Dataset Information

Hypoalbuminemia and Pharmacokinetics: When the Misunderstanding of a Fundamental Concept Leads to Repeated Errors over Decades.

ABSTRACT: Surprisingly, misinterpretation of the influence of hypoalbuminemia on pharmacokinetics and the clinical effects of drugs seems to be a current problem, even though hypoalbuminemia has no impact on the pharmacologically active exposure. Exceptions to this fact are highly protein-bound anaesthetics with high elimination capacity (i.e., <5 drugs on the market). To assess the frequency of misinterpretation of the influence of hypoalbuminemia on pharmacokinetics and the clinical effects of drugs between 1975 and 2021, a PubMed literature review was conducted. Each paragraph on albumin binding was classified as correct, ambiguous or incorrect, creating two acceptable categories: (1) content without any errors, and (2) content containing some incorrect and/or ambiguous statements. The analyses of these articles showed that fewer than 11% of articles contained no interpretation errors. In order to contain this misinterpretation, several measures are proposed: (1) Make the message accessible to a wide audience by offering a simplified and didactic video representation of the lack of impact of albumin binding to drugs. (2) Precise terminology (unbound/free form/concentration) should be used for highly bound drugs. (3) Unbound/free forms should be systematically quantified for highly plasma protein bound drugs for clinical trials as well as for therapeutic drug monitoring.

SUBMITTER: Gandia P

PROVIDER: S-EPMC10044130 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Hypoalbuminemia and Pharmacokinetics: When the Misunderstanding of a Fundamental Concept Leads to Repeated Errors over Decades.

Gandia Peggy P Decheiver Sarah S Picard Manon M Guilhaumou Romain R Baklouti Sarah S Concordet Didier D

Antibiotics (Basel, Switzerland) 20230304 3

Surprisingly, misinterpretation of the influence of hypoalbuminemia on pharmacokinetics and the clinical effects of drugs seems to be a current problem, even though hypoalbuminemia has no impact on the pharmacologically active exposure. Exceptions to this fact are highly protein-bound anaesthetics with high elimination capacity (i.e., <5 drugs on the market). To assess the frequency of misinterpretation of the influence of hypoalbuminemia on pharmacokinetics and the clinical effects of drugs bet ...[more]

PMID: 36978382

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Project description:In a much-cited 1964 paper entitled "Reproductive efficiency in relation to colony size in hymenopterous societies," Charles Michener investigated the correlation between a colony's size and its reproductive efficiency - the ability of its adult females to produce reproductives, measured as per-capita output. Based on his analysis of published data from destructively sampled colonies in 18 species, he reported that in most of these species efficiency decreased with increasing colony size. His conclusion that efficiency is higher in smaller groups has since gained widespread acceptance. But it created a seeming paradox: how can natural selection maintain social behaviour when a female apparently enjoys her highest per-capita output by working alone? Here we treat Michener's pattern as a hypothesis and perform the first large-scale test of its prediction across the eusocial Hymenoptera. Because data on actual output of reproductives were not available for most species, Michener used various proxies, such as nest size, numbers of brood, or amounts of stored food. We show that for each of Michener's data sets the reported decline in per-capita productivity can be explained by factors other than decreasing efficiency, calling into question his conclusion that declining efficiency is the cause of the pattern. The most prominent cause of bias is the failure of the proxy to capture all forms of output in which the colony invests during the course of its ontogeny. Other biasing factors include seasonal effects and a variety of methodological flaws in the data sets he used. We then summarize the results of 215 data sets drawn from post-1964 studies of 80 species in 33 genera that better control for these factors. Of these, 163 data sets are included in two meta-analyses that statistically synthesize the available data on the relationship between colony size and efficiency, accounting for variable sample sizes and non-independence among the data sets. The overall effect, and those for most taxonomic subgroups, indicates no loss of efficiency with increasing colony size. Two exceptional taxa, the halictid bees and independent-founding paper wasps, show negative trends consistent with the Michener hypothesis in some species. We conclude that in most species, particularly those with large colony sizes, the hypothesis of decreasing efficiency with increasing colony size is not supported. Finally, we explore potential mechanisms through which the level of efficiency can decrease, be maintained, or even increase, as colonies increase in size.

