Prolonged Use Research Articles

Therapeutic Potential of Rosmarinic Acid in Tramadol-Induced Hepatorenal Toxicity: Modulation of Oxidative Stress, Inflammation, RAGE/NLRP3, ER Stress, Apoptosis, and Tissue Functions Parameters.

Tramadol (TRM), a widely used opioid analgesic for moderate to severe pain, is associated with liver and kidney toxicity at high doses or prolonged use. This study investigates the protective role of rosmarinic acid (RA), a natural phenolic compound known for its antioxidant, anti-inflammatory, and cell-protective properties, against TRM-induced hepatorenal toxicity. Thirty-five male Wistar rats were divided into five groups: Control, TRM, RA, TRM+RA25, and TRM+RA50. Rats received TRM (50 mg/kg) and RA (25 or 50 mg/kg), with liver and kidney function tests, oxidative stress, inflammation, ER stress, apoptosis, and tissue damage indicators assessed through qRT-PCR, ELISA, Western blotting, H&E, and immunohistochemical analysis. TRM induced liver and kidney dysfunctions, evident from increased ALT, AST, ALP, urea, creatinine, nephrin, TIM-1 and 8-OHdG levels, along with activated oxidative stress, inflammation, ER stress, and apoptosis pathways. RA significantly reduced these effects, ameliorating histologic and immunohistochemical markers of tissue damage and inflammation. RA demonstrates therapeutic potential by mitigating TRM-induced hepatorenal toxicity and preserving tissue integrity.

Synthesis, antifungal activity, and molecular simulation study of nootkatone-based thiazole-hydrazone compounds as novel succinate dehydrogenase inhibitor.

Plant diseases cause huge losses in agriculture worldwide every year, but the prolonged use of current commercial fungicides has led to the development of resistance in plant pathogenic fungi. Therefore, there is an urgent need to develop new, efficient, and green fungicides. Twenty-three nootkatone-based thiazole-hydrazone compounds were designed, synthesized, and characterized by Fourier-transform infrared (FTIR), proton (1H) nuclear magnetic resonance (NMR), carbon-13 (13C) NMR, and high-resolution mass spectrometry (HRMS). The antifungal activities results showed that all the target compounds displayed certain antifungal activity against eight tested fungi. Among them, target compounds 3a (88.7%), 3b (92.5%), 3d (88.7%), 3f (84.9%), 3j (88.7%), and 3l (92.5%) were comparable or superior to the positive control boscalid (88.7%) in their inhibitory activities against Physalospora piricola. Meanwhile, target compound 3l had half maximal effective concentration (EC50) values of 18.0172, 18.8236, 16.5914, 18.5044, and 16.5660 μg/mL against Fusarium oxysporum f. sp. cucumerinum, Alternaria solani, Gibberella zeae, Bipolaris maydis, and Colleterichum orbicalare, respectively, exhibiting outstanding and broad-spectrum fungicidal activity. Moreover, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out to investigate the relationship between the molecular structures of target compounds 3a-3w and their antifungal activity. Furthermore, the target compound 3l [half maximal inhibitory concentration (IC50) = 4.936 μmol/L] showed significantly better inhibitory activity against succinate dehydrogenase (SDH) than boscalid (IC50 = 6.631 μmol/L). The possible binding mode between target compound 3l and homology-modeling built SDH, was also explored by molecular docking. Target compound 3l deserved further study as the promising candidate for the development of novel SDH inhibitor. © 2025 Society of Chemical Industry.

Symptomatic early coronary graft failure in bypass surgery patients: incidence, predictors and clinical impact.

