-
British Journal of Clinical Pharmacology Oct 2020Even the most effective drug product may be used improperly and thus ultimately prove ineffective if it does not meet the perceptual, motor and cognitive capacities of... (Review)
Review
Even the most effective drug product may be used improperly and thus ultimately prove ineffective if it does not meet the perceptual, motor and cognitive capacities of its target users. Currently, no comprehensive guideline for systematically designing user-centric drug products that would help prevent such limitations exists. We have compiled a list of approximate but nonetheless useful strategies-heuristics-for implementing a user-centric design of drug products and drug product portfolios. First, we present a general heuristic for user-centric design based on the framework of Human Factors and Ergonomics (HF/E). Then we demonstrate how to implement this general heuristic for older drug users (i.e., patients and caregivers aged 65 years and older) and with respect to three specific challenges (use-cases) of medication management: (A) knowing what drug product to take/administer, (B) knowing how and when to take/administer it, and (C) actually taking/administering it. The presented heuristics can be applied prospectively to include existing knowledge about user-centric design at every step during drug discovery, pharmaceutical drug development, and pre-clinical and clinical trials. After a product has been released to the market, the heuristics may guide a retrospective analysis of medication errors and barriers to product usage as a basis for iteratively optimizing both the drug product and its portfolio over their life cycle.
Topics: Drug Development; Ergonomics; Heuristics; Humans; Pharmaceutical Preparations; Retrospective Studies
PubMed: 31663157
DOI: 10.1111/bcp.14134 -
Macromolecular Bioscience Mar 2023Although photopolymerization reactions are commonly used to form hydrogels, these strategies rely on light and may not be suitable for delivering therapeutics in a...
Although photopolymerization reactions are commonly used to form hydrogels, these strategies rely on light and may not be suitable for delivering therapeutics in a minimally invasive manner. Here, hyaluronic acid (HA) macromers are modified with norbornene (Nor) or tetrazine (Tet) and upon mixing click into covalently crosslinked Nor-Tet hydrogels via a Diels-Alder reaction. By incorporating a high degree of Nor and Tet substitution, Nor-Tet hydrogels with a broad range in elastic moduli (5 to 30 kPa) and fast gelation times (1 to 5 min) are achieved. By pre-coupling methacrylated HANor macromers with thiolated peptides via a Michael addition reaction, Nor-Tet hydrogels are peptide-functionalized without affecting their physical properties. Mesenchymal stem cells (MSCs) on RGD-functionalized Nor-Tet hydrogels adhere and exhibit stiffness-dependent differences in matrix mechanosensing. Fluid properties of Nor-Tet hydrogel solutions allow for injections through narrow syringe needles and can locally deliver viable cells and peptides. Substituting HA with enzymatically degradable gelatin also results in cell-responsive Nor-Tet hydrogels, and MSCs encapsulated in Nor-Tet hydrogels preferentially differentiate into adipocytes or osteoblasts, based on 3D cellular spreading regulated by stable (HA) and degradable (gelatin) macromers.
Topics: Hydrogels; Gelatin; Mesenchymal Stem Cells; Norbornanes; Hyaluronic Acid
PubMed: 36493315
DOI: 10.1002/mabi.202200425 -
Journal of Evidence-based Integrative... 2022Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The... (Review)
Review
Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The multi-component and multi-targeted approach of natural products have the potential to manage CVDs.This review aims to provide a comprehensive insight into the synergistic mechanism of natural product combinations in protecting the endothelium against various cardiovascular risk factors.Databases (PubMed, MEDLINE and EMBASE) and Google Scholar were searched, and studies in English published between January 2000 and February 2022 were collated. Clinical and pre-clinical studies of natural product combinations with or without pharmaceutical medicines, compared with monotherapy and/or proposing the underlying mechanism in protecting endothelial function, were included.Four clinical studies demonstrated that natural product combinations or natural product-pharmaceutical combinations improved endothelial function. This was associated with multi-targeted effects or improved absorption of the active substances in the body. Seventeen preclinical studies showed that natural product combinations produced synergistic (demonstrated by combination index or Bliss independence model) or enhanced effects in protecting the endothelium against hyperlipidemia, hypertension, diabetes mellitus, platelet activation, oxidative stress and hyperhomocysteinemia. The molecular targets included reactive oxygen species, Nrf2-HO-1, p38MAPK, P13K/Akt and NF-κB.Thus, the current available evidence of natural product combinations in targeting endothelial dysfunction is predominantly from preclinical studies. These have demonstrated synergistic/enhanced pharmacological activities and proposed associated mechanisms. However, evidence from larger, well-designed clinical trials remains weak. More cohesion is required between preclinical and clinical data to support natural product combinations in preventing or slowing the progression of CVDs.
