Search Results (164)

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

The resilience of the pharmaceutical supply chain (PSC) is crucial to ensuring the availability of medical products. However, increasing complexity and logistical bottlenecks have exposed weaknesses within PSC frameworks. These challenges underscore the urgent need for more resilient and intelligent supply chain solutions. Recently, Artificial Intelligence and machine learning (AI/ML) have emerged as transformative technologies to enhance PSC resilience. This study presents a systematic review evaluating the role of AI/ML in advancing PSC resilience and their applications across PSC functions. A comprehensive search of five academic databases (Scopus, the Web of Science, IEEE Xplore, PubMed, and EMBASE) identified 89 peer-reviewed studies published between 2019 and 2025. PRISMA 2020 guidelines were implemented, resulting in a final dataset of 32 studies. In addition to analyzing applications, this study identifies the AI/ML grouped into five main categories, providing a clearer understanding of their impact on PSC resilience. The findings reveal that despite AI/ML’s promise, significant research gaps persist. Particularly, AI/ML-driven regulatory compliance and real-time supplier collaboration remain underexplored. Over 59.3% of studies fail to address regulatory frameworks and ethical considerations. In addition, major challenges emerge such as the limited real-world deployment of AI/ML-driven solutions and the lack of managerial impacts on PSC resilience. This study emphasizes the need for stronger regulatory frameworks, broader empirical validation, and AI/ML-driven predictive modeling. This study proposes recommendations for future research to foster more efficient, transparent and ethical PSCs capable of navigating the complexities of global healthcare. Full article

Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography–tandem mass spectrometry (LC-MS/MS) toxicology testing on available urine samples from patients presenting to two hospitals in Philadelphia, PA, who fit two clinical phenotypes, intoxication or withdrawal. Samples also underwent glucuronidase pre-treatment to assess impact on the yield of medetomidine and xylazine metabolite detection. Testing identified universal exposure to medetomidine (58/58 samples) via the 3-hydroxy-medetomidine (3-OH-M) metabolite, post glucuronidase treatment and variable xylazine exposure (40/58 samples). Importantly, 32% of medetomidine exposures would have been missed without enzymatic pre-treatment. Patients exhibited two distinct clinical phenotypes: intoxication, characterized primarily by sedation; bradycardia; and often hypotension, and withdrawal, presenting with life-threatening tachycardia; hypertension and often encephalopathy. Notably, clinical phenotype correlated with urinary concentrations of 3-OH-M but not xylazine. These findings underscore the critical need for heightened clinical awareness and need for contemporaneous toxicologic screening mechanisms for medetomidine exposure, emphasizing its distinct clinical presentations and the potential public health implications posed by its widespread adulteration in illicit opioids. Full article

Expensive medical devices, especially in the areas of orthopedics, and cardiology, have a significant impact on hospital costs and the delivery of high-quality services. These medical supplies are known as physician preference items (PPIs), as they act as “surrogate buyers”—impacting the selection and sourcing of products. There is a gap between the purchasing strategy and the adoption of tactical activities for these complex medical supplies. In the context of the healthcare exceptionalism thesis, this research investigates how healthcare organizations can successfully adopt suitable sourcing levers aiming to achieve different purchasing results. This research conducts a multi-case study in 15 healthcare organizations in nine countries. Three new sourcing levers specific to the healthcare sector emerged, based on the healthcare exceptionalism thesis. It was possible to identify five main sourcing levers clusters. The fit between strategy and tactical level can be allowed by the implementation of suitable sourcing levers—facilitating the achievement of the desired objectives. Healthcare procurement practitioners should assess the fit between strategy and the tactical level by employing suitable sourcing levers. Organizations wishing to move towards a value-based procurement approach should adopt a set of supporting sourcing levers to enable this transition. Full article

In the new context of information sharing to reshape the supply chain’s interruption risk propagation mechanism, this paper focuses on the interruption risk propagation and resilience of the supply chain of emergency medical supplies in the background of emergencies. Firstly, an emergency supply chain’s risk propagation model under information sharing is proposed by combining the information sharing mechanism with the supply chain’s risk propagation theory. Secondly, an interruption risk propagation model for the supply chain of emergency medical supplies based on a Bayesian Network is constructed, and the do-calculus technique is introduced to transform the intervention effect of information sharing into the quantification of the supply chain’s risk probability. Thirdly, a system dynamics method is used to construct a supply chain model for emergency medical supplies, which takes into account different interruption scenarios caused by emergencies and evaluates the supply chain’s resilience through the key variable “demand fulfillment rate” in the model. The results of the study indicate that the impact of different types of interruption scenarios on supply chain resilience varies significantly. Information sharing can effectively reduce the negative impact of interruption risk. This study provides theoretical basis and practical guidance for improving the resilience of the supply chain of emergency medical supplies, which is of great significance for maintaining social stability and promoting the sustainable development of the public health system. Full article

