Top POEMs of 2017 Consistent with the Principles of the Choosing Wisely Campaign: Additional Top POEMs

Top 20 POEMs of 2017 Consistent with the Principles of the Choosing Wisely Campaign

Empiric Treatment of Onychomycosis with Terbinafine is Most Cost-Effective Strategy

Clinical question
Is confirmatory diagnostic testing cost-effective for the management of clinically suspected onychomycosis?

Bottom line
The most cost-effective approach to the patient with clinically suspected onychomycosis is empiric therapy with oral terbinafine. The chance of liver injury is estimated to be only 1 in 50,000 to 1 in 120,000, so testing to confirm the diagnosis would cost tens of millions of dollars per case of liver injury avoided. If you plan to prescribe the much more expensive topical solution efinaconazole 10% (Jublia), then confirmatory testing with periodic acid-Schiff (PAS) reduces costs (LOE = 2a)(www.essentialevidenceplus.com)

Reference
Mikailov A, Cohen J, Joyce C, Mostaghimi A. Cost-effectiveness of confirmatory testing before treatment of onychomycosis. JAMA Dermatol 2016;152(3):276-281.

Study design: Decision analysis

Funding source: Unknown/not stated

Setting: Outpatient (any)

Synopsis
An annoyance of clinical practice is the requirement by many insurance companies to perform confirmatory diagnostic testing prior to initiating treatment for patients with clinically suspected onychomycosis. This was based on analyses done 15 years ago, when terbinafine was significantly more expensive. Terbinafine is now affordable (approximately $10 for a full 12-week course), but the topical solution efinaconazole 10% provides a new, more expensive option (more than $500 for each 4-mL bottle in the United States). These authors performed a decision analysis that compared 3 strategies: (1) treat all patients empirically; (2) if in-office potassium hydroxide testing result is positive, treat; if negative, order PAS stain and treat if positive; or (3) order PAS stain on all patients and treat only if positive. They assumed, on the basis of previous studies, that between 65% and 95% of patients presenting with clinical nail dystrophy have a fungal infection, and that the cost of a course of treatment was $2307 for efinaconazole and $53 for terbinafine (including monitoring liver function). They concluded that if you are going to prescribe terbinafine, empiric therapy without confirmatory testing is the preferred strategy (and the least expensive overall) with a very low risk of serious adverse effects. If you are going to prescribe efinaconazole, then confirmatory testing with PAS is preferred. However, this is a much more expensive treatment option.

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

Pregabalin Does Not Decrease the Pain of Sciatica

Clinical question
Is pregabalin an effective treatment for the pain of acute or chronic sciatica?

Bottom line
Pregabalin does not relieve pain in patients with sciatica. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Mathieson S, Maher CG, McLachlan A, et al. Trial of pregabalin for acute and chronic sciatica. N Engl J Med 2017;376(12):1111-1120.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Synopsis
The closely related drugs gabapentin and pregabalin are widely used for the treatment of neuropathic pain, including sciatica. This Australian trial recruited patients with moderate to severe sciatica, defined as pain radiating below the knee and accompanied by evidence of nerve root or spinal nerve involvement such as sensory deficits, diminished reflexes, or weakness. The pain had to have been present for between 1 week and 1 year. The average age of the 207 participants was 54 years, 85% had dermatomal pain, 37% had a neurologic deficit, and 30% had a motor deficit. The patients were randomly assigned to receive either pregabalin in a dose of 75 mg twice daily, increasing to a final target dose of 300 mg twice daily at 8 weeks, or matching placebo. The primary outcome was pain on a 10-point scale, with a difference of 1.5 points considered to be the minimal clinically important difference. Patients were followed up for up to 1 year, and a variety of secondary outcomes were measured, as well. Groups were balanced at the start of the study, and analysis was by intention to treat. At both 8 weeks and 52 weeks, there was no significant difference in the primary outcome, and no difference in secondary outcomes including disability, back pain intensity, global perception of the effect, and quality of life.

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

Steroid Injections Ineffective for Knee Osteoarthritis

Clinical question
Do intra-articular corticosteroids improve pain and function and decrease cartilage loss in adults with osteoarthritis of the knee?

