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Materials (Basel, Switzerland) Mar 2023Biochar (BC), a byproduct of agricultural waste pyrolysis, shows potential as a sustainable substitute material for ordinary silicate cement (OPC) in concrete...
Biochar (BC), a byproduct of agricultural waste pyrolysis, shows potential as a sustainable substitute material for ordinary silicate cement (OPC) in concrete production, providing opportunities for environmental sustainability and resource conservation in the construction industry. However, the optimal biochar dosage and fineness for enhancing concrete performance are still unclear. This study investigated the impact of these two factors on the mechanical and durability properties of biochar concrete. Compressive and flexural strength, carbonation resistance, and chloride ion penetration resistance were evaluated by varying biochar dosages (0%, 1%, 3%, 5%, 10%) and fineness dimensions (44.70, 73.28, 750, 1020 μm), with the 0% dosage serving as the control group (CK). The results showed that the addition of 1-3 wt% of biochar could effectively reduce the rapid carbonation depth and chloride diffusion coefficient of concrete. The compressive and flexural strength of BC concrete initially increased and then decreased with the increase in biocarbon content, BC with a fineness of 73.28 μm having the most significant effect on the mechanical strength of concrete. At the dosage of 3 wt%, BC was found to promote the hydration degree of cement, improving the formation of cement hydration products. These findings provide valuable insights for the development of sustainable and high-performance cement-based materials with the appropriate use of biochar as an additive.
PubMed: 37049102
DOI: 10.3390/ma16072809 -
Tidsskrift For Den Norske Laegeforening... May 2024A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a...
BACKGROUND
A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review.
CASE PRESENTATION
The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level.
INTERPRETATION
Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.
Topics: Humans; Medication Errors; Female; Methotrexate; Aged; Dyspnea; Leucovorin; Antidotes; Antirheumatic Agents
PubMed: 38747669
DOI: 10.4045/tidsskr.23.0657 -
Discover Mental Health 2023(1) To summarize the mental conditions that may accompany persistent symptoms following acute infection by SARS-CoV-2, often termed Long Covid; (2) to formulate... (Review)
Review
PURPOSES
(1) To summarize the mental conditions that may accompany persistent symptoms following acute infection by SARS-CoV-2, often termed Long Covid; (2) to formulate treatment based upon the brain cells that are dominantly affected.
METHODS
(1) Review the reports relating to the mental symptoms occurring in Long Covid. (2) Review the drugs that address the brain cells affected in Long Covid, and suggest pharmacotherapy for those patients whose response to psychotherapy is suboptimal.
RESULTS
Long Covid affects ~ 10% of patients infected by SARS-CoV-2, and mental symptoms affect ~ 20% of persons with Long Covid. The brain cell-types that have been demonstrated as dominantly affected in Long Covid are astrocytes, oligodendrocytes, neurons, endothelial cells/pericytes, and microglia. Lithium and fluoxetine each address all of those four cell-types. Low dosage of each is likely to be well-tolerated and to cause neither clinically important adverse events (AE) nor serious adverse events (SAE).
CONCLUSION
For those patients whose response to psychotherapy is suboptimal, lithium and fluoxetine should be administered in combination for both depth of benefit and reduction of dosages.
PubMed: 36618714
DOI: 10.1007/s44192-022-00027-w -
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 -
Harm Reduction Journal May 2024Naloxone is an effective FDA-approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public and can be administered through intramuscular... (Review)
Review
Naloxone is an effective FDA-approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public and can be administered through intramuscular (IM), intravenous (IV), and intranasal spray (IN) routes. Our literature review investigates the adequacy of two doses of standard IM or IN naloxone in reversing fentanyl overdoses compared to newer high-dose naloxone formulations. Moreover, our initiative incorporates the experiences of people who use drugs, enabling a more practical and contextually-grounded analysis. The evidence indicates that the vast majority of fentanyl overdoses can be successfully reversed using two standard IM or IN dosages. Exceptions include cases of carfentanil overdose, which necessitates ≥ 3 doses for reversal. Multiple studies documented the risk of precipitated withdrawal using ≥ 2 doses of naloxone, notably including the possibility of recurring overdose symptoms after resuscitation, contingent upon the half-life of the specific opioid involved. We recommend distributing multiple doses of standard IM or IN naloxone to bystanders and educating individuals on the adequacy of two doses in reversing fentanyl overdoses. Individuals should continue administration until the recipient is revived, ensuring appropriate intervals between each dose along with rescue breaths, and calling emergency medical services if the individual is unresponsive after two doses. We do not recommend high-dose naloxone formulations as a substitute for four doses of IM or IN naloxone due to the higher cost, risk of precipitated withdrawal, and limited evidence compared to standard doses. Future research must take into consideration lived and living experience, scientific evidence, conflicts of interest, and the bodily autonomy of people who use drugs.
