Drug Administration Research Articles

Dutasteride for the Treatment of Androgenetic Alopecia: An Updated Review.

Androgenetic alopecia (AGA) is a common skin disease characterized by progressive hair loss, with negative psychological impacts on patients, especially young people. The primary pathogenesis of AGA involves the action of 5α-reductase converting testosterone to dihydrotestosterone, leading to gradual miniaturization of genetically susceptible hair follicles. Finasteride inhibits type II 5α-reductase, while dutasteride simultaneously inhibits type I and type II 5α-reductase. Currently, finasteride is approved by the Food and Drug Administration (FDA) for the treatment of AGA, but its efficacy remains poor in some patients. This article aims to review the treatment of androgenetic alopecia with dutasteride. Oral dutasteride, intradermal injection of dutasteride (mesotherapy) and other related treatment methods are included. We performed a Medical Subject Heading search in the PubMed database using "androgenetic alopecia" and "dutasteride". Compared to finasteride, oral dutasteride has better efficacy and comparable tolerability, and most adverse events are mild and reversible, making it an effective treatment option for AGA. Mesotherapy with dutasteride is a therapeutic option to reduce the systemic adverse effects of the drug, but there are no standardized treatment protocols and large-scale clinical trials. Microneedling combined with dutasteride solution also has its own unique efficacy for treating AGA. Liposomes or nanoparticles of dutasteride are still under development and may become a more optimized topical formulation in the future.

Preventive treatment of pigeons - a myth that fanciers will avenge

In today's world, high demands are placed on the performance and health of racing pigeons. A pleasing appearance and the ability to deliver top performance are the two most significant qualities that breeders strive to achieve in their stock. To ensure and time the pigeons' peak condition properly, the functionality of the musculoskeletal, cardiovascular, and immune systems is crucial, as well as preventing acquired diseases during the racing season. To enhance their racers' performance, breeders often use various supplements and veterinary medications. Many of them believe that to maintain form during the racing season, they must continually administer these medications to their pigeons, a practice known as "constant treatment." However, they do not realize that frequent administration of various drugs (especially antibiotics and corticosteroids) disrupts the immune system. This leads to immunodeficiency, where homeostasis and pH levels are disturbed, gut microflora deteriorates, and the risk of various diseases increases. It is important to remember that improper and reckless application of any supplements and medications can harm the entire stock.

276 Use of triaxial accelerometers and a machine learning algorithm for behavioral identification to assess the effectiveness of a joint supplement in old domestic cats (Felis catus)

Abstract Degenerative joint disease (DJD) has a 90% prevalence in older cats and adversely affects quality of life1. Long-term administration of non-steroidal anti-inflammatory drugs is usually required but can have adverse effects2. Nutraceuticals have been shown to relieve joint pain in cats without such side effects; however, due to differences in dose rates and formulations there is no consensus as to their efficacy. Most studies have utilized subjective insensitive measures such as veterinary or owner-assessed changes in activity. Accelerometers can provide objective data on cat activity and can identify specific behaviors3.Triaxial accelerometers (ActiGraph, Pensacola, FL) were fitted to the collars of 16 cats (aged 11 to 16 yr; Massey University, Palmerston North, NZ) for 20 wk to assess their activity and behavior. The cats were fed the same diet (Chef: Kraft Heinz Wattie’s Ltd., Hastings, NZ) for 4 wk to collect baseline acceleration data, before being divided into two groups balanced for physical activity. After 4 wk, a blood sample were taken from all of the cats to establish their baseline levels of a range of inflammatory markers (e.g., IL-6, TNFα, INF- γ, SDF-1). The test group (n = 8) then received a joint supplement added to the baseline diet while the control group (n = 8) were fed the diet unsupplemented for 16 wk. The commercial joint supplement contained glucosamine, chondroitin sulphate, and green-lipped mussel (Tandem, Wellington, NZ), at daily doses shown previously to be effective in cats4,5,6. The aim of the work was to assess the efficacy of the joint supplement in maintaining or promoting activity and specific behaviors in the cats. At the end of the period of supplementation a second blood sample was taken and assessed for the same range of inflammatory markers. Overall physical activity was not different between groups at baseline but was greater over the study in the test group compared with the control (P < 0.03). Grooming, as identified by the algorithm, showed a tendency (P = 0.051) to be greater in the test group than the control. These results suggest that the supplement had a positive effect on both overall activity and more specifically on grooming behavior in old cats. However, no differences in the range of inflammatory markers were seen before or after supplementation. While the behavioral measures could indicate the supplement reduced the effects of DJD, further research is required to confirm this.1Cunningham et al (2022) Journal of Feline Medicine and Surgery 24, 962-974. 2Lemetayer and Taylor (2014) Journal of Feline Medicine and Surgery 16, 547-562; 3Smit et al., (2023) Sensors 23, 7165; 4Corbee (2022) Veterinary Medicine and Science 8, 1025–1035; 5Corbee et al. (2013) Journal of Animal Physiology and Animal Nutrition 97, 846–853; 6Lascelles et al. (2010) Journal of Veterinary Internal Medicine, 24, 487–495.

