Search Results (182)

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of “One Health” strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy. Full article

Developing a new drug costs approximately one to three billion dollars and takes around ten years; however, this process has only a ten percent success rate. To address this issue, new technologies that combine artificial intelligence (AI) and quantum computing can be leveraged in the pharmaceutical industry. The RSA cryptographic algorithm, developed by Rivest, Shamir, and Adleman in 1977, is one of the most widely used public-key encryption schemes in modern digital security. Its security foundation lies in the computational difficulty of factoring the product of two large prime numbers, a problem considered intractable for classical computers when the key size is sufficiently large (e.g., 2048 bits or more). A future application of using a detailed structural model of a protein is that digital drug design can be used to predict potential drug candidates, thereby reducing or eliminating the need for time-consuming laboratory and animal testing. Knowing the molecular structure of a possible candidate drug can provide insights into how drugs interact with targets at an atomic level, at significantly lower expenditures, and with maximum effectiveness. AI and quantum computers can rapidly screen out potential new drug candidates, determine the toxicity level of a known drug, and eliminate drugs with high toxicity at the beginning of the drug development phase, thereby avoiding expensive laboratory and animal testing. The Food and Drug Administration (FDA) and other regulatory bodies are increasingly supporting the use of in silico to in vitro/in vivo validation methods and assessments of drug safety and efficacy. Full article

Background and Objectives: The worldwide shift toward psychiatric deinstitutionalization has aimed to enhance patient autonomy, social integration, and overall quality of life. However, limited studies have examined how concurrent substance use—particularly alcohol, marijuana, and inhalable drugs—affects clinical outcomes in these populations. This study aimed to evaluate psychiatric patients with varying degrees of institutionalization and investigate whether substance use complicates or exacerbates treatment outcomes. We hypothesized that individuals using substances would demonstrate worse psychosocial functioning, higher healthcare costs, and increased readmission rates. Methods: We performed a cross-sectional study of 95 participants recruited from long-term care facilities. Participants completed the SF-36 survey validated in Romanian. Financial data were collected to gauge direct and indirect healthcare expenditures. Results: Results indicated that 34.7% of participants reported alcohol use, 12.6% used marijuana, and 9.5% used inhalable substances. Substance-using patients experienced higher mean hospitalization costs of approximately USD 3251.8, compared to non-users (USD 2743.6, p = 0.032). Quality-of-life scores were significantly lower among substance users (mean SF-36 score 58.4 vs. 66.7, p = 0.027). Rates of relapse and readmission were also notably higher in the substance-using cohort (42.1%) relative to non-users (29.8%, p = 0.041). Conclusions: To our knowledge, this is the first Romanian study—and one of only a handful in Europe—to quantify how specific substance-use profiles simultaneously alter quality of life and direct healthcare costs in a deinstitutionalized psychiatric population. Our findings highlight the need for integrated interventions targeting both mental health and substance abuse. Full article

Nuclear receptors are proteins located in the nucleus that are involved in gene transcription and play an important role in regulating metabolism and inflammation. Systemic metabolic abnormalities and chronic inflammation in diabetic patients are associated with gene expression and activity of bile acid metabolism, lipid and carbohydrate metabolism, energy expenditure, and inflammation regulated by nuclear receptors. As a major metabolic organ, the nuclear receptor regulation signal of the liver is the key to regulating the dialog between the liver and other organs. In this review, we discuss the newly discovered role of hepatic nuclear receptor signaling in diabetes metabolism and inflammation and focus on recent advances in drug research targeting nuclear receptors in diabetes, including the use of traditional Chinese medicine. Full article

