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Alimentary Pharmacology & Therapeutics Sep 2014Obesity surgery is acknowledged as a highly effective therapy for morbidly obese patients. Beneficial short-term effects on common comorbidities are practically... (Review)
Review
BACKGROUND
Obesity surgery is acknowledged as a highly effective therapy for morbidly obese patients. Beneficial short-term effects on common comorbidities are practically undisputed, but a growing data pool from long-term follow-up reveals increasing evidence of potentially severe nutritional and pharmacological consequences.
AIMS
To assess the prevalence, causes and symptoms of complications after obesity surgery, to elucidate and compare therapy recommendations for macro- and micronutrient deficiencies, and to explore surgically-induced effects on drug absorption and bioavailability, discussing ramifications for long-term therapy and prophylaxis.
METHODS
PubMed, Embase and MEDLINE were searched using terms including, but not limited to, bariatric surgery, gastric bypass, obesity surgery and Roux-en-Y, coupled with secondary search terms, e.g. anaemia, micronutrients, vitamin deficiency, bacterial overgrowth, drug absorption, pharmacokinetics, undernutrition. All studies in English, French or German published January 1980 through March 2014 were included.
RESULTS
Macro- and micronutrient deficiencies are common after obesity surgery. The most critical, depending on surgical technique, are hypoalbuminemia (3-18%) and deficiencies of vitamins B1 (≤49%), B12 (19-35%) and D (25-73%), iron (17-45%) and zinc (12-91%). Many drugs commonly administered to obese patients (e.g. anti-depressants, anti-microbials, metformin) are subject to post-operative and/or PPI-associated changes affecting bioavailability and absorption.
CONCLUSIONS
Complications are associated with pre-operative and/or post-operative malnutrition or procedure-related changes in intake, absorption and drug bioavailability. The high prevalence of nutrient deficiencies after obesity surgery makes life-long nutritional monitoring and supplementation essential. Post-operative changes to drug absorption and bioavailability in bariatric patients cast doubt on the validity of standard drug dosage and administration recommendations.
Topics: Bariatric Surgery; Biological Availability; Deficiency Diseases; Humans; Hypoalbuminemia; Obesity, Morbid; Pharmaceutical Preparations; Pharmacokinetics; Postoperative Complications
PubMed: 25078533
DOI: 10.1111/apt.12872 -
Journal of Controlled Release :... Sep 2023Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum,...
Microneedle Array Patches (MAPs) are an emerging dosage form that creates transient micron-sized disruptions in the outermost physical skin barrier, the stratum corneum, to facilitate delivery of active pharmaceutical ingredients to the underlying tissue. Numerous MAP products are proposed and there is significant clinical potential in priority areas such as vaccination. However, since their inception scientists have hypothesized about the risk of a clinically significant MAP-induced infection. Safety data from two major Phase 3 clinical trials involving hundreds of participants, who in total received tens of thousands of MAP applications, does not identify any clinically significant infections. However, the incumbent data set is not extensive enough to make definitive generalizable conclusions. A comprehensive assessment of the infection risk is therefore advised for MAP products, and this should be informed by clinical and pre-clinical data, theoretical analysis and informed opinions. In this article, a group of key stakeholders identify some of the key product- and patient-specific factors that may contribute to the risk of infection from a MAP product and provide expert opinions in the context of guidance from regulatory authorities. Considerations that are particularly pertinent to the MAP dosage form include the specifications of the finished product (e.g. microbial specification), it's design features, the setting for administration, the skill of the administrator, the anatomical application site, the target population and the clinical context. These factors, and others discussed in this article, provide a platform for the development of MAP risk assessments and a stimulus for early and open dialogue between developers, regulatory authorities and other key stakeholders, to expedite and promote development of safe and effective MAP products.
Topics: Humans; Administration, Cutaneous; Drug Delivery Systems; Epidermis; Needles; Pharmaceutical Preparations; Risk Assessment; Skin; Clinical Trials, Phase III as Topic
PubMed: 37437849
DOI: 10.1016/j.jconrel.2023.07.001 -
Revista de Saude Publica Dec 2017Quaternary prevention consists in the identification of persons at risk of excessive medicalization and their protection against new unnecessary interventions, avoiding...
Quaternary prevention consists in the identification of persons at risk of excessive medicalization and their protection against new unnecessary interventions, avoiding iatrogenic damages. Here, we argue about the importance of quaternary prevention in specific primary and secondary prevention. The recent great development of preventive medicine, biomedicalization of risks and their treatment as if they were diseases, and the powerful influence of the commercial interests of pharmaceutical industries on the production of medical-sanitary knowledge alter classifications, create diseases and pre-diseases, lower cutoff points, and erase the distinction between prevention and healing. This situation converts larger amounts of asymptomatic persons into sick individuals and diverts clinical attention and resources from sick persons to the healthy, from older adults to young persons, and from the poor to the rich. Quaternary prevention facilitates and induces the development and systematization of operational knowledge and guidelines to contain hypermedicalization and the damages of preventive actions in professional care, especially in primary health care.
Topics: Asymptomatic Diseases; Humans; Medicalization; Preventive Health Services; Unnecessary Procedures
PubMed: 29211199
DOI: 10.11606/S1518-8787.2017051000041 -
Advanced Drug Delivery Reviews 2020Considering the multifaceted protective and homeostatic roles of the complement system, many consequences arise when drug carriers, and particulate pharmaceutical... (Review)
Review
Considering the multifaceted protective and homeostatic roles of the complement system, many consequences arise when drug carriers, and particulate pharmaceutical formulations clash with complement proteins, and trigger complement cascade. Complement activation may induce formulation destabilization, promote opsonization, and affect biological and therapeutic performance of pharmaceutical nano- and micro-particles. In some cases, complement activation is beneficial, where complement may play a role in prophylactic protection, whereas uncontrolled complement activation is deleterious, and contributes to disease progression. Accordingly, design initiatives with particulate medicines should consider complement activation properties of the end formulation within the context of administration route, dosing, systems biology, and therapeutic perspective. Here we examine current progress in mechanistic processes underlying complement activation by pre-clinical and clinical particles, identify opportunities and challenges ahead, and suggest future directions in nanomedicine-complement interface research.
Topics: Animals; Complement Activation; Complement System Proteins; Drug Carriers; Humans; Microspheres; Nanoparticles; Pharmaceutical Preparations
PubMed: 32389761
DOI: 10.1016/j.addr.2020.04.012 -
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 -
Expert Review of Neurotherapeutics Dec 2016Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the brain and spinal cord. Treatment development... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the brain and spinal cord. Treatment development for ALS is complicated by complex underlying disease factors. Areas covered: Numerous tested drug compounds have shown no benefits in ALS patients, although effective in animal models. Discrepant results of pre-clinical animal studies and clinical trials for ALS have primarily been attributed to limitations of ALS animal models for drug-screening studies and methodological inconsistencies in human trials. Current status of pre-clinical and clinical trials in ALS is summarized. Specific blood-CNS barrier damage in ALS patients, as a novel potential reason for the clinical failures in drug therapies, is discussed. Expert commentary: Pathological perivascular collagen IV accumulation, one unique characteristic of barrier damage in ALS patients, could be hindering transport of therapeutics to the CNS. Restoration of B-CNS-B integrity would foster delivery of therapeutics to the CNS.
Topics: Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Humans; Pharmaceutical Preparations
PubMed: 27362330
DOI: 10.1080/14737175.2016.1207530 -
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