Diabetic Kidney Disease: Contribution of Phenyl Sulfate Derived from Dietary Tyrosine upon Gut Microbiota Catabolism.

Deranged gut microbiota can release increased levels of uremic toxins leading to exacerbated kidney injury. In diabetic kidney disease (DKD), phenyl sulfate (PS) derived from tyrosine catabolism by gut microbiota has been demonstrated to be both an early diagnostic marker and a therapeutic target. In this perspective article, we summarize PS generation pathways and recent findings on PS and kidney injury in DKD. Increasing evidence has shown that the underlying mechanisms of PS-induced kidney injury mainly involve oxidative stress, redox imbalance, and mitochondrial dysfunction, which all may be targeted to attenuate PS-induced kidney injury. For future research directions, we think that a deeper understanding of the pathogenic role of PS in kidney injury using a variety of diabetic animal models should be investigated. Moreover, we also suggest beneficial approaches that could be used to mitigate the deleterious effect of PS on the kidney. These approaches include caloric restriction, tyrosine restriction, and administration of ketogenic drugs, ketogenic diets or natural products; all of which should be conducted under obese and diabetic conditions.

Antibiotics-induced pulmonary embolism: A disproportionality analysis in Food and Drug Administration database of Adverse Event Reporting System using data mining algorithms

Antibiotics-induced pulmonary embolism: A disproportionality analysis in Food and Drug Administration database of Adverse Event Reporting System using data mining algorithms

Clinical trials in-a-dish for cardiovascular medicine.

Cardiovascular diseases persist as a global health challenge that requires methodological innovation for effective drug development. Conventional pipelines relying on animal models suffer from high failure rates due to significant interspecies variation between humans and animal models. In response, the recently enacted Food and Drug Administration Modernization Act 2.0 encourages alternative approaches including induced pluripotent stem cells (iPSCs). Human iPSCs provide a patient-specific, precise, and screenable platform for drug testing, paving the way for cardiovascular precision medicine. This review discusses milestones in iPSC differentiation and their applications from disease modelling to drug discovery in cardiovascular medicine. It then explores challenges and emerging opportunities for the implementation of 'clinical trials in-a-dish'. Concluding, this review proposes a framework for future clinical trial design with strategic incorporations of iPSC technology, microphysiological systems, clinical pan-omics, and artificial intelligence to improve success rates and advance cardiovascular healthcare.

PVA-based formulations as a design-technology platform for orally disintegrating film matrices

In the majority of pharmaceutical applications, polymers are employed extensively in a diverse range of pharmaceutical products, serving as indispensable components of contemporary solid oral dosage forms. A comprehensive understanding of the properties of polymers and selection the appropriate methods of characterization is essential for the design and development of novel drug delivery systems and manufacturing processes. Orally disintegrating film (ODF) formulations are considered to be a potential substitute to traditional oral dosage forms and an alternative method of drug administration for children and uncooperative adult patients, including those with swallowing difficulties. A multitude of pharmaceutical formulations with varying mechanical and biopharmaceutical properties have emerged from the modification of the original polymeric bulk. Here we propose different formulation approaches, i.e. solvent casting (SC), 3D printing (3DP), electrospinning (ES), and lyophilization (LP) that enabled us to adjust the disintegration time and the release profile of poorly water soluble haloperidol (HAL, BCS class II) from PVA (polyvinyl alcohol) based polymer films while maintaining similar hydrogel composition. In this study, the solubility of haloperidol in aqueous solution was improved by the addition of lactic acid. The prepared films were evaluated for their morphology (SEM, micro-CT), physicochemical and biopharmaceutical properties. TMDSC, TGA and PXRD were employed for extensive thermal and structural analysis of fabricated materials and their stability. These results allowed us to establish correlations between preparation technology, structural characteristics and properties of PVA films and to adapt the suitable manufacturing technique of the ODFs to achieve appropriate HAL dissolution behaviour.