Topics: Biological Products; Cardiovascular Diseases; Endothelium; Heart Disease Risk Factors; Humans; Hypertension; Pharmaceutical Preparations; Risk Factors
PubMed: 35849068
DOI: 10.1177/2515690X221113327 -
Biomedicine & Pharmacotherapy =... Sep 2021Repositioning or "repurposing" of existing therapies for indications of alternative disease is an attractive approach that can generate lower costs and require a shorter... (Review)
Review
Repositioning or "repurposing" of existing therapies for indications of alternative disease is an attractive approach that can generate lower costs and require a shorter approval time than developing a de novo drug. The development of experimental drugs is time-consuming, expensive, and limited to a fairly small number of targets. The incorporation of separate and complementary data should be used, as each type of data set exposes a specific feature of organism knowledge Drug repurposing opportunities are often focused on sporadic findings or on time-consuming pre-clinical drug tests which are often not guided by hypothesis. In comparison, repurposing in-silico drugs is a new, hypothesis-driven method that takes advantage of big-data use. Nonetheless, the widespread use of omics technology, enhanced data storage, data sense, machine learning algorithms, and computational modeling all give unparalleled knowledge of the methods of action of biological processes and drugs, providing wide availability, for both disease-related data and drug-related data. This review has taken an in-depth look at the current state, possibilities, and limitations of further progress in the field of drug repositioning.
Topics: Animals; Big Data; Computer Simulation; Drug Delivery Systems; Drug Discovery; Drug Repositioning; Humans; Machine Learning; Pharmaceutical Preparations
PubMed: 34153846
DOI: 10.1016/j.biopha.2021.111638 -
American Journal of Ophthalmology Feb 2021To assess the feasibility of automated text parsing screening of physician notes in the electronic health record (EHR) to identify glaucoma patients with poor medication...
PURPOSE
To assess the feasibility of automated text parsing screening of physician notes in the electronic health record (EHR) to identify glaucoma patients with poor medication compliance.
DESIGN
Cross-sectional study.
METHODS
An automated EHR extraction identified a cohort of patients at the University of Michigan with a diagnosis of glaucoma, ≥40 years old, taking ≥1 glaucoma medication, and having no cognitive impairment. Self-reported medication adherence was assessed with 2 validated instruments: the Chang scale and the Morisky medication adherence scale. In tandem, a text parsing tool that abstracted data from the EHR was used to search for combinations of the following words in patient visit notes: "not," "non," "n't," "no," or "poor" accompanied by "adherence," "adherent, "adhering," "compliance," "compliant," or "complying." The proportion of patients with self-reported poor adherence was compared between the EHR extraction and text parsing identification using a Fisher exact test.
RESULTS
Among 736 participants, 20.0% (n = 147) self-reported poor adherence and 6.1% (n = 45) had EHR documentation of poor adherence (P < .0001). Using text parsing as a pre-screening tool, 22 of the 45 patients (48.9%) with non-adherence identified by text parsing also self-reported poor medication adherence compared to the 20.0% by self-report overall (P < .0001).
CONCLUSIONS
Text parsing physician notes to identify patients' noncompliance to their medications identified a larger proportion of patients who then self-reported poor medication adherence than an automated EHR pull alone but was limited by the small number of patients identified. Optimizing the documentation of medication adherence would maximize the utility of this automated approach to identify medication noncompliance.
Topics: Aged; Antihypertensive Agents; Cross-Sectional Studies; Electronic Health Records; Female; Glaucoma; Humans; Intraocular Pressure; Male; Medication Adherence; Middle Aged; Ophthalmic Solutions; Self Report; Surveys and Questionnaires; Text Messaging
PubMed: 32926847
DOI: 10.1016/j.ajo.2020.09.008 -
Patient Preference and Adherence 2022To investigate clinical management of primary open-angle glaucoma (POAG) in the United States using real-world evidence and to examine healthcare resource utilization...
PURPOSE
To investigate clinical management of primary open-angle glaucoma (POAG) in the United States using real-world evidence and to examine healthcare resource utilization (HCRU), medication adherence/persistence, and procedure use.