Bottom line
This well-done study found that regular three-month intra-articular injections of triamcinolone for two years resulted in no significant difference in pain and function assessments compared to saline. However, a significant increase in cartilage loss and damage did occur in patients receiving steroids compared to saline. This study confirms the findings of the only other published study with a low risk of bias (see Synopsis). (LOE = 1b)(www.essentialevidenceplus.com)

Reference
McAlindon TE, LaValley MP, Harvey WF, et al. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. JAMA 2017;317(19):1967-1975.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Synopsis
Although intra-articular corticosteroids are commonly used for the treatment of knee osteoarthritis, data are limited in terms of benefits and safety. The most recent Cochrane Review on this topic evaluated 27 randomized controlled trials (26 with a high risk of bias) and found minimal improvement in pain and function in the short-term with steroids compared with placebo. The only study with low risk of bias found no benefit from steroids (Jüni P, et al. Cochrane Database Syst Rev 2015;(10):CD005328). These investigators recruited 140 adults, 45 years or older, with knee osteoarthritis diagnosed using standard national criteria. Eligible patients randomly received (concealed allocation assignment) either ultrasound-guided intra-articular triamcinolone (40 mg) or saline injections every 3 months for 2 years. Patients, clinicians administering the injections, and outcome assessors remained masked to treatment group assignment. Pain and function assessments based on validated questionnaires and physical examination occurred regularly throughout the study. Periodic magnetic resonance imaging occurred at 0, 12, and 24 months to evaluate changes in knee cartilage volume over the 2-year period. Complete follow-up occurred for 95% of patients at 2 years. Using intention-to-treat analysis, pain and function scores did not significantly differ between the 2 groups. However, the rate of cartilage loss and damage was significantly greater in the triamcinolone treatment group. There were no significant group differences in serious adverse events. The authorship of this POEM is attributed to Emma J. Pace, MD, Fellow and Instructor, Department of Family Medicine, University of Virginia, Charlottesville, VA.

David Slawson, MD
Professor and Vice Chair for Education and Scholarship
University of North Carolina Chapel Hill, Carolinas HealthCare System
Charlotte, NC

Treatment of Subclinical Hypothyroidism Ineffective in Older Adults

Clinical question
Is there a clinical benefit to treating subclinical hypothyroidism in older adults?

Bottom line
Treatment of patients with a minimally elevated thyrotropin (thyroid-stimulating hormone) level did not result in any improvement in symptoms. If patients present with a thyrotropin level between 4.6 mIU and 10 mIU per liter, repeat the test as the levels often normalize (this occurred in 60% of the patients initially referred for the study). Only consider treatment if levels increase to above 10.0 mIU/L. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Stott DJ, Rodondi N, Kearney PM, et al, for the TRUST Study Group. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med 2017;376(26):2534-2544.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Synopsis
Whether to treat patients with subclinical hypothyroidism (slightly elevated thyrotropin, normal T4, and no or minimal symptoms) remains controversial. The authors of this study recruited 737 such adults, 65 years and older, and randomized them to receive thyroid replacement or matching placebo. The mean baseline thyrotropin level was 6.4 mIU/L (normal range: 0.4 to 4.59 mIU/L), and few had a value greater than 10.0 mIU/L. The groups were balanced, allocation was appropriately concealed, and analysis was by intention to treat. Patients were followed up for 1 year, and the primary outcomes were the 4-item ThyPRO thyroid symptom score and a 7-item Tiredness Score. The treatment dose of levothyroxine was started at 50 mcg daily for most patients, and gradually increased until the thyrotropin was in the normal range (the placebo group had sham titration of their "dose"). The final achieved average thyrotropin level was just over 3.0, which is a bit higher than the target 2.5 mIU/L recommended by some guidelines (Eur Thyroid J 2013;2:215-28). At the end of the study period, there was no difference in any clinical outcomes. A subset of slightly more than half the patients in each group had extended follow-up for a median of 2 years, and at that time there was a slightly greater improvement in the Tiredness Score in the levothyroxine group, but this was of marginal clinical and statistical significance. There was no difference in harms, including cardiovascular events, although the study was not powered to detect a difference if there was one.

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

Bare Arm Best for BP Measurement

Clinical question
What is the best way to measure blood pressure?

