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Pharmaceuticals (Basel, Switzerland) Feb 2021In the treatment of pediatric diseases, suitable dosages and dosage forms are often not available for an adequate therapy. The use of innovative additive manufacturing...
In the treatment of pediatric diseases, suitable dosages and dosage forms are often not available for an adequate therapy. The use of innovative additive manufacturing techniques offers the possibility of producing pediatric dosage forms. In this study, the production of mini tablets using fused deposition modeling (FDM)-based 3D printing was investigated. Two pediatric drugs, caffeine and propranolol hydrochloride, were successfully processed into filaments using hyprolose and hypromellose as polymers. Subsequently, mini tablets with diameters between 1.5 and 4.0 mm were printed and characterized using optical and thermal analysis methods. By varying the number of mini tablets applied and by varying the diameter, we were able to achieve different release behaviors. This work highlights the potential value of FDM 3D printing for the on-demand production of patient individualized, small-scale batches of pediatric dosage forms.
PubMed: 33670158
DOI: 10.3390/ph14020143 -
Clinical Pharmacokinetics Mar 2020The clinical pharmacology of elagolix was extensively evaluated in clinical studies in healthy subjects and in women with endometriosis. Elagolix pharmacokinetics (PK)... (Review)
Review
The clinical pharmacology of elagolix was extensively evaluated in clinical studies in healthy subjects and in women with endometriosis. Elagolix pharmacokinetics (PK) show significant population variability, however they are minimally affected by patients' baseline characteristics and demographics, except for clinically relevant extrinsic and intrinsic factors such as coadministrated strong organic anion transporting polypeptide (OATP) 1B1 inhibitors and severe hepatic impairment, which are contraindications for the use of elagolix. These studies enabled a comprehensive understanding of elagolix mechanism of action and the downstream pharmacodynamic (PD) effects on gonadotropin and ovarian hormones, as well as full characterization of the PK/PD (PKPD) relationships of elagolix at various dosages, including the approved 150 mg once daily and 200 mg twice daily dosing regimens for the management of moderate to severe pain associated with endometriosis. Several model-based analyses have contributed to understanding of the benefit-risk profile of elagolix in patients with endometriosis, through characterization of the exposure relationship with responder rates, with changes in bone mineral density over time, as well as the interaction with coadministered drugs. Collectively, these studies and analyses served as supportive evidence for the effectiveness of the approved dosages and provided general dosing instructions of the first approved oral gonadotropin-releasing hormone receptor antagonist.
Topics: Administration, Oral; Bone Density; Drug Interactions; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Hydrocarbons, Fluorinated; Liver Diseases; Organic Anion Transporters; Pain; Pharmacogenetics; Pharmacology, Clinical; Pyrimidines; Receptors, LHRH; Treatment Outcome
PubMed: 31749075
DOI: 10.1007/s40262-019-00840-7 -
Frontiers in Pharmacology 2022Pharmacotherapy is one of the primary treatments for patients with Assisted reproductive technology (ART). Despite the publication of various research on ART treatment,...
Pharmacotherapy is one of the primary treatments for patients with Assisted reproductive technology (ART). Despite the publication of various research on ART treatment, there is no clear conclusion regarding the choice of drug treatment in China. Our research intends to examine the trend of widely prescribed medications for ART patients in China. For instance, the study examines the logic of drug indications, usage, and dose in patient prescriptions. We did a cross-sectional study of the data from the hospital prescription analysis cooperation project supervised by the China Medical Association. The information is extracted from the prescriptions of reproductive assistance outpatients from January 2016 to December 2020. We used the U.S. Food and Drug Administration (FDA) classification to quantify the frequency of drug use and the categories of drugs. We manually extract the information of patients who require ART treatment, divide the patients into various age groups and geographies, followed by study the indications, utilization, and rationale of the most important therapeutic medications. Among the 225225 patients included in this study, Guangzhou (47.83%), Shanghai (19.84%), and Zhengzhou (9.36%) were the top three cities. In the past 5 years, the average age was 32.99, and 60.38% of women were between the age of 25 and 34. The main therapeutic medicines taken by each patient, primarily hormone therapies, were tallied. Eleven types of primary therapeutic medicines were employed. Different progesterone preparations (47472, 21.08%), chorionic gonadotrophin gondotrophin for injection (38932, 17.29%), dydrogesterone