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Cureus Feb 2024Aspirin is a recognized and affordable antiplatelet medicine. Low amounts of aspirin have been used to prevent cardiovascular events, and it is still widely used for... (Review)
Review
Aspirin is a recognized and affordable antiplatelet medicine. Low amounts of aspirin have been used to prevent cardiovascular events, and it is still widely used for primary and secondary stroke prevention. The purpose of this review article is to evaluate the effects of using low doses of aspirin among elderly people. Although taking large dosages of aspirin (500 mg daily) reduces the long-term risk of colorectal cancer, its effectiveness for long-term prevention may be limited by adverse effects. Studies have assessed the relationship between aspirin dosage, incidence, and death in patients with colorectal cancer. Research has indicated that those with diabetes mellitus have an increased risk of cardiovascular events. Low amounts of aspirin have been used to prevent cardiovascular events. However, there is uncertainty regarding the potential benefits and risks associated with preventing the development of cardiovascular problems in individuals with diabetes. The use of aspirin lowers the risk of occlusive vascular events but raises the possibility of bleeding. More attention should be paid to reducing inappropriate aspirin usage in light of its prevalence, particularly among older persons, as the substantial continuous usage of this drug increases the chances of bleeding.
PubMed: 38524052
DOI: 10.7759/cureus.54658 -
Thrombosis Journal Sep 2023Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960's to reduce blood loss in various conditions. TXA is a lysine analogue... (Review)
Review
Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960's to reduce blood loss in various conditions. TXA is a lysine analogue that competes for the lysine binding sites in plasminogen and tissue-type plasminogen activator impairing its interaction with the exposed lysine residues on the fibrin surface. The presence of TXA therefore, impairs the plasminogen and tPA engagement and subsequent plasmin generation on the fibrin surface, protecting fibrin clot from proteolytic degradation. However, critical lysine binding sites for plasmin(ogen) also exist on other proteins and on various cell-surface receptors allowing plasmin to exert potent effects on other targets that are unrelated to classical fibrinolysis, notably in relation to immunity and inflammation. Indeed, TXA was reported to significantly reduce post-surgical infection rates in patients after cardiac surgery unrelated to its haemostatic effects. This has provided an impetus to consider TXA in other indications beyond inhibition of fibrinolysis. While there is extensive literature on the optimal dosage of TXA to reduce bleeding rates and transfusion needs, it remains to be determined if these dosages also apply to blocking the non-canonical effects of plasmin.
PubMed: 37700271
DOI: 10.1186/s12959-023-00540-0 -
Clinical Rehabilitation Dec 2023To review the use (dosage parameters and combination with other therapeutic interventions) of cervical extensor muscle exercises and their effect on pain, disability...
OBJECTIVE
To review the use (dosage parameters and combination with other therapeutic interventions) of cervical extensor muscle exercises and their effect on pain, disability (primary outcomes), range of motion, endurance and strength (secondary outcomes) in people with neck pain.
DATA SOURCES
An extensive literature search was conducted through MEDLINE (Ovid), Scopus (Elsevier) and Physiotherapy Evidence Database (PEDro) up to May 2023. The reference lists of all included studies and relevant reviews were screened for additional studies.
REVIEW METHODS
Randomised controlled trials reporting the use of cervical extensor muscle exercises (alone or combined) applied to adults with idiopathic or traumatic neck pain were included. Study selection, data extraction and critical appraisal (PEDro assessment scale) were performed by two blinded reviewers. Data extraction included dosage parameters, other modalities combined with these exercises and outcomes.
RESULTS
Thirty-five randomised controlled trails (eight of which were complementary analyses) with 2409 participants fulfilled the inclusion criteria. Twenty-six were of moderate to high quality. In most studies, cervical extensor muscle exercises were combined with various other therapeutic modalities and applied at different dosages. Only two studies (one high and one low quality) specifically assessed their effectiveness. The high-quality study showed significant improvements in neck pain and disability, pressure point threshold and neck mobility after both low load and high load training for 6 weeks.
