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Molecules (Basel, Switzerland) Mar 2021The aim of this work is to present an approach to enhance the dissolution of progestin medication, megestrol acetate (also known as MEGACE), for improving the...
The aim of this work is to present an approach to enhance the dissolution of progestin medication, megestrol acetate (also known as MEGACE), for improving the dissolution rate and kinetic solubility by incorporating nano graphene oxide (nGO). An antisolvent precipitation process was investigated for nGO-drug composite preparation, where prepared composites showed crystalline properties that were similar to the pure drug but enhanced aqueous dispersibility and colloidal stability. To validate the efficient release profile of composite, in vitro dissolution testing was carried out using United States Pharmacopeia, USP-42 paddle method, with gastric pH (1.4) and intestinal pH (6.5) solutions to mimic in vivo conditions. Pure MA is practically insoluble (2 µg/mL at 37 °C). With the incorporation of nGO, it was possible to dissolve nearly 100% in the assay. With the incorporation of 1.0% of nGO, the time required to dissolve 50% and 80% of drug, namely T and T, decreased from 138.0 min to 27.0 min, and the drug did not dissolve for 97.0 min in gastric media, respectively. Additionally, studies done in intestinal media have revealed T did not dissolve for 92.0 min. This work shows promise in incorporating functionalized nanoparticles into the crystal lattice of poorly soluble drugs to improve dissolution rate.
Topics: Biological Availability; Chemistry, Pharmaceutical; Drug Compounding; Excipients; Graphite; Hydrophobic and Hydrophilic Interactions; Megestrol Acetate; Nanoparticles; Solubility
PubMed: 33807401
DOI: 10.3390/molecules26071972 -
Journal of Women's Health (2002) Sep 2020To evaluate the effects of a 24/4 regimen combined oral contraceptive (COC) containing 1.5 mg 17β-estradiol (E2) and 2.5 mg nomegestrol acetate (NOMAC) compared to...
To evaluate the effects of a 24/4 regimen combined oral contraceptive (COC) containing 1.5 mg 17β-estradiol (E2) and 2.5 mg nomegestrol acetate (NOMAC) compared to on-demand nonsteroidal anti-inflammatory drugs (NSAIDs) on women affected by endometriosis-associated chronic pelvic pain (the primary end point) and their quality of life (QoL) and sexual function (the secondary end points). Ninety-nine women on E2/NOMAC constituted the study group; and 63 women on NSAIDs constituted the control group. The visual analogic scale was used to measure the levels of pelvic pain, dysmenorrhea, and dyspareunia. To assess their QoL, sexual function, and sexual distress, the Short Form-36 (SF-36), the Female Sexual Function Index (FSFI), and the Female Sexual Distress Scale (FSDS) were used, respectively. The study included two follow-ups at 3 and 6 months. Improvement in chronic pelvic pain was observed in the study group at both the 3- and 6-month follow-ups ( < 0.001). SF-36, FSFI, and FSDS had a similar trend at the 3- and 6-month follow-ups ( < 0.001). Women on NSAIDs did not report any reduction in pain symptoms or improvement in QoL ( ≤ 0.4). However, they had a limited improvement of their FSFI and FSDS ( < 0.001). The improvement of the pain symptoms, QoL, FSFI, and FSDS, was more evident in women on E2/NOMAC than in those on NSAIDs, when the study group and control group values were compared at the 3- and 6-month follow-ups ( < 0.001). Women on E2/NOMAC COC showed a better reduction of endometriosis-associated chronic pelvic pain and an improvement of their QoL and sexual activity than those of the women on NSAIDs.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Child; Contraceptives, Oral; Drug Combinations; Dyspareunia; Endometriosis; Estradiol; Female; Humans; Megestrol; Norpregnadienes; Pelvic Pain; Quality of Life; Treatment Outcome
PubMed: 32678691
DOI: 10.1089/jwh.2020.8291 -
Gynecologic Oncology Jul 2023To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC)...
Fertility-sparing hormonal treatment in patients with stage I endometrial cancer of grade 2 without myometrial invasion and grade 1-2 with superficial myometrial invasion: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-2001).