Coronary graft failure (CGF) may occur early after coronary bypass graft surgery (CABG). The study aimed to identify clinical and perioperative risk factors and to evaluate the long-term clinical impact of symptomatic early CGF. Patients who underwent clinically indicated coronary angiography (CAG) prior to post-CABG discharge between 2012 and 2022 were included. Symptomatic early CGF was defined as adysfunctional coronary graft, evaluated on clinically indicated CAG, caused by stenosis of the proximal or distal anastomosis or bypass conduit, bypass occlusion, thrombosis, reduced flow (TIMI < 1) and kinking/tenting. Patients were divided into symptomatic early CGF and non-early CGF groups. Kaplan-Meier and multivariateanalysis estimated cumulative survival free of major adverse cardiovascular events (MACE: death, myocardial infarction and revascularisation) up to 5years' follow-up and identified predictors of symptomatic early CGF. Atotal of 92patients (79% male, 66.1 ± 10years old) were included, of whom 55(59.8%) had symptomatic early CGF. Baseline characteristics, surgical parameters and post-surgical parameters potentially indicative of ischaemia were comparable between groups. Patients with symptomatic early CGF had asignificantly lower MACE rate over amedian follow-up period of 33months (p = 0.023). Venous graft integration (p = 0.005), Y‑graft configuration (p = 0.002) and prolonged inotropic support (p = 0.032) were associated with symptomatic early CGF. Symptomatic early CGF was observed in the majority of post-CABG patients undergoing clinically indicated CAG prior to discharge. Patients with symptomatic early CGF exhibited higher MACE rates over amedian follow-up period of 33months. Venous graft integration, Y‑graft configuration and prolonged use of inotropic agents were associated with symptomatic early CGF. However, these clinical findings should be interpreted with caution.

Translated article] Prospective observational follow-up study of psychoactive drug treatment initiated in the intensive care unit.

The treatment and prevention of delirium in the intensive care unit (ICU) have gained significant importance in patient care in recent years. Some studies have linked delirium with increased risks of mortality, prolonged hospital stay, and more days of mechanical ventilation. This study aims to analyse the use of psychotropic drugs initiated in the ICU and their continuation upon hospital discharge, as well as to evaluate their contribution to polypharmacy and associated adverse clinical effects. A multicentre prospective observational case study was designed, focusing on patients over 18 years old admitted to the ICU and treated with psychotropic drugs. Data on demographics, variables related to admission and psychotropic drug treatment, as well as clinical outcomes and adverse effects, will be collected. Among other variables, the frequency of psychotropic treatments initiated in the ICU and continued upon discharge from the ICU and the hospital will be measured. Data collection will be performed through review of electronic medical records and prescription programmes, and IBM SPSS 20.0 statistical package will be used for analysis. Delirium is common in ICU patients and is associated with long-term negative consequences. Although antipsychotics are used to treat delirium, their prolonged use can have adverse effects, and their continuation after ICU discharge contributes to polypharmacy. This study aims to provide information on the use of psychotropic drugs initiated in the ICU and their continuation upon discharge, with the goal of identifying opportunities for intervention and reducing unnecessary use of these medications.

Digital devices usage and neck and shoulder pain among college students: a cross-sectional study in China

ABSTRACT Neck and shoulder pain (NSP) is a common issue among college students, yet no studies have linked digital device usage to NSP prevalence in China. This cross-sectional survey aimed to explore this relationship among students in Shanghai. A total of 6,000 students were randomly selected, with 4,848 (80.8%) completing a self-reported questionnaire on NSP prevalence and severity. The results showed a 39.1% NSP prevalence, higher in females (45.0%) than males (32.4%). Logistic regression revealed significant correlations between NSP and factors such as gender, poor posture, and prolonged digital device use. Additionally, neck muscle activity increased with spinal inclination, as assessed by the AnyBody platform. The findings suggest promoting a healthy spinal curvature lifestyle to reduce NSP among college students..

Artemisia herba-alba Essential Oil: Chemical Composition, Phytotoxic Activity and Environmental Safety.

Weeds cause a decrease in the quantity and quality of agricultural production and economic damage to producers. The prolonged use of synthetic pesticides causes problems of environmental pollution, the possible alteration of agricultural products and problems for human health. For this reason, the scientific community's search for products of natural origin, which are biodegradable, safe for human health and can act as valid alternatives to traditional herbicides, is growing. Essential oils can have useful implications in agriculture by acting as effective alternatives to chemical herbicides. In this work, the chemical composition of an EO from Artemisia herba-alba and its herbicidal properties were studied on two weeds (Lolium multiflorum and Trifolium pratense) and two crops (Brassica napus and Hordeum vulgare) and its environmental safety was also assessed using three model organisms: Chaoborus sp., Tubifex tubifex and Eisenia foetida. The principal component of the EO was camphor (26.02%), with α- and β-thujone (9.60 and 8.38%, respectively), 1,8-cineole (8.02%), piperitenone (5.29%) and camphene (4.95%) as the main components. The EO demonstrated variable phytotoxic effects with a dose-dependent manner, inhibiting both the germination and the radical elongation of the tested seeds, and was also found to be environmentally safe for the selected organisms. The results lay the foundation for considering this EO as a potential weed control agent.