CONCLUSION
The results suggest cervical extensor muscle exercises may reduce neck pain and disability; however firm conclusions cannot be drawn because of the few studies that addressed this question and the heterogeneity of the dosage parameters.
PubMed: 37424506
DOI: 10.1177/02692155231184973 -
Journal of Controlled Release :... Sep 2023Classic methods for evaluating the disintegration and dissolution kinetics of solid dosage forms are no longer sufficient to meet the growing demands in the... (Review)
Review
Classic methods for evaluating the disintegration and dissolution kinetics of solid dosage forms are no longer sufficient to meet the growing demands in the pharmaceutical field. Hence, scientists have turned to imaging techniques and computer technology to develop innovative visualization methods. These methods allow for a visual understanding of the disintegration or dissolution process and offer valuable insights into the drug release kinetics. This article aims to provide an overview of the commonly used imaging techniques and their applications in studying the disintegration or dissolution of solid dosage forms. Therefore, imaging presents a novel and alternative approach to understanding the mechanisms of disintegration and dissolution in the formulation study of solid dosages.
Topics: Chemistry, Pharmaceutical; Tablets; Solubility; Drug Liberation; Kinetics; Dosage Forms
PubMed: 37567508
DOI: 10.1016/j.jconrel.2023.08.013 -
Cells Sep 2023Immunosuppressants are emerging as promising candidates for cancer therapy with lower cytotoxicity compared to traditional chemotherapy drugs; yet, the intrinsic side...
Immunosuppressants are emerging as promising candidates for cancer therapy with lower cytotoxicity compared to traditional chemotherapy drugs; yet, the intrinsic side effects such as immunosuppression remain a critical concern. Herein, we introduce a photoactivatable antitumor immunosuppressant called dmBODIPY-FTY720 (BF) that shows no cytotoxicity but can be temporally and locally activated by deep-red light illumination to induce tumor cell apoptosis. To further reduce potential side effects, we integrate BF with another classic photosensitizer called methylene blue (MB) that is activated under the same wavelength of deep-red light (>650 nm) and successfully establish a red-light-activatable AND Boolean logic gate through a mechanism that we found to be synergetic apoptotic induction. At further decreased dosages, deep-red light illumination does not induce cell death in the presence of either BF or MB, but significant cancer cell death is triggered in the presence of both drugs. Therefore, the dosage of BF is further reduced, which will be highly beneficial to minimize any potential side effects of BF. This AND-gated strategy has been successfully applied in vivo for effective suppression of hepatocarcinoma tumors in living mice.
Topics: Mice; Animals; Photochemotherapy; Cell Line, Tumor; Immunosuppressive Agents; Light; Photosensitizing Agents
PubMed: 37830565
DOI: 10.3390/cells12192351 -
Journal of Clinical Pharmacology Nov 2023Pediatric obesity is a global public health concern. Obesity-related physiological changes may affect the pharmacokinetics of drugs and lead to therapeutic failure or... (Review)
Review
Pediatric obesity is a global public health concern. Obesity-related physiological changes may affect the pharmacokinetics of drugs and lead to therapeutic failure or toxicities. An earlier review of pediatric drug development programs from 2007 to 2016 found that, of 89 programs listing obesity-related terms, only 4 (4%) products described pharmacokinetic changes associated with obesity. This review examined obesity considerations for 185 drug products for which pediatric drug development programs were submitted to the US Food and Drug Administration (FDA) between 2016 and 2021. The FDA-authored review documents and drug product labeling were queried for obesity-related terms and the review found 97/185 (52%) drug products had obesity-related terms in these sources. Of the 97 drug products, 55/97 (57%) had obesity-related terms in the FDA-authored reviews only, 13/97 (13%) had obesity-related terms in the drug product labeling only, and 29/97 (30%) had obesity-related terms in both FDA-authored reviews and drug product labeling. Most of the obesity-related information in the drug product labeling originated from data collected from adults. Only 13/185 (7%) drug product labeling contained obesity-related terms in reference to drug pharmacokinetics. Specific dosage recommendations for the use of the drug products in pediatric patients who are obese remain lacking. The dearth of available information to guide drug dosages in the obese pediatric population suggests that further research, innovative approaches, and evidence-based guidelines are needed to inform the optimal therapeutic use of drugs in this population.