Neglecting preventive healthcare policies has contributed to the global surge in chronic diseases, increased hospitalizations, declining quality of care, and escalating costs. Non-communicable diseases (NCDs)—notably cardiovascular conditions, diabetes, and cancer—consume over 80% of healthcare expenditure and account for more than 60% of global deaths, which are projected to exceed 75% by 2030. Poor diets, sedentary lifestyles, regulatory loopholes, and underfunded public health initiatives are driving this crisis. Compounding the issue are flawed policies, congressional lobbying, and conflicts of interest that prioritize costly, hospital-based, symptom-driven care over identifying and treating to eliminate root causes and disease prevention. Regulatory agencies are failing to deliver their intended functions. For instance, the U.S. Food and Drug Administration’s (FDA) broad oversight across drugs, devices, food, and supplements has resulted in inefficiencies, reduced transparency, and public safety risks. This broad mandate has allowed the release of unsafe drugs, food additives, and supplements, contributing to the rising childhood diseases, the burden of chronic illness, and over-medicalization. The author proposes separating oversight responsibilities: transferring authority over food, supplements, and OTC products to a new Food and Nutraceutical Agency (FNA), allowing the FDA to be restructured as the Drug and Device Agency (DDA), to refocus on pharmaceuticals and medical devices. While complete reform requires Congressional action, interim policy shifts are urgently needed to improve public health. Broader structural changes—including overhauling the Affordable Care Act, eliminating waste and fraud, redesigning regulatory and insurance systems, and eliminating intermediaries are essential to reducing costs, improving care, and transforming national and global health outcomes. The information provided herein can serve as a White Paper to help reform health agencies and healthcare systems for greater efficiency and lower costs in the USA and globally. Full article

Objectives: We investigate the long-run impact of changes in prescription drug sales on mortality and hospital utilization in Belgium during the first two decades of the 21st century. Methods: We analyze the correlation across diseases between changes in the drugs used to treat the disease and changes in mortality or hospital utilization from that disease. The measure of the change in prescription drug sales we use is the long-run (1998–2018 or 2000–2019) change in the fraction of post-1999 drugs sold. A post-1999 drug is a drug that was not sold during 1989–1999. Results: The 1998–2018 increase in the fraction of post-1999 drugs sold is estimated to have reduced the number of years of life lost before ages 85, 75, and 65 in 2018 by about 438 thousand (31%), 225 thousand (31%), and 114 thousand (32%), respectively. The 1995–2014 increase in in the fraction of post-1999 drugs sold is estimated to have reduced the number of hospital days in 2019 by 2.66 million (20%). Conclusions: Even if we ignore the reduction in hospital utilization attributable to changes in pharmaceutical consumption, a conservative estimate of the 2018 cost per life-year before age 85 gained is EUR 6824. We estimate that previous changes in pharmaceutical consumption reduced 2019 expenditure on inpatient curative and rehabilitative care by EUR 3.55 billion, which is higher than the 2018 expenditure on drugs that were authorized during the period 1998–2018: EUR 2.99 billion. Full article

Background: Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that shows significant efficacy in treating obesity. However, its associated side effects, including poor patient compliance and gastrointestinal inflammation, are concerning and may be largely attributed to its administration methods (e.g., injection vs. oral) and the pronounced fluctuations in systemic drug concentrations. To address these challenges, we investigated an innovative drug delivery system (Transdermal Drug Delivery System, TDDS) designed to maintain therapeutic efficacy while improving patient adherence. Results: Both transdermal and injection treatments of semaglutide decreased body weight, carcass weight, blood glucose, and triglyceride levels in male mice compared with the vehicle-treated control group. In addition, transdermal semaglutide in mice reduced the expression of feeding neuropeptides and the mass of the digestive tract, but increased brown adipose tissue (BAT) mass, metabolic rate, and physical activity, compared with the semaglutide injection group. Additionally, transdermal semaglutide had anxiolytic effects on behavior and did not alter tissue pathology in mice. Conclusion: Compared with the injection paradigm, transdermal semaglutide treatment achieved superior weight loss results in two possible ways: It may reduce energy intake by decreasing the expression of feeding neuropeptides and reducing the weight of the digestive tract. It may also facilitate energy expenditure by enhancing physical activity and increasing BAT mass to boost the metabolic rate. Transdermal semaglutide treatment also has an anxiolytic effect on behavior. Together, our data suggest that TDDS treatment of GLP-1RA may have superior clinical safety and sustainability, providing a novel, efficient, and low-risk obesity treatment. Full article

