Statin Associated Autoimmune Myonecrosis: Case Report With Delayed Onset and Treatment Challenges.

PURPOSE: A case of delayed statin associated autoimmune myopathy (SAAM) is presented along with review of clinical findings and treatment strategies. SUMMARY: A 54 year old male presented with proximal extremity weakness, difficulty ambulating, and dysphagia. Symptoms began when restarting atorvastatin 40 mg daily for a recent NSTEMI, following 10 years of statin use, interrupted after diagnosis of NASH. Relevant labs included CK of 13,618 IU/L, ALT/ AST of 568/407 IU/L, while additional liver, renal, and toxicology tests were normal. Following treatment response to prednisone 40 mg daily for 3 days, outpatient testing for anti-HMGCR antibodies was ordered.Twelve days from discharge, the patient was readmitted for myalgia and dysphagia, CK = 6042 IU/L, ALT/AST = 360/112 IU/L, and positive anti-HMGCR antibodies. Newly diagnosed with SAAM, symptoms improved with methylprednisolone and intravenous immunoglobulin (IVIG), continuing outpatient as daily prednisone and monthly IVIG. Four days later, the patient relapsed with worsened weakness and dysphagia, CK = 5812 IU/L, and ALT/AST = 647/337 IU/L. After response to methylprednisolone and rituximab, the patient was discharged on a corticosteroid taper, biweekly rituximab, and monthly IVIG. Two weeks later, a final admission involved a syncopal episode and fall, with a CK = 1461 IU/L. Treatment included IVIG, rituximab, and corticosteroid taper, which lead to remission for greater than 6 months. CONCLUSION: Statin associated autoimmune myopathy occurred when restarting atorvastatin, following 10 years of statin use. Clinical findings and positive anti-HMGCR antibodies confirmed the diagnosis. Recurrent relapses required triple combination therapy including addition of rituximab to achieve remission.

Managing hospitalized patients with a COPD exacerbation: the role of hospitalists and the multidisciplinary team.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with high rates of hospitalizations, costs, and morbidity. Therefore, hospitalists and the multidisciplinary team (hospital team) need to take a proactive approach to ensure patients are effectively managed from hospital admission to postdischarge. Comprehensive screening and diagnostic testing of patients at admission will enable an accurate diagnosis of COPD exacerbations, and severity, as well as other factors that may impact the length of hospital stay. Depending on the exacerbation severity and cause, pharmacotherapies may include short-acting bronchodilators, systemic corticosteroids, and antibiotics. Oxygen and/or ventilatory support may benefit patients with demonstrable hypoxemia. In preparation for discharge, the hospital team should ensure that patients receive the appropriate maintenance therapy, are counseled on their medications including inhalation devices, and proactively discuss smoking cessation and vaccinations. For follow-up, effective communication can be achieved by transferring discharge summaries to the primary care physician via an inpatient case manager. An inpatient case manager can support both the hospitalist and the patient in scheduling follow-up appointments, sending patient reminders, and confirming that a first outpatient visit has occurred. A PubMed search (prior to 26 January 2021) was conducted using terms such as: COPD, exacerbation, hospitalization. This narrative review focuses on the challenges the hospital team encounters in achieving optimal outcomes in the management of patients with COPD exacerbations. Additionally, we propose a novel simplified algorithm that may help the hospital team to be more proactive in the diagnosis and management of patients with COPD exacerbations.

Evidence-based treatment during the SARS-CoV-2 pandemic: Identifying the knowns and unknowns of nebulization.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus 19 (COVID-19), has resulted in a worldwide pandemic and currently represents a major public health issue. Among the considerations for patients with respiratory disease is the optimal delivery of inhaled bronchodilators to maximize patient care. Despite the lack of evidence, there is heightened concern about the potential risk for transmission of SARS-CoV-2 in the form of aerosolized respiratory droplets during the nebulized treatment of patients with COVID-19. In this commentary, the lack of evidence regarding nebulization and transmission of coronaviruses are discussed.

Impact of distance education via interactive videoconferencing on students' course performance and satisfaction.

