Pharmacokinetic analysis of morphine-3-glucuronide after acute morphine intravenous bolus administration to rats with traumatic brain injury.

This study investigates the effects of traumatic brain injury (TBI) on the pharmacokinetics of morphine and its metabolite, morphine-3-glucuronide (M3G), and their influence on neuroinflammation and systemic inflammation. We hypothesized that disruptions in the blood-brain barrier (BBB) due to TBI would enhance M3G exposure to the brain, which could potentially trigger inflammatory responses. We implemented a rat model of controlled cortical impact (CCI) injury to assess systemic pharmacokinetics of morphine and M3G over 24 hours postintravenous bolus administration.

Topical Gel/Microsphere Eyedrop for Combined Delivery of Brimonidine and Timolol: A Comparative Study With Traditional Eye Drops in Rabbits.

Purpose: Topical eye drops combining multiple antiglaucoma agents are often required when monotherapy fails to reduce intraocular pressure (IOP). However, their effectiveness is compromised by low bioavailability and poor patient compliance. To address these issues, we developed a novel gel/microsphere eye drop (GME) containing brimonidine and timolol, aimed at enhancing ocular bioavailability, reducing dosing frequency, and improving patient compliance.

Using Machine Learning to Predict Medication Therapy Problems among Patients with Chronic Kidney Disease.

Introduction: Patients with chronic kidney disease (CKD) are at risk of medication therapy problems (MTPs) due to high comorbidity and medication burden. Using data from the Kidney Coordinated HeAlth Management Partnership (Kidney CHAMP) trial, we used machine learning to build a predictive model to identify MTP high-risk patients with CKD in the primary care setting.

Methods: We used baseline data from patients enrolled in the intervention arm of the Kidney CHAMP trial, completed May 2019-July 2022, which tested a population health management strategy, including medication management, for improving CKD care.

Population Health Management Impact on Healthcare Utilization and Costs in CKD: Post Hoc Analysis of the Kidney Coordinated HeAlth Management Partnership Trial.

Key Points: A population health management intervention for CKD reduced inpatient hospitalizations by 27% compared with usual care over a 1-year follow-up. Despite lower hospitalizations, total healthcare costs were not significantly different between population health management and usual care.

Background: CKD represents a substantial economic burden, particularly in the Medicare population in the latter stages of disease progression.

Effect of a Population Health Management Intervention on Medication Therapy Problems in People With Chronic Kidney Disease: Post Hoc Analysis of the K-CHAMP Cluster-Randomized Trial.

Rationale & Objective: Medication therapy problems (MTPs) are therapeutic issues related to medications that may cause undesirable events. People with chronic kidney disease (CKD) are at high risk of experiencing MTPs owing to comorbid conditions and medication burden. This study characterizes MTPs in individuals enrolled in the Kidney Coordinated Health Management Partnership trial and evaluates the intervention's effect on MTPs.

Sustained metabolic reduction and hypothermia in humans.

Metabolic reduction is an adaptation employed by animals encountering environmental stressors or scarce resources. Lowering metabolism in humans may be useful to reduce consumables, oxygen utilization and carbon dioxide excretion. This is relevant for payload optimization or resource-restricted scenarios such as long-duration spaceflight or austere terrestrial environments (e.

The survival of B cells is compromised in kidney disease.

Antibody-mediated protection against pathogens is crucial to a healthy life. However, the recent SARS-CoV-2 pandemic has shown that pre-existing comorbid conditions including kidney disease account for compromised humoral immunity to infections. Individuals with kidney disease are not only susceptible to infections but also exhibit poor vaccine-induced antibody response.

Moving forward from Cockcroft-Gault creatinine clearance to race-free estimated glomerular filtration rate to improve medication-related decision-making in adults across healthcare settings: A consensus of the National Kidney Foundation Workgroup for Implementation of Race-Free eGFR-Based Medication-Related Decisions.