Background: Fungal infections, particularly among immunocompromised individuals, present significant challenges due to rising incidence rates, treatment costs, and increasing resistance to antifungal agents. This study evaluates trends in antifungal use among Medicaid beneficiaries, focusing on prescribing patterns, costs, and pricing to optimize therapy. Methods: Using the national Medicaid outpatient pharmacy claims data collected by the US Center of Medicare and Medicaid Services, a retrospective drug utilization analysis was conducted for antifungal medications from 2009 to 2023. Antifungal medications were categorized based on therapeutic use. The study examined annual utilization, reimbursement, and pricing trends, along with the market share. Results: Overall Medicaid utilization of superficial fungal infections’ (SFIs’) medications increased from 3.95 million prescriptions in 2009 to 6.16 million in 2023. Nystatin was the most frequently utilized SFI agent, while fluconazole emerged as the most commonly prescribed agent for invasive fungal infections (IFIs). In 2022, a notable spike occurred in the number of prescriptions for both SFIs and IFIs. Medicaid’s total expenditure on SFI medications rose from USD 121.9 million in 2009 to USD 155 million in 2023, while spending on IFI medications fluctuated substantially, peaking at USD 156.8 million in 2022 before declining to USD 80.7 million in 2023. After being introduced to the market, efinaconazole became the most expensive SFI agent over the years. Isavuconazole, the latest approved IFI medication, demonstrated sustained utilization, reimbursement, and price increases. Conclusions: The substantial rise in antifungal utilization and spending underscores the growing financial burden on Medicaid, emphasizing the need for policy interventions to manage costs and generic drug substitution while ensuring equitable access to these essential treatments. However, this study is limited by the lack of clinical outcome data and information on off-label use. Additionally, reimbursement data may not accurately reflect actual drug prices. Full article

Aims: To describe and analyze trends in the utilization, spending, and average per prescription price of disease-modifying antirheumatic drugs (DMARDs) in the US Medicaid population. Methods: Using the publicly available national outpatient Medicaid State Drug Utilization Data, a retrospective, descriptive trend analysis was conducted on DMARDs from 1991 to 2022. Annual prescription counts and reimbursement amounts were calculated for nonbiologic and biologic DMARDs. Average per prescription price and Market share competition were calculated and analyzed for DMARDs. Results: Medicaid utilization of nonbiologic peaked in 2021 with 884,000 while biologic DMARDs with 688,000 prescriptions. In 2022, biologic utilization took the lead and exceed nonbiologic with 1.5 million prescriptions. Over the last 32 years, biologics captured 94% of Medicaid expenditures toward DMARDs, of which, 56% was toward adalimumab alone. On the other hand, spending on conventional DMARDs accounted for 33% while 67% accounted toward Janus Kinase Inhibitors. Biologic DMARDs average prices increased from around $800 to around $6000. However, the average adalimumab price increased 12-fold from around $1200 in 2003 to over $15,000 in 2021. Medicaid spending toward adalimumab increased by 179%. Conclusions: The substantial increase of DMARDs utilization and expenditure contributed significant burden to Medicaid budget. Introducing biosimilars into the market in the past few years is eroding the market share for several established biologics. Further cost-containment policies may be necessary for costly DMARD pharmacotherapy. Full article

Background: The global health burden of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS) affects billions of people and is associated with high levels of healthcare expenditure. Conventional therapies (bronchodilators and corticosteroids) provide symptomatic benefit but take no effect on disease progression, demonstrating the need to develop new therapies. Emerging therapies treat the underlying mechanisms of these chronic diseases, which provide symptomatic relief and benefit the underlying disease. Methods: This review assesses the evolution of therapeutic interventions for chronic lung diseases from a series of established inhaled combination therapies to biologics, gene therapy, and even AI-based stratification of therapies for patients. In addressing these issues, we review the mechanisms of action, evidence of efficacy, and clinical trial evidence, while discussing access issues affecting the implementation of these therapies and ethical issues in relation to their use. Results: The review highlights recent developments in treatment approaches, such as gene therapies aimed at cystic fibrosis mutations, advanced drug delivery pathways for more accurate targeting, and stem cell-based therapies designed to replace damaged lung tissue. These developments have the potential to improve outcomes for chronic lung diseases, but the challenges, including a lack of access, adequate patient selection, and long-term safety, need to be addressed. Conclusions: New therapies offer tremendous potential, but their transition from laboratory to clinic still face numerous barriers including access, regulation, and a need for personalized therapy approaches. The review indicates that future research should develop strategies to reduce barriers to access, improve distribution, and improve clinical guidelines to successfully implement these new therapies. Full article

