Mary Barna Bridgeman

Denosumab for the reduction of bone loss in postmenopausal osteoporosis: a review.

BACKGROUND Osteoporosis is a prevalent condition that may lead to increased risks for bone fracture and other morbidities and increased health care costs. Treatment modalities for osteoporosis aim to prevent further bone loss and to reduce the risk for fracture. Denosumab is a human monoclonal antibody developed for use in osteoporosis. It inhibits the receptor activator of nuclear factor κB ligand, a cytokine that mediates osteoclast-mediated bone resorption. OBJECTIVE The intent of this article was to review the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, efficacy, and tolerability of denosumab in the prevention and treatment of postmenopausal osteoporosis. METHODS The MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations databases were searched for English-language reviews, abstracts, presentations, and clinical trials of denosumab in humans, published from 1995 through July 2011. Search terms included denosumab, osteoporosis, RANK ligand, and bone resorption. Available data were evaluated, and relevant clinical data were selected for inclusion. RESULTS Three Phase II and 4 Phase III studies that evaluated the efficacy of denosumab in postmenopausal women were identified. In a Phase III study, the percentage change from baseline in bone mineral density (BMD) was significantly greater with denosumab compared with placebo (+6.5% vs -0.6%, respectively; P < 0.0001). In another Phase III trial, the cumulative prevalence of vertebral fractures was significantly lower with denosumab compared with placebo (2.3% vs 7.2%; 95% CI, 0.26-0.41; P < 0.001). Denosumab treatment was associated with significantly greater changes in BMD at the total hip (+4.5% vs +3.4%; P < 0.0001) and distal radius (+1.1% vs +0.6%; P = 0.0001) compared with alendronate. Adverse events reported with the use of denosumab have included back pain (34.7%); pain in the extremities (11.7%); general musculoskeletal pain (7.6%); elevated cholesterol (7.2%); inflammation of the bladder (5.9%); and dermatologic conditions including dermatitis, eczema, and rashes (combined prevalence, 10.8%). Serious adverse events have included hypocalcemia (1.7%), pancreatitis (0.2%), and severe infection (0.2%). Several cases of osteonecrosis of the jaw have also been reported. CONCLUSIONS Based on the data from the available literature, denosumab is an efficacious and well-tolerated treatment for postmenopausal osteoporosis.

Myoclonus in renal failure: Two cases of gabapentin toxicity☆☆☆

Gabapentin, an AED approved for the adjunctive treatment of partial seizures with/without secondary generalization and for the treatment of postherpetic neuralgia, is frequently used off-label for the treatment of both psychiatric and pain disorders. Since gabapentin is cleared solely by renal excretion, dosing requires consideration of the patients renal function. Myoclonic activity may occur as a complication of gabapentin toxicity, especially with acute kidney injury or end-stage renal disease. We report 2 cases of myoclonic activity associated with gabapentin toxicity in the setting of renal disease which resolved with discontinuation of gabapentin and treatment with hemodialysis and peritoneal dialysis. As gabapentin has multiple indications and off-label uses, an understanding of myoclonus, neurotoxicity, and renal dosing is important to clinicians in multiple specialties.

Constipation in Elderly Patients with Noncancer Pain: Focus on Opioid-Induced Constipation

Constipation is a common and often debilitating condition in the elderly, which may be caused by underlying disease conditions, structural abnormalities in the bowel, and a variety of medications such as anticholinergics, antidepressants, and opiates. In this review, we focus on opioid-induced constipation (OIC), which is often underrecognized and undertreated in the elderly. When opioid therapy is initiated, healthcare providers are encouraged to evaluate risk factors for the development of constipation as part of a thorough patient history. To this end, the patient assessment should include the use of validated instruments, such as the Bristol Stool Scale and Bowel Function Index, to confirm the diagnosis and provide a basis for evaluating treatment outcomes. Healthcare providers should use a stepwise approach to the treatment of OIC in the elderly. Conventional laxatives are a first-line option and considered well tolerated with short-term use as needed; however, evidence is lacking to support their effectiveness in OIC. Moreover, because of the risk of adverse events and other considerations, such as chewing difficulties and swallowing disorders, conventional oral laxatives may be inappropriate for the treatment of OIC in the elderly. Thus, the availability of new pharmacologic agents such as the peripherally acting µ-opioid receptor antagonists methylnaltrexone and naloxegol, which target the underlying causes of OIC, and the secretagogue lubiprostone may provide more effective treatment options for elderly patients with OIC.