Bottom line
Bare those arms, folks. To get the most accurate measure, let patients chill for a few minutes, and then measure their blood pressure on a completely bare arm. Does a difference of 4 mm systolic and 6 mm to 7 mm diastolic matter? It might; especially when deciding whether to add a second or third drug. Also, remember to confirm office-based blood pressures with an out-of-office measurement (either ambulatory blood pressure monitoring or home blood pressure measurements), as many patients have white coat hypertension. (LOE = 2c)(www.essentialevidenceplus.com)

Reference
Ozone S, Shaku F, Sato M, Takayashiki A, Tsutsumi M, Maeno T. Comparison of blood pressure measurements on the bare arm, over a sleeve, and over a rolled-up sleeve in the elderly. Fam Pract 2016;33(5):517-522.

Study design: Cross-sectional

Funding source: Self-funded or unfunded

Setting: Outpatient (primary care)

Synopsis
It is important that we measure blood pressure in our offices in the same way it is done in studies of hypertension diagnosis and treatment. Otherwise, we risk misclassifying patients and may either overtreat or undertreat them. This simple cross-sectional study recruited 186 adults in a Japanese primary care clinic and in 2 adult daycare facilities. Blood pressure was measured using an automated cuff in 3 conditions: a completely bare arm, an arm covered by a sleeve no more than 1 mm thick to the wrist (a cardigan with a 1-mm thick sleeve was provided, if necessary), or an arm with the sleeve rolled up over the elbow. All patients were first asked to sit in a chair for 5 minutes prior to the measurement, with their arm supported and level. The researchers systematically varied the order in which blood pressure was measured. For each condition, the final blood pressure was the average of 3 measurements. The participants had a mean age of 75 years, 62% were female, and approximately 63% were hypertensive. The mean blood pressures were 129/67 taken on a bare arm, 133/73 on a fully sleeved arm, and 133/74 on an arm with the rolled-up sleeve. The difference persisted after adjusting for age and measurement order in an ANOVA model. It is also interesting that the mean blood pressure decreased from the first measurement (135/74) to the second measurement (131/71) and to the third measurement (129/70).

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

Home Glucose Monitoring Offers No Benefit to Patients Not Using Insulin

Clinical question
Does home monitoring of blood glucose levels improve glycemic control or quality of life in patients with type 2 diabetes who are not using insulin?

Bottom line
Lots of numbers, lots of money, lots of strips in landfills, little to show for it. Home glucose monitoring of patients in primary care does not improve hemoglobin A1c scores or quality of life over 1 year in patients who are not taking insulin. Patients did not feel more empowered or satisfied as a result of home monitoring nor have fewer hypoglycemic episodes, and their physicians did not seem to respond to the home glucose levels to any beneficial effect. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Young LA, Buse JB, Weaver MA, et al, for the Monitor Trial Group. Glucose self-monitoring in non-insulin-treated patients with type 2 diabetes in primary care settings. A randomized trial. JAMA Intern Med 2017;177(7):920-929.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Synopsis
These researchers identified adults (average age: 61 years) with type 2 diabetes not treated with insulin and hemoglobin A1c levels between 6.5% and 9.5%. Most of the patients (75%) monitored their blood glucose levels at home prior to the study but had not been seen by an endocrinologist. The 450 patients (who had type 2 diabetes for an average 8 years) were randomly assigned, using concealed allocation, to 1 of 3 arms: (1) no home glucose monitoring; (2) standard once-daily monitoring; and (3) enhanced once-daily monitoring, consisting of glucose values immediately reported to the patient plus automated, tailored messaging delivered via the meter. The patients' physicians were given the home glucose monitoring results but were not asked to follow a specific protocol to respond to them. After both 6 months and 1 year, there was no difference, on average, among the groups in hemoglobin A1c levels, hospitalizations, episodes of severe hypoglycemia, or quality of life scores. Similarly, there was no difference among groups in treatment satisfaction or feelings of empowerment.

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

Physical Therapy Doesn't Add Anything to Standard Treatment of Ankle Pain

Clinical question
In patients with mild to moderate ankle sprain, does physical therapy (physiotherapy) hasten or improve recovery?

