The need to individualize a drug dosage and adjust it to a patient's physiological and/or pathophysiological status is rarely satisfied in routine clinical practice, primarily because of complexity ...of the adjustment task.
The aim of this article is to shed light to basic principles of drug dosage individualization in the most frequent clinical states that affect pharmacokinetics of drugs. The principles are derived from published clinical studies conducted on diverse patient populations, using non-compartmental pharmacokinetic model.
Simple, but sufficiently exact, way to calculate appropriate drug dose for a patient is the one based on target average steady-state concentration and non-compartmental pharmacokinetic model. If target steady-state drug concentration and dosage interval are considered fixed, maintenance dose could be adjusted on the basis of expected changes of total drug clearance and bioavailability, while loading dose should be related to changes of volume of distribution and bioavailability. Relative increase or decrease of these pharmacokinetic parameters in regard to normal values in healthy persons is translated to relative (percentual) increase or decrease of maintenance and loading doses recommended in the drug monograph.
Although scientometry gradually became prevalent way of measuring one's research output, there are many inherent drawbacks in main indices that are used: impact factor, number of citations, number of ...published papers and Hirsch's index.
The aim of this study was to analyze effects of inflated co-authorship on values of scientometric indices among authors in biomedicine who participated in published papers with more than 30 co-authors.
The study was of cross-sectional type, based on 100 publications randomly extracted from the MEDLINE database. The inclusion criterion was publication with more than 30 authors. The studies with topics not related to humans were excluded from further analysis.
On average about 10% of papers published by the surveyed authors had more than 30 co-authors, but these papers brought more than 40% of all citations and more than 40% of Hirsch's index attributed to these authors. The duration of scientific activity was well correlated to number of citations, Hirsch's index and the number of publications themselves with 30 or less co-authors, while the correlation did not exist with number of citations, Hirsch's index and the number of publications with more than 30 authors. In summary, publications with > 30 authors carry more scientometric points than publications with less co-authors, and the researchers with shorter scientific activity had larger scientometric benefit from publications with more than 30 authors than senior researchers.
Unjustified and prolific co-authorship is one of methods for inflation of scientometric indices that are not further reflecting true quality of research output of an individual. Further improvement of scientometric indicators may prevent unjustified co-authorship if it reflects the work invested in a research result.
Background
Niemann–Pick disease type C (NP-C) is a progressive neurodegenerative disorder with early infantile (< 2 years), late infantile (2–6 years), juvenile (7–15 years) and adolescent (> ...15 years) onset. The mainstay of therapy for NP-C patients with neurological symptoms is miglustat, a drug that may modify the course of the disease.
Aim
Our aim was to evaluate the cost-effectiveness of miglustat in comparison to symptomatic therapy in patients with NP-C in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy.
Method
The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was eighty years. The main outcomes of the study were quality-adjusted life years gained with miglustat and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Discrete-Event Simulation model. The model results were obtained after Monte Carlo microsimulation of a sample with 1000 virtual patients.
Results
Treatment with miglustat was not cost-effective when compared with symptomatic therapy and was associated with negative values of net monetary benefit regardless of the onset of neurological manifestations (− 110,447,627.00 ± 701,614.00 RSD, − 343,871,695.00 ± 2,577,441.00 RSD, − 1,397,908,502.00 ± 23,084,235.00 RSD and − 2,953,680,879.00 ± 33,297,412.00 RSD) for early infantile, late infantile, juvenile and adolescent cohorts, respectively).
Conclusion
When traditional pharmacoeconomic evaluation is employed, miglustat is not a cost-effective option in comparison to symptomatic therapy for the treatment of NP-C. However, given the proven efficacy of miglustat, there is a need to find ways to make this drug available to all patients with NP-C.
