ABSTRACT
Immune checkpoint inhibitors targeting programmed cell death protein 1 and cytotoxic T-lymphocyte associated protein 4 have improved survival in patients with metastatic melanoma, especially in combination (i.e., ipilimumab-nivolumab). Postmarketing surveillance has identified rare but at times life-threatening adverse effects associated with these agents in combination and as monotherapy, which include myocarditis, myositis, myasthenia gravis (MG), and hepatotoxicity. Further evaluation of immune checkpoint therapy-induced MG identified the rapid clinical progression, prolonged treatment/supportive therapy course, and higher frequency of myasthenic crisis in these patients versus those with idiopathic MG. More rapid incorporation of aggressive treatment options (i.e., intravenous immunoglobulin, plasmapheresis) may be necessary in these cases. Anti-striational antibodies are often detected in individuals with myasthenia gravis and concurrent myositis and myocarditis. A high-index of suspicion is necessary to assist with rapid treatment initiation as these patients can rapidly deteriorate into respiratory compromise. A case of a 78-year-old woman with metastatic melanoma status after combination therapy with ipilimumab-nivolumab that developed transaminitis, myositis, myocarditis, and myasthenia gravis (with positive anti-striational antibodies) five days after the first cycle, is presented. Despite high dose intravenous methylprednisolone and intravenous immunoglobulin treatment, she ultimately entered hospice care eight days after hospital admission, 36 days after her first cycle.
ABSTRACT
Miracle mouthwash (MMW) is a commonly prescribed oral formulation compounded with varying active ingredients, depending on purpose of treatment. Due to patient-to-patient customization, the solubility, stability, and solid-state characteristics of the active ingredients may not be known after compounding. This study found that the common antibiotic, tetracycline hydrochloride (HCl), compounded in MMW formulations that contained dexamethasone elixir and diphenhydramine, underwent significant physical-chemical changes. Simulated patient conditions demonstrated appreciable fluctuations from the target content of 50 mg tetracycline HCl per teaspoon over 15 days. The lowest tetracycline content sampled was 32.5 mg, while the highest content sampled was 53.0 mg. Although tetracycline HCl went into solution after compounding, tetracycline did not remain in solution. In fact, the amount of tetracycline in solution declined exponentially, with over two-thirds of tetracycline precipitating out within the first day of compounding and 14% remaining in solution after 15 days. Crystals that formed within the MMW formulation were analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and powder X-ray diffraction (PXRD), which confirmed a solvent-mediated phase transformation of tetracycline HCl to tetracycline hexahydrate. For tetracycline in solution, pH had a significant effect on chemical degradation. Therefore, tetracycline HCl compounded in MMW formulations can have significant physical-chemical stability changes, possibly impacting patient dosing.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Mouthwashes/chemistry , Tetracycline/administration & dosage , Tetracycline/chemistry , Drug Compounding , Drug Stability , Excipients , HumansABSTRACT
Systemic inflammatory disorders frequently involve the skin, and when cutaneous disease develops, such dermatologic manifestations may represent the initial sign of disease and may also provide valuable prognostic information about the underlying disorder. Familiarity with the various skin manifestations of systemic disease is therefore paramount and increases the likelihood of accurate diagnosis, which may facilitate the implementation of an appropriate treatment strategy. An improvement in quality of life and a reduction in the degree of morbidity may also be a realized benefit of accurate recognition of these skin signs. With this context in mind, this review highlights the salient clinical features and unique dermatologic manifestations of rheumatoid arthritis, adult-onset Still's disease, and the crystal arthropathy, gout.
Subject(s)
Arthritis, Rheumatoid/diagnosis , Crystal Arthropathies/complications , Gout/complications , Rheumatoid Vasculitis/etiology , Skin Diseases/etiology , Skin Diseases/therapy , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Dermatitis/etiology , Felty Syndrome/complications , Granuloma/etiology , Humans , Leg Ulcer/etiology , Panniculitis/etiology , Pyoderma Gangrenosum/diagnosis , Pyoderma Gangrenosum/drug therapy , Pyoderma Gangrenosum/etiology , Rheumatoid Vasculitis/drug therapy , Skin Diseases/diagnosis , Still's Disease, Adult-Onset/complications , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/drug therapyABSTRACT
BACKGROUND/PURPOSE: The purpose of this study was to evaluate the effectiveness of supplemental diabetes-related training modalities and volunteer activities in increasing first-year medical students' knowledge/comfort in providing diabetes self-management education and support (DSMES) to patients. METHODS: A group of medical students developed supplemental diabetes-related training/volunteer programs. The training modalities included an optional 7-session interprofessionally taught Diabetes Enrichment Elective and a 3-hour endocrinologist-led training session intended to prepare students for involvement in an inpatient DSMES volunteer program. The volunteer program provided the students with the opportunity to provide DSMES to patients with diabetes admitted to an academic medical center. Those participating in any of the stated programs were compared to those with no such training regarding confidence in providing DSMES using an optional online survey. The results were analyzed by using Mann-Whitney U test and descriptive analyses. RESULTS: A total of 18 first-year medical students responded to the optional survey with a response rate of ~30% (10 of 33) among participants in any training/volunteer program. First-year medical students who attended any of the offered optional programs had statistically significant higher comfort level in 4 of the 6 areas assessed regarding providing DSMES compared with those with no such training (p<0.05), with medium to large effect size (r=0.48-0.59). CONCLUSION: This study suggests that the supplemental preclerkship diabetes-specific training modalities/volunteer programs can provide benefit in providing medical students with practical knowledge while improving their confidence in providing DSMES to patients with diabetes.