Bottom line
Physical therapy (up to 7 sessions) does not hasten resolution of symptoms or improve function in adults with ankle sprain: Approximately 60% of patients who receive usual care or physical therapy do not achieve "excellent" resolution. Send patients home with the usual RICES protocol: rest, ice, compression, elevation, and splinting. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Brison RJ, Day AG, Pelland L, et al. Effect of early supervised physiotherapy on recovery from acute ankle sprain: randomised controlled trial. BMJ 2016;355:i5650.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Emergency department

Synopsis
These authors studied the effect of longitudinal, supervised, stepwise physical therapy in addition to usual acute management of mild to moderate ankle sprain (grade 1 or 2) in 503 patients, 16 years or older, who presented to an emergency department in Canada. It's interesting that 84% of patients received an x-ray although approximately 30% of patients had mild (grade 1) sprain and any patients who required immobilization were excluded. One week after evaluation and basic management with RICES (rest, ice, compression, elevation, splinting), patients were randomized, using concealed allocation, to continue with usual care or to add stepwise physical therapy of up to seven 30-minute visits combined with home exercise. The main outcome was a score of "excellent" (at least 450) at 3 months on a 500-point patient questionnaire of symptoms, stiffness, pain, function, recreational activity, and quality of life. At 3 months approximately 40% of patients scored at least 450, with no difference between groups (42% vs 40%). After 6 months, the percentage of patients experiencing excellent recovery was slightly higher in the usual care group than in the intervention group, but the difference was not statistically significant between groups (65% vs 56%; P = .09). In addition to patient reports of symptoms and function, the researchers also conducted clinical and biomechanical evaluation, again not finding any difference between the groups. The study had the power of at least 80% to find an increase in excellent recovery from 60% to 75%, if one existed.

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

Gabapentinoids for Chronic Low Back Pain: Limited Evidence, More Harm Than Benefit

Clinical question
Are gabapentinoids safe and effective in treating patients with chronic low back pain?

Bottom line
The existing data on gabapentinoids for chronic low back pain are limited in number and quality. The amount of pain reduction is low to moderate, while the rate of adverse effects is high. The few studies that assessed function found no improvement. (LOE = 2a-)(www.essentialevidenceplus.com)

Reference
Shanthanna H, Gilron I, Rajarathinam M, et al. Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials. PLoS Med 2017;14(8):e1002369.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Synopsis
These authors searched 2 databases and the Cochrane clinical trials register to identify randomized trials of gabapentinoids (gabapentin, pregabalin) for treating adults with back pain lasting at least 3 months. Two authors independently assessed the inclusion of articles and they resolved disagreements by consensus or through third-party adjudication. Ultimately they included 8 small studies with 3 different comparison treatments. Most of the studies had methodologic quality issues, including selection bias and inadequate concealment of randomization. Three studies with 185 patients compared gabapentinwith placebo, finding minimal improvement in pain. Three studies with 332 patients compared pregabalin with other analgesics, finding pregabalin was more effective in average pain response. The remaining studies, which assessed pregabalin as an adjunct to pain management, were heterogeneous and the authors chose not to pool the data. The largest of these studies, however, found that adding pregabalin didn't improve pain. We have commented frequently on the inconsistent reporting of treatment harms in clinical trials and these studies are no exception. However, the authors were able to pool data and estimate the number needed to treat to harm (NNTH) for several adverse effects: dizziness (NNTH = 7; 95% CI 4 - 30), fatigue (NNTH = 8; 4 - 44), altered mentation (NNTH = 6; 4 - 15), and vision disturbance (NNTH = 6; 4 - 13). The studies generally did not report on functional outcomes.

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

Treating Sleep Apnea with Positive Airway Pressure Does Not Reduce Adverse CV Outcomes or Mortality

Clinical question
Does positive airway pressure for adults with sleep apnea reduce cardiovascular disease morbidity and mortality?

Bottom line
The use of positive airway pressure (PAP) for adults with sleep apnea does not reduce adverse cardiovascular events or mortality. Patients who experience daytime fatigue at baseline benefit from reduced sleepiness and improved physical and mental well-being. Order sleep testing only in patients with signs or symptoms of sleep apnea who also experience clinically significant symptoms of daytime fatigue. No one else will benefit. (LOE = 1a)(www.essentialevidenceplus.com)