Thirty-five Years of Reporting of Sex and Race in Clinical Studies of U.S. FDA-Authorized Orthopaedic Devices.

At the U.S. Food and Drug Administration (FDA), the mission of the Center for Devices and Radiological Health (CDRH) is to ensure that all patients and providers have timely and continued access to safe, effective, and high-quality medical devices and safe radiation-emitting products. Although the CDRH has observed enrollment differences in some clinical trials, no systematic analysis has been conducted regarding enrollment differences in baseline demographics, to our knowledge. The CDRH has summarized information on study participants and their baseline demographics in public-facing documentation for all authorized medical devices that involved orthopaedic clinical studies from 1985 to 2020. Descriptive analyses and exploratory statistical testing have been conducted to investigate the reported percentages by sex and race compared with those reported in the U.S. National Census and the American Joint Replacement Registry (AJRR), respectively. We identified 94 submissions and corresponding combined clinical trials from 261 original clinical study arms with 34,193 participants. Most of the submissions reported age and sex, while only 36 submissions (38.3%) reported racial demographics. Among the 88 trials providing enrollment by sex, the female enrollment percentage ranged from 22.2% to 88.7%, with a mean of 55.0%. In the submissions that reported racial data (38.3%), White and Black patients had a mean enrollment of 89.2% (range, 64.8% to 98.7%) and 6.2% (range, 0.4% to 20.7%), respectively. The enrollment for other minority groups ranged from 0% to 3.0%. These clinical trials have shown numerically lower female representation (55.0%) but higher White representation (89.2%) than what has been reported in the AJRR. The other racial groups have participated much less than their corresponding percentages in the U.S. population, but they are similarly represented in the AJRR. The clinical trials supporting the FDA's authorization of orthopaedic devices had a wide range of sex and racial enrollments. It appears that female enrollment mirrors the percentage of women in the U.S. population. However, despite prior efforts, some racial groups are still underrepresented. The FDA has made a commitment to advancing health equity as part of the 2022-2025 Strategic Priorities of the CDRH. We hope that the results of this study will help health-care professionals make informed clinical decisions when using medical devices.

Breast Implant Rupture Surveillance Practices among Plastic Surgeons in Publicly Funded Healthcare Systems.

The United States Food and Drug Administration (FDA) recommends silicone breast implant rupture surveillance using MRI or ultrasound beginning at 5-6 years post-insertion and every 2-3 years thereafter. No surveillance guidelines exist in Canada or the UK. This study aims to identify surveillance practices and perceived barriers to surveillance among plastic surgeons in Canada and the UK and compare surgeon practices between public and private sectors. All active members of the Canadian Society of Plastic Surgeons (CSPS) and British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) with an interest in breast surgery were surveyed. Surgeon demographics, screening practices and perceived barriers to screening were analyzed. Fisher's exact test was used to detect significant associations. The survey response rate was 16%. Most surgeons (68%, n=58/85) were familiar with FDA guidelines; however, only 2.4% (n=2/85) followed them. Surgeons in private practice screened significantly more than surgeons in the public sector [45% (n=13/29) vs 13% (n=7/56), p<0.002]. Among surgeons, ultrasound and high-definition ultrasound were the most common screening modalities and a perceived lack of clinical necessity followed by a perceived lack of satisfactory evidence qualifying these guidelines was the most reported barrier to screening. Despite awareness of FDA guidelines, compliance among surgeons surveyed remains low, reportedly due to a perceived lack of necessity or evidence base. Most public sector surgeons opt not to screen and do not recommend surveillance, even without barriers. While governing bodies should consider current practices to shape guidelines, increasing surgeons' awareness on their evidentiary foundation and potential consequences of silent ruptures is imperative. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A metabolic crosstalk between liposarcoma and muscle sustains tumor growth

Dedifferentiated and Well-differentiated liposarcoma are characterized by a systematic amplification of the Murine Double Minute 2 (MDM2) oncogene. We demonstrate that p53-independent metabolic functions of chromatin-bound MDM2 are exacerbated in liposarcoma and mediate an addiction to serine metabolism to sustain tumor growth. However, the origin of exogenous serine remains unclear. Here, we show that elevated serine levels in mice harboring liposarcoma-patient derived xenograft, released by distant muscle is essential for liposarcoma cell survival. Repressing interleukine-6 expression, or treating liposarcoma cells with Food and Drugs Administration (FDA) approved anti-interleukine-6 monoclonal antibody, decreases de novo serine synthesis in muscle, impairs proliferation, and increases cell death in vitro and in vivo. This work reveals a metabolic crosstalk between muscle and liposarcoma tumor and identifies anti-interleukine-6 as a plausible treatment for liposarcoma patients.