In this study, we conceptualize the demands imposed on emergency supply chains during extraordinary emergency events as “stress” and develop a scenario-based stress evolution (SE) analytical approach in emergency mobilization decision-making. First, we characterize emergency supply chain stress by uncertainty, abruptness, urgency, massiveness of scale, and latency. Leveraging lifecycle theory and aligning it with the event’s natural lifecycle progression, we construct a dual-cycle model—the emergency event-stress dual-cycle curve model—to intuitively conceptualize the SE process. Second, taking China’s emergency medical supply chain as an illustrative example, we employ set theory to achieve a structured representation of emergency supply chain stress evolution (ESCSE). Third, we propose a novel ESCSE modeling methodology based on stochastic Petri nets and establish both an ESCSE model and a corresponding isomorphic Markov chain model. To address parameter uncertainties inherent in the modeling process, the fuzzy theory is integrated for parameter optimization, enabling realistic simulation of emergency supply chain stress evolution dynamics. Finally, the SE of the ibuprofen supply chain in Beijing during the COVID-19 pandemic is presented as a case study to demonstrate the working principle of the model. The results indicate that the ESCSE model effectively simulates the SE process, identifies critical states, and triggers actions. It also reveals the evolution trends of key scenario elements, thereby assisting decision-makers in deploying more targeted mobilization strategies in dynamic and changing environments. Full article

This work presents a current-controlled CMOS ring oscillator (CCRO) optimized for ultra-low-voltage applications in next-generation energy-constrained systems. Leveraging bulk voltage tuning in 22 nm FDSOI differential inverter stages, the topology enables frequency adjustment while operating MOSFETs in the subthreshold region—critical for minimizing power in sub-1 V environments. Simulations at 0.4 V supply demonstrate robust performance: a three-stage oscillator achieves a 537–800 MHz tuning range with bias current (I_BIAS) modulation from 30–130 nA, while a four-stage configuration spans 388–587 MHz. At 70 nA I_BIAS, the three-stage design delivers a nominal frequency of 666.8 MHz with just 10.23 µW power dissipation, underscoring its suitability for ultra-low-power IoT and biomedical applications. The oscillator’s linear frequency sensitivity (2.63 MHz/nA) allows precise, dynamic control over performance–power tradeoffs. To address diverse application needs, the design integrates three tunability mechanisms: programmable capacitor arrays for coarse frequency adjustments, configurable stage counts (three- or four-stage topologies), and supply voltage scaling. This multi-modal approach extends the operational range to 1 MHz–1 GHz, ensuring compatibility with low-speed sensor interfaces and high-speed edge-computing tasks. The CCRO’s subthreshold operation at 0.4 V—coupled with nanoampere-level current consumption—makes it uniquely suited for battery-less systems, wearable health monitors, and implantable medical devices where energy efficiency and adaptive clocking are paramount. By eliminating traditional voltage-controlled oscillators’ complexity, this topology offers a compact, scalable solution for emerging ultra-low-power technologies. Full article

Background/Objectives: Philadelphia has experienced a surge in illicit fentanyl adulterated with alpha-2 agonist sedatives. Initially, xylazine (“tranq”) was the predominant adulterant, and a novel multimodal withdrawal protocol was effective at mitigating symptoms. However, since mid-2024, medetomidine—a more potent sedative—has largely supplanted xylazine. Clinicians have reported more severe, treatment-resistant opioid withdrawal during this transition. To assess whether a previously effective withdrawal management protocol retained efficacy after the emergence of medetomidine as the primary fentanyl adulterant in a community. Methods: We conducted a retrospective cohort study of patients receiving protocol-based opioid withdrawal treatment at two emergency departments in Philadelphia between September 2022 and April 2025. Patients were divided into the xylazine era (September 2022–July 2024) and medetomidine era (August 2024–April 2025). The primary outcome was a change in Clinical Opioid Withdrawal Scale (COWS) score from pre- to post-treatment. Secondary outcomes included rates of discharge against medical advice (AMA) and ICU admission, as well as the impact of a revised treatment protocol. Results: Among 1269 encounters with full data, 616 occurred during the xylazine era and 770 during the medetomidine era. Median COWS reduction was greater in the xylazine group (−9.0 vs. −4.0 points, p < 0.001), with more patients achieving symptom relief (COWS ≤ 4: 65.6% vs. 14.2%, p < 0.001). ICU admission occurred in 8.5% of xylazine era patients and 16.8% of medetomidine era patients (p < 0.001). Rates of AMA were higher during the medetomidine era as well (6.5% vs. 3.6%) (p = 0.038). Revision of treatment protocols showed promise. Conclusions: The protocol was significantly less effective during the medetomidine era, though a protocol change may be helping. Findings highlight the need to adapt withdrawal treatment protocols in response to changes in the illicit drug supply. Full article

