Primecuts – This Week in the Journals

July 25, 2017

50mgtramadolhclakymaKelsey Luoma, MD
Peer Reviewed

Opioid-related morbidity and mortality has reached crisis levels in the United States. According to the CDC, between 1999 and 2014 more than 165,000 people died due to opioid drug overdose [1]. This week, our first article questions whether a multicomponent primary care intervention can mitigate the risk of prescription opioid abuse, thereby potentially saving lives. Next, we’ll review a study on the effects of long-term inhaled corticosteroid use on fracture risk; we’ll compare various non-invasive testing strategies for workup of stable CAD; and, finally, we will address the age-old question of whether glucose self-monitoring in non-insulin-treated T2DM patients actually improves glycemic control. Most importantly, we’ll take a look at whether your coffee addiction—ahem, habit—is associated with mortality risk.

Improving Adherence to Long-term Opioid Therapy Guidelines to Reduce Opioid Misuse in Primary Care

In an effort to mitigate over-prescription of opioids, the CDC and other professional medical societies have published guidelines for medical providers regarding long term opioid prescription. Included in these guidelines are recommendations for patient-clinician agreements, urine drug testing, prescription drug monitoring programs and opioid assessment tools. Unfortunately, observational studies suggest prescriber compliance with these guidelines is poor.

In a JAMA study published online this week, a group of investigators affiliated with Boston Medical Center performed a cluster-randomized clinical trial to examine the effects of a multicomponent intervention on clinician adherence to opioid prescribing guidelines and opioid misuse risk [2]. The study included 53 primary care clinicians (PCCs) and 985 patients on opioid therapy for chronic pain. It was conducted in 4 safety-net primary care practices between January 2014 and March 2016. The multifaceted primary care intervention included nurse care management, electronic registry, academic detailing, and electronic decision tools. This was compared to a control of electronic decision tools alone. Primary outcomes were documentation of guideline-concordant care (both a patient-PCC agreement in the electronic health record and at least one urine drug test) over 12 months and 2 or more early opioid refills. Other outcomes included opioid dose reduction and opioid treatment discontinuation.

Study authors found that patients in the intervention group were significantly more likely to receive guideline-concordant care (65.9% vs 37.8%; P < .001; CI 3.6-10.2), to have a patient-PCC agreement (53.8% vs 6.0%; P < .001; CI 4.4-32.2) and to undergo at least 1 urine drug test (74.6% vs 57.9%; P < .001; CI 1.8-5.0) compared with controls. There was no difference in early opioid refills between groups (20.7% vs 20.1%; CI 0.7-1.8). With respect to secondary outcomes, primary care providers in the intervention group were more likely to discontinue opioid treatment (21.3% vs 16.8%; P = .04; CI 1.02-2.1), and to decrease opioid dose of patients remaining on therapy (32.8% vs 22.9%; P = .01; CI 1.1-2.4). In this study, a multifaceted primary care intervention resulted in improved adherence to established guidelines regarding opioid prescription. Although there was no significant difference in early opioid refill between intervention and control groups, rates of opioid discontinuation and opioid dose reduction were higher in the intervention group. These findings suggest that a comprehensive multidisciplinary approach can successfully mitigate opioid overuse, and similar interventions should be further studied. Long-term use of inhaled corticosteroids in COPD and the risk of fracture

Use of inhaled corticosteroids (ICS) for management of chronic obstructive pulmonary disease (COPD) is widespread and becoming increasingly common. These medications, however, are not without risk. Observational studies have shown that ICS use is correlated with decreased bone-mineral density in a dose-dependent fashion [3,4]. Whether or not this decrease in bone mineral density translates into fracture risk remains unclear as existing evidence has been conflicting.

