• Top POEMs of 2020

    American Family Physician's annual collection of the top 20 research studies for primary care addresses a variety of topics with the potential to change practice. A group of primary care clinicians with expertise in evidence-based practice rated these studies highly based on their clinical relevance, validity, and reported outcomes. Known as POEMs, for patient-oriented evidence that matters, the studies are organized by topic and summarized with a clinical question, bottom-line answer, and brief discussion.

    See related AFP article, "Top 20 Research Studies of 2020 for Primary Care Physicians."

    Top POEMs Collection

    COVID-19

    COVID-19 Research Briefs: Handwashing Reduces Transmission of Respiratory Infections

    Clinical question
    Can advice to wash hands frequently reduce the transmission of respiratory infections?

    Bottom line
    A brief online handwashing intervention reduced respiratory infections.

    Reference
    Little P, Stuart B, Hobbs FD, et al. An internet-delivered handwashing intervention to modify influenza-like illness and respiratory infection transmission (PRIMIT): a primary care randomised trial. Lancet 2015;386(10004):1631-639.

    Study design: Randomized controlled trial (nonblinded)

    Allocation: Concealed

    Setting: Population-based

    Synopsis
    Research Brief #4 (Little, 2015) A UK trial randomized 20,066 persons living in households with others to receive either access to a brief online handwashing intervention or no access. The primary outcome - the likelihood that a participant had a respiratory tract infection during a 4-month period - was decreased in the intervention group (51% vs 59%; P < .001; number needed to treat [NNT] = 12). The intervention also decreased the number of gastrointestinal infections (21% vs 25%; P < .001; NNT = 25) and the number of respiratory infections in a household member (44% vs 49%;P < .001; NNT = 20). The intervention has been updated for COVID-19 and is freely available at germdefence.org.

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    COVID-19 Research Briefs: SR Shows Consistent Benefit of Quarantine Measures to Reduce the Spread of An Epidemic

    Clinical question
    Do quarantine measures reduce the spread of infection during a pandemic?

    Bottom line
    High-quality evidence shows that quarantine measures, particularly in conjunction with other public health measures, are consistently effective for reducing the spread of an epidemic.

    Reference
    Nussbaumer-Streit B, Mayr V, Dobrescu AI, et al. Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review. Cochrane Database Syst Rev 2020;4:CD013574. Published 2020 Apr 8. doi:10.1002/14651858.CD013574.

    Study design: Systematic review

    Setting: Various (meta-analysis)

    Synopsis
    Research Brief #10: The Cochrane Collaboration published a Rapid Review on April 8, 2020, that evaluated 29 studies: 10 modelling studies of COVID-19, 4 observational studies, and 15 modelling studies of SARS or MERS. This review demonstrates that quarantine measures are consistently found to be effective in damping the spread of an epidemic. Quarantine is most effective when implemented early and in conjunction with other public health measures, such as closing schools, restricting travel, and social distancing. The Ohio Department of Health released this clever public service announcement illustrating why social distancing works: https://www.youtube.com/watch?v=YxVxc6ccqtQ.

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    COVID-19 Research Briefs: Stay-at-Home and Social Distancing Policies Are Effective at Reducing the Spread of SARS-CoV-2

    Clinical question
    Do stay-at-home orders or social distancing policies reduce the spread of COVID-19?

    Bottom line
    Retrospective data suggest that the implementation of stay-at-home and social distancing policies in US counties slowed the spread of COVID-19.

    Reference
    Lyu W, Wehby GL. Comparison of estimated rates of coronavirus disease 2019 (covid-19) in border counties in Iowa without a stay-at-home order and border counties in Illinois with a stay-at-home order. JAMA Netw Open. Published online May 1, 2020. doi:10.1001/jamanetworkopen.2020.11102.

    Ebell MH, Bagwell-Adams G. Mandatory social distancing associated with increased doubling time: an example using hyperlocal data. Am J Prev Med. Pre-proof published online 2020. doi: https://doi.org/10.1016/j.amepre.2020.04.006.

    Study design: Cross-sectional

    Setting: Not applicable

    Synopsis
    Research Brief #28: This study compared daily changes in COVID-19 cases in 8 Iowa counties that border Illinois (where no stay-at-home orders were in place) with 7 Illinois counties that border Iowa (where stay-at-home orders were in place). Sensitivity analysis was used to account for differences in other factors, such as the closing of schools and nonessential businesses, county population densities, and poverty rates. Trends in cumulative COVID-19 incidence were compared before and after March 21, 2020, the day the stay-at-home order went into effect in Illinois. At 10, 20, and 30 days after that date, the number of cases increased more quickly in the Iowa counties than in the Illinois counties, with a difference of 4.71 additional cases per 10,000 residents (95% CI -8.64 to -0.78; P = .02) at 30 days. The estimated excess cases in Iowa was as high as 217 cases during that 30 days, which represents 30.4% of the 716 cases diagnosed in those counties by that date. The sensitivity analysis supported these findings. Lyu W, Wehby GL. Comparison of estimated rates of coronavirus disease 2019 (covid-19) in border counties in Iowa without a stay-at-home order and border counties in Illinois with a stay-at-home order. JAMA Netw Open. Published online May 1, 2020. Research Brief #29: Clarke County, Georgia, implemented mandatory social distancing policies on March 20, 2020, 14 days prior to statewide implementation on April 3. The counties surrounding Clarke followed the statewide guidelines. Using statewide case reports by county, these investigators estimated doubling time, an accepted measure of spread of infection, for Clarke and its surrounding counties. By April 26, the 5-day rolling average doubling time was twice as long in Clarke than in surrounding counties (40 days vs 20 days). The social distancing policy that prohibited events and gatherings of more than 10 people and required individuals to remain at home, with limited exceptions for essential travel, was effective in slowing the spread of COVID-19. Ebell MH, Bagwell-Adams G. Mandatory social distancing associated with increased doubling time: an example using hyperlocal data. Am J Prev Med. Pre-proof published online 2020. doi: https://doi.org/10.1016/j.amepre.2020.04.006.