Reference
Yu J, Zhou Z, McEvoy D, et al. Association of positive airway pressure with cardiovascular events and death in adults with sleep apnea. A systematic review and meta-analysis. JAMA 2017;318(2):156-166.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Synopsis
These investigators thoroughly searched multiple databases including MEDLINE, EMBASE, and the Cochrane Library, as well as reference lists from clinical trials, review articles, conference abstracts, and the clinicaltrials.gov website. Eligible studies included randomized clinical trials that assessed the use of PAP compared with standard care or sham PAP among adults, 18 years or older, with either obstructive sleep apnea (OSA) or central sleep apnea (CSA). No language restrictions were applied. Two individuals independently assessed studies for inclusion criteria and for methodologic quality using a standard risk of bias assessment tool. Disagreements were resolved by consensus. A total of 10 studies that assessed the use of PAP in adults (N = 7266) with OSA and CSA met the inclusion criteria—9 evaluated continuous positive airway pressure and 1 evaluated adaptive servo-ventilation. The overall risk of bias was low to medium; all studies concealed allocation assignment and masked outcomes assessment. No significant associations occurred between the use of PAP and major adverse cardiovascular events, cardiovascular mortality, or all-cause mortality in patients with both OSA and CSA. In addition, there was no significant association with length of follow-up, adherence with using PAP, and baseline apnea-hypopnea index. The use of PAP was significantly associated with improvements in sleepiness and quality of life. A formal analysis found no evidence of publication bias and minimal heterogeneity of assessed outcomes.

David Slawson, MD
Professor and Vice Chair for Education and Scholarship
University of North Carolina Chapel Hill, Carolinas HealthCare System
Charlotte, NC

BP Goals in Patients Older Than 60 Years

Clinical question
When should treatment be initiated in older patients with hypertension, and what are reasonable goals?

Bottom line
Try to remember 60 – 150 – 140. That is: In patients older than 60 years, consider treatment if the systolic blood pressure is 150 mm Hg or higher, or 140 mm Hg or higher in patients with a history of stroke or transient ischemic attack and those at high cardiovascular risk. The guidelines suggest initiating therapy only after a discussion of the benefits and risks with each patient; so, no knee-jerk reactions or mechanical decisions based just on the numbers. The evidence is insufficient to guide therapy on the basis of diastolic blood pressure. (LOE = 5)(www.essentialevidenceplus.com)

Reference
Qaseem A, Wilt TJ, Rich R, et al, for the Clinical Guidelines Committee of the American College of Physicians and the Commission on Health of the Public and Science of the American Academy of Family Physicians. Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2017;166:430-437.

Study design: Practice guideline

Funding source: Foundation

Setting: Various (guideline)

Synopsis
These guidelines were based on a systematic review (doi:10.7326/M16-1754) and were developed by a combined working group representing the American College of Physicians and the American Academy of Family Physicians. The recommendations focus on improving patient-oriented outcomes and are based on graded evidence. The committee represented 2 primary care specialties and members had no reported financial conflicts of interest. For patients older than 60 years the working group strongly recommends a blood pressure target of less than 150 mm Hg to reduce the risk for mortality, stroke, and cardiac events (high-quality evidence), but only after discussion with the patient regarding the benefits and risks of treatment. For patients with a history of stroke or transient ischemic attack, the committee suggests treatment with a goal of 140 mm Hg to reduce the risk for recurrent stroke (weak recommendation, moderate-quality evidence). For patients at high cardiovascular risk, they similarly suggest a target systolic blood pressure of less than 140 mm Hg to reduce the risk for stroke or cardiac events. (weak recommendation, low-quality evidence). The committee provided no recommendations for treating on the basis of diastolic blood pressure, given insufficient evidence, and no recommendations for patients with chronic illnesses, other than as those illnesses affect cardiovascular risk.

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

Older Patients Do Not Like Discussions Involving Choices Based on "Limited Life Expectancy"

Clinical question
How do older patients react to the idea of stopping cancer screening toward the end of life?

Bottom line
It seems that we don't want to be reminded that we are approaching what Harlan Ellison calls "the downhill side" of life. When bringing up the idea that cancer screening may no longer be beneficial given a patient's limited life expectancy, using direct language such as "You may not live long enough to benefit from this test" is perceived by many patients as overly harsh. Instead, statements such as "This test will not help you live longer" may be better received. Although not studied, this same approach may be helpful for de-prescribing efforts. (LOE = 4)(www.essentialevidenceplus.com)

Reference
Schoenborn NL, Lee K Pollack CE, et al. Older adults' views and communication preferences about cancer screening cessation. JAMA Intern Med 2017;177(8):1121-1128.