tables (33591, 14.91%), and triptorelin for injection (26959, 11.97%) rounded out the top five. According to the data on outpatient medications in major cities in China, the variety and proportion of injections are the highest, including the most frequent types of ovulation induction and urotropia, as well as triptorelin and progesterone. Even though the total dosage of urotropin was the highest in 5 years, it showed a declining trend. The dosages of progesterone and didroxyprogesterone increased, with progesterone showing the most rapid increase. The top five most expensive prescription medications are triptorelin, urotropin, progesterone, didroxyprogesterone, and leuprorelin, in that order. Goserelin, leuprorelin, triptorelin, growth hormone, and didroxyprogesterone are among the top five most expensive medications per capita. The average age of patients has not increased considerably over the past 5 years. However, the opportunity cost of childbirth for women has increased, which has significantly enhanced their willingness for childbearing intentions. The medication selection is reasonable overall. In this study, the recommended dosages of first-line medicines (urotropin and chorionic gonadotropin) are likewise high. In contrast, the dosage of oral first-line treatment for ovarian stimulation in unexplained infertility is modest, and the dosage of progesterone is steadily increasing. In addition, the price of certain medicines is high, which will increase the patients' financial burden. Future research will focus on enhancing the degree of rational drug use among outpatients and realizing the economical, safe, and effective use of pharmaceuticals to lessen the economic burden of patients.
PubMed: 36467066
DOI: 10.3389/fphar.2022.1021150 -
Pharmaceutics Oct 2021Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication...
Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger-Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone.
PubMed: 34684010
DOI: 10.3390/pharmaceutics13101717 -
Environmental Health Insights 2022Consumption of polluted surface waters are leading to waterborne diseases, especially in developing countries, which results in the deaths of millions of people annually...
BACKGROUND
Consumption of polluted surface waters are leading to waterborne diseases, especially in developing countries, which results in the deaths of millions of people annually around the world. Ethiopia, like the rest of developing countries, suffers a lot of water-associated health problems. Chemical disinfectants are in use to disinfect water with some drawbacks like expensiveness, unavailability, and detrimental effect on human health. Researchers are on the search for non-expensive and locally available methods, and natural plants are the ones in the study. Thus, this study is designed to test removal efficiency of () and () from surface water.
METHODS
A cross-sectional study was conducted from June to July 2021. A 14 L water sample was collected from Lake Hawassa. A 30, 60, and 100 mg weights of the leaf and seed powder dosages of and at contaminant settling times of 30, 60, and 90 minutes were used. Each 1-L water sample was treated with each of the dosages. count, temperature, pH and turbidity were measured using standard methods for water and wastewater analysis. Statistical package for social sciences (SPSS) version.23 was used for analysis. Treatment differences between plant parts and association between variables were also tested.
RESULT
The result indicated that raw water samples having 18 initial colonies per 100 mL of water showed zero colonies per 100 mL of water after treatment with 30 mg dosage of seed, 30 mg dosage of seed, and 60 mg dosage of leaf after 90 minutes of settling time, but leaf was unable to reduce colonies to 0 per 100 mL of water. leaf showed the highest turbidity reduction of 83.3% at 60 mg dosage. A pH of 7.30 and 8.50 and a temperature of 20°C to 23.5°C were recorded. There was a significant difference in removal between seed and leaf. Turbidity was identified as a factor that positively affects removal during seed and leaf. Dosage and settling time were also identified as predictors of removal.
CONCLUSION
and have antimicrobial properties against , but only showed , turbidity, and pH values within the recommended World Health Organization standards. So, we suggest as a promising natural disinfectant that needs attention from organizations working on the water.
PubMed: 35846165
DOI: 10.1177/11786302221111842 -
Spine Aug 2020Longitudinal Cohort Study OBJECTIVE.: The aim of this study was to determine whether duration of postoperative opioids is associated with long-term outcomes, and if...
STUDY DESIGN
Longitudinal Cohort Study OBJECTIVE.: The aim of this study was to determine whether duration of postoperative opioids is associated with long-term outcomes, and if initial postoperative opioid dosage is associated with opioid cessation after spine surgery.
SUMMARY OF BACKGROUND DATA
Preoperative opioid use is associated with poor outcomes, but little evidence exists regarding the implications of opioid dosage and duration after spine surgery.
