T04-O-05 High dose Testosterone (T) treatment has no adverse effects on the endometrium of Female to Male transsexuals (FtM)

Objective To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. Data Sources PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords “semaglutide” and “obesity,” “weight,” “high dose,” “high-dose,” or “2.4.” Study Selection and Data Extraction Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. Data Synthesis Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. Relevance to Patient Care and Clinical Practice High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. Conclusions High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.

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Tamoxifen-associated eye disease. A review.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.3.1018 ◽

1996 ◽

Vol 14 (3) ◽

pp. 1018-1026 ◽

Cited By ~ 112

Author(s):

S G Nayfield ◽

M B Gorin

Keyword(s):

Breast Cancer ◽

Adverse Effects ◽

Macular Edema ◽

Case Reports ◽

Eye Disease ◽

High Dose ◽

Ocular Toxicity ◽

Early Stage Disease ◽

Clinical Series

PURPOSE The oral antiestrogen tamoxifen has demonstrated efficacy in the treatment of metastatic breast cancer and as adjuvant therapy in early-stage disease. Clinical trials of tamoxifen in chemoprevention of breast cancer among high-risk women have focused attention on potential adverse effects of long-term tamoxifen use, including the possibility of ocular toxicity. This review evaluates the published case reports, clinical series, and clinical trial data on ocular toxicities attributed to tamoxifen. Clinical issues of surveillance, differential diagnosis, and management of tamoxifen-related eye disease are discussed. DESIGN National Library of Medicine online bibliographic services were used to identify case reports and clinical studies of ocular adverse effects that occurred in patients receiving tamoxifen published through the fall of 1994. The medical literature relevant to issues raised by the reports and studies was similarly identified and reviewed. RESULTS Case reports and case series identify crystalline retinal deposits, macular edema, and corneal changes as potential tamoxifen ocular toxicities. Extensive retinal lesions and macular edema with visual impairment have been reported in a few patients receiving high-dose tamoxifen. Less extensive retinal changes may occur in patients receiving low doses for long periods, and isolated retinal crystals may be observed in patients without visual symptoms. CONCLUSION Ocular toxicity is uncommon in the current clinical setting of long-term, low-dose tamoxifen use. Physicians should be aware of the potential for ocular toxicity among patients receiving the drug and should assure appropriate surveillance and prompt evaluation of visual complaints.

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Therapeutic Controversies in the Treatment of Asthma

Annals of Pharmacotherapy ◽

10.1177/106002809402800716 ◽

1994 ◽

Vol 28 (7-8) ◽

pp. 904-914 ◽

Cited By ~ 11

Author(s):

Alan K. Kamada

Keyword(s):