Topics: Adult; United States; Child; Humans; Pharmaceutical Preparations; Drug Development; Pediatric Obesity; Drug Labeling; United States Food and Drug Administration
PubMed: 37942908
DOI: 10.1002/jcph.2305 -
Journal of Ocular Pharmacology and... May 2024Insulin and insulin-like growth factor (IGF)-1 receptors are present in ocular tissues such as corneal epithelium, keratocytes, and conjunctival cells. Insulin plays a... (Review)
Review
Insulin and insulin-like growth factor (IGF)-1 receptors are present in ocular tissues such as corneal epithelium, keratocytes, and conjunctival cells. Insulin plays a crucial role in the growth, differentiation, and proliferation of corneal epithelial cells, as well as in wound healing processes in various tissues. This review explores the potential role of topical insulin in the treatment of ocular surface diseases. Specifically, it examines its impact on corneal nerve regeneration, sub-basal plexus corneal nerves, and its application in conditions like corneal epithelial defects, dry eye disease, and diabetic keratopathy. The review analyzes studies conducted over the past decade that have investigated the use of topical insulin in ocular surface diseases. It focuses on indications, drug preparation methods, side effects, efficacy outcomes, and variations in insulin concentrations and dosages used. While off-label use of topical insulin has shown promising results in refractory corneal epithelial defects, its efficacy in dry eye disease is yet to be demonstrated. Variations in concentrations, dilutions, and dosing guidelines have been reported. However, limited data on ocular penetration, ocular toxicity, and systemic side effects pose challenges to its widespread utility. This review synthesizes findings from ocular investigations on topical insulin to assess its potential applicability in treating ocular surface and corneal diseases. By highlighting indications, preparation methods, side effects, and efficacy outcomes, it aims to provide insights into the current status and future prospects of using topical insulin in ophthalmic practice.
Topics: Humans; Insulin; Dry Eye Syndromes; Ophthalmic Solutions; Corneal Diseases; Animals; Administration, Ophthalmic; Administration, Topical; Cornea
PubMed: 38527183
DOI: 10.1089/jop.2024.0016 -
Clinical Neurology and Neurosurgery Oct 2023Hyperammonemia can occur after acute overdose or chronic use of valproic acid (VPA). Although VPA-related hyperammonemic encephalopathy (VHE) is a rare complication of... (Review)
Review
BACKGROUND
Hyperammonemia can occur after acute overdose or chronic use of valproic acid (VPA). Although VPA-related hyperammonemic encephalopathy (VHE) is a rare complication of VPA therapy, early recognition of VHE and identifying its risk factors are important because VHE can lead to loss of consciousness and increased seizure frequency.
PURPOSE
The purpose of our study is to evaluate the risk factors of hyperammonemia in epilepsy patients during treatment with VPA therapy.
METHODS
We reviewed the medical records of 1084 adult patients with epilepsy and enrolled 116 patients with VPA therapy who had results of blood levels of ammonia over a 3-year period. Hyperammonemia was defined as a blood ammonia level exceeding 80 µg/dL. Correlations of blood levels of ammonia with dosages and blood levels of VPA were evaluated. We further performed univariate and multivariate linear regression analyses to identify risk factors for hyperammonemia in epilepsy patients treated with VPA therapy.
RESULTS
Blood levels of ammonia were well correlated with dosages of VPA (p = 0.036), but not with blood levels of VPA (p = 0.463). Hyperammonemia was more common in patients with higher VPA dosage and higher total drug loads of concurrent antiseizure medications (ASMs). Hyperammonemia was also associated with the use of topiramate and phenobarbital. In multivariate analysis, we identified total drug load of ASMs (p = 0.003) and use of topiramate (p = 0.007) as independent predictors of hyperammonemia. Four patients (4/116, 3.4 %) had clinical symptoms of VHE. Three of them had hyperammonemia while the other patient had normal blood level of ammonia with a high blood level of VPA.
