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Life (Basel, Switzerland) May 2024To identify subgroups of patients with primary osteoarthritis of the hip joint (pHOA) with similar imaging and laboratory findings, disease evolution, and response to...
To identify subgroups of patients with primary osteoarthritis of the hip joint (pHOA) with similar imaging and laboratory findings, disease evolution, and response to conventional therapies. We performed further statistical analyses on patient data from two published, double-blind, randomized, and placebo-controlled studies (DB-RCTs), which examined the effects of intra-articular corticosteroids (ia-CSs), hyaluronic acid (ia-HA)-KИ-109-3-0008/14.01.2014, and intravenous bisphosphonates (iv-BPs) -KИ- 109-3-0009/14.01.2014 compared to the country's standard pHOA therapy. The data span an 8-year follow-up of 700 patients with pHOA, including: 1. Clinical parameters (WOMAC-A, B, C, and T; PtGA). 2. Laboratory markers (serum calcium and phosphate levels; 25-OH-D and PTH, markers for bone sCTX-I and cartilage uCTX-II turnover). 3. Radiological indicators: X-ray stage (Kellgren-Lawrence (K/L) and model (Bombelli/OOARSI), width (mJSW), speed (JSN mm/year), and zone of maximum narrowing of the joint space (max-JSN)-determining the type of femoral head migration (FHM). 4. DXA indicators: bone geometry (HAL; NSA; and MNW); changes in regional and total bone mineral density (TH-BMD, LS-BMD, and TB-BMD). 5. Therapeutic responses (OARSI/MCII; mJSW; JSNmm/yearly) to different drug regimens (iv-BP -zoledronic acid (ZA/-5 mg/yearly for 3 years)); ia-CS 40 mg methylprednisolone acetate, twice every 6 months; and ia-HA with intermediate molecular weight (20 mg/2 mL × 3 weekly applications, two courses every 6 months) were compared to standard of care therapy (Standard of Care/SC/), namely D3-supplementation according to serum levels (20-120 ng/mL; target level of 60 ng/mL), simple analgesics (paracetamol, up to 2.0 g/24 h), and physical exercises. The abovementioned data were integrated into a non-supervised hierarchical agglomerative clustering analysis (NHACA) using Ward's linkage method and the squared Euclidean distance to identify different endophenotypes (EFs). Univariate and multivariate multinomial logistic regression analyses were performed to determine the impact of sex and FHM on clinical and radiographic regression of pHOA. A baseline cluster analysis using incoming (M0) patient data identified three EFs: hypertrophic H-HOA, atrophic A-HOA, and intermediate I-HOA. These EFs had characteristics that were similar to those of patients grouped by radiographic stage and pattern ('H'-RPs, 'I'-RPs, and 'A'-RPs), < 0.05). The repeated cluster analysis of M36 data identified four EF pHOAs: 1. Hypertrophic (slow progressors, the influence of the type of femoral head migration (FHM) outweighing the influence of sex on progression), progressing to planned total hip replacement (THR) within 5 (K/LIII) to 10 (K/LII) years. 2. Intermediate (sex is more important than the FHM type for progression) with two subgroups: 2#: male-associated (slow progressors), THR within 4 (K/LIII) to 8 years. (K/LII). 2* Female-associated (rapid progressors), THR within 3 (K/LIII) to 5 (K/LII) years. 3. Atrophic (rapid progressors; the influence of FHM type outweighs that of sex), THR within 2 (K/LIII) to 4 (K/LII) years. Each EF, in addition to the patient's individual progression rate, was also associated with a different response to the aforementioned therapies. Clinical endophenotyping provides guidance for a personalized approach in patients with pHOA, simultaneously assisting the creation of homogeneous patient groups necessary for conducting modern genetic and therapeutic scientific studies.
