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Influenza and Other Respiratory Viruses Nov 2021Standard-dose seasonal influenza vaccines often produce modest immunogenic responses in adults ≥65 years old. MF59 is intended to elicit a greater magnitude and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Standard-dose seasonal influenza vaccines often produce modest immunogenic responses in adults ≥65 years old. MF59 is intended to elicit a greater magnitude and increased breadth of immune response.
OBJECTIVE
To determine the effectiveness of seasonal MF59-adjuvanted trivalent/quadrivalent influenza vaccine (aTIV/aQIV) relative to no vaccination or vaccination with standard or high-dose egg-based influenza vaccines among people ≥65 years old.
METHODS
Cochrane methodological standards and PRISMA-P guidelines were followed. Real-world evidence from non-interventional studies published in peer-reviewed journals and gray literature from 1997 through to July 15, 2020, including cluster-randomized trials, were eligible. Two reviewers independently extracted data; risk of bias was assessed using the ROBINS-I tool.
RESULTS
Twenty-one studies conducted during the 2006/07-2019/20 influenza seasons were included in the qualitative review; 16 in the meta-analyses. Meta-analysis of test-negative studies found that aTIV reduced medical encounters due to lab-confirmed influenza with pooled estimates of 40.7% (95% CI: 21.9, 54.9; I = 0%) for non-emergency outpatient visits and 58.5% (40.7, 70.9; I = 52.9%) for hospitalized patients. The pooled estimate of VE from case-control studies was 51.3% (39.1, 61.1; I = 0%) against influenza- or pneumonia-related hospitalization. The pooled estimates for the relative VE of aTIV for the prevention of influenza-related medical encounters were 13.9% (4.2, 23.5; I = 95.9%) compared with TIV, 13.7% (3.1, 24.2; I = 98.8%) compared with QIV, and 2.8% (-2.9, 8.5; I = 94.5%) compared with HD-TIV.
CONCLUSIONS
Among adults ≥65 years, aTIV demonstrated significant absolute VE, improved relative VE compared to non-adjuvanted standard-dose TIV/QIV, and comparable relative VE to high-dose TIV.
Topics: Adjuvants, Immunologic; Adult; Aged; Humans; Influenza Vaccines; Influenza, Human; Polysorbates; Seasons; Squalene
PubMed: 34081398
DOI: 10.1111/irv.12871 -
Current Neuropharmacology 2022Poloxamer 188 (P188) is an FDA-approved biocompatible block copolymer composed of repeating units of Poly(Ethylene Oxide) (PEO) and poly(propylene oxide) (PPO). Due to...
Poloxamer 188 (P188) is an FDA-approved biocompatible block copolymer composed of repeating units of Poly(Ethylene Oxide) (PEO) and poly(propylene oxide) (PPO). Due to its amphiphilic nature and high Hydrophile-Lipophile Balance (HLB) value of 29, P188 is used as a stabilizer/emulsifier in many cosmetics and pharmaceutical preparations. While the applications of P188 as an excipient are widely explored, the data on the pharmacological activity of P188 are scarce. Notably, the neuroprotective potential of P188 has gained a lot of interest. Therefore, this systematic review is aimed at summarizing evidence of neuroprotective potential of P188 in CNS disorders. The PRISMA model was used, and five databases (Google Scholar, Scopus, Wiley Online Library, ScienceDirect, and PubMed) were searched with relevant keywords. The search resulted in 11 articles, which met the inclusion criteria. These articles described the protective effects of P188 on traumatic brain injury or mechanical injury in cells, neurotoxicity, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), and ischemia/ reperfusion injury from stroke. All the articles were original research in experimental or pre-clinical stages using animal models or in vitro systems. The reported activities demonstrated the potential of P188 as a neuroprotective agent in improving CNS conditions such as neurodegeneration.
