Jordan R. Covvey

Intravenous Ketamine for Treatment-Resistant Major Depressive Disorder

OBJECTIVE: To evaluate the literature regarding the efficacy and safety of intravenous ketamine for treatment-resistant major depressive disorder (MDD). DATA SOURCES: A MEDLINE search (1966-September 2011) was performed using the terms treatment-resistant depression and ketamine. The search was restricted to articles published in English and reporting on use of ketamine in humans. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data search were evaluated. Data were eligible for inclusion if they were primary literature and evaluated the efficacy of ketamine for depressive symptoms in treatment-resistant MDD. One case report, 3 case series, 3 open-label trials, and 1 randomized crossover trial were included. DATA SYNTHESIS: Several medications are available for treatment-resistant MDD; however, they are often limited by a slow onset of therapeutic effect and tolerability. It has been suggested that ketamine, a rapid-acting, N-methyl-D-aspartate glutamate receptor antagonist, may have antidepressant effects. Case reports, case series, and select trials evaluating ketamine use for depressive symptoms in treatment-resistant MDD have demonstrated a rapid effect for reductions of scores on a number of depression scales; however, its sustainability effect remains unknown. Several studies reported a large or moderate to large effect size for ketamine. Additionally, these studies showed that ketamine use in this patient population is associated with relatively well-tolerated adverse effects. CONCLUSIONS: Ketamine for treatment-resistant MDD requires further evaluation before it can be considered a viable treatment option.

An association between socioeconomic deprivation and primary care antibiotic prescribing in Scotland

OBJECTIVEnTo evaluate the association between socioeconomic deprivation and antibiotic prescribing in Scotland.nnnPATIENTS AND METHODSnData for dispensed antibiotic prescriptions written by general practitioners were obtained for all Scottish National Health Service boards from 2010 to 2012. Deprivation was assessed linking dispensing events to the Scottish Index of Multiple Deprivation (SIMD) score for the patients datazone (neighbourhood area). The relationship between the deprivation area and antibiotic use (items per 1000 persons per day) was stratified according to the patients age and sex and the antibiotic class dispensed. A multivariate Poisson regression model was used to formally test the associations.nnnRESULTSnApproximately 12 million prescription items during 2010-2012 were assessed. Patients in the most deprived SIMD quintile had an overall prescription rate that was 36.5% higher than those in the least deprived quintile. The effect of deprivation upon prescription rates was most pronounced for women aged 40-59 years, and for penicillins and metronidazole.nnnCONCLUSIONSnDeprivation was found to have a consistent association with increased rates of antibiotic prescribing in Scotland, which may have significant implications for antimicrobial stewardship and public health campaigns.

A comparison of medication adherence/persistence for asthma and chronic obstructive pulmonary disease in the United Kingdom.

To describe and compare adherence and persistence with maintenance therapies in patients with asthma or chronic obstructive pulmonary disease (COPD) in the United Kingdom (UK).

Recent developments toward the safer use of opioids, with a focus on hydrocodone

Opioids have become a mainstay of treatment for pain in the United States, with over 250 million prescription issued in 2012 alone. The increased prescribing of these medications has also contributed to the unintended consequence of a widening prevalence of abuse and misuse, and therefore safety has become a top agenda item for both government and health care providers alike. The move toward new abuse-deterrent formulation technologies, enhanced regulatory requirements from the Food and Drug Administration (FDA) and Drug Enforcement Administration (DEA), and developments in national/state policies have worked together to target a goal of promoting safer clinician prescribing, pharmacy dispensing and patient use of opioids. Hydrocodone in particular, as the most widely prescribed opioid product, has recently been subject to a myriad of changes, both through the federal rescheduling of hydrocodone-combination products (HCPs) to Schedule II, as well as the introduction of two new extended-release formulations to the USA market. These efforts represent a first step toward tackling the opioid harms epidemic, although continuing follow-up through research and policy implementation is needed to see any measureable impact on safety in the future.