PubMed: 38792642
DOI: 10.3390/life14050622 -
International Journal of Molecular... May 2024Drug induced fatty liver disease (DIFLD) is a form of drug-induced liver injury (DILI), which can also be included in the more general metabolic dysfunction-associated... (Review)
Review
Drug-Induced Fatty Liver Disease (DIFLD): A Comprehensive Analysis of Clinical, Biochemical, and Histopathological Data for Mechanisms Identification and Consistency with Current Adverse Outcome Pathways.
Drug induced fatty liver disease (DIFLD) is a form of drug-induced liver injury (DILI), which can also be included in the more general metabolic dysfunction-associated steatotic liver disease (MASLD), which specifically refers to the accumulation of fat in the liver unrelated to alcohol intake. A bi-directional relationship between DILI and MASLD is likely to exist: while certain drugs can cause MASLD by acting as pro-steatogenic factors, MASLD may make hepatocytes more vulnerable to drugs. Having a pre-existing MASLD significantly heightens the likelihood of experiencing DILI from certain medications. Thus, the prevalence of steatosis within DILI may be biased by pre-existing MASLD, and it can be concluded that the genuine true incidence of DIFLD in the general population remains unknown. In certain individuals, drug-induced steatosis is often accompanied by concomitant injury mechanisms such as oxidative stress, cell death, and inflammation, which leads to the development of drug-induced steatohepatitis (DISH). DISH is much more severe from the clinical point of view, has worse prognosis and outcome, and resembles MASH (metabolic-associated steatohepatitis), as it is associated with inflammation and sometimes with fibrosis. A literature review of clinical case reports allowed us to examine and evaluate the clinical features of DIFLD and their association with specific drugs, enabling us to propose a classification of DIFLD drugs based on clinical outcomes and pathological severity: Group 1, drugs with low intrinsic toxicity (e.g., ibuprofen, naproxen, acetaminophen, irinotecan, methotrexate, and tamoxifen), but expected to promote/aggravate steatosis in patients with pre-existing MASLD; Group 2, drugs associated with steatosis and only occasionally with steatohepatitis (e.g., amiodarone, valproic acid, and tetracycline); and Group 3, drugs with a great tendency to transit to steatohepatitis and further to fibrosis. Different mechanisms may be in play when identifying drug mode of action: (1) inhibition of mitochondrial fatty acid β-oxidation; (2) inhibition of fatty acid transport across mitochondrial membranes; (3) increased de novo lipid synthesis; (4) reduction in lipid export by the inhibition of microsomal triglyceride transfer protein; (5) induction of mitochondrial permeability transition pore opening; (6) dissipation of the mitochondrial transmembrane potential; (7) impairment of the mitochondrial respiratory chain/oxidative phosphorylation; (8) mitochondrial DNA damage, degradation and depletion; and (9) nuclear receptors (NRs)/transcriptomic alterations. Currently, the majority of, if not all, adverse outcome pathways (AOPs) for steatosis in AOP-Wiki highlight the interaction with NRs or transcription factors as the key molecular initiating event (MIE). This perspective suggests that chemical-induced steatosis typically results from the interplay between a chemical and a NR or transcription factors, implying that this interaction represents the primary and pivotal MIE. However, upon conducting this exhaustive literature review, it became evident that the current AOPs tend to overly emphasize this interaction as the sole MIE. Some studies indeed support the involvement of NRs in steatosis, but others demonstrate that such NR interactions alone do not necessarily lead to steatosis. This view, ignoring other mitochondrial-related injury mechanisms, falls short in encapsulating the intricate biological mechanisms involved in chemically induced liver steatosis, necessitating their consideration as part of the AOP's map road as well.
Topics: Humans; Fatty Liver; Chemical and Drug Induced Liver Injury; Adverse Outcome Pathways; Liver; Oxidative Stress
PubMed: 38791241
DOI: 10.3390/ijms25105203 -
Biomedicines May 2024Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal...
Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since β-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus β-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and β-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of β-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with β-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.
PubMed: 38790999
DOI: 10.3390/biomedicines12051037 -
Children (Basel, Switzerland) Apr 2024Fever is one of the most frequent symptoms highlighted during medical assistance. Due to this great impact, our study has the purpose of analyzing the demographic and...