    John Hickner, MD, MS
    Professor Emeritus
    Dept of Family Medicine
    Michigan State University
    East Lansing, MI

    COVID-19 Research Briefs: Not All Face Coverings Offer Similar Degrees of Protection

    Clinical question
    How effective are the different types of face masks for preventing the spread of COVID-19?

    Bottom line
    Based on laser testing, N95 masks transmitted less than 0.1% of respiratory droplets of COVID-19.

    Reference
    Fischer EP, Fischer MC, Grass D, Henrion I, Warren WS, Westman E. Low-cost measurement of facemask efficacy for filtering expelled droplets during speech. Sci Adv 2020;6(36):eabd3083.

    Study design: Other

    Funding source: Unknown/not stated

    Setting: Other

    Synopsis
    Research Brief #57: Although face masks have become a foundation of public health measures to mitigate the spread of respiratory illnesses such as COVID-19, they have also become lightning rods for various political agendas. Some people have used "face coverings" (eg, bandanas, gaiters, etc.) as a more comfortable or fashionable alternative to face masks. Analogous to other studies we have reported on the spread of respiratory droplets, this study used laser technology to evaluate the effectiveness of 14 different face coverings. The researchers included commercial and homemade masks, various materials, various numbers of layers, bandanas, gaiters, and a simple swath of mask material. They also included an unmasked control individual. One operator wearing each type of facial garb spoke into the darkened laser chamber and the flow of respiratory droplets were recorded and analyzed. An additional 4 operators wore a selection of the face coverings. The authors are proud to point out that their main equipment cost about $200; owning a cellphone camera means you can cheaply replicate their work! The clear winner was the commercially made, fitted N95 masks that transmitted less than 0.1% of the droplets compared with no mask. The clear loser was the gaiter-type neck fleece that actually transmitted more droplets than no mask (110%)! Bandanas were only slightly better than nothing. Although the study does not assess real-world performance, we have other empiric data that show various degrees of protection from commercial and homemade masks.

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    COVID-19 Research Briefs: 44% of Secondary Infections of SARS-CoV2 Occur When the Index Case Is Presymptomatic

    Clinical question
    How common is the presymptomatic transmission of the COVID-19 virus?

    Bottom line
    This analysis of the temporal pattern of viral shedding of COVID-19 finds that a high proportion of secondary cases were infected when the index case was presymptomatic.

    Reference
    He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. [published online ahead of print, 2020 Apr 15] Nat Med 2020;10.1038/s41591-020-0869-5. doi:10.1038/s41591-020-0869-5.

    Study design: Not applicable

    Setting: Not applicable

    Synopsis
    Research Brief #13: COVID-19 is highly contagious. Transmission during the presymptomatic and early symptom phases, such as occurs with the influenza virus, could make it difficult to institute effective quarantine procedures. These researchers from China studied the temporal pattern of viral shedding in 94 patients who tested positive for COVID, and they modeled viral shedding in another 77 infector-infectee transmission pairs. The 94 COVID-19 patients had a total of 414 throat cultures for COVID-19 from symptom onset to 32 days after onset. The greatest viral load shedding was at the time of symptom onset, and the authors surmise that infectiousness peaks at or before symptom onset. In the study of 77 infector-infectee pairs, based on epidemiologic modeling and a mean incubation period of 5.2 days, the authors inferred that infectiousness starts 2.3 days before symptom onset with a peak infectiousness at 0.7 days prior to symptom onset. They estimated that 44% of the secondary cases they studied were infected during the presymptomatic phase of the person who infected them. The researchers conclude that there is substantial presymptomatic transmission of COVID-19.

    John Hickner, MD, MS
    Professor Emeritus
    Dept of Family Medicine
    Michigan State University
    East Lansing, MI

    Prevention and Screening

    The Balance of Benefits and Harms No Longer Favors Aspirin for Primary Prevention

    Clinical question
    Does aspirin still provide a net benefit as primary prevention?

    Bottom line
    The balance of benefits and harms is equally weighted, so we should no longer recommend aspirin for most of our patients for primary prevention. The European Society of Cardiology and the American College of Cardiology and the American Heart Association agree and no longer recommend aspirin for primary prevention. Perhaps we are doing a better job of screening for cancer and preventing cardiovascular events through use of statins and antihypertensives, so there is less prevention for aspirin to do.

    Reference
    Moriarty F, Ebell MH. A comparison of contemporary versus older studies of aspirin for primary prevention. Fam Pract 2020;37(3):290-296.