Recent Evidence for Pharmacological Treatment of Idiopathic Pulmonary Fibrosis

Objective: To describe emerging evidence for the pharmacological treatment of idiopathic pulmonary fibrosis (IPF). Data Sources: A search of PubMed (1966 to July 2014) was performed using the terms idiopathic pulmonary fibrosis and treatment. Study Selection and Data Extraction: Review of articles was restricted to articles in English and relating to placebo-controlled or comparative clinical trial data of recent significance. Evidence statements from the most recent international guidelines and some historical trial data were also included for context. Data Synthesis: Numerous treatment options have been evaluated for IPF. Therapies evaluated in large trials have either resulted in increased mortality (anticoagulation, triple-therapy with N-acetylcysteine [NAC], azathioprine, and prednisone) or demonstrated a lack of efficacy (endothelin receptor antagonists, single-agent NAC). Pirfenidone, a novel antifibrotic and anti-inflammatory agent, has demonstrated efficacy in several recent analyses and is the only approved medication for the treatment of IPF in more than 30 countries outside of the United States, with resubmission to the Food and Drug Administration (FDA) recently made. Nintedanib, a tyrosine kinase inhibitor, has demonstrated encouraging results in phase III studies and has also recently been submitted for FDA approval. Conclusions: Limited options have existed for the treatment of IPF. New evidence suggests that safe and efficacious treatment options for IPF are on the horizon in the form of pirfenidone and nintedanib, although both agents await FDA decisions.

Is the BTS/SIGN guideline confusing? A retrospective database analysis of asthma therapy.

Background: The British guideline on the management of asthma produced by the British Thoracic Society (BTS) and the Scottish Intercollegiate Guidelines Network (SIGN) describes five steps for the management of chronic asthma. Combination therapy of a long-acting β2-agonist (LABA) and an inhaled corticosteroid (ICS) is recommended as first-line therapy at step 3, although the dose of ICS at which to add a LABA is subject to debate. Aims: To classify the inhaled therapy prescribed to patients with asthma in NHS Forth Valley according to two interpretations of the BTS/SIGN guideline and to evaluate the use of combination therapy in this population. Methods: A retrospective analysis including patients from 46 general practitioner surgeries was conducted. Patients with physician-diagnosed asthma were classified according to the BTS/SIGN guideline based on treatment prescribed during 2008. Patient characteristics were evaluated for the overall step classification, and specifically for therapy in step 3. Results: 12,319 patients were included. Guideline interpretation resulted in a shift of 9.2% of patients (receiving medium-dose ICS alone) between steps 2 and 3. The largest proportion of patients (32.3%) was classified at step 4. Age, sex, smoking status, chronic obstructive pulmonary disease co-morbidity, and utilisation of short-acting β2-agonists and oral corticosteroids all correlated with step; however, no differences in these characteristics were evident between low-dose combination therapy and medium-dose ICS alone at step 3. Conclusions: Further studies are needed to evaluate prescribing decisions in asthma. Guideline recommendations regarding the use of ICS dose escalation versus combination therapy need to be clarified relative to the published evidence.

Predictors of gabapentin overuse with or without concomitant opioids ina commercially-insured US population

Research suggests the medical consequences of gabapentin overuse depend on whether gabapentin is abused alone or with opioids to potentiate an opioid “high.” The objective of this study was to assess predictors of gabapentin overuse with or without concomitant opioids.

Examining pharmacy workforce issues in the United States and the United kingdom

Objective. To examine available data and actions surrounding current pharmacy workforce issues in the United States and United Kingdom. Methods. Published pharmacy workforce data from the United States and United Kingdom were gathered from various sources, including PUBMED, Internet search engines, and pharmacy organization websites. Data was collated from additional sources including scientific literature, internal documents, news releases, and policy positions. Results. The number of colleges and schools of pharmacy has expanded by approximately 50% in both the United States and United Kingdom over the previous decade. In the United States, continued demand for the pharmacy workforce has been forecasted, but this need is based on outdated supply figures and assumptions for economic recovery. In the United Kingdom, workforce modeling has predicted a significant future oversupply of pharmacists, and action within the profession has attempted to address the situation through educational planning and regulation. Conclusion. Workforce planning is an essential task for sustaining a healthy profession. Recent workforce planning mechanisms in the United Kingdom may provide guidance for renewed efforts within the profession in the United States.

Glimepiride-Induced Hypoglycemia With Ciprofloxacin, Metronidazole, and Acute Kidney Injury

A 79-year-old white male presented to the emergency room with altered mental status and a blood glucose of 28 mg/dL. He was taking glimepiride 1 mg by mouth daily prior to admission and had recently been prescribed ciprofloxacin and metronidazole for diverticulitis. The patient was also found to have acute-on-chronic renal failure upon presentation. Escalated dextrose infusion with repeated doses of D50W and glucagon failed to sustain his blood glucose, which remained in the range of 30 to 50 mg/dL. Salvage treatment with intravenous octreotide was implemented successfully; only one dose of D50W was required after octreotide initiation and blood glucose normalized within several hours. In the presence of this patients complex medication therapy, we explore the contributing causes of hypoglycemia. Fluoroquinolones are widely associated with dysglycemias, particularly in diabetic patients receiving hypoglycemic agents. Similarly, renal insufficiency has been implicated to precipitate hypoglycemia with sulfonylureas, with dosage adjustment being required almost class-wide. We also recognize a theoretical drug interaction mediated by metronidazole-induced CYP 2C9 inhibition of glimepiride metabolism. Sulfonylurea-induced hypoglycemia can be serious and refractory to traditional therapy and can be exacerbated by multiple factors, such as drug interactions or impaired renal function. In the era of complex medication therapy for patient populations with multiple disease states, we present a severe episode of glimepiride-induced hypoglycemia with multiple causative factors.