Acute exacerbations of chronic obstructive pulmonary disease: diagnosis, management, and prevention in critically ill patients.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is a substantial source of disability in the United States. Moderate‐to‐severe acute exacerbations of COPD (AECOPD) can progress to respiratory failure, necessitating ventilator assistance in patients in the intensive care unit (ICU). Patients in the ICU with AECOPD requiring ventilator support have higher morbidity and mortality rates as well as costs compared with hospitalized patients not in the ICU. The mainstay of management for patients with AECOPD in the ICU includes ventilator support (noninvasive or invasive), rapid‐acting inhaled bronchodilators, systemic corticosteroids, and antibiotics. However, evidence supporting these interventions for the treatment of AECOPD in critically ill patients admitted to the ICU is scant. Corticosteroids have gained widespread acceptance in the management of patients with AECOPD necessitating ventilator assistance, despite their lack of evaluation in clinical trials as well as controversies surrounding optimal dosage regimens and duration of treatment. Recent studies evaluating the safety and efficacy of corticosteroids have found that higher doses are associated with increased adverse effects, which therefore support lower dosing strategies, particularly for patients admitted to the ICU for COPD exacerbations. This review highlights recent findings from the current body of evidence on nonpharmacologic and pharmacologic treatment and prevention of AECOPD in critically ill patients. In addition, the administration of bronchodilators using novel delivery devices in the ventilated patient and the conflicting evidence surrounding antibiotic use in AECOPD in the critically ill is explored. Further clinical trials, however, are warranted to clarify the optimal pharmacotherapy management for AECOPD, particularly in critically ill patients admitted to the ICU.

Implementation of a pharmacist‐driven pain management consultation service for hospitalised adults with a history of substance abuse

Pain management in adult patients with concomitant substance use disorders (SUDs) presents a clinical challenge in the absence of objective assessment criteria. Effective pain management is dependent on the clinicians ability to differentiate true pain symptoms from manipulative behaviours. Successful strategies for achieving effective pain control in these patients include implementing a multidisciplinary team approach, use of non‐opioid and non‐pharmacologic alternatives, and judicious use of opioid analgesics.

Mirabegron: β3-Adrenergic Receptor Agonist for the Treatment of Overactive Bladder

OBJECTIVE To review the place in therapy of mirabegron, a new oral β3-adrenergic receptor agonist, for the treatment of overactive bladder (OAB). DATA SOURCES A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-April 2013) was conducted using the key words mirabegron, receptor, adrenergic, beta-3; adrenergic beta-3 receptor; beta-3 receptor, and overactive bladder; urinary bladder; overactive. All published articles regarding mirabegron were included. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. STUDY SELECTION AND DATA EXTRACTION Available English-language data from reviews, abstracts, presentations, and clinical trials of mirabegron in humans were reviewed; relevant clinical data were selected and included. DATA SYNTHESIS Mirabegron is the newest option for treatment of OAB with symptoms of urge incontinence. As a β3-receptor agonist, it reduces bladder muscle contractions. In two 12-week, randomized, double-blind, placebo-controlled Phase 3 studies, mirabegron significantly reduced the number of incontinence episodes per 24 hours from baseline (−1.47, −1.63, and −1.13; p < 0.05; and −1.57, −1.46, and −1.17; p < 0.05; all values for mirabegron 50 mg, 100 mg, and placebo). Micturitions per 24 hours were also reduced from baseline (−1.66, −1.75, and −1.05; p < 0.05; and −1.93, −1.77, and −1.34; p < 0.05; all values for mirabegron 50 mg, 100 mg, and placebo). A 12-month trial found mirabegron to have a safety and efficacy profile similar to that of tolterodine. CONCLUSIONS Treatment of OAB initially includes lifestyle and nonpharmacologic intervention; for patients with persistent symptoms despite these treatments, drug therapy represents a next-step approach for symptom control. Mirabegron alleviates symptoms of OAB while having a mechanism of action that provides an alternative for patients who are intolerant of or who have contraindications to anticholinergic agents. The place in therapy of mirabegron relative to anticholinergics in the treatment of urge incontinence has not yet been established.