Recent Advancements in Cell-Based Therapies in Melanoma.

Malignant melanoma outcomes have drastically changed in recent years due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients still experience intolerable side effects, therapy resistance, and disease progression on ICI therapy. Therefore, there remains a need for novel therapeutics that address this gap in treatment options. Cell-based therapies have gained wide attention as a therapeutic option that could address this gap in treatment options for advanced melanoma. These therapies work by extracting certain cell types produced in the human body such as T-cells, modifying them based on a specific target, and transfusing them back into the patient. In the realm of cancer therapy, cell-based therapies utilize immune cells to target tumor cells while sparing healthy cells. Recently, the Food and Drug Administration (FDA) has approved the usage of lifileucel, a tumor-infiltrating lymphocyte (TIL) therapy, in advanced melanoma. This came following recent results from the C-144-01 study (NCT02360579), which demonstrated the efficacy and safety of TILs in metastatic melanoma patients who otherwise failed on standard ICI/targeted therapy. Thus, the results of this trial as well as the recent FDA approval have proven the viability of utilizing cell-based therapies to fill the gap in treatment options for patients with advanced melanoma. This review aims to provide a comprehensive overview of major cell-based therapies that have been utilized in melanoma by delineating results of the most recent multi-center phase II/ III clinical trials that evaluate the efficacy and safety of major cell-based therapies in melanoma. Additionally, we provide a summary of current limitations in each cell-based therapeutic option as well as a future direction of how to further extrapolate these cell-based therapies in advanced melanoma.

Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.

Fast, Easy, and Reproducible Fingerprint Methods for Endotoxin Characterization in Nanocellulose and Alginate-Based Hydrogel Scaffolds.

Nanocellulose- and alginate-based hydrogels have been suggested as potential wound-healing materials, but their utilization is limited by the Food and Drug Administration (FDA) requirements regarding endotoxin levels. Cytotoxicity and the presence of endotoxin were assessed after gel sterilization using an autoclave and UV treatment. A new fingerprinting method was developed to characterize the compounds detected in cellulose nanocrystal (CNC)- and cellulose-nanofiber (CNF)-based hydrogels using both positive- and negative-ion mode electrospray ionization Fourier transform ion cyclotron resonance mass spectroscopy (ESI FT-ICR MS). These biobased hydrogels were used as scaffolds for the cultivation and growth of human dermal fibroblasts to test their biocompatibility. A resazurin-based assay was preferred over all other biocompatibility methodologies since it allowed for the evaluation of viability over time in the same sample without causing cell lysis. The CNF dispersion of 6 EU mL-1 was slightly above the limits, and it did not affect the cell viability, whereas CNC hydrogels induced a reduction of metabolic activity by the fibroblasts. The chemical structure of the detected endotoxins did not contain phosphates, but it encompassed hydrophobic sulfonate groups, requiring the development of new high-pressure sterilization methods for the use of cellulose hydrogels in medicine.

Standardized Data Elements for Patients With Acute Pulmonary Embolism: A Consensus Report from the Pulmonary Embolism Research Collaborative.

Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment. We set out to standardize data collection in patients with PE undergoing evaluation and treatment, and thus establish the foundation for an expanding evidence base that will address gaps in evidence and inform future care for acute PE. To do so, >100 international PE thought leaders convened in Washington, DC, in April 2022 to form the Pulmonary Embolism Research Collaborative. Participants included physician experts, key members of the US Food and Drug Administration, patient representatives, and industry leaders. Recognizing the multidisciplinary nature of PE care, the Pulmonary Embolism Research Collaborative was created with representative experts from stakeholder medical subspecialties, including cardiology, pulmonology, vascular medicine, critical care, hematology, cardiac surgery, emergency medicine, hospital medicine, and pharmacology. A list of critical evidence gaps was composed with a matching comprehensive set of standardized data elements; these data points will provide a foundation for productive research, knowledge enhancement, and advancement of clinical care within the field of acute PE, and contribute to answering urgent unmet needs in PE management. Evidence produced through the Pulmonary Embolism Research Collaborative, as it is applied to data collection, promises to provide crucial knowledge that will ultimately produce a robust evidence base that will lead to standardization and harmonization of PE management and improved outcomes.