The impact of distance education via interactive videoconferencing on pharmacy students' performance in a course was assessed after implementation of a distance campus. Students filled out a "Student Demographic Survey" and a "Precourse Knowledge Assessment" at the start of the course and a "Postcourse Knowledge Assessment" and a "Postcourse Student Perceptions Survey" at the end of the course. The primary end point, a comparison of course grades (%) between the main and distance campuses, was examined using the two-sample t-test. We examined the relationships among demographics, campus location, course grades, grade point average, pre- and postcourse knowledge assessments, and postcourse perceptions as our secondary end points with parametric and nonparametric tests. Data from 93 students were included in the analysis [main campus ( n = 81); distance campus ( n = 12)]. Students on the main campus achieved a significantly higher final course grade (87 vs. 81%; P = 0.02). Scores on the Postcourse Knowledge Assessment were also significantly higher compared with those of students on the distance education campus (77 vs. 68%; P = 0.04). Students on both campuses reported self-perceived improvement in their knowledge base regarding various aspects of infectious diseases. Compared with the students on the distance campus, those on the main campus were more likely to subjectively perceive that they had succeeded in the course ( P = 0.04). Our study suggests that students on the main campus achieved a higher final course grade and were more likely to feel that they had succeeded in the course. Students on both campuses reported improvement in knowledge.

Managing drug-resistant organisms in acute care.

The purpose of this article is to provide practitioners with therapeutic considerations for infections caused by drug-resistant organisms in the acute care setting. Proper identification of organisms and appropriate use of antibiotics are imperative strategies to help reduce the development and spread of antimicrobial resistance.

The Roles of ACE Inhibitors in Lower Extremity Peripheral Artery Disease.

Peripheral artery disease (PAD) is an age-dependent atherosclerotic disorder associated with an increased prevalence of cardiovascular morbidity and mortality. Approximately 35% of patients with PAD complain of lower extremity claudication, which may worsen to impair daily function. ACE inhibitors may possess vasoactive properties that improve symptoms of claudication. We designed a meta-analysis to quantify the effectiveness of ACE inhibitors on walking capacities in patients with lower extremity PAD. We reviewed MEDLINE and Cochrane databases from 1966 to 2013, in addition to relevant bibliographies to obtain our clinical trials. From the original findings, 4 randomized, placebo-controlled, double-blind studies qualified for inclusion. Using a random-effects model, ACE inhibitors were associated with an increase of 126 m [95% confidence interval (CI), -95 to 346] (P = 0.264) in maximal walking distance and a rise in Ankle-Brachial Index of 0.09 (95% CI, 0.024-0.205) (P = 0.12). However, pain-free walking distance was significantly increased by 86 m (95% CI, 13-156) (P = 0.021). Contradictions in study outcomes between more recent and earlier trials of ACE inhibitors in claudication impeded the interpretation of effectiveness. Early trials failed to demonstrate improvement in walking capacities, possibly because of omissions in patient enrollment criteria and inadequate sample size. Recent guidelines recommend consideration of ACE inhibitors in patients with PAD for cardioprotective effects. Although ACE inhibitors were well tolerated, vigilance for clinical predictors of renal arterial stenosis and renal instability after initiation will ensure safe administration in all patients with PAD.

Cannabinoid Hyperemesis Syndrome: An Emerging Drug-Induced Disease.

Cannabinoid hyperemesis is a relatively rare but significant adverse effect of chronic marijuana use characterized by severe, cyclic nausea, vomiting, and abdominal pain and marked by compulsive hot-water bathing for temporary symptom relief. A 37-year-old African American male with no significant medical history other than the habitual abuse of marijuana was admitted for intractable nausea, vomiting, and abdominal pain. With the exception of abdominal skin hyperpigmentation and scarring secondary to the direct application of heat through a heating pad, physical examination of the abdomen was unremarkable. Laboratory studies revealed a mild leukocytosis and acute renal dysfunction. All diagnostic examinations were found to be unremarkable or noncontributory to the patient's presenting state. Consistent with previous admissions, the patient's urine toxicology screening was found to be positive for marijuana. After several days of aggressive IV fluid hydration and as needed antiemetics and pain management, all laboratory studies and vital signs returned to baseline and the patient was subsequently discharged. Symptoms of cannabinoid hyperemesis resolve with cannabis cessation and recur when cannabis use is reinitiated, supporting an association between chronic use and cyclic vomiting. A Naranjo algorithm score of 5 revealed a probable incidence of cyclic vomiting associated with chronic cannabis abuse in our patient. Marijuana use, both legal and illegal, is becoming more prevalent in the United States. Given the nationwide increase in marijuana use for recreational and medical reasons, pharmacists and other health care providers should be aware of this interesting drug-induced phenomenon.

Corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic and progressive disease that affects an estimated 10% of the world's population over the age of 40 years. Worldwide, COPD ranks in the top ten for causes of disability and death. Given the significant impact of this disease, it is important to note that acute exacerbations of COPD (AECOPD) are by far the most costly and devastating aspect of disease management. Systemic steroids have long been a standard for the treatment of AECOPD; however, the optimal strategy for dosing and administration of these medications continues to be debated. OBJECTIVE: To review the use of corticosteroids in the treatment of acute exacerbations of COPD. MATERIALS AND METHODS: Literature was identified through PubMed Medline (1950-February 2014) and Embase (1950-February 2014) utilizing the search terms corticosteroids, COPD, chronic bronchitis, emphysema, and exacerbation. All reference citations from identified publications were reviewed for possible inclusion. All identified randomized, placebo-controlled trials, meta-analyses, and systematic reviews evaluating the efficacy of systemic corticosteroids in the treatment of AECOPD were reviewed and summarized. RESULTS: The administration of corticosteroids in the treatment of AECOPD was assessed. In comparison to placebo, systemic corticosteroids improve airflow, decrease the rate of treatment failure and risk of relapse, and may improve symptoms and decrease the length of hospital stay. Therefore, corticosteroids are recommended by all major guidelines in the treatment of AECOPD. Existing literature suggests that low-dose oral corticosteroids are as efficacious as high-dose, intravenous corticosteroid regimens, while minimizing adverse effects. Recent data suggest that shorter durations of corticosteroid therapy are as efficacious as the traditional treatment durations currently recommended by guidelines. CONCLUSION: Systemic corticosteroids are efficacious in the treatment of AECOPD and considered a standard of care for patients experiencing an AECOPD. Therefore, systemic corticosteroids should be administered to all patients experiencing AECOPD severe enough to seek emergent medical care. The lowest effective dose and shortest duration of therapy should be considered.

Aclidinium bromide: an alternative long-acting inhaled anticholinergic in the management of chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the efficacy and safety of aclidinium bromide, a novel, long-acting inhaled muscarinic receptor antagonist approved by the Food and Drug Administration (FDA) in July 2012, as a treatment in the management of moderate to severe chronic obstructive pulmonary disease (COPD). DATA SOURCES: Literature was identified through PubMed/MEDLINE (2000-March 2013) and International Pharmaceutical Abstracts using the search terms aclidinium, COPD, chronic bronchitis, emphysema, anticholinergic, and muscarinic antagonist. In addition, US government websites, including fda.gov and clinicaltrials.gov, were reviewed for pertinent information. Forest Laboratories, Inc provided previously unpublished clinical trial data. All reference citations from identified publications were reviewed for possible inclusion. STUDY SELECTION AND DATA EXTRACTION: All identified Phase 1, 2a, 2b, and 3 studies evaluating the safety and efficacy of aclidinium bromide were reviewed. DATA SYNTHESIS: Once- and twice-daily aclidinium bromide was assessed for efficacy and safety in patients with moderate to severe COPD. In comparison to placebo, aclidinium significantly improves trough and peak forced expiratory volume in 1 second (FEV1). Significant increases in trough and peak FEV1 were sustainable for up to 64 weeks. In addition to improvement in trough and peak FEV1, twice-daily aclidinium 400 µg induced clinically meaningful improvements in the health status of patients with moderate to severe COPD. Aclidinium was generally well tolerated, with headache, cough, diarrhea, and nasopharyngitis the most common treatment-related adverse effects noted in clinical trials. Aclidinium did not demonstrate a difference in the incidence of systemic anticholinergic-associated adverse effects in comparison to placebo or active comparator. CONCLUSIONS: Aclidinium bromide is a novel, inhaled, long-acting anticholinergic that, when administered at the FDA-approved dose, safely produces clinically and statistically significant bronchodilation and improves health status in patients with moderate to severe COPD. Long-term clinical trials assessing the efficacy and safety of aclidinium are warranted.

Strategies to preserve the use of statins in patients with previous muscular adverse effects.