A Systematic Review of the Effect of Cancer Treatment on Work Productivity of Patients and Caregivers

BACKGROUNDnCancer is a leading cause of death with substantial financial costs. While significant data exist on the economic burden of care, less is known about the indirect costs of treatment and, specifically, the effect on work productivity of patients and their caregivers. To examine the full effect of cancer and the potential value of new therapies, all aspects of care, including indirect costs and patient-reported outcomes, should be evaluated.nnnOBJECTIVEnTo perform a systematic review of the literature examining the effect of cancer treatment on work productivity in patients and their caregivers.nnnMETHODSnArticles, abstracts, and bibliographies were searched in MEDLINE, Cochrane, Scopus, CINAHL, and conference lists from the American Society of Clinical Oncology, International Society for Pharmacoeconomics and Outcomes Research, and Academy of Managed Care Pharmacy up to January 2016. The PRISMA guidelines were used. Controlled search terminology included individual pharmacologic therapies for cancer and terms related to patient and caregiver work productivity. Citations were included if they evaluated the effect of cancer treatment on work productivity, used and described productivity assessments and instruments, and were written in English. Studies that reported only clinical outcomes or assessed only nonpharmacological treatments were excluded. Identified studies were screened and extracted for study inclusion by 2 independent reviewers, with adjudication by 2 secondary reviewers during the final eligibility phase.nnnRESULTSnOf 978 potential citations, 62 articles or abstracts were included. Forty-six studies (74.2%) evaluated patient-related productivity; 10 studies (16.1%) focused on caregivers, and 6 studies (9.7%) were a combination. Sixteen countries contributed literature, including 26 studies (41.2%) conducted in the United States. The most commonly studied cancer was breast cancer (53.2%). Nearly 22% of the studies were conducted on multiple types of cancer. The significant diversity of study methodologies and measurements rendered a single unifying conclusion difficult. A variety of metrics were used to quantify productivity (hours lost, return to work, change of status, and activity impairment). The Work Productivity and Activity Impairment questionnaire was the most commonly used standardized tool (n = 9; 14.5%). Factors found to be associated with impairment in productivity included disease- and treatment-related effects, such as disease progression and severity, cognitive and neurological impairments, poor physical and psychological status, receipt of chemotherapy, and time and expenses required to receive therapy.nnnCONCLUSIONSnThis review highlights the considerable variety of studies that have assessed work productivity for cancer treatment and the multifaceted reasons affecting patients and caregivers. With increasing emphasis being given to understanding the value that patients assign to various aspects of cancer treatment, more streamlined information on productivity may be important to patients as they play a greater role in selecting treatment goals through shared decision making with their providers.nnnDISCLOSURESnThis study was funded by Novartis Pharmaceuticals, which provided the concept, general oversight, and research collaboration on the project. Covvey and Kamal received research funding from Novartis Pharmaceuticals and the College of Psychiatric and Neurologic Pharmacists. Zacker is employed by, and owns stock in, Novartis Pharmaceuticals. A related poster abstract was presented at the Academy of Managed Care Pharmacy April 2016 Annual Meeting and published as Kamal KM, Covvey JR, Dashputre A, Ghosh S, Zacker C. A conceptual framework for valuebased oncology treatment: a societal perspective. J Manag Care Spec Pharm. 2016;22(4 Suppl A):S28. A publication-only abstract was presented at the American Society of Clinical Oncology 2016 Annual Meeting and published as Covvey JR, Kamal KM, Dashputre A, Ghosh S, Zacker C. The impact of cancer treatment on work productivity of patients and caregivers: a systematic review of the evidence. J Clin Oncol. 2016;34(Suppl):e18249. Study concept and design were contributed by Zacker, Kamal, and Covvey. Dashputre and Ghosh took the lead in data collection, along with Kamal and Covvey, and data interpretation was performed primarily by Shah and Bhosle, along with Ghosh, Dashputre, Covvey, and Kamal. The manuscript was written by Kamal, Covvey, Shah, and Bhosle and revised primarily by Zacker, along with Shah, Bhosle, Kamal, and Covvey.