying high-quality candidates for drug discovery. While it is possible to exhaustively screen chemical spaces that number on the order of billions, indirect combinatorial approaches are needed to efficiently navigate larger, synthon-based virtual spaces. We describe Shape-Aware Synthon Search (SASS), a synthon-based virtual screening method that carries out shape similarity searches in the synthon space instead of the enumerated product space. SASS can replicate results from exhaustive searches in ultralarge, combinatorial spaces with high recall on a variety of query molecules while only scoring a small subspace of possible enumerated products, thereby significantly accelerating large-scale, shape-based virtual screening.
Topics: Drug Discovery; Small Molecule Libraries
PubMed: 38335044
DOI: 10.1021/acs.jcim.3c01865 -
Journal of Pharmaceutical Sciences Jun 2024This study addresses the identification of undesirable microorganisms (MOs) recovered during the environmental monitoring in manufacture of sterile medicinal products....
This study addresses the identification of undesirable microorganisms (MOs) recovered during the environmental monitoring in manufacture of sterile medicinal products. We developed a methodology evaluation based on a decision tree; then, such approach was applied to hypothetical scenarios of uncommon MOs isolation in sterile drugs production settings. The scenarios were formulated on the basis of our field experience, in terms of both MOs selection and types of sampling site. The MOs were chosen in order to include emerging pathogens and MOs responsible for drug recall, and several sampling sites were considered for their detection (air, surfaces, and personnel). The classification of the unusual MOs revealed that most of them were undesirable, because they represented the loss of environmental control or a potential impact on the quality of the product. In some cases, the uncommon MOs were not considered as undesirable. Therefore, our results demonstrated the importance of a methodology, also in terms of recovery rate of unusual MOs and of the threshold probability for the unacceptability (e.g., 1% or 5%). The proposed methodology allowed an easy and documented evaluation for the undesirable MOs isolated from the environment of the analyzed settings for sterile drugs production.
Topics: Drug Contamination; Environmental Monitoring; Sterilization; Drug Industry; Bacteria; Decision Trees; Environmental Microbiology
PubMed: 38325736
DOI: 10.1016/j.xphs.2024.01.019 -
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 -
JMIR Formative Research Feb 2024The prevalence of childhood obesity and comorbidities is rising alarmingly, and diet is an important modifiable determinant. Numerous dietary interventions in children...
BACKGROUND
The prevalence of childhood obesity and comorbidities is rising alarmingly, and diet is an important modifiable determinant. Numerous dietary interventions in children have been developed to reduce childhood obesity and overweight rates, but their long-term effects are unsatisfactory. Stakeholders call for more personalized approaches, which require detailed dietary intake data. In the case of primary school children, caregivers are key to providing such dietary information. However, as school-aged children are not under the full supervision of one specific caregiver anymore, data are likely to be biased. Recent technological advancements provide opportunities for the role of children themselves, which would serve the overall quality of the obtained dietary data.
OBJECTIVE
This study aims to conduct a child-centered exploratory sequential mixed methods study to identify user requirements for a dietary assessment tool for children aged 5 to 6 years.
METHODS
Formative, nonsystematic narrative literature research was undertaken to delineate initial user requirements and inform prototype ideation in an expert panel workshop (n=11). This yielded 3 prototype dietary assessment tools: FoodBear (tangible piggy bank), myBear (smartphone or tablet app), and FoodCam (physical camera). All 3 prototypes were tested for usability by means of a usability task (video analyses) and user experience (This or That method) among 14 Dutch children aged 5 to 6 years (n=8, 57% boys and n=6, 43% girls).
RESULTS
Most children were able to complete FoodBear's (11/14, 79%), myBear's (10/14, 71%), and FoodCam's (9/14, 64%) usability tasks, but all children required assistance (14/14, 100%) and most of the children encountered usability problems (13/14, 93%). Usability issues were related to food group categorization and recognition, frustrations owing to unsatisfactory functioning of (parts) of the prototypes, recall of food products, and the distinction between eating moments. No short-term differences in product preference between the 3 prototypes were observed, but autonomy, challenge, gaming elements, being tablet based, appearance, social elements, and time frame were identified as determinants of liking the product.