METHODS
Data from our state's prescription drug database was linked to our prospective clinical spine registry to analyze opioid dispensing and outcomes in elective surgical spine patients between 2010 and 2017. Patients were stratified based on preoperative chronic opioid use and multivariable regression was used to assess associations between duration of postoperative opioids and outcomes at one year, including satisfaction, chronic opioid use, and meaningful improvements in pain, disability, and quality of life. In a secondary aim, a Cox proportional hazards model was used to determine whether initial postoperative opioid dosage was associated with time to opioid cessation.
RESULTS
Of 2172 patients included, 35% had preoperative chronic opioid use. In patients without preoperative chronic opioid use, a postoperative opioid duration of 31 to 60 days was associated with chronic opioid use at 1 year (adjusted odds ratio [aOR]: 4.1 [1.7-9.8]) and no meaningful improvement in extremity pain (aOR: 1.8 [1.3-2.6]) or axial pain (aOR: 1.6 [1.1-2.2]); cessation between 61 and 90 days was associated with no meaningful improvement in disability (aOR: 2 [1.3-3]) and dissatisfaction (aOR:1.8 [1-3.1]). In patients with preoperative chronic opioid use, postoperative opioids for ≥90 days was associated with dissatisfaction. Cox regression analyses showed lower initial postoperative opioid dosages were associated with faster opioid cessation in both groups.
CONCLUSION
Our results suggest that a shorter duration of postoperative opioids may result in improved 1-year patient-reported outcomes, and that lower postoperative opioid dosages may lead to faster opioid cessation.
LEVEL OF EVIDENCE
2.
Topics: Adult; Aged; Analgesics, Opioid; Cohort Studies; Drug Administration Schedule; Elective Surgical Procedures; Female; Humans; Longitudinal Studies; Male; Middle Aged; Opioid-Related Disorders; Pain, Postoperative; Patient Reported Outcome Measures; Prospective Studies; Retrospective Studies; Spinal Diseases; Time Factors
PubMed: 32675616
DOI: 10.1097/BRS.0000000000003446 -
Artificial Intelligence in Medicine Jan 2020Antibiotic resistance is one of the major challenges we face in modern times. Antibiotic use, especially their overuse, is the single most important driver of antibiotic...
Antibiotic resistance is one of the major challenges we face in modern times. Antibiotic use, especially their overuse, is the single most important driver of antibiotic resistance. Efforts have been made to reduce unnecessary drug prescriptions, but limited work is devoted to optimising dosage regimes when they are prescribed. The design of antibiotic treatments can be formulated as an optimisation problem where candidate solutions are encoded as vectors of dosages per day. The formulation naturally gives rise to competing objectives, as we want to maximise the treatment effectiveness while minimising the total drug use, the treatment duration and the concentration of antibiotic experienced by the patient. This article combines a recent mathematical model of bacterial growth including both susceptible and resistant bacteria, with a multi-objective evolutionary algorithm in order to automatically design successful antibiotic treatments. We consider alternative formulations combining relevant objectives and constraints. Our approach obtains shorter treatments, with improved success rates and smaller amounts of drug than the standard practice of administering daily fixed doses. These new treatments consistently involve a higher initial dose followed by lower tapered doses.
Topics: Algorithms; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; Models, Theoretical; Stochastic Processes; Treatment Outcome
PubMed: 31980097
DOI: 10.1016/j.artmed.2019.101759 -
Animals : An Open Access Journal From... Nov 2021Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential... (Review)
Review
Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential pathogens. Furthermore, the intestine is a reactor of antibiotic resistance emergence, and the presence of antibiotics exacerbates the selection of resistant bacteria that can disseminate in the environment and propagate to further hosts. We reviewed studies analyzing the effect of antibiotics on the intestinal microbiota and antibiotic resistance conducted on animals, focusing on the main food-producing and companion animals. Irrespective of antibiotic classes and animal hosts, therapeutic dosage decreased species diversity and richness favoring the bloom of potential enteropathogens and the selection of antibiotic resistance. These negative effects of antibiotic therapies seem ineluctable but often were mitigated when an antibiotic was administered by parenteral route. Sub-therapeutic dosages caused the augmentation of taxa involved in sugar metabolism, suggesting a link with weight gain. This result should not be interpreted positively, considering that parallel information on antibiotic resistance selection was rarely reported and selection of antibiotic resistance is known to occur also at low antibiotic concentration. However, studies on the effect of antibiotics as growth promoters put the basis for understanding the gut microbiota composition and function in this situation. This knowledge could inspire alternative strategies to antibiotics, such as probiotics, for improving animal performance. This review encompasses the analysis of the main animal hosts and all antibiotic classes, and highlights the future challenges and gaps of knowledge that should be filled. Further studies are necessary for elucidating pharmacodynamics in animals in order to improve therapy duration, antibiotic dosages, and administration routes for mitigating negative effects of antibiotic therapies. Furthermore, this review highlights that studies on aminoglycosides are almost inexistent, and they should be increased, considering that aminoglycosides are the first most commonly used antibiotic family in companion animals. Harmonization of experimental procedures is necessary in this research field. In fact, current studies are based on different experimental set-up varying for antibiotic dosage, regimen, administration, and downstream microbiota analysis. In the future, shotgun metagenomics coupled with long-reads sequencing should become a standard experimental approach enabling to gather comprehensive knowledge on GIM in terms of composition and taxonomic functions, and of s. Decorticating GIM in animals will unveil revolutionary strategies for medication and improvement of animals' health status, with positive consequences on global health.