OBJECTIVES
To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC) without myometrial invasion (MI) or grade 1-2 with superficial MI.
METHODS
Multicenter data of patients with stage I grade 2 EC without MI or grade 1-2 EC with superficial MI, who received FST between 2005 and 2021, were analyzed. Cox regression analysis identified independent factors for progressive disease (PD) during the FST.
RESULTS
Altogether, 54 patients received FST [medroxyprogesterone acetate (500-1000 mg) in 44, megestrol acetate (40-800 mg) in 10] with concurrent levonorgestrel-releasing intrauterine devices use in 31. With median time to achieve a complete response (CR) of 10 (3-24) months, 39 patients (72.2%) achieved CR. Of the 15 patients who attempted to conceive after achieving CR, 7 (46.7%) became pregnant (2 abortions, 5 live births). During a median FST duration of 6 (3-12) months, nine patients (16.6%) were diagnosed with PD. Fifteen (38.5%) experienced recurrence with a median recurrence-free survival of 23 (3-101) months. In the multivariable analysis, tumor size before FST ≥2 cm (HR 5.456, 95% CI 1.34 to 22.14; p = 0.018) was significantly associated with a high PD rate during FST.
CONCLUSION
The overall response rate to FST was promising, however, the PD rate was significant during the first 12 months of FST. Therefore, performing thorough endometrial biopsy and imaging studies is essential to strictly evaluate the extent of the disease every 3 months from FST initiation.
Topics: Female; Humans; Pregnancy; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Fertility Preservation; Proportional Hazards Models; Retrospective Studies; Treatment Outcome; Progestins; Disease Progression; Neoplasm Staging; Adolescent; Young Adult; Adult; Biopsy
PubMed: 37172410
DOI: 10.1016/j.ygyno.2023.04.027 -
Water Research Jun 2024The safety of municipal sewage sludge has raised great concerns because of the accumulation of large-scale endocrine disrupting chemicals in the sludge during wastewater...
The safety of municipal sewage sludge has raised great concerns because of the accumulation of large-scale endocrine disrupting chemicals in the sludge during wastewater treatment. The presence of contaminants in sludge can cause secondary pollution owing to inappropriate disposal mechanisms, posing potential risks to the environment and human health. Effect-directed analysis (EDA), involving an androgen receptor (AR) reporter gene bioassay, fractionation, and suspect and nontarget chemical analysis, were applied to identify causal AR agonists in sludge; 20 of the 30 sludge extracts exhibited significant androgenic activity. Among these, the extracts from Yinchuan, Kunming, and Shijiazhuang, which held the most polluted AR agonistic activities were prepared for extensive EDA, with the dihydrotestosterone (DHT)-equivalency of 2.5 - 4.5 ng DHT/g of sludge. Seven androgens, namely boldione, androstenedione, testosterone, megestrol, progesterone, and testosterone isocaproate, were identified in these strongest sludges together, along with testosterone cypionate, first reported in sludge media. These identified androgens together accounted for 55 %, 87 %, and 52 % of the effects on the sludge from Yinchuan, Shijiazhuang, and Kunming, respectively. This study elucidates the causative androgenic compounds in sewage sludge and provides a valuable reference for monitoring and managing androgens in wastewater treatment.
Topics: Sewage; China; Androgens; Water Pollutants, Chemical; Endocrine Disruptors; Receptors, Androgen
PubMed: 38657313
DOI: 10.1016/j.watres.2024.121652 -
BioMed Research International 2021Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was...
Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study.
Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 g/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98-0.99; = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48-4.67; = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41-4.60; = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.
Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Female; Humans; Hydrocortisone; Male; Multiple Myeloma; Prevalence; Retrospective Studies; Risk Factors
PubMed: 34938804
DOI: 10.1155/2021/2330417 -
Clinical & Translational Oncology :... Jun 2024Cancer-related anorexia-cachexia syndrome (CACS) is a debilitating condition afflicting up to 80% of advanced-stage cancer patients. Characterized by progressive weight...