Topics: Animals; Central Nervous System Diseases; Humans; Neuroprotective Agents; Poloxamer; Reperfusion Injury
PubMed: 34077349
DOI: 10.2174/1570159X19666210528155801 -
Journal of Clinical Pharmacy and... Dec 2021Despite the large body of evidence demonstrating equivalent efficacy and safety for branded drugs and their generic counterparts, some patients and providers have the...
WHAT IS KNOWN AND OBJECTIVES
Despite the large body of evidence demonstrating equivalent efficacy and safety for branded drugs and their generic counterparts, some patients and providers have the perception that generics may be less safe and effective than branded agents. Authorized generics (AGs) are a category of generic drugs defined by the United States Food and Drug Administration (FDA) as being the same as the brand-name drug without the brand's name on the label and which may have minor differences, such as tablet or capsule markings for identification. Studies in which AGs are considered along with other generics may increase our understanding of factors that may influence perceptions about generics and shed light on areas where education may be impactful. The objectives of this paper are to provide information about AGs, review studies in which they have been evaluated and explore the role that AGs may fill in the individualized treatment of patients.
METHODS
A literature review was conducted on 30 September 2019 with follow-up search on 4 March 2020. The search was focussed on published papers and meeting abstracts that provided information on AGs with respect to medical and health outcomes of therapy as well as switching in individuals receiving branded, AG, or other generic agents. Information about patients' perceptions of generic medications and adherence to therapy was also included. Additional information, including relevant government sources, such as the FDA website and the Federal Trade Commission Report, was included as appropriate.
RESULTS
The literature specific to AGs is limited, but available data clearly highlight the importance of patient perception of generics as well as medication appearance as factors that may affect adherence and potentially more frequent switchbacks to branded agents from generics or AGs.
WHAT IS NEW AND CONCLUSION
To our knowledge, this is the first narrative review to provide a summary of the published evidence about AGs with respect to clinical and health outcomes and switching. There is a need for more research and education regarding the use of AGs in clinical practice if they are to become more recognized as a potential treatment choice for patients. Generic medications play an important role in the healthcare system, and AGs may be able to provide an option to meet the specific needs of individual patients.
Topics: Drug Utilization; Drugs, Generic; Excipients; Health Knowledge, Attitudes, Practice; Health Resources; Health Services; Humans; Patient Preference; Therapeutic Equivalency; United States; United States Food and Drug Administration
PubMed: 33829528
DOI: 10.1111/jcpt.13426 -
Pharmacotherapy Apr 2021Cannabidiol (CBD), a non-psychotropic phytocannabinoid from the Cannabis plant, is increasingly being pursued as a treatment for differing ailments. The bioavailability...
Cannabidiol (CBD), a non-psychotropic phytocannabinoid from the Cannabis plant, is increasingly being pursued as a treatment for differing ailments. The bioavailability and pharmacokinetics of CBD are not well understood, and proper dosing schemes have not been adequately developed for its clinical use. CBD is a lipophilic molecule and exhibits low water solubility, so its formulation expectedly impacts its gastrointestinal absorption and subsequent blood plasma concentrations. In this review article, the food effects on CBD pharmacokinetics were analyzed. Clinical trials focusing on the performance of Epidiolex, the FDA-approved CBD formulation, were found in several databases and systematically analyzed in terms of administration method, dosing schedules, and patient characteristics. 44 data sets from clinical trials were found to be useful in the quantitative analysis. Following the normalization of all the pharmacokinetic data sets by dose and patient weight, CBD exhibited a much greater bioavailability in fed patients. For Epidiolex, administration in the fed state led to lower interindividual variability and more predictable pharmacokinetics. Considering all the different oral formulations of CBD, further analysis points to the main excipient of oral CBD formulations (refined sesame seed oil) as a major contributor to the dose-dependent variations in CBD pharmacokinetics, especially affecting the fasted state. We discuss the implications of these results on the downstream pharmacodynamics of endocannabinoid receptor modulation and its broad physiological implications.