DESIGN
A cross-sectional, retrospective analysis of Optum's de-identified Market Clarity Dataset (July 1, 2013-December 31, 2019).
PATIENTS AND METHODS
Patients ≥18 years with POAG diagnosis and continuous enrollment for 1-year pre- and post-index were eligible and categorized into four mutually exclusive cohorts: CH1, treated with antiglaucoma medication(s) only; CH2, underwent glaucoma procedure(s) only; CH3, treated with antiglaucoma medication(s) and underwent procedure(s); and CH4, received no treatment for POAG. Adherence and persistence with antiglaucoma medications, and disease-specific HCRU were analyzed. Pairwise two-sample comparisons and multivariate regressions were conducted.
RESULTS
Examined 232,572 eligible patients (CH1=60,895; CH2=4330; CH3=6027; CH4=161,320). Prostaglandin analogs were most prescribed antiglaucoma medications (CH1: 69.7%; CH3: 62.7%), of which latanoprost was most common (CH1: 51.3%; CH3: 46.1%). Disease-specific office visits occurred in 26.3%, 78.2%, 75.0%, 23.8%, and surgical services visits occurred in 3.8%, 36.3%, 42.5%, 3.3%, in CH1-CH4, respectively. Adherence was higher (medication possession ratio: 47.1% vs 39.4%; P<0.0001), and more patients remained persistent across 1-year post-index period in CH1 vs CH3 (25.4% vs 16.1%; P<0.0001). Positive predictors of medication persistence included being female, ≥55 years, and history of dyslipidemia or thyroid disease (all P≤0.0003).
CONCLUSION
Overall, 70% POAG patients might not have received antiglaucoma treatment. Since POAG is a slowly progressive blinding disease, the lack of antiglaucoma treatment and suboptimal adherence/persistence with medications are of major concerns. Targeted screening and educational approaches are needed to improve POAG management.
PubMed: 36003802
DOI: 10.2147/PPA.S367443 -
British Journal of Clinical Pharmacology Jun 2023Infusion of lipid emulsion for drug overdose arose as a treatment for local anaesthetic systemic toxicity (LAST) initially based on laboratory results in animal models...
Infusion of lipid emulsion for drug overdose arose as a treatment for local anaesthetic systemic toxicity (LAST) initially based on laboratory results in animal models with the subsequent support of favourable case reports. Following successful translation to the clinic, practitioners also incorporated lipid emulsion as a treatment for non-local anaesthetic toxicities but without formal clinical trials. Recent clinical trials demonstrate a benefit of lipid emulsion in antipsychotic, pesticide, metoprolol and tramadol overdoses. Formal trials of lipid emulsion in LAST may never occur, but alternative analytic tools indicate strong support for its efficacy in this indication; for example, lipid emulsion has obviated the need for cardiopulmonary bypass in most cases of LAST. Herein, we describe the pre-clinical support for lipid emulsion, evaluate the most recent clinical studies of lipid emulsion for toxicity, identify a possible dose-based requirement for efficacy and discuss the limitations to uncontrolled studies in the field.
Topics: Animals; Emulsions; Xenobiotics; Drug Overdose; Anesthetics, Local; Tramadol
PubMed: 36454165
DOI: 10.1111/bcp.15620 -
Medicina (Kaunas, Lithuania) May 2021Tuberculosis (TB), a bacterialinfectious disease caused by (), which causes significant mortality in humans worldwide. Current treatment regimen involve the... (Review)
Review
Tuberculosis (TB), a bacterialinfectious disease caused by (), which causes significant mortality in humans worldwide. Current treatment regimen involve the administration of multiple antibiotics over the course of several months that contributes to patient non-compliance leading to relapse and the development of drug-resistant (MDR and XDR) strains. Together, these facts highlight the need for the development of shorter TB treatment regimens. Host-directed therapy (HDT) is a new and emerging concept that aims to augment host immune response using drugs/compounds with or without adjunct antibiotics against infection. Autophagy is a natural catabolic mechanism of the cell that involves delivering the cytosolic constituents to the lysosomes for degradation and recycling the components; thereby maintaining the cellular and energy homoeostasis of a cell. However, over the past decade, an improved understanding of the role of autophagy in immunity has led to autophagy activation by using drugs or agents. This autophagy manipulation may represent a promising host-directed therapeutic strategy for human TB. However, current clinical knowledge on implementing autophagy activation by drugs or agents, as a stand-alone HDT or as an adjunct with antibiotics to treat human TB is insufficient. In recent years, many reports on high-throughput drug screening and measurement of autophagic flux by fluorescence, high-content microscopy, flow cytometry, microplate reader and immunoblotting have been published for the discovery of drugs that modulate autophagy. In this review, we discuss the commonly used chemical screening approaches in mammalian cells for the discovery of autophagy activating drugs against infection. We also summarize the various autophagy-activating agents, both pre-clinical candidates and compounds approved for advanced clinical investigation during mycobacterial infection. Finally, we discuss the opportunities and challenges in using autophagy activation as HDT strategy to improve TB outcome and shorten treatment regimen.