Low Bone Mineral Density and Associated Factors Among People Living With HIV in Kerman, Iran: A Cross-Sectional Study in 2021-2022.

Chronic diseases such as osteoporosis and low bone mineral density (BMD) are significant public health concerns for people living with HIV (PLWH), especially with the increased life expectancy because of antiretroviral therapy (ART). This study evaluated the prevalence and associated factors of low BMD among 94 PLWH in Kerman, Iran, from September 2021 to February 2022. Using dual-energy X-ray absorptiometry, BMD was measured, with low BMD defined by specific T-scores and Z-scores. Predictors were assessed through interviews, medical records, and blood tests. Bivariable and multivariable logistic regression models identified associations between low BMD and various factors. The study found a 51.1% prevalence of low BMD, with significant associations with hypogonadism (adjusted odds ratio [aOR]: 3.19), longer ART duration (aOR per month: 1.02), and lower body mass index (aOR per unit: 0.83). The findings highlight the need for regular screening and timely intervention for low BMD among PLWH, particularly with prolonged ART use.

METABOLIC SURGERY VERSUS CLINICAL TREATMENT

Morbid obesity is a chronic and progressive condition associated with various comorbidities, such as type 2 diabetes, hypertension and cardiovascular diseases. In the management of this condition, clinical treatments and surgical interventions have been widely debated, with metabolic surgery standing out as an alternative for cases refractory to clinical treatment. To compare the costs and efficacy of metabolic surgery and clinical treatment in the management of morbid obesity, assessing the economic impacts and clinical outcomes in the medium and long term. This is a literature review with a qualitative approach, based on studies available in the PubMed, Scopus and Web of Science databases. Health descriptors such as “Bariatric Surgery,” “Obesity Management,” and “Type 2 Diabetes Treatment” were used, covering the period from 2015 to 2023. The selection followed specific inclusion and exclusion criteria to ensure the relevance and quality of the articles included. Studies show that metabolic surgery is more effective in sustained weight loss and in controlling metabolic comorbidities, with type 2 diabetes remission rates of over 70%. In terms of costs, although the initial investment for the surgical procedure is high, there are savings in the long term due to the reduction in expenditure on medication, hospitalizations and monitoring of complications. In contrast, clinical treatment has lower initial costs, but often requires prolonged use of medication and interventions, with lower success rates in weight maintenance and remission of comorbidities. Metabolic surgery stands out as an effective and economically viable option for morbidly obese patients, especially those with severe comorbidities. However, the choice of treatment must be individualized, taking into account the surgical risks, the ability to adhere to lifestyle changes and the resources available in the health system.

Management of Recurrent Ventriculoperitoneal Shunt Infections in Adult Patients.

Objective: The objective of this study was to evaluate the demographic, clinical, laboratory, and microbiological features of ventriculoperitoneal shunt (VPS) infections through a 13-year retrospective study. VPS bacterial agents and their antibiotic susceptibility were also investigated through the occurrence of single VPS (SVPS) and recurrent VPS (RVPS) infections. Methods: This study included 110 patients with SVPS infections and 55 patients with RVPS infections. Results: In patients who developed multiple infections, Gram-negative organisms were found to be the most predominant (60%, 54/90). The resistance rates were 85.2% for third-generation cephalosporins (3GCs), 83.3% for piperacillin-tazobactam, and 10.4% for carbapenem. Of the patients in the SVPS infection group, 49% were treated with combinations with carbapenem; of the patients in the RVPS infection group, 84.4% were treated in the same way. Central nervous system (CNS) tuberculosis as the etiology of hydrocephalus; short duration of antibiotics used for treatment; high cerebrospinal fluid (CSF) protein and blood C-reactive protein (CRP) levels; and prolonged use of prophylactic antibiotics were found to be related to an increased rate of recurrent infection occurrence. A two-stage shunt change approach decreased the risk of recurrent infections. Conclusions: Based on the findings of our study, it is essential to closely monitor patients with independent risk factors for RVPS infection development, due to the high rates of resistant Gram-negative bacterial growth and the initiation of empirical antimicrobial treatment with glycopeptide plus carbapenem. Certain treatment options, such as 3GCs plus glycopeptide, should be revised based on clinical progress and microbiological culture results.