Background: Previous studies suggested that decreased saliva lactoferrin (LF) levels might be used to differentiate subjects with mild cognitive impairment (MCI) from subjects with normal cognitive function (NCF). Here, we aimed to assess differences in plasma LF concentrations between subjects with NCF and MCI. Methods: In total, 113 NCF subjects and 113 MCI individuals were included in this study. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and anthropometric parameters, body composition, physical activity, cardio-metabolic parameters, and LF levels were measured. Results: MCI subjects had significantly lower LF levels than NCF participants (p < 0.0001). There were also significant differences between the study groups in the smoking history (p = 0.0190), alcohol consumption (p = 0.0036), intake of hypoglycaemic drugs (p = 0.0140), vigorous activity (MET-min/day: p = 0.0223, min/day: p = 0.0133), and energy expenditure associated with activity (p = 0.0287). Moreover, the MoCA test results significantly correlated with LF levels (p = 0.0026), and there were significant differences between MoCA tertiles and LF levels (p = 0.0189). Also, adjusted logistic regression analysis results showed that LF concentrations (p = 0.0382), alcohol consumption (p = 0.0203), and intake of hypoglycaemic drugs (p = 0.0455) were independent predictors of MCI prevalence. Conclusions: In conclusion, MCI subjects are characterised by lower plasma LF concentrations than NCF individuals, but further studies are needed to confirm these findings. Full article

Background: Volume-based drug procurement is regarded as a pharmaceutical cost-containment measure in healthcare provision globally. The Centralized Volume-Based Drug Procurement (CVBDP) launched in March 2019 in China, also known as the ‘4+7’ policy. 11 cities, including Xi’an city in Shaanxi Province, were set up as pilots. This study aims to examine the intended and unintended impacts of the ‘4+7’ policy on the use of original and generic drugs in city-level and county-level hospitals in Shaanxi, China. Methods: The data used in this study came from the Shaanxi Drug and Apparatus Centralized Procurement Platform (SDACPP). In total, 111,999 drug procurement order records of 118 policy-related drugs (including 25 ‘4+7’ policy-list drugs and 93 alternative drugs by generic name) from April 2017 to November 2019 were included in analyses. Policy-list drugs were divided into bid-winning and non-winning drug products. The volume and the expenditure of the drugs served as the outcome variables, measured by Defined Daily Doses (DDDs) and Chinese yuan (CNY), respectively. A difference-in-differences (DID) approach was used to estimate the policy’s net effect. Results: After the ‘4+7’ policy, the volume of bid-winning, policy-list, and policy-related drugs increased. An unexpected increase in volume was observed among alternative drugs, especially original drugs in city-level hospitals. The expenditure of policy-list and non-winning drugs declined, whereas that of alternative drugs unanticipatedly increased. Changes in volume and expenditure were both greater in generic drugs and in city-level hospitals, compared to their original and county-level hospital counterparts. Conclusions: Our findings highlight the positive effects of the ‘4+7’ policy on generic drug substitution and pharmaceutical expenditure containment, which are greater in city-level hospitals. The unanticipatedly incremental volume of original drugs in city-level hospitals suggests the potential risk of the poor quality of bid-winning drugs, lower compliance with bid-winning drugs among patients, or physicians’ profit-seeking behaviors in urban areas. More regulations and supervisions for the prescription and financial incentives of physicians are needed to address these concerns. Full article

