Hyaluronic acid injections don't help knee DJD

- Jennifer Middleton, MD, MPH

Options for helping patients with knee degenerative joint disease (DJD) seem to be getting more limited. A POEM in the April 15 AFP reviews a meta-analysis showing that hyaluronic acid injection is no better than sham injection for treating pain from knee DJD. This meta-analysis confirms what other recent studies have found; hyaluronic acid injections don't meaningfully help patients with knee DJD.

The meta-analysis included 19 randomized controlled trials comparing hyaluronic acid injections to sham injections (14 trials), usual care (2 trials), or combined with some other treatment (3 trials). The non-blinded trials did show modest improvement in pain scores, but the double-blinded trials showed negligible improvements, if any. Although early studies of hyaluronic acid suggested it was effective, these studies tended to be small and were frequently unblinded or inadequately blinded. Higher quality double-blinded studies, especially when considered in aggregate in this meta-analysis, did not confirm this benefit.

The placebo effect can be powerful, as evidenced by participants' perceived improvements in the non-blinded trials compared to the double-blind trials. And, perhaps, that is not always a negative; I suspect those participants who did feel better in the non-blinded trials were pleased with the improvements they noted in their pain. Unfortunately, the placebo effect with hyaluronic acid comes with cost and risk; injections can cost hundreds of dollars for one dose, and typical therapeutic regimens involve a series of 3-5 injections over several weeks. Injecting into a joint is also not a zero-risk procedure; although rare, serious complications like joint infection can occur.

Hyaluronic acid injections' limitations should not come as a surprise; a web search of "hyaluronic acid knee injections" reveals many critical lay press articles over the last couple of years, and the American Association of Orthopedic Surgeons (AAOS) even states "We cannot recommend using hyaluronic acid for symptomatic arthritis of the knee" in their Summary of Recommendations for Treatment of Osteoarthritis of the Knee (which was cited in this 2014 AFP article). I suspect, though, that I am not alone in seeing this intervention still commonly offered for patients, both by family physician colleagues and local orthopedists. 

With glucosamine and chondroitin also now out of favor for treating knee DJD, non-surgical options for helping patients are currently limited to oral analgesics and, possibly, intra-articular corticosteroid injections - though the AAOS cites a lack of data regarding corticosteroid injections' efficacy in their summary statement as well. Given the prevalence of knee DJD, we can only hope that researchers are investigating novel treatment methods to help those patients who are not yet (or will never be) candidates for knee joint replacement.

You can read more at the AFP By Topic on Arthritis and Joint Pain, and you might also want to check out the Choosing Wisely recommendations from the AAOS (though Dr. Lin critiqued the limitations of these recommendations in this post from last year). The AFP Choosing Wisely search tool is a handy way to review other interventions shown to be of little utility for orthopedic conditions as well as other specialties; you can access it from the AFP home page or bookmark it on your personalized AFP Favorites page.

How are you treating knee DJD in your office?

Obstacles to stopping cancer screening in older adults

- Kenny Lin, MD, MPH

I recognized a glitch in my electronic medical record's decision support software when it prompted me to consider prostate and colorectal cancer screening in a 93 year-old man, who, though remarkably vigorous for his age, was unlikely to live for the additional 10 years needed to benefit from either test. Although deciding not to screen this patient was easy, determining when to stop cancer screening in older patients is often more challenging. In the April 15th issue of American Family Physician, Drs. Brooke Salzman, Kathryn Beldowski, and Amanda de la Paz present a helpful framework for decision making in these clinical situations, where population-level guidance derived from studies of screening younger patients "generally do not address individual variations in life expectancy, comorbid conditions, functional status, or personal preference."

The authors recommend that clinicians take into account not only average life expectancy at a given age, but also significant variations in life expectancy linked to functional impairment and comorbid conditions, using one or more validated prognostic tools. Although the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence about screening mammography in women 75 years or older, modeling studies suggest that women with projected life expectancies of greater than 10 years may still benefit from this test - with these important caveats:

Although the sensitivity and specificity of mammography increase with age, overdiagnosis also increases because of reduced life expectancy and an increased proportion of slower-growing cancers. In other words, women with breast cancer diagnosed at an older age are more likely to die of something else, compared with younger women. In addition, treatment of breast cancer in advanced age is associated with greater morbidity, including an increased risk of postoperative complications and toxicity from chemotherapy.

Similar considerations apply to screening for colorectal cancer, which the USPSTF made a "C" grade recommendation (small population-level benefit, use individual decision making) for adults 76 to 85 years of age and recommended against screening adults older than 85 years, when the harms clearly exceed the potential benefits. Nonetheless, surveys have found that 31% of adults age 85 years and older, and 41% of adults with a life expectancy of less than 10 years, received screening colonoscopies. To discourage overuse of cancer screening without alienating patients, the authors advise: "It is important to convey that a decision to stop cancer screening does not translate into decreased health care. Rather, discussions can focus on health promotion strategies that are most likely to benefit patients in the more immediate future, such as exercise and immunizations."

A recent qualitative study in JAMA Internal Medicine explored the reluctance of primary care clinicians to explicitly incorporate long-term prognosis in the care of older adults. Most study participants relied on their own clinical experience, rather than validated tools, to estimate a patient's life expectancy, and were reluctant to stop screening in relatively younger patients even with limited life expectancies. Barriers mentioned by participants included inadequate training, time constraints, concern about negative patient reactions, competing practice incentives, and fear of lawsuits. Do you share these concerns? What strategies do you use to communicate with an older adult whose age or life expectancy suggests stopping cancer screenings?