Topics: Biological Availability; Cannabidiol; Clinical Trials as Topic; Food; Humans
PubMed: 33583102
DOI: 10.1002/phar.2512 -
PloS One 2021The vaginal microbiota in bacterial vaginosis (BV) typically has low abundance of lactic acid producing lactobacilli. Lactic acid has properties that may make it...
OBJECTIVE
The vaginal microbiota in bacterial vaginosis (BV) typically has low abundance of lactic acid producing lactobacilli. Lactic acid has properties that may make it effective for treating BV and/or restoring an optimal lactobacillus-dominated vaginal microbiota. We conducted a systematic review to describe the effect of intravaginal lactic acid-containing products on BV cure, and their impact on vaginal microbiota composition (PROSPERO registration: CRD42018115982).
METHODS
PubMed, Embase and OVID were searched from inception to November 2019 to identify eligible studies. Included studies evaluated an intravaginal lactic acid-containing product and reported BV cure using established diagnostic methods, and/or vaginal microbiota composition using molecular methods. Studies were independently screened and assessed, and the proportion of women cured post-treatment was calculated. Study results were described in a qualitative manner.
RESULTS
We identified 1,883 articles and assessed 57 full-texts for eligibility. Seven different lactic acid-containing products were evaluated and differed with respect to excipients, lactic acid concentration and pH. Most studies had medium or high risk of bias. Three trials compared the efficacy of a lactic acid-containing product to metronidazole for BV cure. One study found lactic acid to be equivalent to metronidazole and two studies found lactic acid to be significantly inferior to metronidazole. Two studies included a control group receiving a placebo or no treatment. One reported lactic acid to be superior than no treatment and the other reported lactic acid to be equivalent to placebo. Lactic acid-containing products did not significantly impact the vaginal microbiota composition.
CONCLUSION
There is a lack of high-quality evidence to support the use of lactic acid-containing products for BV cure or vaginal microbiota modulation. However, adequately powered and rigorous randomised trials with accompanying vaginal microbiota data are needed to evaluate the efficacy of lactic acid as a BV treatment strategy.
Topics: Administration, Intravaginal; Female; Humans; Lactic Acid; Microbiota; Publication Bias; Risk; Vagina; Vaginosis, Bacterial
PubMed: 33571286
DOI: 10.1371/journal.pone.0246953 -
European Journal of Pharmaceutics and... Jan 2021Acceptable palatability of an oral dosage form is crucial to patient compliance. Excipients can be utilised within a formulation to mask the bitterness of a drug. One...
Acceptable palatability of an oral dosage form is crucial to patient compliance. Excipients can be utilised within a formulation to mask the bitterness of a drug. One such category is the bitter-blockers. This term is used inconsistently within the literature and has historically been used to describe any additive which alters the taste of an unpleasant compound. This review defines a bitter-blocker as a compound which interacts with the molecular pathway of bitterness at a taste-cell level and compiles data obtained from publication screening of such compounds. Here, a novel scoring system is created to assess their potential utility in a medicinal product using factors such as usability, safety, efficacy and quality of evidence to understand their taste-masking ability. Sodium acetate, sodium gluconate and adenosine 5'monophophate each have a good usability and safety profile and are generally regarded as safe and have shown evidence of bitter-blocking in human sensory panels. These compounds could offer a much needed option to taste-mask particularly aversive medicines where traditional methods alone are insufficient.