CONCLUSIONS
Our results suggest that children can play a complementary role in dietary data collection to enhance the data collected by their parents. Incorporation of a training program, auditory or visual prompts, reminders and feedback, a user-friendly and intuitive interaction design, child-friendly food groups or icons, and room for children's autonomy were identified as requirements for the future development of a novel and usable dietary assessment tool for children aged 5 to 6 years. Our findings can serve as valuable guidance for ongoing innovations in the field of children's dietary assessment and the provision of personalized dietary support.
PubMed: 38300689
DOI: 10.2196/47850 -
Pharmaceutical Medicine Mar 2024Cyproterone acetate (CPA) is a synthetic progesterone derivative introduced in the 1970s and prescribed as antiandrogenic therapy for inoperable prostate cancer, sexual...
BACKGROUND
Cyproterone acetate (CPA) is a synthetic progesterone derivative introduced in the 1970s and prescribed as antiandrogenic therapy for inoperable prostate cancer, sexual deviations in men, and signs of androgenization in women. In 2020, the CPA summary of product characteristics (SmPC) was revised to include an updated special warning and precaution about (1) the risk of meningioma with increasing cumulative dose and (2) contraindication in patients with meningioma or history of meningioma. A Direct Healthcare Professional Communication (DHPC) was distributed. The European Medicine Agency's Pharmacovigilance Risk Assessment Committee requested that marketing authorization holders in Europe conduct a survey to assess physicians' knowledge of the updated key safety information. The primary objective of this study was to measure physicians' awareness (i.e., did they receive and review the revised SmPC and DHPC) and level of knowledge and understanding of the key safety information pertaining to the restricted use of CPA monotherapy because of the risk of meningioma.
METHODS
This cross-sectional web-based survey was administered to dermatologists, endocrinologists, gynecologists, urologists, oncologists, psychiatrists, and general practitioners in France, Germany, Poland, Spain, and the Netherlands who had prescribed CPA monotherapy in the previous 12 months to assess awareness of the risk of meningioma associated with CPA monotherapy.
RESULTS
Of the 613 physicians who participated, 85% correctly indicated that CPA monotherapy should be prescribed with the lowest effective dose, 75% correctly indicated that the risk of meningioma increases with increasing cumulative CPA monotherapy doses, and 73% correctly indicated that treatment with CPA-containing products must be stopped permanently if a patient is diagnosed with meningioma. Overall, 40% of physicians reported having received the DHPC, and 42% reported having received the revised SmPC.
CONCLUSIONS
Despite low recall of receipt of the updated SmPC and DHPC, most physicians surveyed are aware of the meningioma risk and actions to mitigate the risk.
Topics: Male; Humans; Female; Cyproterone Acetate; Meningioma; Cross-Sectional Studies; Europe; Physicians; Meningeal Neoplasms; Phospholipid Ethers
PubMed: 38296916
DOI: 10.1007/s40290-023-00510-x -
Computers in Biology and Medicine Mar 2024The HER2 expression status in breast cancer liver metastases is a crucial indicator for the diagnosis, treatment, and prognosis assessment of patients. And typical...
The HER2 expression status in breast cancer liver metastases is a crucial indicator for the diagnosis, treatment, and prognosis assessment of patients. And typical diagnosis involves assessing the HER2 expression status through invasive procedures like biopsy. However, this method has certain drawbacks, such as being difficult in obtaining tissue samples and requiring long examination periods. To address these limitations, we propose an AI-aided diagnostic model. This model enables rapid diagnosis. It diagnoses a patient's HER2 expression status on the basis of preprocessed images, which is the region of the lesion extracted from a CT image rather than from an actual tissue sample. The algorithm of the model adopts a parallel structure, including a Branch Block and a Trunk Block. The Branch Block is responsible for extracting the gradient characteristics between the tumor sub-environments, and the Trunk Block is for fusing the characteristics extracted by the Branch Block. The Branch Block contains CNN with self-attention, which combines the advantages of CNN and self-attention to extract more meticulous and comprehensive image features. And the Trunk Block is so designed that it fuses the extracted image feature information without affecting the transmission of the original image features. The Conv-Attention is used to calculate the attention in the Trunk Block, which uses kernel dot product and is responsible for providing the weight for the self-attention in the process of using convolution induced deviation calculation. Combined with the structure of the model and the method used, we refer to this model as TBACkp. The dataset comprises the enhanced abdominal CT images of 151 patients with liver metastases from breast cancer, together with the corresponding HER2 expression levels for each patient. The experimental results are as follows: (AUC: 0.915, ACC: 0.854, specificity: 0.809, precision: 0.863, recall: 0.881, F1-score: 0.872). The results demonstrate that this method can accurately assess the HER2 expression status in patients when compared with other advanced deep learning model.