Pulmonary Co-Infection of Pneumocystis jirovecii and Aspergillus species

Abstract In this multicenter study of 387 immunocompromised patients, 4.5% with invasive pulmonary aspergillosis (IPA) also had Pneumocystis jirovecii pneumonia (PCP). Predictors of co-infection included elevated β-D-glucan and prolonged corticosteroid use. IPA-PCP co-infection correlated with reduced 30-day survival (22% vs. 57%), suggesting early identification and prophylaxis may improve outcomes

Safety and Efficacy of a 48-Month Efinaconazole 10% Solution Treatment/Maintenance Regimen: 24-Month Daily Use Followed by 24-Month Intermittent Use

Background/Objectives: In an 18- to 24-month Treatment Phase with once-daily efinaconazole 10% solution, subjects with onychomycosis showed an increased rate of cure at Month 24 versus the phase III trials. In order to further improve efficacy, we initiated an extended intermittent efinaconazole Maintenance Phase with use 2–3 times weekly for an additional 24 months from Month 24 to Month 48. These are the first data presented for a 48-month efinaconazole use period. Methods: For patients completing 18–24 months of once-daily efinaconazole, the target great toenail from the Treatment Phase was graded as ‘Clinical Cure’ (≤10% affected area) or ‘No Clinical Cure’ (&gt;10% affected area) at Month 24. Mycological and clinical outcomes were assessed every 4 months from Month 24 to Month 48. There were 35 patients who enrolled in the extension and continued intermittent efinaconazole use to Month 48. Patients with ‘Clinical Cure’ at M24 were reviewed for sustained cure at M48; patients with ‘No Clinical Cure’ were reviewed for development of ‘Cure’ at M48. All patients were reviewed at all visits for adverse events that may be related to efinaconazole use. Results: ‘Clinical Cure’ was found in 6 of 35 enrolled patients at Month 24, and clinical cure status was sustained to Month 48 with intermittent efinaconazole maintenance use. For 29 patients with ‘No Clinical Cure’, 3/29 achieved ‘Clinical Cure’ status at Month 48 with intermittent efinaconazole. Effective Cure and Complete Cure rates improved over the maintenance period to Month 48 in subjects without clinical cure at Month 24. Younger patients showed higher cure rates over the maintenance period, but age group cure differences did not reach statistical significance in this dataset, and 49% of the ≥70-year population had at least a 20% reduction in nail area with maintenance therapy to Month 48. There was only 1 case of possible efinaconazole application site reaction in the Intermittent Maintenance Period to Month 48; prolonged efinaconazole use to Month 48 does not appear to increase the risk of reaction. Efinaconazole use periods are associated with very low positive culture rates in this dataset, including typical contaminant organisms, suggesting efinaconazole presence in the nail plate is providing prophylactic therapy. Conclusions: Intermittent efinaconazole may provide suitable prophylaxis of onychomycosis relapse. Prolonged efinaconazole therapy to Month 48 appears to be safe for all ages and can continue to provide prophylaxis of onychomycosis with Intermittent Maintenance use beyond Month 24 to Month 48.

Investigation of the effects of silymarin and vitamin C on kidney damage and aquaporin-2 downregulation in lithium-induced nephrogenic diabetes insipidus in rats

Although lithium (LIT) therapy is key in managing bipolar disorder long-term, prolonged use significantly contributes to acquired Nephrogenic Diabetes Insipidus (NDI). This study examined whether combining Silymarin (SIL) with Vitamin C (Vit C) enhances protection against lithium-induced nephrotoxicity in rats, comparing their individual antioxidant effects as well. Rats subjected to Li exposure were provided with a standard commercial diet supplemented with 80 mmol LiCl per kilogram for 28 days. Concurrently, SIL and Vit C were administered orally at dosages of 200 and 100 mg/kg body weight, respectively, throughout the 28 days. The study assessed levels of reactive oxygen species (ROS), glutathione (GSH), and malondialdehyde (MDA), as well as the enzyme activity of superoxide dismutase (SOD), to evaluate the protective effects of SIL and Vit C against oxidative stress. Aquaporin-2 (AQP2) levels in kidney tissues were evaluated using immunohistochemistry and ELISA. Serum and urine parameters (sodium, potassium, creatinine, blood urea nitrogen [BUN], and urea) and serum lithium levels were also measured. Lithium-induced nephrotoxicity showed increased renal toxicity markers and decreased antioxidant enzyme activity. SIL administration significantly reduced markers of kidney tissue toxicity, increased antioxidant enzyme activities, regulated the aforementioned physiological parameters in blood and urine, and downregulated AQP2 expression in the kidney. However, Vit C administration did not demonstrate a significant protective effect against lithium-induced renal toxicity. These findings indicate that SIL effectively protects against lithium-induced nephrotoxicity, whereas Vitamin C does not exhibit this protective effect.