    Study design: Meta-analysis (randomized controlled trials)

    Funding source: Foundation

    Setting: Outpatient (any)

    Synopsis
    Aspirin is recommended as primary prevention by the United States Preventive Services Task Force, primarily based on studies that recruited patients in the 1980s and 1990s. Those studies concluded that there was more benefit than risk: primarily a reduction in cardiovascular mortality, cardiovascular events, and colorectal cancer. Today, however, when we do a much better job of addressing other risk factors, such as tobacco use, hypertension, and hyperlipidemia, and when we routinely screen for colorectal cancer, does that benefit persist? The researchers (yes, I was one of them!) performed a meta-analysis of 4 large studies of aspirin for primary prevention that recruited patients after 2005, and compared them with individual patient data meta-analyses that recruited patients before 2000. In the newer studies, there was no longer any reduction in cancer death (relative risk [RR] 1.11; 95% CI 0.92 - 1.34) or cancer incidence (RR 1.06; 0.99 - 1.14). There was also no longer a significant reduction in nonfatal myocardial infarction (RR 0.90; 0.76 - 1.06) or cardiovascular mortality (RR 0.92; 0.81 - 1.06). Overall, for every 1200 persons who take aspirin instead of placebo for 5 years, there will be 4 fewer major cardiac events and 3 fewer ischemic strokes, but there will be 3 more intracranial hemorrhages and 8 more major bleeding events.

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    Increased Daily Steps Associated with Reduced All-Cause Mortality

    Clinical question
    Is the daily step count and/or the intensity of the steps associated with the risk of premature mortality?

    Bottom line
    This study found that a greater number of daily steps was significantly associated with lower all-cause mortality. Step intensity was not significantly associated with mortality after controlling for total daily steps.

    Reference
    Saint-Maurice PF, Troiano RP, Bassett Jr DR, et al. Association of daily step count and step intensity with mortality among US adults. JAMA 2020;323(12):1151-1160.

    Study design: Cohort (prospective)

    Funding source: Foundation

    Setting: Population-based

    Synopsis
    These investigators reviewed data obtained from the National Health and Nutrition Examination Survey (NHANES) focusing on participants who were asked to wear a hip accelerometer during waking hours for a 7-day period from 2003 to 2006. Individuals with at least 1 day of valid wear (at least 10 hours) were included. Additional data collection included demographic information (eg, age, gender, education), smoking status, alcohol intake, and diagnoses of chronic medical conditions (eg, diabetes, heart disease, stroke, cancer, chronic bronchitis). In addition to counting steps, step intensity was estimated based on extended bouts of stepping and peak 1-minute and 30-minute cadences. Assessments of mortality occurred via the US National Death Index. Participants (N = 4840) took a mean of 9124 steps per day. The incidence of all-cause mortality was 76.7 per 1000 person-years for individuals who took fewer than 4000 steps per day; 21.4 per 1000 person-years for individuals who took 4000 to 7999 steps per day; 6.9 per 1000 person-years for the individuals who took 8000 to 11,999 steps per day; and 4.8 per 1000 person-years for individuals who took at least 12,000 steps per day. After controlling for total steps per day, greater step intensity was not significantly associated with lower mortality.

    David C. Slawson, MD
    Professor and Vice Chair of Family Medicine for Education and Scholarship
    Atrium Health
    Professor of Family Medicine, UNC Chapel Hill
    Charlotte, NC

    BMD Testing: One and Done

    Clinical question
    Are repeat bone mineral density tests necessary to identify women who are susceptible to fracture?

    Bottom line
    Rechecking bone mineral density (BMD) after 3 years does not add additional prognostic information. In other words, not much changes in 3 years with regard to estimating fracture risk and, presumably, need for treatment, so serial testing is not useful. Another study found similar results in older patients, and, similarly, a third study found that BMD monitoring is not necessary after starting treatment with a bisphosphonate.

    Reference
    Crandall CJ, Larson J, Wright NC, et al. Serial bone density measurement and incident fracture risk discrimination in postmenopausal women. JAMA Intern Med 2020;180(9):1232-1240.

    Study design: Cohort (prospective)

    Funding source: Government

    Setting: Outpatient (any)

    Synopsis
    This study evaluated 7419 women who were enrolled in the Women's Health Initiative study. These postmenopausal women, aged 50 and 79 years (mean age 66.1 years), underwent a baseline BMD measurement and a second BMD measurement in 3 years and did not have treatment other than calcium and vitamin D supplementation in the intervening years. The women were followed up for an average of 12.1 years after the initial test. Over this time, 1.9% of the women experienced a hip fracture and 9.9% had a major osteoporotic fracture, defined as hip, clinical spine, forearm, or shoulder fracture. Compared with the baseline BMD test result, a change in BMD over 3 years or the combination of change in BMD with baseline BMD did not predict subsequent hip or major fracture to a greater degree. In other words, the follow-up BMD testing after 3 years did not provide any more clinical information. Associations between bone density and fracture risk were the same when analyzed by risk factors such as the presence of diabetes, age, race and ethnicity, body weight, and baseline T-score.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Human Papillomavirus Vaccine, Especially Before Age 17, Is Associated with a Large Reduction in Invasive Cervical Cancer

    Clinical question
    Is the human papillomavirus vaccination associated with a lower risk of invasive cervical cancer?

    Bottom line
    Human papillomavirus (HPV) vaccination is associated with a significant reduction in the likelihood of invasive cervical cancer (adjusted incidence rate ratio [IRR] 0.37; 95% CI 0.21 - 0.57). The magnitude of this reduction was greater in women who were vaccinated before age 17 years (adjusted IRR 0.12; 0.00 - 0.34). 

    Reference
    Lei J, Ploner A, Elfstrom KM, et al. HPV vaccination and the risk of invasive cervical cancer. N Engl J Med 2020;383(14):1340-1348.