Topics: Female; Humans; Algorithms; Biopsy; Breast Neoplasms; Liver Neoplasms
PubMed: 38277921
DOI: 10.1016/j.compbiomed.2024.108002 -
JAMA Network Open Jan 2024Kratom products, which are sold legally in most of the US, contain alkaloids with opioidergic, adrenergic, and serotonergic activity. Millions of people use kratom to...
IMPORTANCE
Kratom products, which are sold legally in most of the US, contain alkaloids with opioidergic, adrenergic, and serotonergic activity. Millions of people use kratom to relieve pain, improve mood, or self-manage substance use disorders (SUDs). Kratom use has primarily been examined via surveys, in which recall biases among satisfied users may lead to minimization of transient negative outcomes. Further prospective study of kratom use, such as with ecological momentary assessment (EMA), is needed.
OBJECTIVE
To characterize proximal motivators, effects, and patterns of kratom use and to assess whether use frequency is associated with motivations, effects, past-year criteria for SUD for kratom (KUD), or other substance use.
DESIGN, SETTING, AND PARTICIPANTS
For this prospective cross-sectional study, an intensive longitudinal smartphone-based EMA in which participants' current behaviors and experiences were repeatedly sampled in real time was conducted between July 1 and October 31, 2022. Participants comprised a convenience sample of US adults who used kratom at least 3 days per week for at least 4 weeks at the time of online screening. Criteria for past-year KUD were based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Data analysis was performed between November 2022 and November 2023.
EXPOSURE
The exposure was 13 401 kratom-use events across 15 days.
MAIN OUTCOMES AND MEASURES
A baseline survey covering demographics, health, kratom attitudes and behaviors, use motivations, other substance use, and KUD was administered before EMA. Data for the following EMA entries were then collected: event-contingent entries for kratom use (product, dose, and proximal motivations), follow-up entries (short-term effects and consequences of use events), random-prompt entries (mood), beginning-of-day entries (effects of kratom on sleep), and end-of-day entries (daily subjective descriptions of kratom effects). Bayesian regression was used to estimate means and credible intervals.
RESULTS
A total of 357 participants completed the EMA. Their mean (SD) age was 38.0 (11.1) years; more than half were men (198 [55.5%]). Participants reported overall motivators of use on the baseline survey that involved managing psychiatric and SUD problems, but proximal motivators evaluated during the EMA involved situation-specific needs such as increasing energy and productivity and decreasing pain. Acute effects were considered congruent with daily obligations. Use patterns, despite having some distinguishing features, were generally similar in their motivators and effects; participants used kratom predominantly during the daytime and seemed to find use frequencies that suited their needs. Higher use patterns were associated with symptoms of physical dependence (eg, withdrawal or tolerance). Co-used substances included caffeine, nicotine, vitamins, and cannabis.
CONCLUSIONS AND RELEVANCE
Most participants in this study reported using kratom in a seemingly nonproblematic way. When such use appeared problematic, the key element was usually that withdrawal avoidance became a proximal motivator. Longitudinal studies examining changes in kratom use patterns and effects over time are needed.
Topics: Adult; Female; Humans; Male; Bayes Theorem; Cross-Sectional Studies; Ecological Momentary Assessment; Mitragyna; Motivation; Pain; Prospective Studies; Self Report; Substance-Related Disorders; Middle Aged
PubMed: 38277146
DOI: 10.1001/jamanetworkopen.2023.53401 -
Spine Jan 2024Observational epidemiological study.
STUDY DESIGN
Observational epidemiological study.
OBJECTIVE
This study's primary objective was to examine the risk of recall for novel spine devices over time. Secondarily, we sought to analyze interbody fusion and vertebral body replacement (VBR) devices (corpectomy cages) as a risk factor for recall.
SUMMARY OF BACKGROUND DATA
The recall risk of a novel spine device over time has not been reported. Additionally, FDA regulations were lowered for interbody fusion devices to enter the market in 2007. As well, VBR implants were recently approved by the FDA for use in the cervical spine in 2015.
METHODS
Spine devices cleared between January 1, 2008 and December 31, 2018 were identified from the FDA's 510(k) database. All recall data was collected from the database in January of 2021 to provide a 2-year minimum follow-up for a recall to occur. Product labels were used to classify interbody fusion and VBR devices. Cumulative incidence function was conducted to compare the overall risk of recall for FDA cleared spine devices, and the hazard ratio determined for VBR and all other devices vs interbody implants during the study period.
