Jeremy L. Johnson

A Case of Simvastatin-Associated Pancreatitis and Review of Statin-Associated Pancreatitis

Reduction of low‐density lipoprotein cholesterol (LDL) concentration has become the primary goal and a standard of care in the practice of cholesterol management. The 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors, or statins, are the most frequently prescribed lipid‐lowering agents on the market. As more information is learned through the results of clinical trials, LDL goals become more stringent and difficult to attain. Large doses of high‐potency statins, sometimes given in combination with other lipid‐lowering agents, are frequently necessary to achieve these goals. As a result, the frequency of adverse effects from statin therapy may be expected to increase, and less common adverse effects may occur more often. As statins are used more aggressively, rare and possibly dangerous adverse effects must be identified, especially those that are becoming more frequently encountered. Increased awareness may lead to earlier diagnosis and management of diseases that may be caused by the statins. We describe a 58‐year‐old man who was hospitalized with idiopathic pancreatitis 4 months after starting simvastatin therapy. His oral drug therapy was withheld, and he was treated with bowel rest. The patient was discharged on hospital day 5, and his oral drug regimen, including simvastatin, was resumed. He was admitted again 16 months later with a second diagnosis of acute pancreatitis and was discharged after 3 days of bowel rest with no oral drug therapy. Simvastatin was restarted on discharge, but the patient stopped taking it after experiencing muscle soreness and weakness in his arms. He recalled having similar arm pain that preceded the previous episode of acute pancreatitis. All other causes of the pancreatitis had been ruled out; thus, the correlation between simvastatin‐induced myalgia and onset of acute pancreatitis on two separate occasions made simvastatin the suspected instigating agent. Pancreatitis is a rare adverse effect of statin therapy, but it has been documented in several case reports involving most of the statins. Continued reporting is necessary to increase awareness of this rare adverse effect of simvastatin so that it may be promptly managed or avoided in the future.

Doublecortin-like kinase 1 is elevated serologically in pancreatic ductal adenocarcinoma and widely expressed on circulating tumor cells.

Doublecortin-like kinase 1 (DCLK1) is a putative pancreatic stem cell marker and is upregulated in pancreatic cancer, colorectal cancer, and many other solid tumors. It marks tumor stem cells in mouse models of intestinal neoplasia. Here we sought to determine whether DCLK1 protein can be detected in the bloodstream and if its levels in archived serum samples could be quantitatively assessed in pancreatic cancer patients. DCLK1 specific ELISA, western blotting, and immunohistochemical analyses were used to determine expression levels in the serum and staining intensity in archived tumor tissues of pancreatic ductal adenocarcinoma (PDAC) patients and in pancreatic cancer mouse models. DCLK1 levels in the serum were elevated in early stages of PDAC (stages I and II) compared to healthy volunteers (normal controls). No differences were observed between stages III/IV and normal controls. In resected surgical tissues, DCLK1 expression intensity in the stromal cells was significantly higher than that observed in tumor epithelial cells. Circulating tumor cells were isolated from KPCY mice and approximately 52% of these cells were positive for Dclk1 staining. Dclk1 levels in the serum of KPC mice were also elevated. We have previously demonstrated that DCLK1 plays a potential role in regulating epithelial mesenchymal transition (EMT). Given the increasingly recognized role of EMT derived stem cells in cancer progression and metastasis, we hypothesize that DCLK1 may contribute to the metastatic process. Taken together, our results suggest that DCLK1 serum levels and DCLK1 positive circulating tumor cells should be further assessed for their potential diagnostic and prognostic significance.

Cardiovascular disease and non-steroidal anti-inflammatory drug prescribing in the midst of evolving guidelines.

RATIONALE, AIMS AND OBJECTIVES Responding to safety concerns, the American Heart Association (AHA) published guidelines for non-steroidal anti-inflammatory drug (NSAID) use in patients with pre-existing cardiovascular disease (CVD) during 2005 and revised them in 2007. In the revision, a stepped approach to pain management recommended non-selective NSAIDs over highly selective NSAIDs. This research evaluated NSAID prescribing during and after guideline dissemination. METHOD A cross-sectional sample of 8666 adult, community-based practice visits with one NSAID prescription representing approximately 305 million visits from the National Ambulatory Medical Care Survey (NAMCS) from 2005 to 2010 was studied. Multivariable logistic regression controlling for patient, provider and visit characteristics assessed the associations between diagnosis of CVD and NSAID type prescribed during each calendar year. Visits were stratified by arthritis diagnosis to model short-term/intermittent and long-term NSAID use. RESULTS Approximately one-third (36.8%) of visits involving a NSAID prescription included at least one of four diagnoses for CVD (i.e. hypertension, congestive heart failure, ischaemic heart disease or cerebrovascular disease). Visits involving a CVD diagnosis had increased odds of a prescription for celecoxib, a highly selective NSAIDs, overall [adjusted odds ratio (AOR) = 1.29, 95% confidence interval (CI): 1.06-1.57] and in the subgroup of visits without an arthritis diagnosis (AOR = 1.45, 95% CI: 1.11-1.89). Results were not statistically significant for visits with an arthritis diagnosis (AOR = 1.10, 95% CI: 0.47-2.57). When analysed by year, the relationship was statistically significant in 2005 and 2006, but not statistically significant in each subsequent year. CONCLUSION National prescribing trends suggest partial implementation of AHA guidelines for NSAID prescribing in CVD from 2005 to 2010.