Purpose: The goals of this paper are to (1) provide evidence and expert consensus to support a unified approach to estimating kidney filtration in adults with stable kidney function using race-free estimated glomerular filtration rate (eGFR) in place of Cockcroft-Gault estimated creatinine clearance (C-G eCrCL) for medical and medication-related decisions, and (2) demonstrate how adjusting eGFR results for an individual's body surface area (BSA) when it is higher or lower than 1.73 m2 will improve results for medication-related decisions.

Summary: C-G eCrCL is predominantly used by US pharmacists to determine eGFR for the purposes of medication-related decisions, even though more accurate eGFR equations exist.

Systemic and local chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women.

Unlabelled: Estrogen receptor positive (ER+) breast cancer is the most common subtype of breast cancer and is an age-related disease. The peak incidence of diagnosis occurs around age 70, even though these post-menopausal patients have low circulating levels of estradiol (E2). Despite the hormone sensitivity of age-related tumors, we have a limited understanding of the interplay between systemic and local hormones, chronic inflammation, and immune changes that contribute to the growth and development of these tumors.

Population Health Management and Guideline-Concordant Care in CKD: A Secondary Analysis of Kidney Coordinated HeAlth Management Partnership.

Key Points: Implementation gaps in guideline-concordant care for CKD are associated with poor clinical outcomes. A population health management–based, multidisciplinary approach improved exposure days to sodium-glucose cotransporter-2 inhibitor and glucagon-like peptide-1 receptor agonists compared with usual care. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in albuminuric patients and statin use was not improved, nor was BP control, glycemic control, or albuminuria testing.

Opioid Prescriptions for US Patients Undergoing Long-Term Dialysis or with Kidney Transplant from 2011 to 2020.

Key Points: The rate of prescription of opioid medication decreased between 2011 and 2020 for patients with ESRD. The risk of death for dialysis and kidney transplant patients increased as morphine milligram equivalents in prescriptions increased.

Background: Pain is important for patients with kidney failure, but opioid medication prescriptions are associated with morbidity and mortality.

Alpha-2-adrenergic agonists reduce resting energy expenditure in humans during external cooling.

Intravenous alpha-2-adrenergic receptor agonists reduce energy expenditure and lower the temperature when shivering begins in humans, allowing a decrease in core body temperature. Because there are few data about similar effects from oral drugs, we tested whether single oral doses of the sedative dexmedetomidine (1 µg/kg sublingual or 4 µg/kg swallowed) or the muscle relaxant tizanidine (8 mg or 16 mg), combined with surface cooling, reduce energy expenditure and core body temperature in humans. A total of 26 healthy participants completed 41 one-day laboratory studies measuring core body temperature using an ingested telemetry capsule and measuring energy expenditure using indirect calorimetry for up to 6 hours after drug ingestion.

Underrepresentation of black individuals in pivotal trials for novel anticancer drugs: Potential consequence of using estimated creatinine clearance to assess kidney function?

Background: Black individuals are historically underrepresented in oncology clinical trials. One potential reason for this is the prevalence of kidney disease in Black individuals, utilization of estimated creatinine clearance as a surrogate for glomerular filtration rate (GFR) in oncology, and GFR-based trial eligibility criteria. We characterized the representation of racial minorities in anticancer agent pivotal trials and examined if GFR-based trial eligibility criteria impact the proportion of Black individuals in trial populations.

Simultaneous quantification of five antiretrovirals in human tissues using ultra-high performance liquid chromatography-tandem mass spectrometry methods for therapeutic drug monitoring at the sites of action.

Although antiretroviral therapy (ART) is highly effective for the treatment of HIV-1 infection to suppress virus in the blood, HIV persists in tissues. HIV persistence in the tissues is due to numerous factors, and one of those factors are antiretroviral (ARV) concentrations. ARV concentrations in tissues must be adequate to suppress HIV at the sites of action.

Development and validation of an UPLC-MS/MS method for the simultaneous determination of fexofenadine and olmesartan in human serum: Application to in vivo pharmacokinetic studies.