Background: Pharmaceutical expenditures serve as key indicators of healthcare system efficiency, innovation, and sustainability. South Korea has implemented policies such as the economic evaluation exemption (EEE) and risk-sharing agreements (RSAs) to balance cost control and access to innovative therapies. However, discrepancies persist in the distribution of expenditures across therapeutic areas, raising concerns about alignment with public health needs. Methods: This retrospective observational study analyzed pharmaceutical expenditures in South Korea from 2007 to 2022, focusing on new chemical entities (NCEs). Data sources included the IQVIA MIDAS Global Database, the WHO Global Burden of Disease (GBD) database, and South Korea’s national health insurance records. Expenditure patterns were benchmarked against OECD and A8 countries using disability-adjusted life years (DALYs) and other healthcare metrics to assess the relationship between spending and disease burden. Results: By 2022, South Korea had introduced 276 NCEs, demonstrating progress, but still lagging the OECD average. NCE expenditure increased from 10.0% to 16.0% of total pharmaceutical spending between 2017 and 2022, whereas A8 countries’ share rose from 26.2% to 48.1%. While oncology expenditures were proportionate to disease burden, spending on chronic diseases such as musculoskeletal and cardiovascular conditions remained relatively low compared to their DALY contributions. Conclusions: Although South Korea has strengthened its investment in pharmaceutical innovation, disparities in expenditure distribution persist. Refining policies to enhance resource allocation for chronic diseases and expanding the RSA framework beyond oncology could improve equity and sustainability. Adopting international best practices—such as indication-based pricing and funding mechanisms for high-cost therapies—may further support optimal pharmaceutical expenditure management. Full article

Background/Objectives: Mounting evidence indicates that the short-chain fatty acid butyrate protects against obesity and associated comorbidities, partially through the induction of adipose tissue thermogenesis. However, the effects of butyrate on white adipose tissue (WAT) browning and its molecular mechanism are still elusive. The objective of this study was to investigate butyrate-induced thermogenesis in white adipose tissue and its underlying mechanism. Methods: We studied the effects of butyrate on diet-induced obesity in the humanized APOE*3-Leiden.CETP transgenic mouse model and explored factors related to white adipose browning. Specifically, mice were challenged with a high-fat diet supplemented with butyrate. Adiposity was measured to assess obesity development. Energy metabolism was detected using an indirect calorimetry system. RNA-seq analysis was conducted to analyze the transcription landscape of WAT and responsible targets. Furthermore, the revealed molecular mechanism was verified in vitro. Results: Butyrate alleviated high-fat diet-induced obesity and promoted energy expenditure accompanied by brown adipose tissue activation and WAT browning. Mechanistically, RNA-seq analysis revealed that butyrate downregulated HDAC9 in WAT. Additionally, butyrate decreased HDAC9 while increasing thermogenesis in vitro. Inhibition of HDAC9 with TMP269 promoted thermogenic gene expression, mimicking the effects of butyrate. Conclusions: Butyrate protects against diet-induced obesity accompanied by decreasing the expression of HDAC9 in white adipose tissue and inducing browning. This study reveals a new mechanism whereby butyrate activates adaptive thermogenesis and provides new insights for the development of weight-loss drugs targeting adipose HDAC9. Full article

Background/Objectives: Excessive or inadequate use of antimicrobial drugs may lead to the emergence of resistant strains. For this reason, it is important to monitor consumption indicators to assess drugs’ utilization over time. This study aimed to analyze the consumption of medically prescribed azole antifungal drugs in mainland Portugal from 2014 to 2023, focusing on those directed to genital infections: fluconazole, isoconazole, itraconazole, and sertaconazole. Methods: For each drug, the evaluated parameters were the total number of packages, number of packages per 1000 inhabitants, defined daily dose (DDD) per 1000 inhabitants per day, and total costs. For this purpose, we used data from community pharmacies’ sales, which are available through INFARMED (the Portuguese national authority on medicines and health products). Results: Several trends emerged from data analysis. The COVID-19 pandemic negatively affected the consumption of all azole antifungal drugs included in this study. However, after 2020, fluconazole and sertaconazole consumption has been increasing. In the specific case of fluconazole, there was an increase in expenditure, although the total number of packages suffered a decrease over the 10-year study period. Additionally, the defined daily dose (DDD) per 1000 inhabitants per day for fluconazole and itraconazole was lower compared to estimates from the last available survey (2009). Conclusions: Although our findings represent a lesser pressure on fungi, further monitoring is needed to better understand the evolution of fluconazole and itraconazole consumption over time, particularly due to the trends observed in this study. Full article