    Study design: Cohort (retrospective)

    Funding source: Foundation

    Setting: Population-based

    Synopsis
    There are limited data to date regarding whether HPV vaccination actually prevents invasive cervical cancer. This Swedish study used data from a national health registry of more than 1.6 million girls and women who were between the ages of 10 and 30 years between 2006 and 2017. In Sweden, HPV vaccination was offered for girls aged 13 to 17 years starting in 2007, with expansion to younger and older girls in 2012. Cervical cancer screening in Sweden begins at age 23 and is performed at intervals of 3 years to 7 years, depending on age. A quadrivalent vaccine (types 6, 11, 16 and 18) was used. The researchers reviewed registries with information about cancer diagnoses and vaccination. A total of 1,145,112 patients did not receive an HPV vaccine, while 527,871 received at least one dose during the study period. At baseline, girls who were vaccinated were more likely to have a Swedish-born mother and come from a high-income family. The primary outcome was the IRR for invasive cervical cancer between vaccinated and unvaccinated girls and women, adjusted for age, calendar year of immunization, and parental and residential characteristics. The crude incidence rates were 5.3 per 100,000 person-years for unvaccinated participants and 0.73 per 100,000 person-years for those who had been vaccinated. The fully adjusted IRR was 0.37 (0.21 - 0.57) for invasive cervical cancer. For girls vaccinated before age 17 years, the IRR was 0.12 (0.00 - 0.34), while for those vaccinated between the ages of 17 and 30 years it was 0.47 (0.27 - 0.75).

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    Musculoskeletal

    Physical Therapy Better Than Steroid Injections for Knee Osteoarthritis After 1 Year

    Clinical question
    Is physical therapy or a single glucocorticoid injection more effective for the treatment of osteoarthritis of the knee?

    Bottom line
    The researchers conclude that PT is preferred to glucocorticoid injections for osteoarthritis of the knee. The study is limited by the open label design which could lead to a Hawthorned effect for those in the PT group and a placebo effect for those in the injection group. The rapid and large improvement in the first month for both groups is somewhat surprising, with relatively little further improvement seen in the rest of the year which suggests that regression to the mean may also have contributed to the observed improvement. A Cochrane review concluded that glucocorticoid injections were effective, although primarily in the 2 to 4 weeks following injection, and recent American College of Rheumatology (ACR) guidelines made strong recommendations in favor of both PT and glucocorticoid injections.

    Reference
    Deyle GD, Allen CS, Allison SC, et al. Physical therapy versus glucocorticoid injection for osteoarthritis of the knee. N Engl J Med 2020;382(15):1420-1429.

    Study design: Randomized controlled trial (nonblinded)

    Funding source: Unknown/not stated

    Allocation: Concealed

    Setting: Outpatient (any)

    Synopsis
    These researchers identified patients, 38 years and older, in the Military Health System, including active duty military and retirees, who met ACR criteria for osteoarthritis of the knee (including radiographic evidence). Patients who had received either a glucocorticoid injection in the knee or PT in the previous year were excluded. The authors randomized 156 participants to receive either up to 3 injections of 40 mg triamcinolone plus 7 mL of lidocaine 1% over the course of a year or up to 8 PT sessions in the first 4 to 6 weeks with additional sessions as needed (ultimately, a mean of 11.8 PT visits). Outcomes included a series of standard symptom scales, such as the Western Ontario and McMaster Universities Arthritis Index (WOMAC), assessed in the knee with worse symptoms. The trial was powered to detect a 12% difference in WOMAC scores, which is thought to be the minimal clinically important difference. Analysis was by the intention-to-treat principle, and groups were balanced at the beginning of the study. This was an open-label trial, but the outcomes were assessed by investigators who were masked to treatment assignment. The mean age of patients was 56 years, 48% were women, and the average baseline WOMAC score was similar between groups. During the course of the year, both groups saw a rapid and similar decline in WOMAC scores during the first month. The WOMAC scores continued to decline for the PT group, but plateaued for the injection group. The primary outcome was change in the WOMAC score at 1 year, which decreased more in the PT group than in the injection group (mean scores: 37 points vs 55.8 points; P < .05). Patients in the injection group received a mean of 2.6 injections. There were some crossovers: 9% of patients in the PT group received a glucocorticoid injection and 18% in the injection group received some PT. A secondary measure, the Global Rating of Change score, also improved slightly more in the PT group, and costs for knee care were similar between groups. The study is limited by the open-label design, which could lead to a Hawthorne effect for those in the PT group and a placebo effect for those in the injection group. The rapid and large improvement in the first month for both groups is somewhat surprising, especially for the PT group, with relatively little further improvement seen in the rest of the year, which suggests that regression to the mean may also have contributed to the observed improvement.

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    Acetaminophen (Paracetamol) Is No Better Than Placebo for Most Pain, Except Maybe Tension Headache

    Clinical question
    Is acetaminophen (paracetamol) effective as an analgesic?

    Bottom line
    Despite being discovered in the 1800s and marketed for pain relief since 1950, there are surprisingly few studies of acetaminophen's effectiveness. It is more effective than placebo to provide some pain relief in patients with acute migraine and might help people to a greater extent than placebo (which also works well) with tension-type headache. A single dose is approximately twice as likely as placebo to reduce postpartum perineal pain, and it may be effective - but not as effective as other treatments - for acute renal colic.

    Reference
    Saragiotto BT, Shaheed CA, Maher CG. Paracetamol for pain in adults. BMJ 2019;367:l6693.