BACKGROUND
Fever is one of the most frequent symptoms highlighted during medical assistance. Due to this great impact, our study has the purpose of analyzing the demographic and laboratory characteristics of patients hospitalized in our center and identifying predictive markers to make the differential diagnosis between infectious and non-infectious fever.
METHODS
Our population included 220 children, collected from January 2017 to August 2022, hospitalized for continuous fever (4 days or more in duration with at least one temperature peak ≥37.5 °C) and excluded cases of discharge against medical advice and/or transfer to other operating units. Demographic (mean age at the time of admission, frequency of hospitalization, and mean days of hospitalization), laboratory, and instrumental variables were analyzed in order to find correlation with fever etiology.
RESULTS
Older age at the time of hospitalization, family history of periodic fever, fever lasting more than 8 days, and longer hospitalization are strongly associated with non-infectious fever, together with anemia, high platelet count, high CRP and ferritin, and hyponatremia at the time of admission. Paracetamol is the preferred antipyretic treatment. Echocardiogram has shown anomalies in patients with infectious fever, while ECG anomalies were detected in non-infectious fever.
CONCLUSIONS
Our data underline the importance of predictive markers, such as clinical and laboratory parameters, to differentiate infectious from non-infectious fevers, but further studies are necessary.
PubMed: 38790534
DOI: 10.3390/children11050539 -
Toxics May 2024In small populations and scattered communities, wastewater treatment through vegetation filters (VFs), a nature-based solution, has proved to be feasible, especially for...
In small populations and scattered communities, wastewater treatment through vegetation filters (VFs), a nature-based solution, has proved to be feasible, especially for nutrient and organic matter removal. However, the presence of pharmaceuticals in wastewater and their potential to infiltrate through the vadose zone and reach groundwater is a drawback in the evaluation of VF performances. Soil amended with readily labile carbon sources, such as woodchips, enhances microbial activity and sorption processes, which could improve pharmaceutical attenuation in VFs. The present study aims to assess if woodchip amendments to a VF's soil are able to abate concentrations of selected pharmaceuticals in the infiltrating water by quantitatively describing the occurring processes through reactive transport modelling. Thus, a column experiment using soil collected from an operating VF and poplar woodchips was conducted, alongside a column containing only soil used as reference. The pharmaceuticals acetaminophen, naproxen, atenolol, caffeine, carbamazepine, ketoprofen and sulfamethoxazole were applied daily to the column inlet, mimicking a real irrigation pattern and periodically measured in the effluent. Ketoprofen was the only injected pharmaceutical that reached the column outlet of both systems within the experimental timeframe. The absence of acetaminophen, atenolol, caffeine, carbamazepine, naproxen and sulfamethoxazole in both column outlets indicates that they were attenuated even without woodchips. However, the presence of 10,11-epoxy carbamazepine and atenolol acid as transformation products (TPs) suggests that incomplete degradation also occurs and that the effect of the amendment on the infiltration of TPs is compound-specific. Modelling allowed us to generate breakthrough curves of ketoprofen in both columns and to obtain transport parameters during infiltration. Woodchip-amended columns exhibited K and μ values from one to two orders of magnitude higher compared to soil column. This augmentation of sorption and biodegradation processes significantly enhanced the removal of ketoprofen to over 96%.
PubMed: 38787113
DOI: 10.3390/toxics12050334 -
Healthcare (Basel, Switzerland) May 2024Caregivers often use paracetamol in the management of pediatric illnesses without a clear rationale. This study evaluated the perception and practices of caregivers...