PURPOSE: The published evidence on strategies for avoiding the discontinuation of statin therapy due to muscular adverse effects is reviewed. SUMMARY: Statin medications are a cornerstone of the prevention and treatment of coronary heart disease, but about 20% of treated patients develop myalgia or other muscle-related adverse effects that can lead to the discontinuation of statin use. As there are no consensus guidelines or firm practice recommendations on continuing or reinitiating statin therapy in patients who experience statin-related muscular adverse effects, a literature search was conducted to evaluate a variety of strategies that have been studied. The search results indicated that the most widely used strategies are (1) alternative statin dosing, (2) co-enzyme Q10 supplementation, (3) vitamin D supplementation, (4) conversion to red yeast rice (RYR) therapy, and (5) conversion to a different statin. While positive results in some patients have been reported with all of the strategies reviewed, the available evidence is insufficient to support the routine use of any of the strategies in clinical practice. In particular, the use of RYR, which contains a naturally occurring statin, is not recommended due to limited and inconsistent study results and uncertainty about the contents of commercially available RYR products. CONCLUSION: In patients intolerant to statin therapy due to myalgia or other muscular adverse effects, strategies such as alternative statin dosing schedules, coenzyme Q10 or vitamin D supplementation, and conversion to RYR or an alternative statin may allow some patients to continue to receive the benefits of lipid-lowering therapy.

An evaluation of inhaled bronchodilator therapy in patients hospitalized for non-life-threatening COPD exacerbations.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) increasingly is a cause of morbidity and mortality in and economic burden on the US healthcare system, and COPD exacerbations continue to be among the top 10 causes of hospitalization in adults. The objective of this study was to evaluate the incidence and potential implications of missed scheduled nebulized bronchodilator therapy in the setting of acute, non-life-threatening COPD exacerbations. MATERIALS AND METHODS: This study was a retrospective chart review of all of the patients with a primary diagnosis of severe, non-life-threatening COPD exacerbations admitted from January 2007 to June 2008 at a university-affiliated hospital. Each patient's inhaled bronchodilator treatment regimen, including potential for nebulization to metered-dose inhaler (MDI) with valved holding chamber (VHC) conversion, was assessed. RESULTS: A total of 259 patients met inclusion criteria: 235 (90.7%) patients received inhaled bronchodilators by nebulization alone in the treatment of COPD exacerbations; 81.1% of these patients could have used MDI with VHC. Patients missed 24.3% of their scheduled, nebulized bronchodilator doses. CONCLUSIONS: Patient care can be improved through the initiation of MDI with VHC, especially considering the number of missed nebulizations that these patients experienced. Development of an inhaled bronchodilator treatment algorithm for COPD exacerbations should be considered to ensure an evidence-bassed medicine approach to these patients.

Matrix remodeling expression in anulus cells subjected to increased compressive load.

STUDY DESIGN: Mechanobiology study of gene expression changes as a result of compressive overload of anular fibrochondrocytes. OBJECTIVE: To test hypotheses regarding phenotype shift in genes coding for representative extracellular matrix (ECM) proteins and matrix modulators. SUMMARY OF THE BACKGROUND DATA: In degenerative disc disease, the transfer of compressive load through the disc shifts largely from the nucleus onto the anulus. In vivo models simulating this condition have shown derangement of the collagenous ultrastructure in the anulus. In vitro models of cultured anulus cells subjected to static compressive stress generally suggest a down-regulation of synthesis. This study evaluated the expression of specific isomers of genes responsible for mechanical viability and metabolism of the disc under cyclic compressive loads. METHODS: Fibrochondrocytes were digested from the anuli of 3, 2-week-old pigs, embedded in 1.5% alginate gel, and hydrostatically compressed at 0.5 Hz for 3 hours to amplitudes of 10 and 30 atm. These levels represented nominal load transfer through the healthy disc and high load transfer through the degenerative disc. Ribonucleic acid was isolated, reverse transcribed, and evaluated by real-time polymerase chain reaction for expression of type I (C-I) and type II (C-II) collagen, aggrecan, the matrix metalloproteinase (MMP-1), and the transforming growth factor beta (TGFbeta-1). Results were expressed at percentages of uncompressed controls. RESULTS: The lower pressure of 10 atm resulted in up-regulation of all ECM protein genes. C-I and C-II both averaged 141%, and aggrecan 121% of controls (P < 0.05). MMP-1 and TGFbeta-1 were essentially unchanged. With the pressure increased to 30 atm, C-II remained approximately at the level expressed under lower pressure, but C-I was reduced to 42% of controls (P < 0.05), indicating a phenotype shift. MMP-1 and TGFbeta-1 also were down-regulated to 71% and 54% of controls, respectively (P < 0.05). CONCLUSIONS: The up-regulation of the ECM genes with nominal pressure highlights the mechanobiological importance of common activity in fibrocartilage homeostasis. Differential regulation of the 2 primary collagen types with high pressure indicates a capacity of the anulus to remodel according to pathomechanical conditions.