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Pathology and therapeutics for pharmacists : a basis for clinical pharmacy practice
Aims to show the rationale and role of drug therapy in the management of some common diseases through a consideration of the mechanisms of disease processes in relation to normal function.
Book
An Insight into the Changes in Skin Texture and Properties following Dietary Intervention with a Nutricosmeceutical Containing a Blend of Collagen Bioactive Peptides and Antioxidants
Background: Skin aging is a multifactorial phenomenon which causes alterations in skin physiological functions and, most visibly, phenotypic changes. In particular, during the aging process, hyaluronic acid, collagen, and elastin fibers undergo structural and functional changes. Aims: This study aimed to give an insight into the photo-protective benefits and efficacy of an oral liquid nutricosmeceutical containing collagen bioactive peptides and antioxidants to counteract the signs of aging. Methods: A double-blind, randomized, placebo-controlled clinical trial was conducted by an independent esthetic clinic on 120 healthy volunteer subjects for 90 days. Subjects were divided into 2 groups: 60 subjects consumed 1 bottle (50 mL) of the nutricosmeceutical daily and the other 60 consumed 1 bottle (50 mL) of the placebo. Outcome measures were related to skin elasticity (expressed as Young's elasticity modulus) and skin architecture (histological analysis). In addition, the subjects recruited in this study underwent observational assessments through self-assessment questionnaires. Results and Conclusions: Overall, we demonstrated a significant increase in skin elasticity (+7.5%), p ≤ 0.001 and an improvement in skin texture after daily oral consumption of the nutricosmeceutical. We also obtained a positive patient feedback through the self-assessment questionnaires. Taken together these results show that this nutricosmeceutical supplement may have photo-protective effects and help improve skin health.
Journal Article
Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial
Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating
BRAF
mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the “on−off” schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of
BRAF
mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases.
Whether intermittent strategies of delivering drugs can improve cancer patients survival is still unclear. Here, the authors reports the results of a randomized phase II clinical trial aimed to compare the efficacy and safety of two dosing regimens (continuous and intermittent) of vemurafenib and cobimetinib combination as first-line treatment of patients with unresectable or metastatic advanced melanoma with BRAFV600 mutation
Journal Article
Comparative Pharmacodynamics and Pharmacokinetics of Oral Direct Thrombin and Factor Xa Inhibitors in Development
For the past five decades, there has been little progress in the development of oral anticoagulants, with the choices being limited to the vitamin K antagonists (VKAs). The situation is changing with the development of orally active small molecules that directly target thrombin or activated factor X (FXa). The two agents in the most advanced stages of development are dabigatran etexilate and rivaroxaban, which inhibit thrombin and FXa, respectively. Both are approved in the EU and Canada for venous thromboprophylaxis in patients undergoing elective hip- or knee-replacement surgery. Other agents in the early stages of development include several FXa inhibitors (apixaban, DU 176b, LY 517717, YM 150, betrixaban, eribaxaban [PD 0348292] and TAK 442) and one thrombin inhibitor (AZD 0837). With a predictable anticoagulant response and low potential for drug-drug interactions, these new agents can be given in fixed doses without coagulation monitoring. This renders them more convenient than VKAs. While the anticoagulant effect of the new thrombin and FXa inhibitors is similar, differences in the pharmacokinetic and pharmacodynamic parameters may influence their use in clinical practice. Here, we compare the pharmacokinetic and pharmacodynamic features of these new oral agents.
Journal Article
Important Flavonoids and Their Role as a Therapeutic Agent
Flavonoids are phytochemical compounds present in many plants, fruits, vegetables, and leaves, with potential applications in medicinal chemistry. Flavonoids possess a number of medicinal benefits, including anticancer, antioxidant, anti-inflammatory, and antiviral properties. They also have neuroprotective and cardio-protective effects. These biological activities depend upon the type of flavonoid, its (possible) mode of action, and its bioavailability. These cost-effective medicinal components have significant biological activities, and their effectiveness has been proved for a variety of diseases. The most recent work is focused on their isolation, synthesis of their analogs, and their effects on human health using a variety of techniques and animal models. Thousands of flavonoids have been successfully isolated, and this number increases steadily. We have therefore made an effort to summarize the isolated flavonoids with useful activities in order to gain a better understanding of their effects on human health.
Journal Article
Perioperative Gabapentin Improves Patient-Centered Outcomes After Inguinal Hernia Repair
Over 5,300 inguinal hernia repairs (IHR) were performed in the Military Health System in 2015. Chronic pain can be a debilitating complication, occurring in up to 34% of patients after IHR and impacts mission readiness. Gabapentin has been shown to be effective for postoperative analgesia in a variety of operations. We evaluated the effect of a short course of perioperative gabapentin on chronic pain after IHR.
This was a double-blinded, randomized study involving male patients ≥18 years old with an initial inguinal hernia and no history of chronic pain or psychiatric disorder. Patients chose laparoscopic or open surgery and were then randomized to receive gabapentin 300 mg before surgery, then three times daily for 6 doses or placebo. There were 50 patients randomized to both the gabapentin and placebo groups for a total of 100 patients. Main outcomes were pain and health status, assessed with a visual analogue scale (VAS) and the Short Form-12v2 (SF-12v2). Assessments were performed preoperatively and 1, 6, 12, and 24 months postoperatively. Analysis of variance was used to compare groups.
From the initial 100 patients, 19 withdrew or were excluded. Thus, 81 patients remained, 40 receiving gabapentin and 41 placebo. Throughout the 24-month follow-up, there was no difference in VAS pain scores between the gabapentin and placebo groups (p = 0.867). Beyond 1 month of follow-up, SF-12v2 physical component score (PCS) scores were improved in the gabapentin group (p = 0.039). When comparing open to laparoscopic groups, SF-12v2 PCS scores were improved in the laparoscopic group (p = 0.046) and SF-12v2 mental component summary scores were improved in the open group (p = 0.041).
Perioperative gabapentin was not effective in decreasing chronic pain after IHR; however, patient perception of physical health, as measured by SF-12v2, did improve.
Journal Article