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Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER. Obesity and cardiovascular disease: the effect of bariatric surgery Although we know that bariatric surgery effectively targets CV risk factors, its effect on cardiovascular disease is not well-established. Interestingly, 15% of all patients were treated with an SGLT2 inhibitor and subgroup analyses suggest a benefit in both, patients with and without SGLT2 inhibitor treatment. [Extracted from the article]

This is the first draft of a concept paper for discussion. It aims to provide a risk assessment strategy and aspects to consider when evaluating whether an essential medicine can be manufactured locally in low- and middle-income countries with relatively limited pharmaceutical manufacturing capability and experience. This concept paper is part of the work that WHO is initiating, in collaboration with UNIDO, to promote quality local production of medicines in developing countries. The paper is intended to be developed into a joint document which provides guidance to manufacturers, regulatory officials and policy makers on how to minimize risk in manufacturing operations by selecting appropriate essential medicines for production in accordance with existing levels of GMP compliance, and how to tailor technical assistance to implement this approach, with the ultimate goal to eventually achieve local production of medicines by fully GMP-compliant manufacturers in developing countries. A second concept paper on Good Manufacturing Practice (GMP) road mapping is being prepared by UNIDO and will also be published in this journal for comments. Comments and suggestions on this paper are invited to facilitate further discussion. They should be sent to druginfo@who.int. [ABSTRACT FROM AUTHOR]

Background: Patient safety is a central healthcare policy worldwide. Adverse drug events (ADE) are among the main threats to patient safety. Children are at a higher risk of ADE in each stage of medication management process. ADE rate is high in the administration stage, as the final stage of preventing medication errors in pediatrics and neonates. The most effective way to reduce ADE rate is using medication administration clinical decision support systems (MACDSSs). The present study reviewed the literature on MACDSS for neonates and pediatrics. It identified and classified the data elements that mapped onto the Fast Healthcare Interoperability Resources (FHIR) standard and the functionalities of these systems to guide future research. Methods: PubMed/ MEDLINE, Embase, CINAHL, and ProQuest databases were searched from 1995 to June 31, 2021. Studies that addressed developing or applying medication administration software for neonates and pediatrics were included. Two authors reviewed the titles, abstracts, and full texts. The quality of eligible studies was assessed based on the level of evidence. The extracted data elements were mapped onto the FHIR standard. Results: In the initial search, 4,856 papers were identified. After removing duplicates, 3,761 titles, and abstracts were screened. Finally, 56 full-text papers remained for evaluation. The full-text review of papers led to the retention of 10 papers which met the eligibility criteria. In addition, two papers from the reference lists were included. A total number of 12 papers were included for analysis. Six papers were categorized as high-level evidence. Only three papers evaluated their systems in a real environment. A variety of data elements and functionalities could be observed. Overall, 84 unique data elements were extracted from the included papers. The analysis of reported functionalities showed that 18 functionalities were implemented in these systems. Conclusion: Identifying the data elements and functionalities as a roadmap by developers can significantly improve MACDSS performance. Though many CDSSs have been developed for different medication processes in neonates and pediatrics, few have actually evaluated MACDSSs in reality. Therefore, further research is needed on the application and evaluation of MACDSSs in the real environment. Protocol Registration: (dx.doi.org/10.17504/protocols.io.bwbwpape). [ABSTRACT FROM AUTHOR]

Introduction: Noncommunicable diseases (NCDs) are associated with high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of National policy, Nigeria has committed to implement the World Health Organization (WHO) Package of Essential Non-communicable Disease interventions for primary care. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems (HMIS), equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the DM component of the WHO package, and the readiness of the health workers in these PHCs to implement a DM screening, evaluation, and management program to inform future adoption and implementation. Methods: This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August and October 2021. The SARA tool was adapted to focus on DM services and the availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain. Results: All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] = 5 [4–9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1–4]. At least one staff member was recently trained in DM care in 11 PHCs (36%). The study also reported high availability of paper-based HMIS (100%), and DM screening services using a glucometer (87%), but low availability of DM job aids (27%), treatment (23%), and national guidelines/protocols (0%). Conclusion: This formative assessment of PHCs' readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs regarding equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and supply essential DM medications. [ABSTRACT FROM AUTHOR]