Stratified analysis of the association between anti-obesity medications and digestive adverse events: a real-world study based on the FDA adverse event reporting system database

BackgroundNumerous digestive system adverse events (dsAEs) have been observed during the use of anti-obesity medications (AOMs), leading to concerns about the safety of these medications. However, most current studies are limited to the association of one class of drugs with specific digestive disorders, and there is no cascading analysis of AOMs in the digestive system. This study aims to use data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) for a stratified analysis of the reported associations between AOMs and dsAEs.MethodsWe analyzed adverse event reports submitted to FAERS between January 2015 and December 2023 related to obesity treatment. It is important to note that FAERS data cannot establish causality or incidence rates. Pharmacovigilance (PV) signals were detected by disproportionate analyses through proportionate reporting ratio (PRR), reporting odds ratios (ROR), and information components (IC) to detect dsAEs associated with AOMs. Reporting rates, severity, and response outcomes of digestive adverse events were compared across AOMs by multivariate logistic regression analysis.ResultsAmong 34,396 adverse events (AEs) related to obesity treatment, 8844 dsAEs were analyzed. Comparing with semaglutide and liraglutide, tirzepatide exhibited fewer reported dsAEs while semaglutide and liraglutide showed a high correlation with non-lethal pancreatitis reports. Bupropion-naltrexone (31.65%) reported the highest number of dsAEs, and a PV signal was detected in mouth and lips AEs (ROR = 2.97, 95% CI: 2.42–3.6). Orlistat (ROR = 3.30, 95% CI: 3.08–3.55) exhibited the highest association with gastrointestinal AEs compared to other AOMs. PV signal for hepatobiliary AEs (ROR = 6.13, 95% CI: 3.45–10.88) with phentermine-topiramate still needs further clarification.ConclusionsTirzepatide may be considered for patients with a history of digestive system disease or an elevated risk of pancreatitis based on the pattern of reported dsAEs. Caution is needed for the orofacial AEs when using bupropion-naltrexone. Orlistat has a higher reporting rate of gastrointestinal AEs, but these events are typically less severe. Phentermine-topiramate’s association with liver impairment requires further clinical investigation. This article provides insights into the reported associations between AOMs and dsAEs, which may aid clinicians in making more informed decisions about individualizing medication and managing potential adverse events.

Hybrid scaffolds for bone tissue engineering: Integration of composites and bioactive hydrogels loaded with hDPSCs

Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

Use of 21-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2024.

On June 17, 2024, the Food and Drug Administration approved 21-valent pneumococcal conjugate vaccine (PCV) (PCV21; CAPVAXIVE; Merck Sharp & Dohme, LLC) for adults aged ≥18 years. PCV21 does not contain certain serotypes that are included in other licensed pneumococcal vaccines but adds eight new serotypes. The Advisory Committee on Immunization Practices (ACIP) recommends use of a PCV for all adults aged ≥65 years, as well as adults aged 19-64 years with certain risk conditions for pneumococcal disease if they have not received a PCV or whose vaccination history is unknown. Previously, options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals, Inc.) alone or a 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme, LLC) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme, LLC). Additional recommendations for use of PCV20 exist for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals, Inc.). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on PCV21 vaccination among U.S. adults. On June 27, 2024, ACIP recommended a single dose of PCV21 as an option for adults aged ≥19 years for whom PCV is currently recommended. Indications for PCV have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides clinical guidance for use of PCV21.

Alpha-asarone alleviates cutaneous hyperalgesia by inhibiting hyperexcitability and neurogenic inflammation via TLR4/NF-κB/NLRP3 signaling pathway in a female chronic migraine rat model