Snakebite envenoming remains a critical yet underrecognized public health issue, particularly in tropical and subtropical regions, with India bearing nearly half of the global burden of snakebite-related deaths. Despite its significant impact, underreporting, delayed medical intervention, and insufficiently trained healthcare professionals continue to exacerbate the problem. In response, the Government of India launched the National Action Plan for Prevention and Control of Snakebite Envenoming (NAPSE) in March 2024, aiming to halve snakebite-related deaths by 2030. Key challenges during the development and implementation of NAPSE included the limited multisectoral engagement initially, variations in state-level capacities, and logistical barriers in reaching remote populations. Lessons learned include the value of early stakeholder consultations, the importance of inter-ministerial collaboration, and the need for continuous community engagement. This comprehensive strategy emphasizes strengthening surveillance systems, enhancing anti-snake venom (ASV) distribution and quality, improving healthcare infrastructure, and promoting community awareness through a One Health approach. The plan also addresses critical challenges such as inadequate training at primary healthcare levels, inconsistent ASV supply, and inefficient emergency referral systems. By fostering multisectoral collaboration and targeted interventions, such as strengthening Regional Venom Centres and establishing Poison Information Centre, targeted training, and awareness campaigns, NAPSE aims to reduce mortality and disability associated with snakebite envenoming, aligning with global health objectives and setting an example for regional efforts in Southeast Asia. Full article

Supplier selection in the medical device manufacturing (MDM) industry significantly affects quality, operational efficiency, and overall organizational performance. Due to the industry’s dependence on advanced technologies and rigorous regulatory standards, identifying critical success factors (CSF) for selecting suppliers is essential. This study aims to analyze relationships among critical success factors (CSF) influencing supplier selection and their influence on supplier quality and the performance outcomes of MDM companies. A structured survey was conducted among MDM companies in Mexico, and the collected data were analyzed through exploratory and confirmatory factor analysis. Structural equation modeling (SEM) was used to quantify the relationships identified. Results indicate that information technology, reliable delivery, Industry 4.0 adoption, resilience, and environmental and social responsibility positively influence supplier quality, which subsequently enhances MDM firm performance. Supplier quality emerges as a critical mediator between supplier selection factors and company performance. Findings emphasize that prioritizing supplier quality, reinforced through Industry 4.0 technologies and resilient practices, ensures operational continuity, enhances competitive advantage, and supports sustainability. Companies incorporating these critical success factors into their supplier selection processes are better equipped to manage supply disruptions, achieve consistent quality, and sustain performance in highly regulated environments. Full article

Unmanned aerial vehicles (UAVs) are emerging as powerful tools for transporting temperature-sensitive payloads, including medical supplies, biological samples, and research materials, to remote or hard-to-reach locations. Effective thermal management is essential for maintaining payload integrity, especially during extended flights or harsh environmental conditions. This review presents a comprehensive analysis of temperature control mechanisms for UAV payloads, covering both passive and active strategies. Passive systems, such as phase-change materials and high-performance insulation, provide energy-efficient solutions for short-duration flights. In contrast, active systems, including thermoelectric cooling modules and Joule heating elements, offer precise temperature regulation for more demanding applications. We examined case studies that highlight the integration of these technologies in real-world UAV applications, such as vaccine delivery, blood sample transport, and in-flight polymerase chain reaction diagnostics. Additionally, we discussed critical design considerations, including power efficiency, payload capacity, and the impact of thermal management on flight endurance. We then presented an outlook on emerging technologies, such as hybrid power systems and smart feedback control loops, which promise to enhance UAV-based thermal management. This work aimed to guide researchers and practitioners in advancing thermal control technologies, enabling reliable, efficient, and scalable solutions for temperature-sensitive deliveries using UAVs. Full article