: Zonisamide is a benzisoxazole with 3-methanesulfonamide side chain, chemically unrelated with other anticonvulsants, and approved as mono-therapy of newly diagnosed focal epilepsy with or without ...secondary generalization in adults or adjunctive therapy in the treatment of partial seizures, with or without secondary generalization, in adults, adolescents, and children aged 6 years and above.
: Pharmacokinetics, clinical efficacy, and the adverse effects of zonisamide are discussed in the article. The discussion is based on data from published preclinical studies, clinical trials, observational studies, systematic reviews, and approved summary of product characteristics.
: Zonisamide is an anticonvulsant with multiple mechanisms of action on neuronal tissue, which achieves seizure freedom in more than 80% of patients with newly-onset focal epilepsy and in 6.2 to 18.1% of patients with focal onset seizures inadequately controlled by first-line anticonvulsants. Within the recommended dose range, it follows linear kinetic of elimination; it is metabolized in the liver by two cytochrome isoforms, so pharmacokinetic interactions are rare and with little clinical significance. Up to 10% of patients taking zonisamide will have problems with weight loss and more than 10% with irritability, confusion or depression, and long-lasting therapy may cause renal calculi in 1.2% of patients.
To satisfy the needs of pediatric and other patients with focal onset seizures who cannot swallow solid dosage forms of zonisamide, an oral liquid form of this drug is necessary in clinical practice. ...Although there are two oral suspensions of zonisamide with marketing authorization (MA), there are issues of availability and high cost which limit their use and inspire extemporaneous compounding. Extemporaneously compounded oral suspensions of zonisamide are prepared according to different formulas and vary in stability; therefore it is essential to test this characteristic. Bioequivalence of extemporaneously compounded oral suspensions has never been tested, and the efficacy and safety of zonisamide oral suspensions have generally not been demonstrated in clinical trials. As a narrow therapeutic window drug, zonisamide requires precision in dosing, which could be achieved only with dosage forms with established bioavailability, efficacy, and safety. In order to avoid underdosing and toxicity with zonisamide oral suspensions and utilize their full therapeutic potential, it is necessary to perform bioequivalence studies with each variation of extemporaneously compounded oral suspension and also clinical trials with both commercial and extemporaneous oral suspensions of zonisamide. Keywords: zonisamide, oral suspension, stability, bioequivalence
While there are already approved anticonvulsants for treatment of children with Dravet syndrome, disease modifying therapy is at its beginning.
This narrative review is updating the latest ...information about efficacy and safety of both anticonvulsant and disease modifying investigational drugs for Dravet syndrome. Relevant publications were searched for in MEDLINE, GOOGLE SCHOLAR, SCINDEKS, and CLINICALTRIALS.GOV databases, from the dates of their foundation till January 2023.
The main advancements were made in the treatment of Dravet syndrome with confirmed haploinsufficiency of SCN1A gene. The application of antisense oligonucleotides has so far proven to be the most successful within disease-modifying therapy, but it also requires further refinement of the methodology of application and delivery to target cells, as well as additional testing of the effectiveness of antisense oligonucleotides outside of TANGO technology. Also, the full potential of gene therapy has yet to be explored, given that high capacity adenoviral vectors that can incorporate the SCN1A gene have recently been prepared.
The calcitonin gene-related peptide transmission was the target for recent development of drugs that effectively prevent attacks of both episodic and chronic migraine. The aim of this narrative ...review was to offer deeper insight into pharmacokinetics of monoclonal antibodies approved for prevention of migraine attacks. For this narrative review, relevant literature was searched for in MEDLINE and Google Scholar databases, covering periods 1966–2023 and 2006–2023, respectively. The ClinicalTrials.gov database was also searched for relevant clinical studies whose results had not been published previously in medical journals, covering the period 2000–2023. The monoclonal antibodies from this group are distributed mainly in the plasma and part of the extracellular space; they are neither metabolized in the liver nor excreted via the kidneys. The elimination of galcanezumab, eptinezumab and fremanezumab takes place only by a non-specific linear process via the reticuloendothelial system in the liver, while erenumab is eliminated by a non-specific process and by a specific, saturable process because of binding to receptors located on the cell membrane. Since the elimination processes do not have a large capacity, the half-life is about 2 weeks for erenumab and about 4 weeks for other monoclonal antibodies. Variability in the pharmacokinetics of these monoclonal antibodies is small in different subpopulations, and body weight is the only parameter to consider when choosing the dose of these drugs.