What we say when we don't give an antibiotic matters

- Jennifer Middleton, MD, MPH

Most patients with upper respiratory infections (URIs) and/or sinusitis don't need an antibiotic, but many physicians still receive requests for one. Physicians may use language to describe the viral nature of the infection, stating perhaps that it's "only a virus" or otherwise implying that the illness is not serious enough to mandate an antibiotic. This type of wording may, paradoxically, increase some patients' belief in the utility of antibiotics, as demonstrated by a recent qualitative study published in the Annals of Family Medicine.

Cabral et al video-recorded 60 encounters of children, ages 3 months to 12 years, seen in primary care offices in the United Kingdom with URI symptoms. They then interviewed some of the children's parents after the visit to learn more about their beliefs regarding antibiotics and URIs. They found that parent belief regarding the lack of utility of antibiotics for viral infections was overall high, but this belief did not always translate into reassurance when one was not provided. Parents who felt that their child's illness was minor were reassured, but parents who felt that their child was significantly ill (which typically correlated with disrupted sleep and/or length of illness) felt oppositely, that their physician was trivializing their child's illness by not deeming it "serious enough" to justify an antibiotic.

Interestingly, physicians in this study used different language with parents to describe the child's illness according to their decision to prescribe antibiotics. If not prescribing antibiotics, they would often describe concrete physical exam findings and observations that they felt were reassuring about a lack of a bacterial cause; if prescribing antibiotics, they would instead describe more subjective concerns about worrisome symptoms, especially if these symptoms were worsening. The researchers deduced that this symptom-driven language further reinforced the parents' beliefs that antibiotics are needed for more serious illness, as most parents found the descriptions of concrete physical exam findings in children not receiving antibiotics reassuring.

This study will change the way I speak with parents - and adult patients - about my decision not to prescribe antibiotics. I will make sure not to trivialize their concerns or refer to an illness as "just" a virus, and I will aim to use objective language to describe my rationale either way. Despite rigorous evidence showing that antibiotics insignificantly aid recovery and can cause adverse effects, as many as 80% of patients who present with an URI and/or sinusitis are prescribed one.  The Choosing Wisely campaign reminds us to avoid prescribing antibiotics for URIs in adults and in children. Besides recommending supportive care, nasal corticosteroids are a treatment option in adults with acute sinusitis as well. This 2012 AFP article reviews other treatment options for URIs in adults and children.

You can find AFP's Choosing Wisely search tool here, and there's also an AFP By Topic on Upper Respiratory Tract Infections if you'd like to read more. Family Practice Management featured an article last year, co-authored by Dr. Lin, on implementing the Choosing Wisely recommendations in your office, and they also published this handy resource on coding URIs using ICD-10.

How are you responding to requests for antibiotics from patients with URIs?

Patient-centered diabetes research needs primary care perspectives

- Kenny Lin, MD, MPH

A Letter to the Editor in AFP's March 15th issue pointed out that a simplified management algorithm in a previous article on noninsulin therapies for type 2 diabetes could have been misinterpreted to suggest the non-recommended combination of a dipeptidyl-peptidase-4 (DPP-4) inhibitor and a glucagon-like-peptide-1 (GLP-1) receptor agonist. According to the American Diabetes Association's 2016 Standards of Medical Care in Diabetes, however, there is little comparative data to guide second-line drug choice after metformin. Few other medications have been shown to lower mortality in patients with type 2 diabetes, and even then only in specific populations, as Dr. Middleton discussed in a recent AFP Community Blog post.

The National Institutes of Health is currently recruiting patients for a multicenter randomized trial, the Glycemia Reduction Approaches to Diabetes: A Comparative Effectiveness (GRADE) study, that will compare the benefits and harms of four medications commonly combined with metformin: 1) glimepride (a sulfonylurea); 2) sitagliptin (a DPP-4 inhibitor); 3) liraglutide (a GLP-1 receptor agonist); and 4) glargine insulin. Since the GRADE study was planned, the sodium glucose cotransporter 2 (SGLT-2) inhibitor class has come on the market, and a randomized trial found that empagliflozin reduces cardiovascular and all-cause mortality in patients with established cardiovascular disease and type 2 diabetes. This surprising result led some experts to suggest that SGLT-2 inhibitors be added to the GRADE trial or incorporated into some other comparative research study.

This kind of pragmatic diabetes research would seem to be a perfect fit for the Patient-Centered Outcomes Research Institute (PCORI). Created by the Affordable Care Act, PCORI's mission is to "improve the quality and relevance of evidence available to help patients, caregivers, clinicians, employers, insurers, and policy makers make informed health decisions" by funding comparative clinical effectiveness research and research methods. However, PCORI received criticism recently after an independent analysis of its first 6 funding cycles by the American Academy of Family Physicians' Robert Graham Center concluded that "less than one-third of PCORI studies involve or are relevant to primary care."

Last month, I represented the AAFP in the PCORI stakeholder workshop "Prioritizing Comparative Effectiveness Research for Second-Line Type 2 Diabetes Treatment." Other workshop participants included fellow primary care clinicians and representatives from relevant subspecialty societies, patient groups, benefits managers, clinical investigators, and the pharmaceutical industry. After listening to presentations on recent trials and the GRADE study, we were asked to formulate a research question in the PICO (Population, Intervention, Comparator, Outcome) format, keeping in mind the following criteria: patient-centeredness, health impact of the condition, assessment of current options, likelihood of implementation in practice, and durability of information.

I was impressed by the high quality of the discussion and the group's determination to come up with practical research questions that would provide meaningful answers to better inform family physicians and other clinicians who care for patients with type 2 diabetes. PCORI Executive Director Joe Selby, MD, MPH, who is also a family physician, told me how important it was to him that Family Medicine be actively engaged in shaping the organization's research agenda and priorities. For interested readers, PCORI offers many opportunities to get involved that range from suggesting new research questions, to providing input on current questions and methods, to serving on standing advisory panels on various cross-cutting topics.