Caregivers often use paracetamol in the management of pediatric illnesses without a clear rationale. This study evaluated the perception and practices of caregivers regarding the use of paracetamol in children in Southwestern Saudi Arabia. This study involved a cross-sectional design involving 373 caregivers of children under twelve. The questionnaire elucidated the reasons, usage frequency, and safe usage practices. Data were analyzed using SPSS, applying Chi-square tests and logistic regression. Most caregivers were in the age range of 31-40 years, and with intermediate education. Paracetamol was mainly used for fever, generalized pain and, diarrhea, with fewer opting for other self-care measures. Caregivers with primary or less education were more likely to perceive paracetamol as safe (AOR = 2.98 (1.3-6.73), = 0.009) and less inclined to check warning labels (AOR: 0.11 (0.05-0.25), < 0.001) and expiry dates (AOR: 0.063 (0.027-0.14), < 0.001). The caregiver's education level significantly influenced the determination of treatment duration (χ = 21.58 (4), < 0.001), dosage (χ = 30.70 (4), < 0.001), and frequency of administration (χ = 17.77 (4), = 0.001). In conclusion, inadequate health literacy can result in a lack of attention towards crucial safety information about pediatric paracetamol use. Hence, counselling initiatives should be undertaken to ensure the safe and effective use of paracetamol in children.
PubMed: 38786457
DOI: 10.3390/healthcare12101047 -
Cirugia Y Cirujanos 2024Transversus abdominis plane (TAP) block is a widely used anesthetic technique of the abdominal wall, where ultrasound guidance is considered the gold standard. In this... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
INTRODUCTION
Transversus abdominis plane (TAP) block is a widely used anesthetic technique of the abdominal wall, where ultrasound guidance is considered the gold standard. In this study, we aimed to compare the effectiveness of laparoscopic-assisted TAP (LTAP) block with ultrasound-assisted TAP (UTAP) block for post-operative pain, nausea, vomiting, duration of the block, and bowel function.
MATERIALS AND METHODS
This study included 60 patients who were randomly assigned to two groups to undergo either the LTAP or UTAP block technique after laparoscopic cholecystectomy. The time taken for administering the block, post-operative nausea and vomiting, post-operative pain, respiratory rate, bowel movements, and analgesia requirements were reported.
RESULTS
The time taken for the LTAP block was shorter (p < 0.001). Post-operative mean tramadol consumption, paracetamol consumption, and analgesic requirement were comparable between the two groups (p = 0.76, p = 0.513, and p = 0.26, respectively). The visual analog scale at 6, 24, and 48 h was statistically not significant (p = 0.632, p = 0.802, and p = 0.173, respectively). Nausea with vomiting and the necessity of an antiemetic medication was lower in the UTAP group (p = 0.004 and p = 0.009, respectively).
CONCLUSION
The LTAP block is an easy and fast technique to perform in patients as an alternative method where ultrasound guidance or an anesthesiologist is not available.
Topics: Humans; Cholecystectomy, Laparoscopic; Female; Male; Pain, Postoperative; Middle Aged; Ultrasonography, Interventional; Nerve Block; Adult; Postoperative Nausea and Vomiting; Abdominal Muscles; Prospective Studies
PubMed: 38782390
DOI: 10.24875/CIRU.23000394 -
Surgical Innovation May 2024This study aimed to evaluate the effectiveness of unilateral external oblique intercostal nerve block (EOIB) in laparoscopic cholecystectomy surgery.
BACKGROUND
This study aimed to evaluate the effectiveness of unilateral external oblique intercostal nerve block (EOIB) in laparoscopic cholecystectomy surgery.
MATERIAL AND METHODS
After ethics committee approval, ASA I-II patients aged 18-70 who would undergo laparoscopic cholecystectomy surgery were included in the study. The patients were divided into two groups, external oblique intercostal nerve block (Group EOIB) and oblique subcostal transversus abdominis plane block (Group OSTAP). After surgery, EOIB or OSTAP block was administered with 20 mL of .25% bupivacaine then routine analgesia protocol was applied with iv paracetamol, and tramadol. Visual analog scale (VAS) scores and patient-controlled analgesia (PCA) consumption were monitored 24 hours after the operation. It was administered 25 mg pethidine as a rescue analgesic to patients with VAS ≥4.