Impact of pharmacist-led educational and error notification interventions on prescribing errors in a family medicine clinic

OBJECTIVES To determine the rate of prescribing errors in a family medicine clinic and the subsequent impact of pharmacist-led educational and error notification interventions on prescribing errors. DESIGN Single site, pre-post study design. SETTING An outpatient academic family medicine clinic serving pediatric and adult populations in Oklahoma from March 1, 2011, through April 30, 2012. PARTICIPANTS 24 resident physicians who prescribed medications during routine outpatient visits. INTERVENTION A prescribing educational program, audit and feedback methods, and weekly newsletter. MAIN OUTCOMES MEASURE Percentage of prescription errors and physician error rate before and after intervention among pediatric and adult populations. RESULTS During the two assessment periods, 24 resident physicians wrote 2,753 prescriptions for 394 pediatric and 899 adult patients. The overall percentage of prescription errors decreased from 18.6% during March 2011 to 14.5% during April 2012 (P = 0.004). Errors were more commonly seen with prescriptions written for pediatric patients (24.9%) than for adult patients (13.9%) (P = 0.001). Individual physician error rates ranged from 5% to 36% (mean ± SD 16.5% ± 8.1). Physicians committed significantly fewer prescribing errors during the postintervention assessment period (14.9%) than during the preintervention assessment period (20.9%) (P = 0.002). Controlling for time, pediatric prescription error rates among physicians who participated in the educational intervention were 36% lower than the error rates among physicians who did not participate (rate ratio 0.64 [95% CI 0.45, 0.91], P = 0.01). CONCLUSION The pharmacist-led educational program was effective in reducing pediatric prescribing errors among resident physicians in a family medicine clinic.

Novel Concentrated Insulin Delivery Devices: Developments for Safe and Simple Dose Conversions.

To aid the burden of large dosing volumes, concentrated insulin products have been available in some form since the 1950s, albeit requiring significant and cumbersome detail in prescribing, converting doses from other products, and educating patients on how to administer. In 2015 and 2016, new concentrated products have been introduced that are available exclusively in pen devices that perform the conversion automatically, and thus, help to bypass the necessity for confusing calculations or administration. Providers and patients accustomed to traditional methods must recognize the differences and utility of these products to avoid dosing errors, as there are major differences in dosing procedures as well as their role in clinical practice. For example, the novel concentrated insulins (aside from U-500 products) are not solely indicated for severe insulin resistance. Use of novel agents may decrease the number of injections required, decrease complexity for patients and providers, reduce errors, and avoid conversion calculations. It is imperative that clinicians appreciate the nuances among the agents to choose an insulin product that is appropriate and fits a patient’s needs and preferences.

Identifying opportunities to improve medication management in transitions of care.

PURPOSE The types and causes of medication discrepancies during the transition from inpatient to ambulatory care were investigated. METHODS A descriptive study was conducted at an academic outpatient group practice affiliated with a private nonacademic hospital to (1) describe discrepancies between inpatient discharge summaries and patient-reported medication lists, (2) identify patient and system factors related to breakdowns in medication documentation, and (3) determine reasons for medication discrepancies. During a four-month period, 17 patients at high risk for medication misadventures while transitioning from hospital care to outpatient follow-up were contacted by telephone soon after discharge and asked to provide information on all medications they were taking. Patient-reported medication lists were compared with the corresponding discharge summaries, and medication discrepancies were categorized by patient- and system-level factors using a validated instrument. RESULTS Of the total of 96 discrepancies identified, more than two thirds (n = 67, 68%) involved the omission of a prescribed medication from either the patient-reported list or the discharge summary. Cardiovascular medications, including antihypertensives, antilipemics, diuretics, and antiarrhythmics, accounted for almost one quarter of all medication discrepancies. About 15% (n = 14) and 16% (n = 15) of identified discrepancies related to medication dose and frequency, respectively. CONCLUSION Among 17 patients transitioning from inpatient to outpatient care, nearly 100 discrepancies between patient-reported medication lists and discharge summaries were identified. Most discrepancies were attributed to nonintentional nonadherence and resumption of home medications without instructions to do so. All 17 patients had at least 1 medication discrepancy categorized as involving a system-level factor.

Nontraditional Considerations with Insulin Needle Length Selection

Ensuring the correct delivery of insulin is essential in the treatment of diabetes. Both proper injection technique and needle length are important considerations for adequate insulin delivery. There have been several studies demonstrating that BMI does not affect efficacy or insulin leakage with shorter pen needles (e.g., 4 or 5 mm vs. 12.7 mm). Additionally, the International Scientific Advisory Board for the Third Injection Technique Workshop released recommendations in 2010 on best practices for injection technique for patients with diabetes, which, with regard to needle length, concluded that 4-mm pen needles were efficacious in all patients regardless of BMI. However, regardless of patients’ BMI, insulin injection technique should always be assessed and physically disabling comorbid conditions taken into consideration when choosing a needle length that will be manageable for patients. The purpose of this article is to raise awareness of unique patient circumstances that may warrant the use of the longer 12.7-mm needle.

