Sunny A. Linnebur

Patient-Level Medication Regimen Complexity Across Populations With Chronic Disease

BACKGROUND Expected treatment effectiveness from medications can be diminished due to suboptimal adherence. Medication nonadherence has been linked to pill burden from the quantity of medications; however, medication regimens with similar quantities of medications vary in complexity due to multiple dosage forms, frequency of dosing, and additional usage directions. Thus, a simple medication count ignores medication regimen complexity, especially as it pertains to a patient-level perspective that includes prescription and over-the-counter medications. A gap exists in the study of a patient-level medication regimen complexity metric across disease-specific populations. OBJECTIVE The goal of this study was to implement the quantitative Medication Regimen Complexity Index (MRCI) at the patient level in defined populations with chronic disease (geriatric depression, HIV, diabetes mellitus, and hypertension). Patient-level medication regimen complexity included all prescribed medications and over-the-counter medications documented in the electronic medication list. METHODS Using electronic medical records at the University of Colorado Hospital ambulatory clinics, we sampled 4 retrospective cohorts of adult patients in active care in 2011 with a qualifying medical diagnosis and prescribed disease-specific medication. Samples were randomly selected from all qualifying patients; de-identified information was coded using the MRCI. RESULTS Cohort-defining disease-specific prescription medications (eg, antidepressants for the depression-defined cohort) contributed <20% to the total patient-level complexity MRCI score; the MRCI score was dominated by complexity associated with all other prescription medications. Within disease-specific cohorts, MRCI scores differentiated patients with the highest and lowest medication counts, comorbidity counts, and the Charlson comorbidity index scores. For example, geriatric depression patients had a highest quartile mean MRCI score of 41 and a lowest quartile mean MRCI score of 13. Between disease-specific cohorts, high and low MRCI scores differed because each cohort had its own MRCI ranges. For example, highest quartile MRCI scores varied from a mean MRCI score of 41 (geriatric depression) to 30 (hypertension); lowest quartile scores ranged from a mean MRCI score of 7 (hypertension and HIV) to 13 (geriatric depression). CONCLUSIONS MRCI components of dosing frequency and prescribed medications outside of the cohort-defining disease medications contributed the most to the patient-level scores. Thus, chronic disease management programs may want to consider all medications that patients are taking and examine ways to reduce complexity, such as reducing multiple dosing frequencies when possible. MRCI scores differentiated high and low patient-level complexity measures, representing possible utility as a prospective tool to identify target patients for intervention. Future work includes simplifying the MRCI and enhancing the scores with medication risk factors, as well as explicitly linking to adherence and health services.

FDA drug safety communications: a narrative review and clinical considerations for older adults.

BACKGROUND The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. OBJECTIVE To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. METHODS The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. RESULTS FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older adults. Finally, several warnings were made about statins. Routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury from statin use; thus, liver enzymes are no longer recommended to be routinely monitored. Statin-induced cognitive changes are rare, and insufficient evidence is currently available to establish causality. Statins appear to moderately increase the risk of developing diabetes (versus placebo), and regular screening for diabetes should be considered, especially for patients taking high-dose statins and patients with multiple risk factors for diabetes. CONCLUSION FDA drug safety communications incorporate complex methodologies that investigate the risks (and relative benefits) of medication therapy. Clinicians caring for older adults need to be aware of the most current evidence behind these drug risks to effectively communicate with and care for their patients.

High-Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long-Term Care Residents: A Randomized Clinical Trial

To determine the efficacy and safety of high‐dose vitamin D supplementation for prevention of acute respiratory infection (ARI) in older long‐term care residents.