Plants require a flexible avoidance mechanism as they need to cope with external stimuli and challenges through complex specialized metabolites, among which volatile terpenoids make outstanding contributions, acting as key media signal substances in the cooperation between plants and surrounding organisms. In recent decades, the research on the identification and functional characterization of terpenoid synthase and factors regulating metabolic shunts has gained significant attention, leading to substantial progress and notable achievements. However, with the popularization of terpenoids in insect and disease prevention, medical care, cosmetics, and other fields, coupled with increasing resistance to artificially produced chemical products, the demand for natural terpenoids has outpaced supply, prompting the emergence and popularity of targeted engineering for the mass production of terpenoids using microorganisms and plants as platforms. In this paper, we provide a detailed overview of the key knowledge and research progress of volatile terpenoids with regard to multiple functions, complex synthetic pathways, key terpenoid synthase genes, related regulatory factors, and target engineering. Full article

With the intensification of aging, the imbalance between the supply and demand of elderly care services has become increasingly prominent. Taking Changsha as a case study, this research constructs an accessibility evaluation system based on the 15-min life circle theory, utilizing multi-source data. Spatial weighting characteristics of elderly care facility locations were analyzed through machine learning algorithms, and service coverage disparities between urban districts and suburban towns were assessed under 5-, 10-, and 15-min walking thresholds. Street view semantic segmentation technology was employed to extract street environmental elements in central urban areas, and a multiple regression model was established to elucidate the impact mechanisms of the built environment on walking accessibility. Key findings include: (1) Significant urban-rural service disparities exist, with 91.4% of urban core facilities offering seven service categories within 15-min walking catchments compared to 26.86% in township areas, demonstrating suburban infrastructure’s heavy reliance on administrative resource allocation. (2) Street environmental factors exhibit significant correlations with walking accessibility scores. At the 15-min walking threshold, building space ratio and transportation infrastructure coverage positively influenced walking convenience, while sky view ratio showed a negative correlation. (3) A random forest-based location prediction framework identified multiple service gaps in existing facilities. Suburban service deficiencies (e.g., 59.8% medical facility coverage within walkable catchments) emerge as critical equity barriers, prompting recommendations for integrated “micro-clinic + smart pharmacy” networks and prioritized mixed-use zoning in new urban planning. This research advances a data-driven framework for reconciling urbanization-aging conflicts, offering practical insights for developing nations in creating age-friendly urban environments. Full article

This study focuses on Vehicle-Integrated Photovoltaic (VIPV) strategy adopted as an energy supply vector in disaster scenarios. As a matter of fact, energy supply may be a very critical issue in a disaster context, when grid networks may be damaged. Emergency vehicles, including ambulances and trucks, as well as mobile units such as containers and operating rooms, can be equipped with photovoltaic modules and can serve as mobile emergency energy sources, supporting both vehicle operations and disaster relief efforts. A methodology was developed to estimate energy production under unpredictable disaster conditions, by adapting existing VIPV simulation approaches. Obtained results show that VIPV strategy, even under minimal daily energy generation, can be a useful aid for disaster resilience and emergency prompt response. Ambulance performance, analyzed for worst-case scenarios (e.g., December), shows that they can power medical devices for 1 to 15 h daily. Additionally, the ambulance can generate up to 2 $\mathrm{M}\mathrm{W}\mathrm{h}$ annually, reducing CO₂ emissions by up to 0.5 tons. In optimal configurations, mobile operating rooms can generate up to 120 times the daily energy demand for medical devices. Full article

Most cardiological drugs need intravenous administration to have a fast effect in an emergency. Intravenous administration is linked to complications, such as tissue infiltration and thrombophlebitis. Aiming to supply an effective tool for the development of appropriate policies, this systematic review provides practical recommendations about the diluent, pH, osmolarity, dosage, vesicant properties, and phlebitis rate of the most commonly used cardiological drugs evaluated in randomized controlled trials (RCTs) till 31 August 2024. The authors searched for available IV cardiological drugs in RCTs in PUBMED EMBASE^®, EBSCO-CINAHL^®, and Cochrane Controlled Clinical trials. Drugs’ chemical features were obtained online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, an osmolarity > 600 mOsm/L, and a high incidence of phlebitis reported in the literature, as well as vesicant drugs, require utmost caution during administration. A total of 857 papers were evaluated and 316 studies were included. A total of 84 cardiological drugs were identified, of which only 31 (37%) can be safely infused via a peripheral route. Thrombolytics and anticoagulants are considered the safest classes of drugs, with only one drug flagged as a “red flag” medication. However, a higher percentage of drugs in other categories meet the “red flag” criteria, including antiarrhythmics (52%), antiplatelet agents (67%), diuretics (67%), antihypertensives (70%), other drugs (77%), and vasoconstrictors and inotropics (89%). Understanding the physicochemical properties of cardiological drugs is essential for significantly improving patient safety and preventing administration errors and local side effects. Full article