    Study design: Systematic review

    Funding source: Self-funded or unfunded

    Setting: Various (meta-analysis)

    Synopsis
    These authors searched 3 databases, including the Cochrane Library, to identify systematic reviews of randomized controlled trials of acetaminophen compared with placebo for pain relief in adults. They also searched clinical guidelines and reference lists of studies. Since they were presenting the results of other systematic reviews, they relied on those reviews for assessment of the original research. Based on a Cochrane review of 8 studies of 5890 patients, acetaminophen is effective for the treatment of episodic tension-type headache, though the effect is small (number needed to treat [NNT] = 22), which is misleading because of a high response to placebo (high-quality evidence). It is also effective, though based on low quality evidence, for complete pain relief of acute migraine (NNT = 12) and some pain relief at 2 hours (NNT = 5). A single dose is twice as likely as placebo to decrease perineal pain postpartum and some patients with renal colic will experience relief (one trial). It has not been shown to be effective for patients with acute low back pain or pain due to knee or hip osteoarthritis.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    No Short-Term Extra Benefit When Muscle Relaxants Are Added to Ibuprofen for Acute Low Back Pain

    Clinical question
    Is treatment for acute low back pain more effective with a combination of ibuprofen and a muscle relaxant as compared with ibuprofen alone to improve functional outcomes and reduce pain?

    Bottom line
    Adding a muscle relaxant to treatment with ibuprofen does not improve functional outcomes or pain, or lessen the number of people reporting moderate to severe back pain one week after starting treatment.

    Reference
    Friedman BW, Irizarry E, Solorzano C, et al. A randomized, placebo-controlled trial of ibuprofen plus metaxalone, tizanidine, or baclofen for acute low back pain. Ann Emerg Med 2019;74(4):512-520.

    Study design: Randomized controlled trial (double-blinded)

    Funding source: Government

    Allocation: Uncertain

    Setting: Emergency department

    Synopsis
    These researchers enrolled 320 patients who presented to 1 of 2 emergency departments with nonradicular low back pain of 2 weeks' duration or less (average 72 hours) with a score of at least 6 of a possible 24 on the Roland-Morris Disability Questionnaire, a self-rated measure of disability due to low back pain. More than 90% of patients had a score of 10 or higher. All patients were given ibuprofen 600 mg to be taken up to 3 times a day, as needed. They were also randomized, concealed allocation unknown, to receive identical-appearing capsules containing placebo, baclofen 10 mg, metaxalone 400 mg, or tizanidine 2 mg, and were instructed to take 1 or 2 capsules up to 3 times a day, as needed. One week later, using intention-to-treat analysis, questionnaire scores improved in all groups, with improvement ranging from an average 10.1 points to 11.2 points across the groups compared with baseline. At this time, approximately 34% of patients across the groups reported moderate to severe back pain. The study had a power of 80% to find a difference of 5 points on the questionnaire if one existed.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Respiratory

    Antibiotic and Corticosteroid Treatment Effective for Acute Exacerbations of COPD

    Clinical question
    What treatments are effective for patients with an exacerbation of chronic obstructive pulmonary disease?

    Bottom line
    Short-term antibiotic treatment and short-term systemic corticosteroids are both associated with a faster resolution of chronic obstructive pulmonary disease (COPD) symptoms and fewer treatment failures. Other treatment approaches? Not so much.

    Reference
    Dobler CC, Morrow AS, Beuschel B, et al. Pharmacologic therapies in patients with exacerbation of chronic obstructive pulmonary disease. A systematic review with meta-analysis. Ann Intern Med 2020;172:413-422. doi:10.7326/M19-3007

    Study design: Meta-analysis (randomized controlled trials)

    Funding source: Foundation

    Setting: Various (meta-analysis)

    Synopsis
    These researchers searched several databases, including Cochrane CENTRAL, for English-language randomized controlled trials that evaluated treatments for exacerbations of COPD. Pairs of reviewers selected studies for inclusion, extracted the data, and evaluated the research quality. Based on 68 randomized trials, they found that antibiotic treatment of an acute exacerbation, regardless of severity, doubled the likelihood of resolution by the end of treatment (odds ratio [OR] = 2.03; 95% CI 1.47 - 2.80) and halved the likelihood of treatment failure (OR = .54; .34 - .86), with a moderate strength of evidence. Systemic corticosteroid treatment for 1 day to 56 days was associated with less frequent treatment failure but higher adverse effects, with a low strength of evidence. Current research does not give us good guidance on which antibiotic is best, or the optimum dose or duration of corticosteroid treatment. Other approaches (inhaled corticosteroids, inhaled bronchodilators, various inhaled combinations, aminophylline, magnesium sulfate, and anti-inflammatory treatments) had little or no effect on outcomes. Given the small number of studies for each comparison, the researchers were unable to determine publication bias. They did not find heterogeneity among study results, again due to the small number of studies.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Messages of Fear and Empowerment Are Best for Reducing Inappropriate Antibiotic Use

    Clinical question
    What is the most effective message to reduce antibiotic-seeking behavior for respiratory infections?

    Bottom line
    When talking to patients about antimicrobial resistance (AMR), it is important to combine a fear-based message (eg, resistance is increasing, antibiotics may not be there for you when you really need them) with empowering information (eg, antibiotics aren't helpful, these infections are self-limited but may last a couple of weeks, and there are lots of other things you can do to feel better). I also advise physicians to avoid the term "acute bronchitis" and instead say "chest cold," which sounds much less frightening to patients.