Topics: Administration, Oral; Drug Compounding; Excipients; Humans; Medication Adherence; Taste
PubMed: 33130339
DOI: 10.1016/j.ejpb.2020.10.017 -
Journal of Controlled Release :... Feb 2021Over the last few years, conventional medicine has been increasingly moving towards precision medicine. Today, the production of oral pharmaceutical forms tailored to... (Review)
Review
Over the last few years, conventional medicine has been increasingly moving towards precision medicine. Today, the production of oral pharmaceutical forms tailored to patients is not achievable by traditional industrial means. A promising solution to customize oral drug delivery has been found in the utilization of 3D Printing and in particular Fused Deposition Modeling (FDM). Thus, the aim of this systematic literature review is to provide a synthesis on the production of pharmaceutical solid oral forms using FDM technology. In total, 72 relevant articles have been identified via two well-known scientific databases (PubMed and ScienceDirect). Overall, three different FDM methods have been reported: "Impregnation-FDM", "Hot Melt Extrusion coupled with FDM" and "Print-fill", which yielded to the formulation of thermoplastic polymers used as main component, five families of other excipients playing different functional roles and 47 active ingredients. Solutions are underway to overcome the high printing temperatures, which was the initial brake on to use thermosensitive ingredients with this technology. Also, the moisture sensitivity shown by a large number of prints in preliminary storage studies is highlighted. FDM seems to be especially fitted for the treatment of rare diseases, and particular populations requiring tailored doses or release kinetics. For future use of FDM in clinical trials, an implication of health regulatory agencies would be necessary. Hence, further efforts would likely be oriented to the use of a quality approach such as "Quality by Design" which could facilitate its approval by the authorities, and also be an aid to the development of this technology for manufacturers.
Topics: Drug Delivery Systems; Drug Liberation; Excipients; Humans; Pharmaceutical Preparations; Printing, Three-Dimensional; Tablets; Technology, Pharmaceutical
PubMed: 33130069
DOI: 10.1016/j.jconrel.2020.10.056 -
Medicine Feb 2020Influenza is a severe disease burden among all age groups. This study aimed to review the efficacy of inactivated influenza vaccines with MF59 adjuvant and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Influenza is a severe disease burden among all age groups. This study aimed to review the efficacy of inactivated influenza vaccines with MF59 adjuvant and non-adjuvanted inactivated influenza vaccines among all age groups against specific influenza vaccine strains.
METHODS
Literature search of PubMed, Embase, Medline, OVID, and Cochrane Library Trials (CENTRAL) was implemented up to March 1, 2019. Homogeneity qualified studies were included forData were extracted such as study country location, demographic characteristics, and measure outcomes, and were analyzed by a random effect model and sensitivity analyses to identify heterogeneity. Risk of bias was evaluated using the Cochrane Risk of Bias Tool.
RESULTS
We retrieved 1,021 publications and selected 31 studies for full review, including 17 trials for meta-analysis and 6 trials for qualitative synthesis. MF59-adjuvanted influenza vaccines demonstrated better immunogenicity against specific vaccine virus strains compared to non-adjuvanted influenza vaccine both in healthy adult group (RR = 2.10; 95% CI: 1.28-3.44) and the healthy aged (RR = 1.26; 95% CI: 1.10-1.44).
CONCLUSION
The quality of evidence is moderate to high for seroconversion and seroprotection rates of influenza vaccine. MF59-adjuvanted influenza vaccines are superior to non-adjuvanted influenza vaccines to enhance immune responses of vaccination in healthy adults and older adults, and could be considered for routine use especially the monovalent prepandemic influenza vaccines.
Topics: Adjuvants, Immunologic; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Child; Female; Humans; Immunogenicity, Vaccine; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Polysorbates; Randomized Controlled Trials as Topic; Seroconversion; Squalene; Vaccines, Inactivated; Young Adult
PubMed: 32049815
DOI: 10.1097/MD.0000000000019095 -
Journal of Ethnopharmacology Mar 2020Before the advent of modern antibiotics, microbial infections were treated with herbal medicine or cauterization. Literature from the latter half of the nineteenth to...
ETHNOPHARMACOLOGICAL RELEVANCE
Before the advent of modern antibiotics, microbial infections were treated with herbal medicine or cauterization. Literature from the latter half of the nineteenth to the early mid-twentieth century, when antibiotics became widely available, arguably holds the most progressive information about herbal remedies to treat bacterial skin diseases. The corpus of literature produced in Italy during that period is not easily accessible and mostly out of print.