Burnout syndrome among healthcare professionals

The well-being of healthcare providers and the influence of healthcare provider mental health and wellness on patient safety have garnered national interest and attention, though the concept of burnout among healthcare professionals is not new.[1][1],[2][2] Healthcare, as an industry, places

Management of Hepatic Encephalopathy: A Primer

Objective: To review the management of hepatic encephalopathy (HE), including lifestyle modifying strategies and pharmacological interventions. Data Sources: A literature search of PubMed through March 2016 was conducted utilizing the keywords hepatic encephalopathy, ammonia, and cirrhosis. All published articles evaluating treatments for HE were considered. Study Selection and Data Extraction: Available English-language data from reviews, abstracts, presentations, and clinical trials of the treatment of HE in humans were reviewed; relevant clinical data were selected and included. Data Synthesis: HE is a prevalent complication of portal hypertension and cirrhosis that results in altered mental status and neuropsychiatric impairment. Although the pathogenesis has not been elucidated, numerous treatment options exist. This review will explore the role of dietary interventions and supplements, including use of zinc, acetyl-l-carnitine, and probiotics, in the management of HE. Additionally, the use of various ammonia-lowering agents will be evaluated. The nonabsorbable disaccharides represent first-line therapies for the management and prophylaxis of HE; rifaximin use has been demonstrated to be effective for both treatment and prophylaxis of HE symptoms, with use relegated to those patients who fail to respond to or tolerate the nonabsorbable disaccharides. In light of toxicities associated with the use of neomycin and metronidazole, recent guidelines recommend both as alternatives for the treatment of HE, with the use of vancomycin discouraged. Conclusion: Although numerous treatment options are available, management of HE remains a clinical challenge. Additional research is needed to explore the pathogenesis and better understand the role of pharmacotherapy in managing this condition.

Febuxostat for the treatment of gout

Introduction: Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues. The xanthine oxidase inhibitor, allopurinol, has historically been the principle agent utilized for reducing elevated uric acid levels and treating underlying cause of gout symptoms; the availability of febuxostat, a newer non-purine selective xanthine oxidase inhibitor, represents an alternative therapy for those patients with contraindications or intolerance to allopurinol. Areas covered: This article reviews the published literature on the pharmacologic characteristics and clinical safety and efficacy data on the use of febuxostat in the treatment of gout. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996–November 2014) was conducted utilizing the key words ‘febuxostat’, ‘allopurinol’, and ‘gout’. All published articles regarding febuxostat were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. Expert opinion: Febuxostat has shown benefit with respect to symptomatic relief and uric acid level reduction. The safety profile of this agent makes it an ideal alternative in those patients with contraindications to or who are intolerant of allopurinol.

Novel Oral Anticoagulants for Stroke Prevention in the Geriatric Population

Prior to the availability of several newer anticoagulant medications, there had been no new advances in anticoagulation management for stroke prevention since the advent of warfarin in the 1950s. The availability of the novel oral anticoagulants (NOACs) dabigatran, rivaroxaban, and apixaban represent improvements over warfarin in many respects, including the elimination of the need for therapeutic drug monitoring, fewer drug and food interactions, and favorable efficacy; however, these agents are not without risk. Specifically, the use of the NOACs in the geriatric population, who are more likely to have an increased risk of stroke due to atrial fibrillation and other medical comorbidities, is not without risk. The objective of this review is to update the clinician on the use of the NOACs in the geriatric population and introduce the controversies and risks surrounding these newer therapies.