Patient-level Medication Regimen Complexity in Older Adults With Depression

PURPOSE Polypharmacy and medication adherence are well known challenges facing older adults. Medication regimen complexity increases the demands of self-care in the home. Some medication regimens may be more complex than others, especially when dosage form, frequency of dosing, and additional usage directions are included in complexity along with the number of medications In older adults with depression, it is unknown what features of their medications most influence their medication regimen complexity. METHODS A sample cohort of 100 adults ≥65 years old with a diagnosis of depression was randomly selected from electronic medical records (EMR) in ambulatory clinics at the University of Colorado (CU) and University of San Diego (SD). Demographic, medical history, and medication-related information was extracted from the EMR. Complexity was determined using the Medication Regimen Complexity Index (MRCI). IRB approval was obtained. FINDINGS The cohort mean age was 74.3 years (SD) and 79.7 years (CU). The mean unweighted Charlson comorbidity index for 1.0 (SD) and 1.8 (CU). The mean number of medications was 7.1 and 8.0, with 1.1 and 1.2 depression meds, 5.4 and 4.3 non-depression prescription meds, and 0.6 and 2.4 OTC meds for the SD and CU cohorts, respectively. 66% of SD adults and 70% of CU adults took six or more meds. Individual MRCI scores were on average 17.62 (SD) and 19.36 (CU). Dosing frequency contributed to 57-58% of the MRCI score, with patients facing an average of 7-8 unique dosing frequencies in their regimen. In both cohorts, there was an average of 3 additional directions added to the regimens to clarify dosing. IMPLICATIONS As expected, in our older adult cohorts with depression the majority of patients took multiple medications. Using a standardized instrument, we characterized the regimen complexity and found that it was increasingly complex due to numerous dosing forms, frequencies and additional directions for use. Patient-level medication regimen complexity should go beyond depression medication to encompass the patients entire regimen for opportunities to reduce complexity and improve ease of self-care.

Timing of ibuprofen use and musculoskeletal adaptations to exercise training in older adults

Prostaglandins (PGs) increase in bone in response to mechanical loading and stimulate bone formation. Inhibition of cyclooxygenase (COX), the enzyme responsible for PG synthesis, by non-steroidal anti-inflammatory drugs (NSAIDs) impairs the bone formation response to loading in animals when administered before, but not after, loading. The aim was to determine whether the timing of ibuprofen use (400 mg before versus after exercise sessions) is a significant determinant of the adaptive response of BMD to exercise training in older adults. We hypothesized that taking ibuprofen before exercise would attenuate the improvements in total hip and lumbar spine BMD in response to 36 weeks of training when compared with placebo or with ibuprofen use after exercise. Untrained women and men (N = 189) aged 60 to 75 years were randomly assigned to 1 of 3 treatment arms: placebo before and after exercise (PP); ibuprofen before and placebo after exercise (IP); and placebo before and ibuprofen after exercise (PI). The difference between groups in the change in BMD was not significant when IP was compared with either PP (hip, − 0.5% (− 1.4, 0.4); spine, 0.1% (− 0.9, 1.2)) or PI (hip, 0.3% (− 0.6, 1.2); spine, 0.5% (− 0.5, 1.5)). Ibuprofen use appeared to have more adverse effects on BMD in women than men. The study demonstrated that ibuprofen use did not significantly alter the BMD adaptations to exercise in older adults, but this finding should be interpreted cautiously. It had been expected that the inhibition of bone formation by ibuprofen would be more robust in men than in women, but this did not appear to be the case and may have limited the power to detect the effects of ibuprofen. Further research is needed to understand whether NSAID use counteracts, in part, the beneficial effects of exercise on bone.

A year in review: new drugs for older adults in 2011.

BACKGROUND New drugs approved by the Food and Drug Administration (FDA) may offer tremendous clinical advances by providing health care providers with new treatment strategies. However, additional care must be taken for safe and effective use of these new agents by older adults. OBJECTIVE Our objective was to identify FDA-approved medications in 2011 most likely to be prescribed to older adults, and to describe medication characteristics that may require special attention in this population. METHODS The FDA Web site was reviewed for new drug approvals from January through December 2011. Approved labeling for each drug was obtained from the manufacturers Web site and PubMed was searched for primary literature published between 1967 and 2012. RESULTS Rivaroxaban, an oral factor Xa inhibitor, is approved for once-daily use in treatment of nonvalvular atrial fibrillation and deep vein thrombosis prophylaxis after replacement of a hip or knee. Drug interactions and renal function must be considered when prescribing this drug to older adults. Fidaxomicin is an oral anti-infective approved for the treatment of Clostridium difficile-associated diarrhea. It has minimal oral absorption or side effects, no relevant drug interactions, but a very high cost. It is a treatment option after failure of oral metronidazole and oral vancomycin. Roflumilast is a selective inhibitor of phosphodiesterase 4 and is approved to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD and a history of exacerbations. It is recommended as a second or alternative choice combined with a long-acting bronchodilator in patients at high risk for hospitalization. Indacaterol is an inhaled long-acting β-agonist approved for COPD maintenance. It is administered once daily, which may improve adherence in older adults compared with currently available twice-daily agents. CONCLUSIONS Four new drugs approved in 2011 applicable to the geriatric population are presented. Clinicians must consider the available evidence, cost, drug-drug interactions, renal function, pharmacokinetic/pharmacodynamic differences, and patient preferences when considering prescribing these agents to older adults.