Topics: Humans; Naloxone; Narcotic Antagonists; Drug Overdose; Fentanyl; Opiate Overdose; Analgesics, Opioid; Administration, Intranasal
PubMed: 38741224
DOI: 10.1186/s12954-024-00994-z -
Antimicrobial Agents and Chemotherapy Mar 2022The pharmacokinetics of ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CEF-AVI) is influenced by renal function. Application of recommended dosages in...
The pharmacokinetics of ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CEF-AVI) is influenced by renal function. Application of recommended dosages in patients with renal impairment requires the use of fractions of the full dose, as only one dosage is available for both antibiotics. The objective of this study was to evaluate the adequacy of alternative dosage regimens based on the full dose. We performed pharmacokinetic/pharmacodynamic (PK/PD) simulations of recommended and alternative dosage regimens in patients with various degrees of renal impairment by using the Pmetrics program. Alternative regimens included longer dosage interval and prolonged infusions of the full dose for both drugs. Probabilities of target attainment (PTA) were assessed considering PK/PD targets defined for cephalosporins and beta-lactamase inhibitors as well as MIC breakpoints. The risk of overexposure was also assessed. Results showed that alternative dosage regimens based on a full dose of TOL-TAZ and CEF-AVI administered every 12 or 24 h were associated with PTA similar to that of recommended dosages, especially when administered as prolonged infusion. The alternative dosage regimens were not associated with overexposure in most cases. In addition, those regimens could reduce dosing errors, drug cost, and nurse labor. Clinical investigation ovf those alternative dosage regimens would be required before implementation.
Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Cephalosporins; Cost-Benefit Analysis; Drug Combinations; Humans; Microbial Sensitivity Tests; Tazobactam
PubMed: 35041500
DOI: 10.1128/AAC.02104-21 -
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 2020Heparin administration in COVID-19 patients is recommended by expert consensus, although evidence about dosage, duration and efficacy are limited. We aim to investigate...
BACKGROUND
Heparin administration in COVID-19 patients is recommended by expert consensus, although evidence about dosage, duration and efficacy are limited. We aim to investigate the association between different dosages of low molecular weight heparin (LMWH) and mortality among COVID-19 hospitalized patients.
METHODS AND RESULTS
Retrospective study of 450 laboratory-confirmed COVID-19 patients admitted to Sant'Orsola Bologna Hospital from March 01 to April 10, 2020. Clinical, laboratory and treatment data were collected and analyzed. The in-hospital mortality between COVID-19 patients treated with standard prophylactic LMWH dosage vs. intermediate LMWH dosage was compared. Out of 450 patients, 361 received standard deep vein thrombosis (DVT) prophylaxis enoxaparin treatment (40-60mg daily) and 89 patients received intermediate enoxaparin dosage (40-60 mg twice daily) for 7 days. No significant differences in the main demographic characteristics and laboratory testings at admission were observed in the two heparin regimen subgroups, except for older age and prevalence of hypertension in the group treated with "standard" prophylaxis LMWH dosage. The intermediate LMWH administration was associated with a lower in-hospital all-cause mortality compared to the "standard" prophylactic LMWH dosage (18.8% vs. 5.8%, p = 0.02). This difference remained significant after adjustment with the propensity score for variables that differed significantly between the dosage groups (OR= 0.260, 95% CI 0.089-0.758, p=0.014).
CONCLUSIONS
Intermediate LMWH dosage seems to be associated with lower incidence of mortality compared to standard DVT prophylaxys in hospitalized COVID-19 patients. Our study paves the way to further pathophysiological investigations and controlled studies of anticoagulation therapy in Covid-19 disease.
PubMed: 32848743
DOI: 10.3389/fphar.2020.01124 -
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 -
BioRxiv : the Preprint Server For... Mar 2024A longstanding challenge in gene therapy is expressing a dosage-sensitive gene within a tight therapeutic window. For example, loss of function causes Rett syndrome,...
A longstanding challenge in gene therapy is expressing a dosage-sensitive gene within a tight therapeutic window. For example, loss of function causes Rett syndrome, while its duplication causes duplication syndrome. Viral gene delivery methods generate variable numbers of gene copies in individual cells, creating a need for gene dosage-invariant expression systems. Here, we introduce a compact miRNA-based, incoherent feed-forward loop circuit that achieves precise control of expression in cells and brains, and improves outcomes in an AAV-based mouse model of Rett syndrome gene therapy. Single molecule analysis of endogenous and ectopic mRNA revealed precise, sustained expression across a broad range of gene dosages. Delivered systemically in a brain-targeting AAV capsid, the circuit strongly suppressed Rett behavioral symptoms for over 24 weeks, outperforming an unregulated gene therapy. These results demonstrate that synthetic miRNA-based regulatory circuits can enable precise in vivo expression to improve the safety and efficacy of gene therapy.
PubMed: 38559034
DOI: 10.1101/2024.03.13.584179