To characterize fracture risk associated with long term ICS use in COPD patients, a group of researchers in Montreal, Quebec performed a nested case-control analysis with a cohort of 240,110 subjects aged 55 or older, who were newly treated for COPD between 1990 and 2005 [5]. During a mean follow-up of 5.3 years, 19,396 fracture cases were selected based on the occurrence of a first hip or upper extremity fracture. These were subsequently age- and sex-matched to 384,478 control person-moments. Study authors found a modest but significant increase in fracture risk with prolonged courses of high dose ICS. Specifically, for those treated with at least 1000 mcg in fluticasone-equivalents for a duration of greater than 4 years, there was a 10% increase in risk of hip or upper extremity fracture (RR 1.10; 95% CI 1.02-1.18). Fracture risk was not significantly increased with ICS treatment courses of < 4 years. Furthermore, the risk increase was not higher in post-menopausal women compared to men. This study adds to the existing literature which suggests that high doses of inhaled corticosteroids affects bone mineral density and can increase risk of fracture in our patients. This is an important lesson for all prescribers to internalize. While many reach to inhaled corticosteroids for treatment of COPD patients with hardly a second thought, this study reminds us to think twice, and perhaps double-check the guidelines for ICS therapy, before signing that script.
Comparison of Anatomic and Clinical Outcomes in Patients Undergoing Alternative Initial Noninvasive Testing Strategies for the Diagnosis of Stable Coronary Artery Disease

Multiple modalities exist for evaluation of suspected stable coronary artery disease. While American guidelines recommend the use of exercise stress test as first line when possible, European guidelines suggest that, in certain groups, stress imaging tests (myocardial perfusion imaging, stress echo) or coronary CTA may be preferred.

This week in the Journal of the American Heart Association (JAHA), a retrospective cohort study examined the relationship between initial non-invasive testing modality and obstructive CAD on invasive angiography [6]. This study used population data from health insurance claims in Ontario, Canada. Adults 20 years of age or older who had undergone one non-invasive test (exercise stress test, myocardial perfusion imaging, stress echo, or coronary CTA), followed by invasive angiography within 6 months, were included. The study’s primary outcome was presence of obstructive CAD on invasive angiography. As a secondary outcome, a composite end-point of all-cause mortality and hospitalization for acute myocardial infarction or unstable angina was evaluated. After a mean follow up of 1.89 years, neither outcome was found to be significantly different amongst the 4 initial testing strategies. Patients who had undergone myocardial perfusion imaging (OR 0.97; CI 0.91-1.04), coronary CTA (OR 1.31; CI 0.89-1.92) or stress echo (OR 0.92; CI 0.82-1.02) did not have significantly different odds of having obstructive CAD compared with subjects who had been initially evaluated with exercise stress test. Furthermore, adjusted analysis showed no statistically significant difference in the composite endpoint—all-cause mortality and hospitalization for MI or unstable angina—between the various initial testing strategies.

While this study certainly has limitations—lack of data on patients with negative non-invasive test results for example—its implications are important. With no statistically significant difference in real-world outcomes amongst various non-invasive testing modalities, these results do not support the routine use of stress imaging or coronary CTA in the workup of stable CAD. In other words, for now we should continue to rely on exercise stress test for initial workup of stable CAD, when possible, as recommended by current American guidelines.

Glucose Self-monitoring in Non-Insulin-Treated Patients with Type 2 Diabetes in Primary Care Settings: A Randomized Trial

There is disagreement on whether self-monitoring of blood glucose (SMBG) has value for patients with non-insulin treated type 2 diabetes mellitus (T2DM). Some trials have shown that SMBG improves glycemic control while others have shown no benefit.

In a randomized controlled trial published in JAMA this week, the authors addressed the question of whether or not SMBG effectively improves hemoglobin A1c levels or health-related quality of life in people with non-insulin-treated T2DM [7]. Three approaches of SMBG were compared in a pragmatic, open-label randomized trial conducted in 15 primary care practices in central North Carolina. 450 adult patients with T2DM with hemoglobin A1c (HbA1c) between 6.5 and 9.5% were randomized to either no SMBG, once-daily SMBG, and once-daily SMBG with enhanced patient feedback. Primary outcomes included HbA1c levels and health-related quality of life at 52 weeks. At the study’s end, there were no significant differences in HbA1c levels across all 3 groups (P = .74; estimated adjusted mean hemoglobin A1c difference, SMBG with messaging vs no SMBG, -0.09%; 95% CI -0.31% to 0.14%; SMBG vs no SMBG, -0.05%; 95% CI -0.27% to 0.17%). Additionally, there were no significant differences in health-related quality of life.