    Reference
    Roope LS, Tonkin-Crine S, Herd N, et al. Reducing expectations for antibiotics in primary care: a randomised experiment to test the response to fear-based messages about antimicrobial resistance. BMC Med 2020;18(1):110.https://doi.org/10.1186/s12916-020-01553-6

    Study design: Randomized controlled trial (nonblinded)

    Funding source: Government

    Allocation: Uncertain

    Setting: Population-based

    Synopsis
    A previous study found that a fear-based message regarding AMR had the effect of increasing the likelihood that patients with a low knowledge of AMR would seek an antibiotic for their next acute respiratory tract infection (ARTI). In this follow-up, these UK researchers compared a fear-based message with empowering information regarding the typical prognosis and benign course of most ARTIs, and explained that antibiotics do not help most ARTIs. They invited randomly selected adults to receive 1 of 3 online messages: (1) fear message only (n = 1000), (2) mild fear message plus empowerment information (n = 1500), and (3) strong fear message plus empowerment information (n = 1500). Participants were first given an illness description resembling an influenza-like illness, and then presented with the message. A total of 8000 people responded to the invitations. The mean age of respondents was 47 years. Overall, 27.8% of respondents believed antibiotics would probably or definitely help with the episode of ARTI, and 25.2% thought the information was somewhat or very new to them. The latter was a bit more likely to be reported by those in the fear-only group (28.5% for fear-only vs 22.4% to 25.9% for fear plus empowerment). Those given one of the fear plus empowerment messages were significantly more likely to report that they would be less likely to visit a doctor for their next ARTI (45.1% - 46.1% vs 29.2%; P < .001) and were also more likely to report that they would be less or much less likely to request an antibiotic (52.5% - 54.7% vs 42.3%; P < .001). There were small and paradoxical increases in the likelihood of seeking medical care and requesting an antibiotic for those in the fear-only message group, as was found previously. Unfortunately, the messaging had less impact on those for whom the information was new and those who believed that antibiotics were helpful for ARTI. Results were similar when adults were asked about requesting an antibiotic for their children.

    Mark H. Ebell, MD, MS
    Professor
    University of Georgia
    Athens, GA

    Miscellaneous

    Easy Rule Identifies Patients with Low-Risk Penicillin Allergies

    Clinical question
    Which adult patients with penicillin allergy by history will have positive allergy testing?

    Bottom line
    A label of "penicillin allergy" clears the shelves of many effective treatments for various infections. A simple rule, outlined in the synopsis, effectively identifies (without allergy testing) low-risk penicillin allergies in patients with a history of a penicillin allergy event.

    Reference
    Trubiano JA, Vogrin S, Chua KY, et al. Development and validation of a penicillin allergy clinical decision rule. JAMA Intern Med 2020;180(5):745-752.

    Study design: Decision rule (validation)

    Setting: Outpatient (any)

    Synopsis
    This PEN-FAST rule was developed using a group of 622 patients with a history of reacting to penicillin who were referred for allergy testing, and then validated on a second group of 945 patients who were referred for allergy testing at 3 other sites. Allergy testing consisted of skin prick, intradermal, or patch testing, with positives confirmed by oral challenge. In the validation group, 27.4% reported a history of angioedema and/or anaphylaxis. Following testing in this group, the prevalence of reacting to any allergy test was 9.9%, but only 21 participants reacted to the oral challenge (2.2%). For patients who report a PENicillin allergy, here is the FAST rule: F (five years or less since the reaction): 2 points A (anaphylaxis or angioedema) or S (severe cutaneous reaction): 2 points T (treatment required for reaction): 1 point Patients with a score of 0 had a likelihood of a positive test result of less than 1%; a score of 1 or 2 yielded a positive test result in 5%. Among the 3 cohorts, sensitivity ranged from 70.4% (prevalence 27%) to 87.5% (prevalence 14.4%).

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Chest X-rays, Electrocardiograms, and Pap Tests in Low-Risk Patients Are Associated with Further Tests and Procedures

    Clinical question
    Are chest x-rays, electrocardiograms, and Pap tests in low-risk patients associated with subsequent additional health care?

    Bottom line
    Low-value tests - screening tests in low-risk patients - such as chest x-rays and electrocardiograms (EKGs) in adults as part of an annual health examination and Papanicolaou (Pap) tests in women younger than 21 years or older than 69 years, are associated with more visits to specialists, more diagnostic tests, and more procedures.

    Reference
    Bouck Z, Calzavar AJ, Ivers NM, et al. Association of low-value testing with subsequent health care use and clinical outcomes among low-risk primary care outpatients undergoing an annual health examination. JAMA Intern Med 2020;180(7):973-983. doi:10.1001/jamainternmed.2020.1611

    Study design: Cohort (retrospective)

    Funding source: Government

    Setting: Outpatient (primary care)