RESULTS
Thirty six patients for Group EOIB and thirty four patients for Group OSTAP were included in the study. Lower VAS scores were observed in all groups. When PCA consumption, side effects, rescue analgesia consumption, and patient satisfaction were evaluated, there was no statistically significant difference between the groups ( > .05).
CONCLUSION
It was observed that EOIB showed similar analgesic activity to the OSTAP block. EOIB may also be a part of postoperative multimodal analgesia by reducing postoperative opioid consumption in LC.
PubMed: 38780355
DOI: 10.1177/15533506241256529 -
International Journal of Pharmaceutics Jun 2024Wet granulation, a particle size enlargement process, can significantly enhance the critical quality attributes of powders and improve the ability to form tablets in...
Wet granulation, a particle size enlargement process, can significantly enhance the critical quality attributes of powders and improve the ability to form tablets in pharmaceutical manufacturing. In this study, a mechanistic-based population balance model is applied to twin screw wet granulation. This model incorporated a recently developed breakage kernel specifically designed for twin screw granulation, along with nucleation, layering, and consolidation. Calibration and validation were performed on Hydrochlorothiazide and Acetaminophen formulations, which exhibit different particle size and wettability characteristics. Utilizing a compartmental experimental dataset, a comprehensive global sensitivity analysis identified critical inputs impacting quality attributes. The study revealed that the nucleation rate process model, effectively represented particle size distributions for both formulations. Adjustments to nucleation and breakage rate parameters, influenced by material properties and screw configuration, improved the model's accuracy. A model-driven workflow was proposed, offering step-by-step guidelines and facilitating PBM model usage, providing essential details for future active pharmaceutical ingredient (API) formulations.
Topics: Acetaminophen; Drug Compounding; Calibration; Hydrochlorothiazide; Particle Size; Workflow; Powders; Wettability; Chemistry, Pharmaceutical; Tablets; Models, Theoretical
PubMed: 38777305
DOI: 10.1016/j.ijpharm.2024.124246 -
Chemosphere Aug 2024This study focuses on the removal and risk assessment of twenty emerging contaminants (ECs) and heavy metals in a REMIX water treatment plant (RWTP) that produces...
This study focuses on the removal and risk assessment of twenty emerging contaminants (ECs) and heavy metals in a REMIX water treatment plant (RWTP) that produces drinking water from combination of wastewater reuse and desalination. The membrane biological reactor (MBR) exhibit removal rates exceeding 95% of pharmaceuticals like acetaminophen, trimethoprim, diclofenac, naproxen, and emtricitabine. The efficiency of brackish reverse osmosis (BWRO) in removing ECs is highlighted, showing substantial efficacy with reduction rates of 99.5%, 75.5%, and 51.2% for sulfamethoxazole, venlafaxine, and benzotriazole, respectively. The advanced oxidation process based on Fenton process reveals removal (>95%) of emtricitabine, efavirenz, and carbamazepine. The study confirms that the combination of treatment units within the RWTP effectively removes heavy metals (>90%), complying with acceptable limits. Risk quotient (RQ) calculations indicate the efficiency of the RWTP in EC removal, serving as benchmarks for public acceptance of reclaimed water. In the context of heavy metals, the study concludes negligible cancer risks associated with reclaimed water consumption over a lifetime. Quantitative structure-activity relationship and occurrence, persistence, bioaccumulation and toxicity (OPBT) models were used to assess EC risk. The study screened and identified potential persistant, bio accumulating and toxic PBT ECs. Critical control points (CCPs) in the RWTP are identified, with brackish and seawater reverse osmosis (BWRO and SWRO) and advanced oxidation process (AOP) recognized as pivotal in hazard management. The study provides valuable insights on the removal of ECs and heavy metals in a wastewater reuse process and demonstrates potential of adopted process configuration in supplying safe drinking water from wastewater recycling.
Topics: Water Pollutants, Chemical; Metals, Heavy; Wastewater; Risk Assessment; Water Purification; Drinking Water; Humans; Waste Disposal, Fluid
PubMed: 38777194
DOI: 10.1016/j.chemosphere.2024.142396