Cancer-related anorexia-cachexia syndrome (CACS) is a debilitating condition afflicting up to 80% of advanced-stage cancer patients. Characterized by progressive weight loss, muscle wasting, and metabolic abnormalities, CACS significantly compromises patients' quality of life and treatment outcomes. This comprehensive review navigates through its intricate physiopathology, elucidating its stages and diagnostic methodologies. CACS manifests in three distinct stages: pre-cachexia, established cachexia, and refractory cachexia. Early detection is pivotal for effective intervention and is facilitated by screening tools, complemented by nutritional assessments and professional evaluations. The diagnostic process unravels the complex interplay of metabolic dysregulation and tumor-induced factors contributing to CACS. Management strategies, tailored to individual patient profiles, encompass a spectrum of nutritional interventions. These include dietary counseling, oral nutritional supplements, and, when necessary, enteral nutrition and a judicious use of parenteral nutrition. Specific recommendations for caloric intake, protein requirements, and essential nutrients address the unique challenges posed by CACS. While pharmacological agents like megestrol acetate may be considered, their use requires careful evaluation of potential risks. At its core, this review underscores the imperative for a holistic and personalized approach to managing CACS, integrating nutritional interventions and pharmacological strategies based on a nuanced understanding of patient's condition.
PubMed: 38822976
DOI: 10.1007/s12094-024-03502-8 -
Annals of Surgery Aug 2022To systematically review the problem of appetite loss after major abdominal surgery. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically review the problem of appetite loss after major abdominal surgery.
SUMMARY OF BACKGROUND DATA
Appetite loss is a common problem after major abdominal surgery. Understanding of etiology and treatment options is limited.
METHODS
We searched Medline, Cochrane Central Register of Controlled Trials, and Web of Science for studies describing postoperative appetite loss. Data were extracted to clarify definition, etiology, measurement, surgical influence, pharmacological, and nonpharmacological treatment. PROSPERO registration ID: CRD42021224489.
RESULTS
Out of 6144 articles, we included 165 studies, 121 of which were also analyzed quantitatively. A total of 19.8% were randomized, controlled trials (n = 24) and 80.2% were nonrandomized studies (n = 97). The studies included 20,506 patients undergoing the following surgeries: esophageal (n = 33 studies), gastric (n = 48), small bowel (n = 6), colon (n = 27), rectal (n = 20), hepatobiliary (n = 6), and pancreatic (n = 13). Appetite was mostly measured with the Quality of Life Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30, n = 54). In a meta-analysis of 4 randomized controlled trials gum chewing reduced time to first hunger by 21.2 hours among patients who had bowel surgery. Other reported treatment options with positive effects on appetite but lower levels of evidence include, among others, intravenous ghrelin administration, the oral Japanese herbal medicine Rikkunshito, oral mosapride citrate, multidisciplin-ary-counseling, and watching cooking shows. No studies investigated the effect of well-known appetite stimulants such as cannabinoids, steroids, or megestrol acetate on surgical patients.
CONCLUSIONS
Appetite loss after major abdominal surgery is common and associated with increased morbidity and reduced quality of life. Recent studies demonstrate the influence of reduced gastric volume and ghrelin secretion, and increased satiety hormone secretion. There are various treatment options available including level IA evidence for postoperative gum chewing. In the future, surgical trials should include the assessment of appetite loss as a relevant outcome measure.
Topics: Abdomen; Appetite; Digestive System Surgical Procedures; Ghrelin; Humans; Quality of Life
PubMed: 35129465
DOI: 10.1097/SLA.0000000000005379 -
Ophthalmology Feb 2021There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other...
PURPOSE
There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to neovascular AMD (nAMD). If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD.
DESIGN
We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender, and recent healthcare use.
PARTICIPANTS
The study population included cases with nAMD and risk set matched controls.
METHODS
We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7 to 24 months, or ever before their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to which they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at P ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0).
MAIN OUTCOME MEASURES
Progression to nAMD.