Adverse Effects ◽

Systemic Absorption ◽

Systemic Effects ◽

High Dose ◽

Adrenergic Agonists ◽

Risk Of Death ◽

Increased Risk ◽

Metered Dose ◽

Systemic Glucocorticoids ◽

Inhaled Glucocorticoids

OBJECTIVE: To introduce readers to the current controversial topics in the area of asthma therapy. Background is provided such that clinicians are aware of these issues and can make rational decisions. DATA SOURCES: Pertinent articles were individually identified and reviewed from each journal. STUDY SELECTION: Relevant studies, determined by topic and other specific criteria, e.g., testing methodology, were included. DATA SYNTHESIS: Further investigation is required in the areas discussed. Systemic effects, specifically growth suppression (in children), adrenal suppression, and osteoporosis, have been demonstrated with high-dose inhaled glucocorticoids; however, the clinical relevance of such intravenous glucocorticoid formulations via nebulizer have not been demonstrated. Likewise, data on the equivalence of the inhaled glucocorticoids, with regard to efficacy and potential systemic effects, and the differences between metered-dose inhalers and dry powder inhalers, with regard to aerosol characteristics and drug delivery, are unclear. Theophylline, when used with inhaled β-adrenergic agonists and systemic glucocorticoids for the treatment of acute asthma, as not been shown to provide clear benefit and may result in increased adverse effects. The use of regular (vs. “as needed” or prn) inhaled β-adrenergic agonists, although shown in two studies to be detrimental to the control of asthma and result in an increased risk of death or near death caused by asthma, has not been conclusively demonstrated to be harmful. CONCLUSIONS: Monitoring for adverse effects and the use of techniques to minimize systemic absorption (spacers and mouth rinsing) are recommended when high-dose inhaled glucocorticoid therapy is used. Intranasal and intravenous glucocorticoid products are not recommended for administration via nebulizer because of safety concerns. Until further data are available, inhaled glucocorticoids are thought to be equivalent on a μg-per-μg basis rather than an actuation-per-actuation basis. Theophylline is no longer recommended for treatment of acute exacerbations in nonhospitalized patients not already receiving the medication, and the link between deterioration of asthma control (and the risk for death) and regular inhaled beta-adrenergic agonists appears weak.

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Astragalus polysaccharide (PG2) Ameliorates Cancer Symptom Clusters, as well as Improves Quality of Life in Patients with Metastatic Disease, through Modulation of the Inflammatory Cascade

Cancers ◽

10.3390/cancers11081054 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1054 ◽

Cited By ~ 5

Author(s):

Wen-Chien Huang ◽

Kuang-Tai Kuo ◽

Oluwaseun Adebayo Bamodu ◽

Yen-Kuang Lin ◽

Chun-Hua Wang ◽

...

Keyword(s):

Quality Of Life ◽

Growth Factor ◽

Adverse Effects ◽

Metastatic Disease ◽

Controlled Trial ◽

High Dose ◽

Advanced Stage ◽

Gm Csf ◽

Anti Inflammatory

Background: Improving patients’ quality of life (QoL) is a principal objective of all treatment in any clinical setting, including oncology practices. Cancer-associated inflammation is implicated in disease progression and worsening of patients’ QoL. Conventional anticancer therapeutics while selectively eliminating cancerous cells, are evaded by stem cell-like cells, and associated with varying degrees of adverse effects, thus reducing patients’ QoL. This necessitates novel therapeutic approaches with enhanced efficacy, minimal or no treatment-related adverse effects, and improved QoL in patients with cancer, especially those with metastatic/advance stage disease. Methods: Sequel to our team’s previous publication, the present study explores probable effects of Astragalus polysaccharides (PG2) on cancer-related inflammatory landscape and known determinants of QoL, as well as the probable link between the two to provide mechanistic insight. In an exploratory double blind randomized controlled trial using patients with metastatic disease (n = 23), we comparatively evaluated the therapeutic efficacy of high (500 mg) or low (250 mg) dose PG2 administered intravenously (i.v.), with particular focus on its suggested anti-inflammatory function and the probable effect of same on QoL indices at baseline, then at weeks 4 and 8 post-PG2 treatment. Results: All 23 patients with metastatic disease treated with either low or high PG2 experienced reduced pain, nausea, vomiting, and fatigue, as well as better appetite and sleep, culminating in improved global QoL. This was most apparent in the high dose group, with significant co-suppression of pro-inflammatory interleukin (IL)-1β, IL-4, IL-6, IL-13, IL-17, monocytes chemotactic protein (MCP)1, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), tumor growth factor (TGF)-β1, interferon (IFN)-γ, and immune suppressors IL-10 and IL-12. Univariate and multivariate analyses revealed that IL-1β, IL-13 and GM-CSF are independent prognosticators of improved QoL. Conclusion: This proof-of-concept study provides premier evidence of functional association between PG2 anti-inflammatory effects and improved QoL in patients with advanced stage cancers, laying the groundwork for future larger cohort blinded controlled trials to establish the efficacy of PG2 as adjuvant anticancer therapy in metastatic or advanced stage clinical settings.

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