Management of a Prediabetes Case With the DPP-4 Inhibitor Sitagliptin

Objective: It is important to prevent or slow the progression of prediabetes to type 2 diabetes and, therefore, reduce the risk of long-term complications. New therapeutic options will allow more patients to be effectively managed. Although theorized to be effective for prediabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors have not been studied in this population. The purpose of this article is to report the results of a case in which a patient with prediabetes was treated with the DPP-4 inhibitor, sitagliptin. Case Summary: A 56-year-old woman was diagnosed with prediabetes at a hemoglobin A1C (A1C) of 6.2%. After 6 months of consistent lifestyle modifications, her A1C was 6.3%, and she wanted to start a medication to prevent disease progression. Because of anticipated risk or intolerability with standard prediabetes treatments, she was started on sitagliptin 100 mg daily; 6 weeks later, she noted improvements in glucometer readings. After 18 months on sitagliptin, her A1C had improved to 5.8% without further lifestyle improvements, and by 32 months, her A1C had improved to 5.6%. Her A1C was maintained within or below the prediabetes range of 5.7% to 6.4% over 3 years of treatment with sitagliptin. Discussion: Although human studies with DPP-4 inhibitors are lacking, the available studies have shown improvements in β-cell function and postprandial and fasting glucose levels. Furthermore, animal studies have shown a delay in progression of prediabetes. No case reports have been found regarding DPP-4 inhibitor use in prediabetes. Conclusion: Sitagliptin may have a role in treating prediabetes and should be further studied.

The role of basal insulin and GLP-1 receptor agonist combination products in the management of type 2 diabetes

The prevalence of type 2 diabetes necessitates the development of new treatment options to individualize therapy. Basal insulin has been a standard treatment option for years, while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have grown in use over the past decade due to glucose-lowering efficacy and weight loss potential. There are two new combination injectable products that have recently been approved combining basal insulins with GLP-1 RAs in single pen-injector devices. United States guidelines recently emphasize the option to use combination injectable therapy with GLP-1 RAs and basal insulin once the basal insulin has been optimally titrated as a second- or third-line agent in addition to metformin without reaching the goal A1c. Insulin glargine/lixisenatide 100/33 (IGlarLixi) can be dosed between 15 and 60 units once daily from a single pen-injector device. Insulin degludec/liraglutide 100/3.6 (IDegLira) can be dosed between 10 and 50 units once daily, also from a single pen-injector device. Maximum doses, while measured in units, correspond to limits defined by each individual GLP-1 RA. The dual use of basal insulin plus GLP-1 RA is non-inferior compared with basal insulin plus a single injection of prandial insulin at the largest meal and compared with twice daily-dosed premixed insulins; and this combination is associated with weight loss and less hypoglycemia. These new combination products could help providers effectively and efficiently follow clinical practice guidelines while enhancing patient adherence with injectable medications.

Pharmacist-managed short-acting beta agonist refill service in a general pediatric clinic

OBJECTIVES To use a pharmacist-managed short-acting beta agonist (SABA) service (1) to determine the patients rationale for SABA refill requests, (2) to assess adherence to current controller therapy and current level of disease control, and (3) to characterize the pharmacists recommendations made in response to a patients SABA refill request. SETTING An academic-based general pediatric clinic. PRACTICE DESCRIPTION SABA overuse is a marker of increased morbidity and mortality in children with asthma. This article describes a pharmacist-managed SABA refill telephone service. PRACTICE INNOVATION The pediatric ambulatory care pharmacy team assessed and authorized (or denied) all SABA refill requests, provided education, and facilitated appropriate follow-up using a telephone service. INTERVENTIONS Upon receiving a patient-requested SABA refill, the pharmacist identified the reason for the SABA request, assessed asthma control, and determined adherence to daily controllers or spacer use, if applicable. Education was also provided. Data obtained were used to determine SABA refill approval. EVALUATION Primary reasons for SABA refill request were for (1) current symptom management and (2) no refills remaining in the absence of symptoms. Forty-two (50%) SABA refill requests were eligible for refill per the clinic algorithm, yet 70% actually received a refill after assessment by the pharmacist. Asthma control was assessed as 26% well controlled, 38% not well controlled, and 36% very poorly controlled. Forty-eight percent of patients prescribed daily controller medications were deemed adherent. Spacers were used in 43 of 76 (56%) patients using metered dose inhalers. Education was provided to 82% of caregivers. Pharmacists facilitated asthma follow-up visits in 41 of 84 (49%) patients contacted, and 61% of those appointments were kept. CONCLUSIONS Pharmacist management of a SABA refill telephone service provides an additional means for delivery of asthma education, facilitates follow-up asthma care, helps to identify patients at risk for increased morbidity and mortality due to the overuse of SABAs, and provides another mechanism for medication refills.