Assessment of blood pressure in patients with hypertension aged 60–79 years before and after the publication of the 2014 Eighth Joint National Committee report

Objectives: In late 2013, the Joint National Committee (JNC 8) published hypertension treatment recommendations endorsing a goal blood pressure (BP) of < 150/90 mmHg starting at age 60 years. This was in contrast to other cardiovascular groups recommending age 80 years for this BP goal. This study examined mean BP in patients from age 60 years to 79 years with hypertension before and after publication of the JNC 8 recommendations. Methods: This retrospective cohort study examined mean BP and number of antihypertensives for a period of 1 year before and after the release of the JNC 8 report. Patients aged 60–79 years with hypertension receiving care at a University of Colorado Hospital primary care clinic were included. Patients with diabetes, chronic kidney disease, or kidney transplant were excluded. A total of 150 BP measurements were included in each of the before and after time frames. The primary outcomes were change in mean BP and number of antihypertensives. Results: A total of 171 patients met the criteria and were included in the study. Most had BPs in both the before and after time frames. Mean BP values were similar in the before and after groups (130.2/75.9 mmHg versus 131.5/76.6, respectively; p = 0.27/p = 0.46). Mean number of antihypertensives were similar in the before and after groups (1.95 versus 1.93, respectively; p = 0.79). Conclusions: Over 1 year at an academic health system, new recommendations from the JNC 8 did not affect mean BP or number of antihypertensives in older patients with hypertension. A similar investigation after more time or in patients with newly diagnosed hypertension may help determine the full impact.

Priapism Induced by Boceprevir-CYP3A4 Inhibition and α-Adrenergic Blockade: Case Report

A 44-year-old white man presented to the emergency department with a 3-day history of priapism requiring a surgically performed distal penile shunt. A drug-drug interaction is the suspected cause whereby CYP3A4 inhibition by boceprevir led to increased exposures of doxazosin, tamsulosin, and/or quetiapine, resulting in additional α-adrenergic blockade.

Moxifloxacin-induced tinnitus in an older adult

An increased risk of bacterial resistance toward fluoroquinolones and the increased risk of disabling and serious adverse effects prompted the US Food and Drug Administration to recommend limiting fluoroquinolone use to the treatment of community-acquired pneumonia, skin and skin-structure infections, bacterial sinusitis, plague, chronic bronchitis exacerbations, and complicated intra-abdominal infections. We report a case of moxifloxacin-induced tinnitus in an older adult prescribed oral moxifloxacin 400 mg for 5 days for the treatment of acute diverticulitis, due to allergies to nonfluoroquinolone preferred agents. A thorough literature review provided few other reported incidents of this rare and serious adverse event.

Dofetilide-induced anorexia in an older adult

An 84-year-old woman presented to her primary care physician with an unexplained 4-month history of weight and appetite loss after initiation of dofetilide 125 mcg orally twice daily for atrial fibrillation. She was noted to have lost 2.5 kg, which was a 3.6% decrease from her initial body weight of 69.4 kg. After excluding other etiologies for her anorexia, such as medication changes or changes in other diseases or conditions, her primary care physician and cardiologists elected to continue dofetilide but monitor the patient’s appetite and body weight. After 7 months of dofetilide use with persistent appetite loss, the cardiology team discontinued dofetilide. Continued weight loss was observed until approximately 1 month after stopping dofetilide, with a maximum weight loss of 2.9 kg or a 4.2% decrease. Improvements in appetite were reported 2 months after discontinuing dofetilide, with minor increases in weight that eventually stabilized. In this case, while taking dofetilide, the patient experienced anorexia leading to weight loss that subsided after discontinuation of the drug. Based on the temporal association between the patient’s changes in appetite and body weight and treatment with dofetilide, the drug was most likely the cause of the patient’s anorexia. We are unaware of other reports of anorexia associated with dofetilide, but clinicians may want to consider the drug as a potential cause for otherwise unexplained changes in appetite or body weight.