Project description:As of 2015, it has been 26 years since the first optical detection and spectroscopy of single molecules in condensed matter. This area of science has expanded far beyond the early low temperature studies in crystals to include single molecules in cells, polymers, and in solution. The early steps relied upon high-resolution spectroscopy of inhomogeneously broadened optical absorption profiles of molecular impurities in solids at low temperatures. Spectral fine structure arising directly from the position-dependent fluctuations of the number of molecules in resonance led to the attainment of the single-molecule limit in 1989 using frequency-modulation laser spectroscopy. In the early 1990s, a variety of fascinating physical effects were observed for individual molecules, including imaging of the light from single molecules as well as observations of spectral diffusion, optical switching and the ability to select different single molecules in the same focal volume simply by tuning the pumping laser frequency. In the room temperature regime, researchers showed that bursts of light from single molecules could be detected in solution, leading to imaging and microscopy by a variety of methods. Studies of single copies of the green fluorescent protein also uncovered surprises, especially the blinking and photoinduced recovery of emitters, which stimulated further development of photoswitchable fluorescent protein labels. All of these early steps provided important fundamentals underpinning the development of super-resolution microscopy based on single-molecule localization and active control of emitting concentration. Current thrust areas include extensions to three-dimensional imaging with high precision, orientational analysis of single molecules, and direct measurements of photodynamics and transport properties for single molecules trapped in solution by suppression of Brownian motion. Without question, a huge variety of studies of single molecules performed by many talented scientists all over the world have extended our knowledge of the nanoscale and many microscopic mechanisms previously hidden by ensemble averaging.

Project description:ObjectiveAs the number of female medical students and surgical residents increases, the increasing number of female academic surgeons has been disproportionate. The purpose of this brief report is to evaluate the AAMC data from 1969 to 2018 to compare the level of female academic faculty representation for surgical specialties over the past four decades.DesignThe number of women as a percentage of the total surgeons per year were recorded for each year from 1969-2018, the most recent year available. Descriptive statistics were performed. Poisson regression examined the percentage of women in each field as the outcome of interest with the year and specialty (using general surgery as a reference) as two predictor variables.SettingData from the American Association of Medical Colleges (AAMC).ParticipantsAll full-time academic faculty physicians in the specialties of obstetrics and gynecology (OB/GYN), general surgery, ophthalmology, otolaryngology (ENT), plastic surgery, plastic surgery, urology, neurosurgery, orthopaedic surgery and cardiothoracic surgery as per AAMC records.ResultsThe percentage of women in surgery for all specialties evaluated increased from 1969 to 2018 (OR 1.04, p<0.001). Compared with general surgery, the rate of yearly percentage change increased more slowly in neurosurgery (OR 0.84; P = .004), orthopaedic surgery (OR 0.82; P = .002), urology (OR 0.59; P < .001), and cardiothoracic surgery (OR 0.38; P < .001). There was no significant difference in the rate of yearly percentage change for plastic surgery (OR 1.01; P = .840). The rate of yearly percentage change increased more rapidly in OB/GYN (OR 2.86; P < .001), ophthalmology (OR 1.79; P < .001) and ENT (OR 1.70; P < .001).ConclusionsRepresentation of women in academic surgery is increasing overall but is increasing more slowly in orthopaedic surgery, neurosurgery, cardiothoracic surgery and urology compared with that in general surgery. These data may be used to inform and further the discussion of how mentorship and sponsorship of female students and trainees interested in surgical careers may improve gender equity in the future.

Dataset Information

Hypoalbuminemia and Pharmacokinetics: When the Misunderstanding of a Fundamental Concept Leads to Repeated Errors over Decades.

Publications

Hypoalbuminemia and Pharmacokinetics: When the Misunderstanding of a Fundamental Concept Leads to Repeated Errors over Decades.

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