    Synopsis
    This study focused on the primary care use of 3 screening tests defined as low value by the Choosing Wisely campaign: (1) chest radiographs for patients at low risk for cardiovascular disease and pulmonary disease, (2) EKGs for patients at low risk of cardiovascular disease, and (3) Pap tests for women younger than 21 years or older than 69 years. This population-based study evaluated all administrative claims over 5 years in Ontario, Canada. For each low-value test the authors identified patients in each cohort who were at low risk. Within these groups they identified patients who had low-value screening at the time of (or shortly after) an annual health examination. Then they charted specialist visits, diagnostic tests, and procedures related to those tests over the subsequent 90 days (up to 180 days following a Pap test or computed tomography (CT) scanning to account for wait times in the province). The authors matched these patients with similar patients who didn't receive testing. Though rates were still fairly low, the results are not surprising: chest x-rays were associated with an almost 3-fold likelihood of a pulmonology visit, an 8-fold increase in bronchoscopy, and a 3-fold increase in CT scans. EKG-receiving patients were 3 times as likely to be sent to a cardiologist, approximately 4 times more likely to receive additional cardiac testing, and almost 3 times more likely to undergo cardiac catheterization. Pap tests triggered slightly more gynecology visits, approximately a 16-fold increase in follow-up Pap tests, and a 5-fold increase in colposcopy rates. There is no way to know if these increased visits were worthwhile. -

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Laboratory Results Are Not An Exact Science

    Clinical question
    How much variation is there in clinical laboratory values, and how should we account for it?

    Bottom line
    "The numbers don't lie." How many times have you said that to yourself or to a patient? Although numbers may not lie, they may not tell the whole truth. For example, a single HbA1c test result of 6.3% (45 mmol/L) could actually be as low as 5.5% (39 mmol/mol) or as high as 7.1% (51 mmol/mol). This range is due to the inherent variability in the analytic process (4.3%), as well as to biologic variability (ie, the variation in the same person over the course of days caused by physiologic changes). As a result, it's hard to tell if a change in a blood level over time is real or just a reflection of these sources of variability. Bookmark this website: www.bmj.com/content/368/bmj.m149 — it's a tool that determines the variability that can be expected in a single laboratory value and calculates the reference change value needed to signify a real difference between the values in the same person over time.

    Reference
    McCormack JP, Holmes DT. Your results may vary: the imprecision of medical measurements. BMJ 2020;368:m149. doi: 10.1136/bmj.m149

    Study design: Other

    Funding source: Self-funded or unfunded

    Setting: Not applicable

    Synopsis
    Just how precise are those test results we read about all the time? Each particular assay has inherent analytical variation, ranging from less than 2% for a bone density test to up to 20% for a single alkaline phosphatase measure. However, the larger contributor to variation in laboratory results is biological variation, the fluctuation in individual patients over time due to physiologic changes. Combined, these challenges to precision can make a single iron, bilirubin, or triglyceride level be inaccurate by as much as 50%. When testing the same person over time, the inherent variation can require at least a 50% change in the levels to be considered valid (that is, outside of the limit of biologic and analytical variability). Fortunately, the authors of this study have created a website that graphs the effect of these variations on many laboratory tests. The website determines the "reference change value," which is the difference that must be seen between 2 test results for the change to be considered "real" and not due to assay variability.

    Allen F. Shaughnessy, PharmD, MMedEd
    Professor of Family Medicine
    Tufts University
    Boston, MA

    Better Primary Care Continuity Is Associated with Lower Mortality Risk

    Clinical question
    Is continuity of care associated with decreased mortality?

    Bottom line
    Most studies in this systematic review found a protective effect of greater primary care continuity and all-cause mortality. 

    Reference
    Baker R, Freeman GK, Haggerty JL, Bankart MJ, Nockels KH. Primary medical care continuity and patient mortality: a systematic review. Br J Gen Pract 2020;70(698):e600-e611.

    Study design: Systematic review

    Funding source: Self-funded or unfunded

    Setting: Outpatient (primary care)

    Synopsis
    These authors searched several databases and the gray literature to identify 13 empiric studies that reported measures of continuity and mortality in patients seen in primary care settings. All the studies evaluated continuity of care via care-use patterns or patient report. Only 2 of the studies included nurse practitioners or physicians assistants. The nature of the studies and their data prevented formal meta-analysis. A limitation of this review is that the studies only evaluated personal continuity (ongoing relationship with a provider), not informational continuity (accessibility of records) or management continuity (coordination between all groups involved in care). Twelve studies evaluated all-cause mortality, 9 of which found a statistically significant lower mortality risk associated with greater continuity, 2 found no association, and 1 found that the association changed based on the measure of continuity used. Two studies found lower risks of coronary heart disease mortality with greater continuity and one found lower mortality risks from cancer or chronic obstructive lung disease. The authors go on and extract from the studies potential mechanisms to explain the associations, but, frankly, it is all just speculation and begs the real issue: How to cultivate more primary care clinicians and how to encourage health care systems to prioritize the delivery of primary care.

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    Practice Guidelines

    American College of Rheumatology Guideline for Managing Patients with Gout

    Clinical question
    How should clinicians manage patients with gout?

    Bottom line
    The following are some of the strong recommendations from the American College of Rheumatology (ACR) for managing patients with gout: start urate-lowering therapy (ULT) for all patients with tophi, frequent gout flares (2 or more per year), or those with radiographic evidence of joint damage attributable to gout; use allopurinol as the preferred first-line medication, including for patients with stage 3 or worse chronic kidney disease; and treat patients to a serum urate target of less than 6 mg/dL. When initiating ULT, the ACR strongly recommends concomitant anti-inflammatory prophylactic therapy for at least 3 months to 6 months. Finally, the ACR strongly recommends using colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), or glucocorticoids (oral, intra-articular, or intramuscular) to manage gout flares.

    Reference
    FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Rheumatol 2020;72(6):879-895.