Eltrombopag for the treatment of refractory connective tissue disease-related thrombocytopenia: a pilot study of 52 cases

BackgroundThe objective of this study was to investigate the therapeutic effectiveness and safety profile of Eltrombopag, a thrombopoietin receptor agonist, as prolonged therapy in refractory CTD-ITP patients.MethodsWe conducted a pilot observational study of Eltrombopag in CTD-ITP patients who were unresponsive to or intolerant of conventional medications. Eltrombopag was administered orally at 25–75 mg/qd and adjusted on the basis of tolerance and efficacy until a minimum dosage of 25 mg/qd was reached. Clinical and laboratory data were collected and analysed monthly. The therapeutic response, relapse, and adverse events during the follow-up were also reviewed and evaluated.ResultsFifty-two patients were enrolled and followed monthly for a median of 6 months. Thirty-six (90%) patients achieved durable overall remission. The remission rates were 67.5% at month 1, 87.5% at month 2, 97.5% at month 3, and 95% at month 6. The platelet count of the patients improved significantly, with the median reaching 50 × 109/L within 2 weeks (p = 0.003). Disease activity indices were reduced in SLE and pSS patients (p = 0.016), allowing glucocorticoid tapering (p = 0.004). One patient had no response, four relapsed, and fifteen (28.8%) experienced clinically relevant adverse events. In the analyses, protopathy, comorbidity, and prior treatment were associated with efficacy.ConclusionsFor refractory CTD-ITP patients, Eltrombopag demonstrated significant clinical improvement, safety, and a steroid-sparing effect with prolonged use. Patient characteristics at baseline may affect treatment efficacy.

Synthetic Strategies for the Development of Ibuprofen Derivatives: A Classified Study.

Ibuprofen, a widely used NSAID from the aryl propionic acid class, effectively relieves pain, fever, and inflammation. On prolonged use, it leads to gastrointestinal, hepatic, and renal toxicities, particularly gastrointestinal ulcers. These side effects are largely attributed to the carboxylic acid functional group common to NSAIDs. The present review highlights the different modifications done to the carboxylic group in Ibuprofen, by various researchers such as estersgramma, amides, hydroxamic acids, and N-substituted hydrazides, along with the integration of heterocyclic moieties like triazoles, tetrazoles, and oxadiazoles. Additionally, Ibuprofen has been hybridized with other drugs and complexed with metals to enhance therapeutic effects. The different synthetic strategies that were employed were esterification, amidation, condensation, Schiff's base formation, etc. These modifications have resulted in derivatives with antimicrobial, antifungal, anticancer, and other biological activities, aiming to reduce side effects while retaining or enhancing antiinflammatory, analgesic, and antipyretic properties.

Metronidazole and Vancomycin Have a Synergic Effect, with Plant Extracts as Helpful Tools to Combat Clostridioides difficile Infections.

Background/Objectives: The prolonged use of antibiotics is closely related to increased infections caused by Clostridioides difficile (Cdiff). Plant-origin compounds have been expanding in recent years as the best opportunity to identify new synergic therapies to combat antibiotic-associated diseases. Mexico has incredible plant biodiversity; natural compounds with antibacterial properties are an alternative treatment. The main objective of this study was to analyze the effect of medicinal plants with an antibacterial action against toxigenic clinical Cdiff strains that have a synergic effect on the antibiotics commonly used to combat this disease. Methods: The plants were selected for plants that were previously used in research, and their extracts were tested against Cdiff strains. The antibacterial activity, synergy, and antagonism between the extracts and their synergic effect with antibiotics were evaluated. Results: Our results demonstrated that some extracts have effective antimicrobial activity and synergic effects with vancomycin and metronidazole. Conclusions: This study suggests that plant extracts and plant compounds derived from these extracts could be used as synergic-antibiotic therapy to combat Cdiff infections.