Introduction: The use of chatbots in healthcare is an area of study receiving increased academic interest. As the knowledge base grows, the granularity in the level of research is being refined. There is now more targeted work in specific areas of healthcare, for example, chatbots for anxiety and depression, cancer care, and pregnancy support. The aim of this paper is to systematically review and summarize the research conducted on the use of chatbots in the field of addiction, specifically the use of chatbots as supportive agents for those who suffer from a substance use disorder (SUD). Methods: A systematic search of scholarly databases using the broad search criteria of ("drug" OR "alcohol" OR "substance") AND ("addiction" OR "dependence" OR "misuse" OR "disorder" OR "abuse" OR harm*) AND ("chatbot" OR "bot" OR "conversational agent") with an additional clause applied of "publication date" ≥ January 01, 2016 AND "publication date" ≤ March 27, 2022, identified papers for screening. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to evaluate eligibility for inclusion in the study, and the Mixed Methods Appraisal Tool was employed to assess the quality of the papers. Results: The search and screening process identified six papers for full review, two quantitative studies, three qualitative, and one mixed methods. The two quantitative papers considered an adaptation to an existing mental health chatbot to increase its scope to provide support for SUD. The mixed methods study looked at the efficacy of employing a bespoke chatbot as an intervention for harmful alcohol use. Of the qualitative studies, one used thematic analysis to gauge inputs from potential users, and service professionals, on the use of chatbots in the field of addiction, based on existing knowledge, and envisaged solutions. The remaining two were useability studies, one of which focussed on how prominent chatbots, such as Amazon Alexa, Apple Siri, and Google Assistant can support people with an SUD and the other on the possibility of delivering a chatbot for opioid-addicted patients that is driven by existing big data. Discussion/Conclusion: The corpus of research in this field is limited, and given the quality of the papers reviewed, it is suggested more research is needed to report on the usefulness of chatbots in this area with greater confidence. Two of the papers reported a reduction in substance use in those who participated in the study. While this is a favourable finding in support of using chatbots in this field, a strong message of caution must be conveyed insofar as expert input is needed to safely leverage existing data, such as big data from social media, or that which is accessed by prevalent market leading chatbots. Without this, serious failings like those highlighted within this review mean chatbots can do more harm than good to their intended audience. [ABSTRACT FROM AUTHOR]

Lastly, in those 80 years or older at the time of cancer diagnosis, CV mortality exceeded cancer mortality for all nine cancer types after follow-up ranging from 1.9 years (melanoma) to 10.6 years (lung cancer). In those aged 6079 years, CV mortality exceeded cancer mortality for seven cancer types after follow-up ranging from 5 years (bladder cancer) to 17 years (lung cancer). Another population-based study on 100 000 patients with 9 different types of cancer from England investigated the risk of CV death.[10] In patients who were diagnosed with cancer below the age of 60 years, cancer mortality generally exceeded CV mortality except for uterine cancer, for which CV and cancer mortality were similar by 11 years of follow-up. [Extracted from the article]

Background: Drug repositioning has the potential to reduce costs and accelerate the rate of drug development, with highly promising applications. Currently, the development of artificial intelligence has provided the field with fast and efficient computing power. Nevertheless, the repositioning of traditional Chinese medicine (TCM) is still in its infancy, and the establishment of a reasonable and effective research method is a pressing issue that requires urgent attention. The use of graph neural network (GNN) to compute the similarity between TCM prescriptions to develop a method for finding their new indications is an innovative attempt. Methods: This paper focused on traditional Chinese medicine prescriptions containing ephedra, with 20 prescriptions for treating external cough and asthma taken as target prescriptions. The remaining 67 prescriptions containing ephedra were taken as to-be-matched prescriptions. Furthermore, a multitude of data pertaining to the prescriptions, including diseases, disease targets, symptoms, and various types of information on herbs, was gathered from a diverse array of literature sources, such as Chinese medicine databases. Then, cosine similarity and Jaccard coefficient were calculated to characterize the similarity between prescriptions using graph convolutional network (GCN) with a self-supervised learning method, such as deep graph infomax (DGI). Results: A total of 1340 values were obtained for each of the two calculation indicators. A total of 68 prescription pairs were identified after screening with 0.77 as the threshold for cosine similarity. Following the removal of false positive results, 12 prescription pairs were deemed to have further research value. A total of 5 prescription pairs were screened using a threshold of 0.50 for the Jaccard coefficient. However, the specific results did not exhibit significant value for further use, which may be attributed to the excessive variety of information in the dataset. Conclusions: The proposed method can provide reference for finding new indications of target prescriptions by quantifying the similarity between prescriptions. It is expected to offer new insights for developing a scientific and systematic research methodology for traditional Chinese medicine repositioning. [ABSTRACT FROM AUTHOR]

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This article proposes a novel method for generating context-rich knowledge about ‘hard-to-access’ places. We ground our discussion in a recent qualitative study of social settings of youth drug use in Denmark. The study confirmed that private house parties are common sites of youth drug use, although these parties presented limited opportunities for fieldwork. In response, a ‘map-task’ was introduced to the study to complement fieldwork and interviews. We assess the most significant methodological and epistemological features of this map-task, and explore how it may to used to conduct observations ‘from a distance’ in hard-to-access places. Further, we argue that the map-task has a number of analytical and logistical advantages for scholars interested in the health and social aspects of ‘hidden’ phenomena, such as youth drug use. [ABSTRACT FROM AUTHOR]