    Study design: Practice guideline

    Funding source: Self-funded or unfunded

    Setting: Outpatient (any)

    Synopsis
    The ACR assembled a guideline development team consisting of the usual suspects plus a general internist, a physician assistant, and a patient representative. This team used modern guideline development methods consisting of 57 (57!) framing-focused questions, systematic reviews (including network meta-analyses) of the literature, and an explicit process to synthesize all their findings into actionable recommendations. They made strong recommendations when there was moderate- or high-certainty evidence that the benefits consistently outweigh the harms, and they made conditional recommendations when the harms and benefits were too close to call or when the evidence was shaky. The following is a brief summary of some of their 42 recommendations. They made strong recommendations for ULT in patients with tophi, frequent gout flares (2 or more per year), or those with radiographic evidence of joint damage attributable to gout. They made a conditional recommendation for ULT in patients with infrequent flares, those with stage 3 or worse chronic kidney disease, with urolithiasis, or those with urate levels exceeding 9 mg/dL. They made conditional recommendations against starting ULT after a first flare and for those with asymptomatic hyperuricemia. The ACR also strongly recommends allopurinol as the drug of first choice, including for those with chronic kidney disease. They recommend switching febuxostat to another agent in patients with cardiovascular disease The panel also strongly recommends adding an anti-inflammatory (colchicine, NSAIDs, or prednisone/prednisolone at the discretion of the clinician) for 3 to 6 months when initialing ULT. They made a strong recommendation to treat to a target urate levels of less than 6 mg/dL. During acute flares, the ACR strongly recommends using low-dose colchicine, NSAIDs, or corticosteroids (oral, intra-articular, or intramuscular) and conditionally recommends ice application to the affected joint. They made conditional recommendations to limit the intake of alcohol, purines, high-fructose corn syrup and a conditional recommendation against the addition of vitamin C. The panel also conditionally recommends switching hydrochlorothiazide to a different antihypertensive in patients who take it. There are many more recommendations, including medication dosing, when to consider pegloticase, when to consider HLA testing, and so forth.

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    The American Thoracic Society Guideline for Managing Patients with Chronic Obstructive Pulmonary Disease

    Clinical question
    What is the optimal approach to the pharmacologic management of patients with chronic obstructive pulmonary disease?

    Bottom line
    The American Thoracic Society (ATS) strongly recommends that patients with chronic obstructive pulmonary disease should be treated with a combination of a long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA). The ATS makes conditional recommendations for the addition of inhaled corticosteroids (ICS) to dual therapy in patients with ongoing dyspnea and exacerbation, and for the withdrawal of the ICS after 1 year in patients who do well. The ATS makes no recommendation for or against the use of ICS in patients with eosinophilia. The ATS makes conditional recommendations against the use of oral steroids in patients with severe and frequent exacerbations and for using opioids in patients with advanced refractory dyspnea despite optimal therapy.

    Reference
    Nici L, Mammen MJ, Charbek E, et al. Pharmacologic management of chronic obstructive pulmonary disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med 2020;201(9):e56-e69.

    Study design: Practice guideline

    Funding source: Unknown/not stated

    Setting: Various (guideline)

    Synopsis
    The ATS convened a guideline development panel composed of a methodology team and a team of experts. Although the co-chairs of the teams and at least 50% of the panel members had to be free of conflicts of interest, many panel members reported ties to industry. They chose not to include patients on the panel because of some nonsense excuse that clinically active "experts" can infer patient value preferences. Otherwise, the panel used explicit approaches to identify key clinical questions, conduct systematic reviews, assess the risk of bias of included studies, construct evidence tables, and assess the safety and effectiveness of interventions. To compare dual therapy (LABA plus LAMA) with monotherapy, they found 24 randomized controlled trials with 45,441 participants that demonstrated the combination of LABA plus LAMA improved symptom scores and reduced exacerbations and hospitalizations more than monotherapy without an increase in adverse events. For patients with dyspnea or exercise intolerance despite dual therapy, the panel identified 4 randomized controlled trials with 9313 patients. The addition of ICS to LABA plus LAMA significantly reduced exacerbations (number needed to treat = 16 for 1 fewer exacerbation), but had no real effect on symptom scores or health-related quality of life. Three of these studies found that pneumonia occurred more frequently in patients treated with the additional ICS (number needed to treat to harm = 67). The authors found 3 studies with 3538 patients that evaluated the withdrawal of ICS in patients using triple therapy who have been stable for 1 year. Overall, they found no difference in the rates of subsequent pneumonia, hospitalizations, exacerbations, or all-cause mortality. The panel identified 8 randomized controlled trials with 9123 patients that evaluated the addition of ICS in patients with eosinophilia. These studies, all post hoc analyses, suggest improvements in exacerbations, dyspnea scores, and health-related quality of life at the risk of increased rates of pneumonia. The panel found 11 studies of oral corticosteroids in patients with severe and frequent exacerbations, however only 4 were randomized controlled trials (477 patients). Overall, these studies identified no differences in mortality, exacerbations, hospitalizations, or dyspnea scores but a significant increase in the risk of adverse events. Finally, the panel identified 14 randomized controlled trials (366 patients) of the use of opioids in patients with severe refractory dyspnea. Although the studies were too small to have any robust estimates on specific event rates, the patients taking opioids had improved health-related quality of life and dyspnea scores.

    Henry C. Barry, MD, MS
    Professor
    Michigan State University
    East Lansing, MI

    Levels of Evidence definitions from Essential Evidence Plus

    POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com.