Curbing the use of nonprescription antibiotics

- Jennifer Middleton, MD, MPH

A just-published review found that antibiotics remain readily available in the United States without a prescription. The authors found that between 1-66% of studied populations reported possession and/or planned use of antibiotics obtained from sources other than a prescriber's order. With implications for both personal side effects and population-wide antibiotic resistance, examining the factors contributing to nonprescription antibiotic use may lead to some solutions.

The authors performed a scoping review with the goal of answering these two questions: "What are the prevalence, sources, and characteristics of nonprescription antibiotic use in the US, and what are the factors influencing it?" They identified 31 articles that met their inclusion criteria:

Several studies focused on the availability of antibiotics without a prescription from flea markets, pet stores, botanical or health food stores, or online. Others explored nonprescription use from a range of sources, including leftover prescribed courses, markets or stores, family or friends, and antibiotics obtained without a prescription from other countries. In 1 study, patients in an STI clinic and a county jail were interviewed about self-treatment with antibiotics. All studies of injection drug users examined self-treatment of abscesses and injection-related wounds with antibiotics obtained on the street.

In reviewing these studies, the authors identified several factors that influenced nonprescription use of antibiotics; wait times to see a physician, cost of the physician visit, and lack of transportation were prominent as might be expected, but concerns about judgment by healthcare staff when seeking care for sexually transmitted infections and injection-drug-use-related infections were also noted. Of course, the ready availability of antibiotics from a multitude of sources enabled nonprescription use, too.

According to the basic tenets of health behavior theory, most adults make decisions about their health that they deem rational in the context of their knowledge, environment, and social norms. It makes sense, for example, that persons with ready access to antibiotics who are concerned about the cost and/or stigma of seeking medical care would choose the easier route of bypassing the physician's office. Tackling the problem of antibiotic resistance may need to include efforts to reduce barriers and stigma around receiving treatment for more potentially sensitive conditions.

The AAFP's Everyone Project toolkit contains a wealth of resources to help your patients who have barriers to accessing healthcare. The Canadian Public Health Association has a toolkit to help practices identify and decrease stigmatizing language and behaviors. Limiting inappropriate antibiotic prescribing remains important, too, as Dr. Lin and I discussed on an AFP tweet chat back in 2017; here are the AFP references we used, which contain pragmatic, evidence-based strategies for reducing antibiotic overuse.

Antibiotic overuse remains a complex challenge, and hopefully we'll see future studies continuing to address not only its multifaceted causes but also successful strategies to combat them.

Deliberate clinical inertia: protecting patients from low value care

- Kenny Lin, MD, MPH

Clinical inertia is usually considered to be a negative term, used to refer to situations in which clinicians do not appropriately initiate or intensify therapy for uncontrolled chronic conditions. For example, a recent study in JAMA Internal Medicine found that less than one-quarter of patients with chronic hypercalcemia in the Veterans Affairs health system received parathyroid hormone level testing, and only about 13 percent of patients who met diagnostic criteria for primary hyperparathyroidism underwent parathyroidectomy.

However, clinical inertia has also been described as a "clinical safeguard" against aggressive consensus guideline prescriptions that do not account for patient preferences and/or potential harms of intensifying treatment. For example, an analysis of the incremental benefits of and harms of the 2017 American College of Cardiology / American Heart Association guideline that redefined hypertension as a sustained blood pressure of >= 130/80 mm Hg concluded:

For most adults newly classified as having high blood pressure under the ACC/AHA guideline (the 80% of those newly diagnosed who have <10% 10-year risk), there is no incremental benefit in CVD risk reduction, but potential incremental harms from disease labeling, and, for those who meet the threshold for drug treatment, from adverse drug effects.

In this instance, a large number of patients with systolic blood pressures between 130 and 140 mm Hg could potentially benefit from clinical inertia by avoiding a hypertension diagnosis, additional testing, or prescription medications.

In a 2011 JAMA commentary, Drs. Dario Giugliano and Katherine Esposito observed that clinical inertia "also may apply to the failure of physicians to stop or reduce therapy no longer needed," but that "this neglected side of clinical inertia does not seem to generate as much concern among physicians or scientific associations." A review of polypharmacy in the July 1 issue of AFP noted that regular use of at least five medications is associated with decreased quality of life, increased mobility problems and falls, greater health system use, and increased long-term care placement. As discussed in a previous AFP Community Blog post, judicious deprescribing can help reduce polypharmacy and improve patient outcomes.