Drug detection in biofluids has always been great importance for clinical diagnosis. Many detection technologies such as chromatography-mass spectrometry, have been applied to the detection of drugs. However, these technologies required multi-step operations, including complicated and time-consuming pretreatment processes and operations of bulky detection instruments, significantly limiting development of drug detection in clinical diagnosis. Herein, a portable 3D-printed paper cartridge was fabricated for fast sample preconcentration and direct drugs quantitative detection in biofluids by a portable Raman spectrometer. This cartridge contained both paper tip with silver nanowires to preconcentrate samples and achieve surface-enhanced Raman Scattering (SERS) measurement, and 3D-printed cartridge to build enclosed environment for the improvement of detection, which cost only one dollar. The preconcentration ability of the cartridge was up to 18.13-fold fluorescence enhancement and compared to the non-preconcentration method, it achieved 9.93-fold improvement of SERS performance. The anticancer drug of epirubicin hydrochloride, cyclophosphamide and their mixtures were quantitatively detected in the bovine serum or artificial urine. The integrated detection procedure required only 1 h, including sample pretreatment and preconcentration, drying, SERS measurements, and quantification analysis. This 3D-printed paper cartridge constituted a portable detection platform that would be potentially a practical and point-of-care detection tool for drug preconcentration and quantification on the clinical diagnosis. [Display omitted] • 3D-printed paper cartridge was fabricated for fast sample preconcentration and direct drugs quantitative detection in biofluids by a portable Raman spectrometer. • The preconcentration ability of the cartridge was up to 18.13-fold fluorescence and 9.93-fold enhancement of SERS. • The anticancer drug of epirubicin hydrochloride, cyclophosphamide and their mixtures were quantitatively detected in the bovine serum or artificial urine. • The integrated detection procedure of 3D-printed paper cartridge required only 1 hour, including sample pretreatment and preconcentration, drying, SERS measurements, and quantification analysis. [ABSTRACT FROM AUTHOR]

This paper explores the multifaceted role of AI in contemporary drug research, emphasizing its ability to analyze vast datasets, predict molecular interactions, and optimize clinical trials. AI's application extends beyond basic research, influencing preclinical studies, pharmaceutical design, clinical trials, and post-approval activities. It also plays a pivotal role in drug repurposing and the advancement of personalized medicine, where treatments are tailored to individual genetic profiles. By integrating AI into various stages of drug development, the industry has achieved increased efficiency, cost-effectiveness, and accuracy. This paper also highlights the regulatory challenges and opportunities posed by AI, stressing the need for a flexible regulatory framework to balance innovation with patient safety. As AI continues to evolve, its impact on the pharmaceutical industry is expected to grow, driving further advancements in drug research and ultimately leading to improved patient outcomes and a more efficient healthcare system. [ABSTRACT FROM AUTHOR]

The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others. [ABSTRACT FROM AUTHOR]

A dual functional molecularly imprinted polymer (MIP) coated paper (MIP-CP) sensor was firstly proposed for rapid fluorescent (FL) and visual analysis of norfloxacin (NOR) in aqueous solutions. The sensor was fabricated via a sol-gel technique, and characterized by FTIR and SEM. The extraction capacity, selectivity, detection limit, and linear range of the MIP-CP sensor were studied by an FL spectrophotometer. The modified paper sensor showed good selectivity and high extraction capacity for NOR and its structural analogues. For FL analysis of NOR, the linear range and detection limit were found to be 10–100 ng/ml and 2.59 ng/ml, respectively. The visual determination of NOR (under UV light) based on the MIP-CP sensor was also explored, and the determination limit was found to be 0.1 μg/ml. Finally, the proposed methods were successfully applied to the direct determination of NOR in pharmaceutical preparations and cross-validated by UPLC. The MIP-CP sensor might be a potential platform for antibiotic determination due to its multifunction and good analytical performance. A dual functional molecularly imprinted polymer coated paper (MIP-CP) sensor was proposed for fluorescent and visual analysis of norfloxacin. Image 1 • A dual functional paper sensor was firstly fabricated via a sol-gel technique. • A simple fluorescence method was proposed for NOR detection. • A visual fluorescence method was established for NOR detection. [ABSTRACT FROM AUTHOR]

Drug transporters are critically important for the absorption, distribution, metabolism, and excretion (ADME) of many drugs and endogenous compounds. Therefore, disruption of these pathways by inhibition, induction, genetic polymorphisms, or disease can have profound effects on overall physiology, drug pharmacokinetics, drug efficacy, and toxicity. This white paper provides a review of changes in transporter function associated with acute and chronic disease states, describes regulatory pathways affecting transporter expression, and identifies opportunities to advance the field. [ABSTRACT FROM AUTHOR]

In this note we describe a four-channel paper microfluidic device (μPAD) that utilizes gold nanoparticles (AuNPs) as colorimetric sensors and specifically tailored aptamers to capture a set of targeted drugs, including cocaine, codeine and methamphetamine. The design utilizes salt-induced aggregation of AuNPs to produce a color change that indicates the presence of target analytes. In the absence of the targets, the aptamers bind to AuNPs, preventing aggregation. This μPAD was developed by optimizing the concentrations of aggregating agents, AuNPs and aptamers. The resultant device is sensitive and specific, producing a positive result upon detection of the target analyte. • A four-channel paper microfluidic device with gold nanoparticles and aptamers has been developed for siezed drugs. • The design is optimized for length and width of channels, moving solution, quantity of gold nanoparticles, and aptamers. • The runtime of this μPAD is under 10 min and the LOD is 4 μg for cocaine, codeine and methamphetamine. [ABSTRACT FROM AUTHOR]