A sensitive, reproducible, robust, high-throughput ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of fexofenadine and olmesartan in human serum. Samples (50 µL) undergo protein precipitation prior to UPLC-MS/MS analysis. The analytes were separated using an Acquity BEH C18 column (2.

Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI).

Introduction: Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI.

Electronic Health Record Population Health Management for Chronic Kidney Disease Care: A Cluster Randomized Clinical Trial.

Importance: Large gaps in clinical care in patients with chronic kidney disease (CKD) lead to poor outcomes.

Objective: To compare the effectiveness of an electronic health record-based population health management intervention vs usual care for reducing CKD progression and improving evidence-based care in high-risk CKD.

Design, Setting, And Participants: The Kidney Coordinated Health Management Partnership (Kidney CHAMP) was a pragmatic cluster randomized clinical trial conducted between May 2019 and July 2022 in 101 primary care practices in Western Pennsylvania.

In Situ Formation of Fibronectin-Enriched Protein Corona on Epigenetic Nanocarrier for Enhanced Synthetic Lethal Therapy.

PARP inhibitors (PARPi)-based synthetic lethal therapy demonstrates limited efficacy for most cancer types that are homologous recombination (HR) proficient. To potentiate the PARPi application, a nanocarrier based on 5-azacytidine (AZA)-conjugated polymer (PAZA) for the codelivery of AZA and a PARP inhibitor, BMN673 (BMN) is developed. AZA conjugation significantly decreased the nanoparticle (NP) size and increased BMN loading.

Impact of the 2021 CKD-EPI equation on anticancer pharmacotherapy in black and non-black cancer patients.

Cancer and kidney disease disproportionately impact Black patients. The CKD-EPI equation was developed to estimate glomerular filtration rate (eGFR) without using race. We assessed the impact of using CKD-EPI instead of CKD-EPI or Cockcroft-Gault (CG) on dosing and eligibility of anticancer drugs in Black and non-Black patients.

Overcoming pancreatic cancer immune resistance by codelivery of CCR2 antagonist using a STING-activating gemcitabine-based nanocarrier.

STING agonist has recently gained much attention for cancer treatment, but the therapeutic potential of STING agonist is hampered by STING-associated tumor immune resistance. In this work, guided by both bioinformatics and computer modeling, we rationally designed a "one stone hits two birds" nanoparticle-based strategy to simultaneously activate STING innate immune response while eliminating STING-associated immune resistance for the treatment of pancreatic ductal adenocarcinoma (PDAC). We discovered that the ultra-small sized micellar system based on gemcitabine-conjugated polymer (PGEM), which showed superior capacity of penetration in pancreatic tumor spheroid model and orthotopic tumor model, could serve as a novel "STING agonist".

Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method to quantify antiretroviral drug concentrations in human plasma for therapeutic monitoring.

Antiretroviral therapy (ART) is highly effective for the treatment of HIV-1 infection. ART previously consisted of concomitant administration of many drugs, multiple times per day. Currently, ART generally consists of two- or three-drug regimens once daily as fixed-dose combinations.

Report of the 2023 AACP Council of Deans Taskforce on Pharmacy Research and Scholarship.

Objective: The objective of this review is to provide the conclusions from the American Association of Colleges of Pharmacy (AACP) Council of Deans (COD) Taskforce on Research and Scholarship.

Findings: The charges and the findings of the committee are: (1) Define the scholarship needs/opportunities to strengthen the outputs. The committee recommends that AACP update its definitions of research/scholarship to include discovery, integration, application/practice, and teaching/learning.

Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method for quantifying lenacapavir plasma concentrations: Application to therapeutic monitoring.

Although current antiretroviral therapy (ART) effectively suppresses HIV in the blood, regimens may fail due to suboptimal treatment history and non-adherence to ART. In these scenarios, accumulation of viral resistance mutations to ART drug classes may occur. For these treatment-experienced people living with HIV (PLWH), activity against resistant viral strains is required; lack of therapeutic efficacy will result in continued viral replication and progression to acquired immunodeficiency syndrome.