PubMed: 34828011
DOI: 10.3390/ani11113280 -
Psychiatry Research. Neuroimaging Dec 2019The rs6994992 polymorphism has been reported as a candidate variant associated with schizophrenia (SZ). Neuroimaging studies have revealed that SZ is associated with...
The rs6994992 polymorphism has been reported as a candidate variant associated with schizophrenia (SZ). Neuroimaging studies have revealed that SZ is associated with widespread structural and functional alterations in brain. However, whether the allele dosage of rs6994992 is associated with brain structural or functional features is unclear. We aimed to investigate the association between the risk allele dosage of rs6994992 and whole-brain structural and functional characteristics and to further explore the relationship between these characteristics and cognition. Magnetic resonance images and the rs6994992 genotype were obtained from 53 healthy participants. A general linear model was used to determine the effects of risk allele dosage of rs6994992 on brain characteristics. Spearman correlation analysis was employed to calculate the correlation between altered brain characteristics and cognitive scores. Our results demonstrated that regions with significant differences in structural characteristics between groups with different dosages of rs6994992 were mainly located in the frontal and temporal lobes, hippocampus and angular gyrus. Moreover, significant regions of functional connectivity (FC) partly overlapped with the structural results. Measurements in those significant regions and FCs were correlated with the cognition scales. This association can inform our understanding of the mechanisms through which rs6994992 variants increase the risk for SZ.
Topics: Adult; Alleles; Brain; Cognition; Female; Genotype; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Polymorphism, Genetic; Schizophrenia; Temporal Lobe; Young Adult
PubMed: 31202487
DOI: 10.1016/j.pscychresns.2019.05.005 -
International Journal of Molecular... Oct 2021Sublethal dosages of imidacloprid cause long-term destructive effects on honey bees at the individual and colony levels. In this review, the molecular effects of... (Review)
Review
Sublethal dosages of imidacloprid cause long-term destructive effects on honey bees at the individual and colony levels. In this review, the molecular effects of sublethal imidacloprid were integrated and reported. Several general effects have been observed among different reports using different approaches. Quantitative PCR approaches revealed that imidacloprid treatments during the adult stage are expressed as changes in immuneresponse, detoxification, and oxidation-reduction response in both workers and queens. In addition, transcriptomic approaches suggested that phototransduction, behavior, and somatic muscle development also were affected. Although worker larvae show a higher tolerance to imidacloprid than adults, molecular evidence reveals its potential impacts. Sublethal imidacloprid treatment during the larval stage causes gene expression changes in larvae, pupae, and adults. Transcriptome profiles suggest that the population and functions of affected differentially expressed genes, DEGs, vary among different worker ages. Furthermore, an early transcriptomic switch from nurse bees to foragers was observed, suggesting that precocious foraging activity may occur. This report comprehensively describes the molecular effects of sublethal dosages of imidacloprid on the honey bee . The corresponding molecular pathways for physiological and neurological responses in imidacloprid-exposed honey bees were validated. Transcriptomic evidence suggests a global and sustained sublethal impact of imidacloprid on honey bee development.
Topics: Animals; Bees; Larva; Neonicotinoids; Nitro Compounds; Transcriptome
PubMed: 34769266
DOI: 10.3390/ijms222111835