Safety assessment of turmeric-boswellia-sesame formulation in healthy adult volunteers: An open-label prospective study.

Turmeric and boswellia supplements have gained popularity for their anti-inflammatory and antioxidant properties. It is important to critically assess the safety of such supplements for prolonged use. To assess the safety and tolerability of turmeric-boswellia-sesame oil formulation (TBSF) in healthy human volunteers. Forty participants were supplemented with TBSF at a dose of 2,000 mg daily for 90 days. Safety assessments were performed at baseline, as well as on day 30, 60 and 90. Adverse events were monitored throughout the study period. Any evidence of hepatotoxicity injury or drug induced liver injury (DILI) was assessed using R value (R ratio/R factor), which is a relative pattern of liver enzymes. Additionally, Hy's law criteria, based on liver enzymes and bilirubin levels, were employed, along with an evaluation of drug-induced serious hepatotoxicity (eDISH) plot. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated, as these values are relevant to the safety of the intervention. The study found that TBSF supplementation did not cause any adverse effects or clinically significant variations in vital signs, hematological parameters, lipid profile, liver function enzymes, and renal function markers, and all were within the normal range after 90 days of TBSF supplementation. Platelet-to-lymphocyte ratio and NLR did not change significantly and were within the normal range. All the participants when plotted were in the normal range quadrant of the eDISH plot throughout the study period. No abnormal findings were observed in R value and Hy's law criteria, indicating that TBSF does not induce any hepatotoxicity. The present study showed a normal estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), creatinine (Cr), Cr clearance, and BUN/Cr ratio throughout the study period. There was no significant change between these values at 4 abovementioned time points. The study findings suggest that TBSF is a safe supplement for regular and long-term consumption.

Association between acid-suppressive drugs and risk of psoriasis: retrospective study using Korean National Health Insurance Service-National Sample Cohort.

Psoriasis is a common inflammatory skin disorder following non-specific triggers. Involvement of immune system is widely accepted for pathogenesis studies have demonstrated importance of gut microbiota in pathogenesis of inflammatory skin diseases. Proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) are acid-suppressive drugs widely used for acid related gastrointestinal diseases, and prolonged use has been associated with altered gut microbiota. This study aimed to investigate association between psoriasis and acid suppressing drugs in Korean population. This study was conducted with 3,662 patients diagnosed with psoriasis between 2002 and 2013 in NHIS-NSC. A total of 14,648 controls were matched at 1:4 based on sex, age, and gastrointestinal disease. ORs were estimated to determine the association between acid suppressing drug use and psoriasis. Our study found a statistically significant association between the prolonged use of acid-suppressive drugs and the development of psoriasis in the Korean population. Specifically, patients with gastrointestinal diseases who used histamine-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) for extended periods exhibited a higher risk of developing psoriasis. The adjusted odds ratio for psoriasis was 1.89 (95% CI, 1.66-2.17) with long-term use, indicating a clear dose-response relationship. Results from our study indicate that prolonged use of H2RA or PPI is associated with the risk of psoriasis among patients with gastrointestinal diseases in Korean population. The risk was increased in dose-response trend after adjusting for confounding variables. Clinicians should be aware of risks associated with prolonged use of acid suppressing drugs.

Prolonged use of chlormadinone acetate and risk of intracranial meningioma: A population-based cohort study.

Chlormadinone acetate (CMA) is a synthetic progestin for which cases of intracranial meningioma have been reported following prolonged exposure. An observational cohort study was conducted based on the French national health data system. Women aged 10-70 years and who started CMA between 2007 and 2017 were included. Participants were considered to be exposed if they had received a cumulative dose >360 mg of CMA during the first 6 months and very slightly exposed (control group) when they had received a cumulative dose ≤360 mg. The outcome was surgery or radiotherapy for one or more intracranial meningioma(s). Poisson models assessed the relative risk (RR) of meningioma. In total, 828,499 women were included: 469,976 in the exposed group (mean age 39.1 years, SD 10.1) and 358,523 in the control group (38.3 years, SD 11.0). Surgery or radiotherapy for intracranial meningioma between 2007 and 2017 was recorded for 164 and 104 women in the exposed and control groups, respectively. The incidence of meningioma was 18.5 and 6.8 per 100,000 person-years for the exposed and control groups respectively (crude RR = 2.7, 95% confidence interval [CI] 2.1-3.5; age-adjusted RR = 3.1, 95% CI 2.4-4.0). Meningioma incidence reached almost 47 cases/100,000 person-years in the most exposed group (>8.64 g), giving an age-adjusted RR of 6.9, 95% CI 5.1-9.2, relative to the control group. A strong dose-effect relationship was observed between prolonged use of CMA and risk of meningiomas. As with other progestogens, meningiomas associated with CMA are more likely to be found at the base of the skull.