Study design: Cohort (prospective)

Funding source: Government

Setting: Outpatient (any)

Synopsis
Many guidelines, such as those from the Choosing Wisely campaign, suggest stopping screening for cancer at an age when early identification is not likely to produce a net benefit. This study enrolled 40 patients, with an average age of 75.7 years, to collect their thoughts about how the topic of stopping screening should be broached. Individuals were interviewed after they were given a brief overview of the benefits and harms of cancer screening, using common cancers as examples. They were also told that someone who will not live for 10 more years might not benefit and might be harmed by screening. Patients were then asked what factors they would consider to stop getting regular screening, and what their reactions would be if a clinician suggested stopping screening. Patients were interviewed by an investigator not known to them and the interviews were recorded, transcribed, and open-coded to identify themes. Transcripts were coded independently by 2 investigators. Three themes emerged: (1) participants were amenable to stopping cancer screening, especially if suggested by a trusted clinician; (2) they objected to the concept that a clinician could accurately predict life expectancy; and (3) they preferred that a clinician explain a recommendation to stop screening by incorporating individual health status, but were divided as to whether life expectancy should be brought into the discussion.

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

Prostate Cancer Screening: No Mortality Benefit After 15 Years of Follow-Up (PLCO)

Clinical question
Does screening of asymptomatic men for prostate cancer improve mortality?

Bottom line
After nearly 2 decades of follow-up from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, there appears to be no mortality benefit to screening asymptomatic men for prostate cancer. (LOE = 1b)(www.essentialevidenceplus.com)

Reference
Pinsky PF, Prorok PC, Yu K, et al. Extended mortality results for prostate cancer screening in the PLCO trial with median follow-up of 15 years. Cancer 2017;123(4):592-599.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Setting: Population-based

Synopsis
We have previously reported data from the original PLCO study (http://www.essentialevidenceplus.com/content/poem/110501) and its 13-year follow-up (http://www.essentialevidenceplus.com/content/poem/140343). In the original trial, more than 76,000 men between the ages of 55 years and 74 years at 10 centers were randomized to receive prostate cancer screening (annual prostate-specific antigen for 6 years plus digital rectal examination for 4 years) or no scheduled screening. This study reports additional follow-up (up to 19 years; median 15 years). The cumulative prostate cancer mortality rates were virtually identical (4.8 and 4.6 per 10,000 person-years, respectively). Additionally, there was no difference in all-cause mortality between the groups (173 and 177 per 10,000 person-years).

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

Detrimental Effect of Tight Glucose Control on CV Mortality Perists Over 9 Years

Clinical question
What is the long-term effect of intensive blood glucose control in patients with type 2 diabetes?

Bottom line
The initial Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which compared standard treatment with intensive control, found that, despite good intentions, cardiovascular and overall mortality is significantly higher when blood glucose levels are lower. This study, which followed up patients for an additional 5 years, found that patients in the intensive treatment group continued to keep their hemoglobin A1c levels lower than in the standard care group; they also continued to be at increased risk of death from a cardiovascular event. Not good. (LOE = 2b)(www.essentialevidenceplus.com)

Reference
The ACCORD Study Group. Nine-year effects of 3.7 years of intensive glycemic control on cardiovascular outcomes. Diabetes Care 2016;39(5):701-708.

Study design: Cohort (prospective)

Funding source: Government

Setting: Outpatient (any)

Synopsis
This report is a follow-up of patients who were enrolled in the ACCORD study, which randomly assigned patients with type 2 diabetes and a high risk for cardiovascular outcomes to receive either usual care or treatment aimed at intensive control of blood glucose. After the 3.7 years of the study, patients were followed up for an additional 5 years to determine the long-term effect of their initial treatment. The patients were no longer on a protocol and their treatment goals were at the discretion of their clinician, but, A1c levels were still lower overall in the patients who had been in the intensive-care group. The investigators did a great job of keeping track of the patients, following up with 98% of them (n = 8601) who did not suffer a primary outcome or death during the original trial. Over this additional time, intensive glucose lowering did not increase or decrease the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death, death from any other cause, or overall mortality. The increased cardiovascular mortality rate seen with intensive control during the active treatment stage decreased in the subsequent years, but was still higher than in the group initially treated with standard treatment (hazard ratio 1.20; 95% CI 1.03 - 1.39; P = .02).

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

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(www.essentialevidenceplus.com).

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