Another (sometimes better) strategy is not starting nonbeneficial medications for unclear reasons in the first place. In a 2018 article in Emergency Medicine Australasia, Dr. Gerben Keijzers and colleagues defined "deliberate clinical inertia" as "the art of doing nothing as a positive response." Arguing that doctors generally have a bias to intervene with diagnostic tests, drugs, or procedures, they suggested reframing the typical decision-making approach:

In clinical practice, 'risk versus benefit' is usually considered in terms of missing a diagnosis rather than potential risks of treatment, so a better approach to care may be to ask, 'Is this intervention more likely to cause harm than the underlying condition with its possible harm or risk?' There are many reasons why 'doing nothing' is difficult, but doing what we can to provide excellent care while preventing medical harm from unnecessary interventions must become one of the pillars of modern holistic healthcare.

Family physicians may readily grasp the rationales behind campaigns to avoid harms and costs of low value care such as Choosing Wisely and Right Care, but our patients often need convincing. Dr. Keijzers and colleagues suggested several ways to support deliberate clinical inertia in practice: empathy and acknowledgment; symptom management; clinical observation; explanation of the natural course of the condition; managing expectations; and shared decision-making ("communicating rather than doing").

Updates in CVD diagnosis, treatment, and prevention

- Jennifer Middleton, MD, MPH

Updates on diagnosis, treatment, and prevention of cardiovascular disease (CVD) abounded in the medical literature over the last month. While these studies' findings were largely non-significant or limited, they still provide clarity regarding current best practices while paving the way for future research.

First, the search for a clinical decision rule to stratify patients presenting to primary care with chest pain regarding risk of acute coronary syndrome (ACS) will have to continue, as the results of a "flash mob" study, published this month in the Annals of Family Medicine, failed to validate the Marburg Heart Score for use in primary care. The investigators recruited nearly 20% of the family physicians in the Netherlands to gather data on patients with suspected ACS during a 2 week time period. The family physicians sent information back to the investigators using a brief case report form, filed either electronically or on paper. Although the study results were disappointing, the feasibility of this novel research method was more promising. Perhaps we'll see more "flash mob" studies in the near future.

In an AFP Medicine By the Numbers summary out today, a Cochrane review of early reperfusion therapy in patients with STEMI received a "no benefits" rating by the thennt.com. The meta-analysis examined data from 8 randomized controlled trials including a total of over 8900 participants, all with chest pain at rest and either EKG changes consistent with STEMI (ST-segment myocardial infarction), NSTEMI (non-ST-segment myocardial infarction), or a previously established diagnosis of coronary artery disease. Participants were randomized to either receive reperfusion immediately or to receive medical therapy first with reperfusion only if symptoms persisted. There was no mortality benefit to early reperfusion, and participants who underwent early reperfusion were also more likely to have a periprocedural myocardial infarction (MI) or a major bleeding event. The risk of these adverse events was deemed to outweigh the found benefits of increased relief from refractory chest pain, decreased repeat hospitalization, and decreased risk of a susbsequent MI in the next year with early reperfusion.

Finally, an umbrella review (a systematic review of prior meta-analyses) sought to identify the best current evidence regarding diet changes and supplements on improving CVD outcomes. These investigators found moderate quality evidence to support reduced salt intake (lower all-cause mortality in individuals without hypertension, and lower cardiovascular mortality in individuals with hypertension). Lower quality evidence correlated omega-3-fatty-acid intake with lower risks for MI and CAD. Folic acid intake correlated with lower stroke risk, though the authors caution that this finding was largely driven by a study based in China, where fewer foods are fortified with folate than in the United States. Interestingly, calcium and vitamin D intake correlated with a higher stroke risk. "Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary inter- ventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low– to moderate-certainty evidence)." Given the relative low quality of many studies, the authors' call for further, more rigorous research is understandable.


Studies finding a lack of benefit (the Marburg score "flash mob" and the early reperfusion meta-analysis) are still useful to help family physicians avoid harm and to spur the search for better alternatives. Hopefully, more rigorous research will come to verify the findings of the nutrition and supplement umbrella review. We'll look forward to reporting on these hoped-for follow-up studies; in the meantime, what research would you like see to regarding CVD in primary care?

Drugs for patients with chronic heart failure: making evidence-based choices

- Kenny Lin, MD, MPH

Two regular features in the July 1 issue of AFP addressed medication management for patients with chronic heart failure.