CONCLUSION
Our study shows that higher total drug loads of concurrent ASMs and use of topiramate were independent risk factors of hyperammonemia in epilepsy patients with VPA therapy. Although the incidence of VHE was not high in our study, clinicians should be aware of this potential adverse effect of VPA therapy, especially in patients with polytherapy of ASMs including topiramate.
Topics: Adult; Humans; Valproic Acid; Anticonvulsants; Topiramate; Hyperammonemia; Ammonia; Epilepsy; Risk Factors
PubMed: 37717359
DOI: 10.1016/j.clineuro.2023.107962 -
The British Journal of Dermatology Jul 2023There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis.
OBJECTIVES
We determined the relative efficacy of monotherapies for dermatophyte toenail onychomycosis with Bayesian network meta-analyses (NMAs).
METHODS
We searched PubMed, Scopus, EMBASE (Ovid) and CINAHL to identify studies that investigated the efficacy of monotherapy with oral antifungals for dermatophyte toenail onychomycosis in adults. In this paper, 'regimen' corresponds to a given agent and its dosage. The relative effects and surface under the cumulative ranking curve (SUCRA) values of the various regimens were estimated; evidence quality was assessed at the study level and across networks.
RESULTS
Data from 21 studies were used. Our two efficacy-related endpoints were: (i) mycological and (ii) complete cure at 1 year; safety--related endpoints were: (i) 1-year count of any adverse event (AE), (ii) 1-year odds of discontinuation due to any AE, (iii) 1-year odds of discontinuation due to liver issues. Thirty-five regimens were identified; the newer agents among these included posaconazole and oteseconazole. We compared the efficacy of newer regimens with traditional ones like 'terbinafine 250 mg daily for 12 weeks' and 'itraconazole 200 mg daily for 12 weeks. We found that an agent's dosage was associated with its efficacy; for example, the 1-year odds of mycological cure with terbinafine 250 mg daily for 24 weeks (SUCRA = 92.4%) were significantly greater than those of terbinafine 250 mg daily for 12 weeks (SUCRA = 66.3%) (odds ratio 2.62, 95% credible interval 1.57-4.54). We also found that booster regimens can increase efficacy. Our results showed that some triazoles could be more effective than terbinafine.
CONCLUSIONS
This is the first NMA study of monotherapeutic antifungals - and their various dosages - for dermatophyte toenail onychomycosis. Our findings could provide guidance for the selection of the most appropriate antifungal agent, especially amid the growing concerns about terbinafine resistance.
Topics: Adult; Humans; Antifungal Agents; Onychomycosis; Terbinafine; Arthrodermataceae; Network Meta-Analysis; Nails; Bayes Theorem; Naphthalenes; Treatment Outcome; Foot Dermatoses; Itraconazole
PubMed: 37253047
DOI: 10.1093/bjd/ljad070 -
Journal of Family Medicine and Primary... Dec 2023Prenatal supplements are commonly used to support maternal health and fetal development during pregnancy. However, there are concerns regarding their efficacy and... (Review)
Review
Prenatal supplements are commonly used to support maternal health and fetal development during pregnancy. However, there are concerns regarding their efficacy and safety. This review article provides a critical evaluation of prenatal supplements, including their types, benefits, criticisms, factors affecting their efficacy, and popular brands. It also offers recommendations for their use and identifies future research directions. Our analysis suggests that while prenatal supplements can offer important benefits, including reduced risk of birth defects and improved fetal growth and development, there are also concerns regarding their regulation, dosages, and potential harm to the mother and fetus. Pregnant women should carefully evaluate the ingredients, dosages, efficacy, and safety of prenatal supplements with the guidance of their healthcare provider. Future research should focus on standardizing dosages and regulation of prenatal supplements to ensure consistent quality, safety, and efficacy.
PubMed: 38361856
DOI: 10.4103/jfmpc.jfmpc_1038_23