MATERIAL AND METHODS
Plant-based remedies utilized in popular Italian medicine to treat anthrax, boils, erysipelas, impetigo, pustules, and whitlow were sourced from literature indexed in and available through the National Library Service website of the Italian Libraries Network. The remedies are assessed for their antimicrobial potential based on a detailed search of the herbal drug species in scientific databases.
RESULTS
A considerable part of the reviewed recipes included specific excipients (41 out of 139) and others were produced with fresh plant material (48 out of 139). Out of the 52 identified herbal drug species used in popular Italian medicine against dermatologic infections, extracts of 43 were shown to have moderate in vitro activity against Gram-positive and Gram-negative bacteria.
CONCLUSION
The antibacterial activity of the extracts and pure compounds as reported in the reviewed literature is mostly based on in vitro assays and generally does not encourage follow up studies. The effectiveness of the reported recipes, which include fresh plant material and excipients can only be assessed through in vivo studies. Those remedies including herbal drugs with reported antimicrobial activity might have the potential as complementary therapies. The reviewed plant based antimicrobial recipes might serve as inspirations in the search for alternative topical antibacterial strategies and the search for their synergistic and potentiating ingredients.
Topics: Anti-Bacterial Agents; History, 19th Century; History, 20th Century; Humans; Italy; Medicine, Traditional; Phytotherapy; Plant Preparations; Skin Diseases, Bacterial
PubMed: 31790819
DOI: 10.1016/j.jep.2019.112443 -
Vaccine Jan 2020Identifying optimal priming strategies for children <2 years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Identifying optimal priming strategies for children <2 years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal influenza vaccines were designed to promote a better immune response among young vaccine-naïve children.
METHODS
We systematically reviewed randomized trials to assess hemagglutination inhibition (HAI) antibody response to MF59-adjuvanted inactivated influenza vaccine (aIIV) versus nonadjuvanted IIV among children. We estimated pooled ratios of post-vaccination HAI geometric mean titer (GMT) for aIIV versus IIV and confidence intervals (CIs) using the pooled variances derived from reported CIs.
RESULTS
Mean age was 28 months (range, 6-72 months). Children received vaccines with either 7.5 μg (6-35 months) or 15 μg (≥36 months) hemagglutinin of each strain depending on age. Seven of eight trials administered trivalent vaccines and one used quadrivalent vaccine. Pooled post-vaccination GMT ratios against the three influenza vaccine strains were 2.5-3.5 fold higher after 2-dose-aIIV versus 2-dose-IIV among children 6-72 months, and point estimates were higher among children 6-35 months compared with older children. When comparing 1-dose-aIIV to 2-dose-IIV doses, pooled GMT ratios were not significantly different against A/H1N1 (1.0; 95% CI: 0.5-1.8; p = 0.90) and A/H3N2 viruses (1.0; 95% CI: 0.7-1.5; p = 0.81) and were significantly lower against B viruses (0.6; 95% CI: 0.4-0.8; p < 0.001) for both age groups. Notably, GMT ratios for vaccine-mismatched heterologous viruses after 2-dose-aIIV compared with 2-dose-IIV were higher against A/H1N1 (2.0; 95% CI: 1.1-3.4), A/H3N2 (2.9; 95% CI: 1.9-4.2), and B-lineage viruses (2.1; 95% CI: 1.8-2.6).
CONCLUSIONS
Two doses of adjuvanted IIV consistently induced better humoral immune responses against Type A and B influenza viruses compared with nonadjuvanted IIVs in young children, particularly among those 6-35 months. One adjuvanted IIV dose had a similar response to two nonadjuvanted IIV doses against Type A influenza viruses. Longer-term benefits from imprinting and cell-mediated immunity, including trials of clinical efficacy, are gaps that warrant investigation.
Topics: Child; Child, Preschool; Female; Humans; Infant; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Influenza, Human; Male; Polysorbates; Randomized Controlled Trials as Topic; Squalene
PubMed: 31735505
DOI: 10.1016/j.vaccine.2019.10.053