Topics: Animals; Antitubercular Agents; Autophagy; Humans; Mycobacterium tuberculosis; Pharmaceutical Preparations; Tuberculosis
PubMed: 34070995
DOI: 10.3390/medicina57060522 -
Clinical Drug Investigation Jan 2021Long-acting injectable antipsychotics (LAIs) are associated with better treatment adherence and persistence than oral antipsychotics (OAPs) in patients with... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVE
Long-acting injectable antipsychotics (LAIs) are associated with better treatment adherence and persistence than oral antipsychotics (OAPs) in patients with schizophrenia. However, real-world evidence assessing the impact of treatment with LAIs in Germany is limited. To fill this gap, we compared antipsychotic medication adherence and risk of treatment discontinuation (TD) among schizophrenia patients newly initiated on LAI or who switched their OAP regimen (overall cohort; OC).
METHODS
Claims data of German schizophrenia patients who initiated LAIs or switched their OAP during 2012-2016 (index date) were retrospectively analyzed. Treatment switch was defined as add-on medication to existing prescription or terminating the existing prescription and initiating another OAP. Adherence and time to treatment discontinuation (TTD) were estimated. Determinants of treatment discontinuation were analyzed using two Cox regression models. Model 1 controlled for age, sex, and Charlson Comorbidity Index (CCI); model 2 also included insurance status, and medication, visit, and psychiatric inpatient stay costs. Sensitivity analysis on patients who terminated existing prescriptions and initiated new OAPs (complete switch cohort; CSC) was performed.
RESULTS
In OC (n = 2650), LAI users had better adherence (35.4% vs. 11.6%), persistence (no 60-day gap; 40.7% vs. 19.8%), and longer TTD (median [95% confidence interval (CI)] 216 [193-249] vs. 50 [46-56] days) than OAP users. OAP usage (hazard ratio [HR] 1.89, 95% CI 1.73-2.06; p < 0.001) and greater CCI (HR 1.04, 95% CI 1.00-1.07; p = 0.023) were associated with greater risk of TD in model 1. Model 2 showed similar results. LAI users in CSC also had better adherence, persistence, and longer TTD. In CSC too, OAP usage and greater CCI were associated with greater risk of TD in model 1, but only CCI was significant in model 2. Higher pre-index psychiatric inpatient costs were associated with lower risk of TD (HR 0.99, 95% CI 0.98-1.00; p = 0.014).
LIMITATIONS
Inherent limitations of claims data and lack of control on OAP administration may have influenced the results.
CONCLUSION
This real-world study associates LAIs with better medication adherence and lower antipsychotic discontinuation risk than OAPs.
Topics: Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Cohort Studies; Delayed-Action Preparations; Female; Germany; Humans; Injections; Male; Medication Adherence; Middle Aged; Proportional Hazards Models; Retrospective Studies; Schizophrenia; Time Factors; Young Adult
PubMed: 33331979
DOI: 10.1007/s40261-020-00990-8 -
Drug Delivery and Translational Research Feb 2023There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is... (Review)
Review
There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" products. However, the underlying challenges involved in the development, scalability, and characterization of these injectable products are critical. Moreover, the guidelines available do not provide a clear understanding of these complex products, making it difficult to anticipate the regulatory requirements. Thus, it becomes imperative to comprehend the criticalities and develop an understanding of these products. This review discusses various complexities involved in the parenteral products such as complex drug substances, excipients, dosage forms, drug administration devices like pre-filled syringes and injector pens, and its different characterization tools and techniques. The review also provides a brief discussion on the regulatory aspects and associated hurdles with other parenteral products.
Topics: Humans; Quality of Life; Liposomes; Suspensions; Excipients; Nanoparticles
PubMed: 35963928
DOI: 10.1007/s13346-022-01223-5