In Cochrane for Clinicians, Dr. Pamela Obi discussed a 2018 Cochrane review that evaluated whether therapies that improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) also help patients with heart failure with preserved ejection fraction (HFpEF). The review included 37 randomized controlled trials (RCTs) with more than 18,000 patients; outcomes assessed included cardiovascular mortality, heart failure hospitalization, all-cause mortality, and quality of life. Beneficial drug classes included mineralocorticoid receptor antagonists (reduce hospitalizations, NNT=42) and beta blockers (reduce cardiovascular mortality, NNT=26). Curiously, although the review found no benefits from angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), the American College of Cardiology recommends considering ARB treatment to reduce hospitalizations in persons with HFpEF.

In FPIN's Help Desk Answers, Drs. Scott Christensen and Rebecca Davis investigated whether the combination of an ACE inhibitor and an ARB improves cardiovascular or overall mortality in patients with symptomatic HFrEF or HFpEF. A 2012 meta-analysis of 7 RCTs (n=8,260) comparing dual therapy vs. monotherapy found that dual therapy was associated with fewer myocardial infarctions and heart failure hospitalizations, but no changes in mortality. Dual therapy was also associated with a greater risk of patients withdrawing from trials due to adverse drug effects (RR=1.34). A small 2008 RCT found that patients with heart failure who received irbesartan in addition to an ACE inhibitor had improvements in disease-oriented outcomes (6-minute walk test distance, metabolic equivalents achieved) and quality of life, but no difference in a composite outcome of mortality and cardiovascular hospitalizations. Overall, the benefits of dual therapy seem to be outweighed by the harms.

Clinicians seeking additional information on diagnosis and management of acute and chronic heart failure should also check out our AFP By Topic collection.

Helping our patients reduce unhealthy alcohol use

- Jennifer Middleton, MD, MPH

The June 15 issue of AFP includes several excellent resources to aid family physicians in efficiently and effectively responding to unhealthy alcohol use. With an estimated 88,000 deaths every year in the United States related to alcohol, screening and intervening can be lifesaving and are recommended by the United States Preventive Services Task Force (USPSTF) (B recommendation).

This AFP USPSTF update article reviews the definition of unhealthy alcohol use:

The USPSTF uses the term unhealthy alcohol use to define a spectrum of behaviors, from risky drinking to alcohol use disorder (e.g., harmful alcohol use, abuse, dependence). Risky or hazardous alcohol use means drinking more than the recommended daily, weekly, or per-occasion amounts, resulting in increased risk for health consequences but not meeting criteria for alcohol use disorder.

The article discusses optimal screening instruments, all of which are very brief, such as the AUDIT-C and the SASQ. The perhaps better known CAGE is less useful because it can miss risky alcohol use that doesn't meet criteria for alcohol dependence disorder. A positive screen should prompt follow-up with a more in-depth instrument such as AUDIT. The meta-analysis that informed the USPSTF recommendation statement, however, noted that in "population groups with lower prevalence of unhealthy alcohol use—older adults, pregnant women, and adolescents—the estimated positive predictive value [of AUDIT] was much lower." For older adults, consider using CARET, and, for pregnant women, consider using TWEAK or T-ACE. Although the USPSTF deemed the evidence insufficient for making a recommendation regarding screening adolescents (I recommendation), CRAFFT is one tool available for family physicians wishing to screen this group.

The USPSTF found that a median of 30 minutes of brief intervention was effective in reducing unhealthy alcohol use. Screening, Brief Intervention, and Referral to Treatment [SBIRT] was commonly employed in these studies as was motivational interviewing, simple education regarding alcohol consumption recommendations, and several cognitive behavioral strategies. 6-12 months following these interventions, the previously mentioned meta-analysis found a mean decrease of 1.6 drinks per week; in binge drinkers (heavy episodic use), total drinks per week decreased from a mean of 26.0 to a mean of 19.1. Trials in pregnant women, which tended to use abstinence as an outcome, found a pooled odds ratio [OR] for abstinence after intervention, compared to no intervention, of 2.26 (95% CI, 1.43 to 3.56). 

After reading the AFP USPSTF update article, you can test your knowledge by reviewing these case studies and accompanying answers. The Substance Abuse and Mental Health Services Administration's (SAMHSA) SBIRT website includes a lengthy list of online resources covering different patient care settings with a variety of methods (articles, videos, patient education, and even a free online training course). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has both in-depth and pocket guides titled "Helping Patients Who Drink Too Much" available online. This FPM article, referenced in an accompanying AFP editorial, reviews alcohol screening and brief intervention strategies, includes an excellent 4-minute video example of a brief intervention, and also reviews billing and coding for these services.