Perioperative Opioid Use in Urogynecologic Mesh Removal.

Forty percent of patients with urogynecologic mesh pain complications are taking narcotics. We aimed to compare comorbidities and pain scores between patients with and without narcotic use and assess postoperative narcotic use rates. This was a secondary analysis of a prospective cohort study of patients undergoing urogynecologic mesh removal. Patients with mesh removal for pain within 7 years were included due to data availability. Narcotic prescriptions were verified using the Pennsylvania Prescription Drug Monitoring Program. Pain scores were assessed at baseline and 6-24 months postoperatively. Of 139 patients, 30 (21.6%) filled narcotic prescriptions within 3 months preceding surgery. These patients were younger and more likely to have a chronic pain condition. Narcotic use did not differ by sling versus prolapse mesh, or presence of exposure. Patients taking preoperative narcotics had a 27-point higher median baseline visual analog scale pelvic pain score (P = 0.01). Patients with pain comorbidities had 6 times odds of using preoperative narcotics. Younger patients had less improvement in pelvic pain after removal. Only 8 (27%) of those taking narcotics discontinued use postoperatively with no significant predictors of prolonged (≥3 months) use. Eighty-seven percent of patients with prolonged postoperative use had a prior pain diagnosis, commonly joint and back pain. In patients with mesh-related pain, those with chronic pain conditions had much higher odds of taking preoperative narcotics, and in most, mesh removal did not eliminate narcotic use. Counseling is warranted in patients with chronic pain conditions that pain and narcotic use are likely to persist after removal.

Treatment of Menopausal Symptoms with Herbal Medicines: A Review

Background: Menopause refers to the natural process of the “cessation of the menstrual cycle.” This phase predominantly affects aged women and can lead to various symptoms such as hot flashes, insomnia, night sweats, and sexual dysfunction, among others. Unfortunately, many women remain unaware of this condition, and some even choose to overlook the symptoms. However, those who recognize the symptoms consult with a doctor, who may recommend Hormone replacement therapy (HRT). Initially, Hormone replacement therapy (HRT) can be effective, but prolonged use can result in side effects. To mitigate these effects, there is a need to explore and investigate herbal therapies as an alternative treatment for menopausal symptoms. Objective: The objective of this review is to explore and summarize various herbs used in managing menopausal symptoms as an alternative to hormone replacement therapy. Methods: For this review, we conducted a literature survey spanning from 1998 to 2023. We used keywords such as menopause, endocrinology, hormone replacement therapy, and herbs used for reducing menopausal symptoms to search databases such as Google Scholar, PubMed, and SciDirect. Relevant data were sourced from various journals like Plos One, JAMA, Frontier, Drug in Context, MDPI, Molecules, BMC Women's Health, Research Gate, Heliyon, Elsevier, Taylor &amp; Francis, Nutrients, JMM, Wiley, OXFORD, Hindawi, Clinical Phytoscience, Pharmaceuticals, Phytomedicine, and Menopause: The Journal of The North American Menopause Society. Results: The literature review encompassed 40 research articles and 200 review articles, including randomized controlled trials. The findings revealed that several herbal plants, including Curcuma longa, Zingiber officinale, Foeniculum vulgare, Trigonella foenum, Actaea racemosa, Glycyrrhiza glabra, Oenothera biennis, Trifolium pratense, Humulus lupulus, Vitex agnus-castus, Valeriana officinalis, Linum usitatissimum, Cannabis sativa, and Asparagus racemosus, have shown efficacy in treating menopausal symptoms. Conclusion: In conclusion, medicinal plants can play a significant role in managing acute menopausal syndrome. The intent of this review is to highlight the most recent research on estrogenic plants for medicinal purposes and their therapeutic impact on cognitive deficiencies brought on by estrogen shortage during menopause and aging.