Migraine is a highly prevalent neurological disorder. Alpha-asarone (ASA), a major active component found in Acorus tatarinowii, plays a crucial role in analgesia and anti-inflammation for neuropathic pain. This study aimed to assess the efficacy of ASA against migraine and elucidate its potential mechanisms using a well-established inflammatory soup (IS) migraine female rat model. Mechanical pain thresholds were assessed daily before IS infusion, followed by post-infusion administration of ASA. Subsequently, spontaneous locomotor activities, exploratory behavior, short-term spatial memory, and photophobia were blindly evaluated after the final drug administration. The rats were then sacrificed for investigation into the underlying mechanisms of action. Network pharmacology was also employed to predict potential targets and pathways of ASA against migraine. The anti-inflammatory activity of ASA and pathway-related proteins were examined in BV2 cells stimulated with lipopolysaccharides (LPS). The results demonstrated that ASA ameliorated cutaneous hyperalgesia and photophobia while improving spatial memory and increasing exploratory behavior in IS rats. ASA attenuated central sensitization-related indicators and excessive glutamate levels while enhancing GABA synthesis. ASA rescued neuronal loss in the cortex and hippocampus of IS rats. Notably, the ability of ASA to improve spatial memory performance in the Y maze test was not observed with sumatriptan, a first-line treatment drug, suggesting the potential involvement of the TLR4 pathway. Moreover, ASA suppressed microglial activation, reduced pro-inflammatory factors, and downregulated TLR4, MyD88, p–NF–κB/NF-κB, NLRP3, caspase-1, IL-1β, and IL-18. Overall, ASA demonstrated its potential to alleviate hyperalgesia and improve behavioral performance in migraine rats by inhibiting hyperexcitability and microglia-related inflammation.

Baseline gut microbiota diversity and composition and albendazole efficacy in hookworm-infected individuals

Soil-transmitted helminth (STH) infections account for a significant global health burden, necessitating mass drug administration with benzimidazole-class anthelmintics, such as albendazole (ALB), for morbidity control. However, ALB efficacy shows substantial variability, presenting challenges for achieving consistent treatment outcomes. We have explored the potential impact of the baseline gut microbiota on ALB efficacy in hookworm-infected individuals through microbiota profiling and machine learning (ML) techniques. Our investigation included 89 stool samples collected from hookworm-infected individuals that were analyzed by microscopy and quantitative PCR (qPCR). Of these, 44 were negative by microscopy for STH infection using the Kato-Katz method and qPCR 21 days after treatment, which entails a cure rate of 49.4%. Microbiota characterization was based on amplicon sequencing of the V3–V4 16S ribosomal RNA gene region. Alpha and beta diversity analyses revealed no significant differences between participants who were cured and those who were not cured, suggesting that baseline microbiota diversity does not influence ALB treatment outcomes. Furthermore, differential abundance analysis at the phylum, family and genus levels yielded no statistically significant associations between bacterial communities and ALB efficacy. Utilizing supervised ML models failed to predict treatment response accurately. Our investigation did not provide conclusive insights into the relationship between gut microbiota and ALB efficacy. However, the results highlight the need for future research to incorporate longitudinal studies that monitor changes in the gut microbiota related to the infection and the cure with ALB, as well as functional metagenomics to better understand the interaction of the microbiome with the drug, and its role, if there is any, in modulating anthelmintic treatment outcomes in STH infections. Interdisciplinary approaches integrating microbiology, pharmacology, genetics and data science will be pivotal in advancing our understanding of STH infections and optimizing treatment strategies globally.Graphical

The effect of education provided with the escape room game on nursing students' learning of parenteral drug administration

AimThe present study was conducted to determine the effect of education provided to first-year nursing students with the escape room game on their learning of parenteral drug administration. BackgroundThe use of escape room games in education supports formal education in providing students with professional knowledge and skills. DesignA randomized controlled study design was used in this study. MethodThe current study was conducted with 72 first-year nursing students. Data were collected with the Descriptive Characteristics Questionnaire (DCQ), Parenteral Drug Administration Information Test (PDAIT), Parenteral Drug Administration Sub-Checklists (PDASC) and Game Evaluation Form (GEF) between May and June 2022. The initial knowledge and skills of all students participating in the study were measured after completing the parenteral drug administration theoretical course and laboratory skills course. Students were assigned to the intervention (n=36) and control (n=36) groups by the stratified block randomization method according to their initial knowledge and skill measurements. Unlike the control group, the intervention group played the escape room game once in groups of four. The control group was allowed to work freely in the laboratory during this period. The final knowledge and skills of the intervention and control groups were measured immediately after the intervention. Students' skills were measured with an objective structured clinical examination. ResultsIt was determined that the post-test knowledge level of the students in the intervention group and their post-test skill mean scores for drug withdrawal from an ampoule, subcutaneous injection administration, intradermal injection administration and intravenous push drug administration were higher than those of the students in the control group (p<0.05). Additionally, Intervention group students evaluated the escape room game positively. ConclusionThis study concluded that the escape room game supported formal education and could be used in teaching parenteral drug administration.