This study shows that, in a real-world setting, self monitoring of blood glucose did not result in improved glycemic control or health-related quality of life, even when done in conjunction with a telehealth intervention. Interestingly enough, however, in the early months of the intervention there did appear to be a statistically significant difference in hemoglobin A1c level between the three groups. As patient compliance fell off over time, the statistical significance was lost as well, suggesting that effectiveness of SMBG may depend on patient motivation. We can conclude that the decision to initiate SMBG should be made on a case-by-case basis, as some patients, especially those who are highly motivated to comply, may indeed benefit from it.


Palliative Care
We have all seen patients reap tremendous benefit from the expert care of our palliative care specialists. But what affect does palliative care referral really have on quality of life in patients with advanced illness? A systematic review and meta-analysis published in the British Medical Journal seeks to answer this intriguing question [8].

PPIs and Memory Loss?

It’s no secret that certain drugs have effects on memory and may be associated with risk of dementia (benzodiazepines and anticholinergic medications come to mind). But should we be concerned about the effects of proton pump inhibitors on risk of Alzheimer’s disease? A study published in the American Journal of Gastroenterology asks exactly that [9].

A Cup of Coffee a day…

Coffee—elixir of life or perfect poison? This week, a prospective cohort study spanning 10 European countries examines the effect of coffee consumption on all-cause and cause-specific mortality [10].

Dr. Kelsey Luoma is a 2nd year Internal Medicine Resident at NYU Langone Health

Peer Reviewed Ian Henderson, MD, Contributing Editor and a Chief Resident in Internal Medicine at NYU Langone Health

Image courtesy of Wikimedia Commons


1. CDC. Multiple cause of death data on CDC WONDER. Atlanta, GA: US Department of Health and Human Services, CDC; 2016.

2. Liebschutz JM, Xuan Z, Shanahan CW, et al. Improving Adherence to Long-term Opioid Therapy Guidelines to Reduce Opioid Misuse in Primary Care JAMA Intern Med. 2017 July 17 [Epub ahead of print]. Accessed July 20, 2017

3. Israel E, et al. Effects of inhaled glucocorticoids on bone density in premenopausal women. New England Journal of Medicine, 2001.

4. Wong CA, et al. Inhaled corticosteroid use and bone mineral density in patients with asthma. Lancet, 2000.

5. Gonzales AV, et al. Long-term use of inhaled corticosteroids in COPD and the risk of fracture. Chest. 2017 Jul 14 [Epub ahead of print]. Accessed July 20, 2017.

6. Roifman I, et al. Comparison of Anatomic and Clinical Outcomes in Patients Undergoing Alternative Initial Noninvasive Testing Strategies for the Diagnosis of Stable Coronary Artery Disease. Journal of the American Heart Association. 2017 Jul 19. Accessed July 20, 2017.

7. Young LA, et alGlucose Self-monitoring in Non-Insulin-Treated Patients With Type 2 Diabetes in Primary Care Settings: A Randomized Trial. JAMA Intern Med 2017 Jul. Accessed July 24.

8. Gaertner J, et al. Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: a systematic review and meta-analysis. BMJ 2017 July 4; 357:j2925.

9. Taipale H, et al. No association between proton pump inhibitor use and risk of alzheimer’s disease. Am J Gastroenterol. 2017 July 11 [Epub ahead of print]. Accessed July 20, 2017.

10. Gunter MJ et al. Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study. Ann Intern Med. 2017 Jul 11. Accessed July 20, 2017.