RESULTS
2,384 spine devices were cleared via 510(k) in the study period. The hazard of recall at 5 years was 5.3% (95% CI: 4.4%-6.2%) and 6.5% (95% CI: 5.4-7.7%) at 10 years. No significant difference in recall risk was identified for interbody fusion and VBR devices.
CONCLUSION
The risk of recall at 5 and 10 years of a novel spine device is about half the 12% rate reported for orthopedic devices in general. Despite lowered FDA regulations for interbody fusion devices and recent approval for VBR device use in the cervical spine, no increased risk of recall was detected. Further research is necessary to explain the reason for the lower risk of recall with spine devices.
LEVEL OF EVIDENCE
V.
PubMed: 38273730
DOI: 10.1097/BRS.0000000000004939 -
Sensors (Basel, Switzerland) Jan 2024Transactional data from point-of-sales systems may not consider customer behavior before purchasing decisions are finalized. A smart shelf system would be able to...
Transactional data from point-of-sales systems may not consider customer behavior before purchasing decisions are finalized. A smart shelf system would be able to provide additional data for retail analytics. In previous works, the conventional approach has involved customers standing directly in front of products on a shelf. Data from instances where customers deviated from this convention, referred to as "cross-location", were typically omitted. However, recognizing instances of cross-location is crucial when contextualizing multi-person and multi-product tracking for real-world scenarios. The monitoring of product association with customer keypoints through RANSAC modeling and particle filtering (PACK-RMPF) is a system that addresses cross-location, consisting of twelve load cell pairs for product tracking and a single camera for customer tracking. In this study, the time series vision data underwent further processing with R-CNN and StrongSORT. An NTP server enabled the synchronization of timestamps between the weight and vision subsystems. Multiple particle filtering predicted the trajectory of each customer's centroid and wrist keypoints relative to the location of each product. RANSAC modeling was implemented on the particles to associate a customer with each event. Comparing system-generated customer-product interaction history with the shopping lists given to each participant, the system had a general average recall rate of 76.33% and 79% for cross-location instances over five runs.
Topics: Humans; Supermarkets; Commerce; Research Personnel; Sprains and Strains; Standing Position
PubMed: 38257460
DOI: 10.3390/s24020367 -
Pharmaceuticals (Basel, Switzerland) Dec 2023Levothyroxine tablets, although highly prescribed in the United States, have been one of the most frequently recalled products. Because of the importance of the...
Levothyroxine tablets, although highly prescribed in the United States, have been one of the most frequently recalled products. Because of the importance of the medication, several efforts have been put in place by the United States Food and Drug Administration (US FDA) to control the quality of levothyroxine tablets available to patients using the drug. The choice of excipients used in the formulation has been shown to impact the hygroscopicity and microenvironment, and ultimately the stability of the levothyroxine tablets formulations. Based on information generated from the US FDA Enforcement Report database, one of the main reasons for recalls is the low potency of different batches of the product. The yearly product recall trends for levothyroxine formulations were determined using the FDA Enforcement Report database. Three brands of levothyroxine tablets were selected with excipient lists similar to those products that have been historically recalled. The samples were placed at ambient (~23 °C), accelerated stability (40 °C/75% RH), and stress (50 °C/75% RH) conditions for up to 6 months. Sample potencies were determined at 0, 1.5, 3, and 6 months using the methods for assay and impurities in the United States Pharmacopeia (USP) monograph for levothyroxine tablets. Additional sample monitoring was conducted by overlaying the initial powder X-ray diffractograms (PXRD) of the samples from 0 months with the patterns generated thereafter. There has been a decline in the number of levothyroxine tablets recalled over the years. The highest numbers of recalls were recorded in the years 2013 [33] and 2020 [23]; no recalls occurred in the years 2019 and 2022. All of the brands evaluated met the USP 95.0-105.0% assay requirements at 1.5 months under accelerated conditions; only one of the brands complied at 3 months. Under ambient conditions, two brands were stable at 6 months, with borderline assay results. For stability, levothyroxine was found in microgram quantities in the formulations and PXRD could not detect changes at these low levels. However, we found some distinguishing data for samples under stress conditions.
PubMed: 38256876
DOI: 10.3390/ph17010042