RESULTS
Of approximately 4000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included (1) drugs with prior evidence for a causal relationship (e.g., megestrol); (2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g., donepezil, epoetin alfa); (3) drugs with alternative biologic explanations for the association (e.g., sevelamer); and (4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons.
CONCLUSIONS
This exploratory drug-screening study identified several potential targets for follow-up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.
Topics: Aged; Aged, 80 and over; Case-Control Studies; Choroidal Neovascularization; Data Mining; Disease Progression; Drug Evaluation, Preclinical; Drug Repositioning; Drugs, Generic; Female; Humans; Insurance Claim Review; Male; Medicare; United States; Wet Macular Degeneration
PubMed: 32777229
DOI: 10.1016/j.ophtha.2020.08.004 -
Palliative Medicine Jun 2022Anorexia (loss of appetite) is a prevalent and distressing symptom in people with cancer, with limited effective interventions. Medicinal cannabis has shown promise in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anorexia (loss of appetite) is a prevalent and distressing symptom in people with cancer, with limited effective interventions. Medicinal cannabis has shown promise in improving appetite-related symptoms in people with cancer.
AIM
To assess the efficacy of medicinal cannabis for improving appetite-related symptoms in people with cancer, considering measures and outcomes, interventions and toxicity.
DESIGN
Systematic review with narrative approach to synthesis and meta-analysis.
DATA SOURCES
Databases (MEDLINE, CINAHL, CENTRAL), websites and trials registries were searched from inception to February 2021. Included studies were randomised controlled trials (RCT) in English peer-reviewed journals comparing medicinal cannabis with placebo and/or another intervention. Study quality was assessed using the Cochrane risk of bias tool.
RESULTS
Five studies were included that compared medicinal cannabis interventions (dronabinol, nabilone and cannabis extract) either with placebo ( = 4) or megestrol acetate ( = 1). Measures and trial endpoints varied, but efficacy was demonstrated in one trial only, in which dronabinol significantly improved chemosensory perception and other secondary outcomes (taste of food, premeal appetite, proportion of calories consumed as protein) compared with placebo. Cannabis interventions were generally well tolerated across studies, regardless of the product or dose, although the comprehensive measurement of toxicities was limited.
CONCLUSION
Evidence from RCTs that medicinal cannabis increases appetite in people with cancer is limited. Measures, outcomes and interventions were variable, and toxicities have not been comprehensively evaluated. Future research should carefully consider biological mechanisms to guide more nuanced selection of endpoints and interventions, including product, dose and administration.
Topics: Analgesics; Appetite; Cannabis; Dronabinol; Humans; Medical Marijuana; Neoplasms
PubMed: 35360989
DOI: 10.1177/02692163221083437 -
Pharmaceuticals (Basel, Switzerland) Jan 2022In this study, the effect of Cremophor RH 40 (CR 40) classic micelles and Soluplus (SP) polymeric micelles were investigated on a novel granule-type drug-delivery system...
In this study, the effect of Cremophor RH 40 (CR 40) classic micelles and Soluplus (SP) polymeric micelles were investigated on a novel granule-type drug-delivery system containing megestrolacetate (MGA). Using a risk assessment-based approach on the formulation via melt technology resulted in the formation of these granules, presented as the dosage, with proper particle size and flow characteristics. Due to the application of a eutectic carrier base composition, gentle process conditions were reached, retaining the crystalline structure of the carrier system and allowing for the proper distribution of MGA in the granules. The increased water solubility (0.111 mg/mL to 2.154 mg/mL), and the decreased nano particle size (102.27 nm) with uniform distribution (polydispersity index of 0.259) and colloid stability (zeta potential of -12.99 mV) resulted in SP polymeric micelles prevailing over CR 40 micelles in this gastric dissolution study, performed in biorelevant fasted and fed state drug-release media. Mathematical characterization and kinetic model fitting supported the fast drug-release mechanism of polymeric micelles over micelles. The value-added polymeric micelle-containing formulation developed can be successfully administered perorally and the enhanced drug release offers the possibility of greater drug absorption in the gastrointestinal tract.
PubMed: 35215226
DOI: 10.3390/ph15020113