Calcitonin gene-related peptide neurotransmission was the target for recent development of monoclonal antibodies that effectively prevent attacks of both episodic and chronic migraine. The aim of ...this narrative review was to offer deeper insight into drug-drug, drug-food and drug-disease interactions of monoclonal antibodies approved for prevention of migraine attacks. For this narrative review, relevant literature was searched for in MEDLINE and Google Scholar databases, covering the 1966–2023 and 2006–2023 periods, respectively. The ClinicalTrials.gov database was also searched for relevant clinical studies whose results had not been published previously in medical journals, covering 2000–2023. Monoclonal antibodies (erenumab, fremanezumab, galcanezumab and eptinezumab) augment prophylactic action of gepants and onabotulinumtoxin A and somewhat increase efficacy of triptans used to abort migraine attacks; however, their adverse reactions may also be augmented. Pharmacokinetic interactions and interactions in general with drugs used for other indications except migraine are negligible, as are drug-food interactions. However, monoclonal antibodies may worsen diseases with already weakened CGRP neurotransmission, Raynaud phenomenon and constipation. Monoclonal antibodies used for prevention of migraine do not engage in significant pharmacokinetic interactions with other drugs; however, they do engage in pharmacodynamic interactions with other anti-migraine drugs, additively augmenting their prophylactic action, but also increasing frequency and severity of adverse reactions, which are a consequence of the CGRP neurotransmission interruption.
The source of scientific information, methods for their evaluation, and methodology of their use are critical for serious scientific research and publishing of the scientific research results. ...Certain methodological principles should be inexcusably followed when designing clinical or observational research to avoid bias and presentation of results that do not reflect the truth about the phenomenon that is the object of the study.
The aim of this study was to compare the methodological quality of clinical trials and observational studies published in medical journals from ex-Yugoslav countries indexed in Web of Science (WoS) and Pubmed/MEDLINE.
Clinical studies published in medical journals of ex-Yugoslav countries were retrieved from the WoS and Pubmed database, and the sample for analysis was randomly chosen from the retrieved publications. The rate of the most common errors in the design of clinical/observational studies was established by a careful reading of the sampled publications and their checking against predefined criteria.
Number and percent of the evaluated studies that failed to meet each of the methodological criteria tested, number of the evaluated criteria not satisfied per database and number of studies that satisfied more than 4 criteria were analyzed per database. When explanatory potential of journal impact factor, number of citations, time elapsed from publication and a database where a journal is referred were tested by linear regression in regard to the number of methodological criteria satisfied per study, the linear regression model was obtained by backward deletion method and achieved R2 adjusted of 0.166 (F=13.827, df1 = 2, df2 = 127, p=0.000). The methodological quality of studies was directly related to impact factor of the journals (B = 0.976, 95% confidence interval 0.539 - 1.413, p=0.000) and inversely with the database where a journal is referred (B =-0.444, 95% confidence interval-0.824 - -0.064, p = 0.022). Each additional unit of impact factor increased number of satisfied methodological criteria for about 1, while referring a journal only in WoS decreased number of satisfied criteria for 0.45 points in comparison with journals referred in both WoS and Pubmed/MEDLINE, and for 0.9 points in comparison to journals referred only in MEDLINE.
Methodological and scientometric quality of clinical studies published in medical journals from ex-Yugoslav region varies significantly, and the variations are higher in journals referenced only in WoS than in journals referenced in Pubmed/MEDLINE only, or in both Pubmed and Web of Science databases.
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