Monthly Archives: August 2014

Opioids for chronic back pain: short-term effectiveness, long-term uncertain

Clinical Question

Are opioids effective in the treatment of chronic low-back pain?

Bottom Line

Overall, in patients with chronic low-back pain, opioids are moderately more effective than placebo in the short term for pain relief and slightly more effective in the short term for improving function. However, data for long term use are pretty much nonexistent. The long-term use of opioids for patients with chronic low-back pain is controversial. Physicians are asked to provide comfort to patients, yet the regulatory and safety concerns of long-term use are a sobering counterpoint. (LOE = 1a-)

Reference

Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC. Opioids compared with placebo or other treatments for chronic low back pain: an update of the Cochrane review. Spine 2014;39(7):556-563.

Study Design: Meta-analysis (randomized controlled trials) Funding: Self-funded or unfunded
Setting: Various (meta-analysis) Allocation: Unknown

Synopsis

This is an update to a Cochrane Review published in 2007. The authors systematically searched several databases to identify randomized trials comparing opioids with placebo or other drugs. The studies had to have masked outcome assessments and evaluated at least one of the following: pain, function, global improvement, or the proportion of patients reporting 30% or 50% pain relief. Two authors independently assessed studies for inclusion, reconciling disagreements by discussion. Additionally, 3 authors independently extracted data from included studies. Finally, they used an explicit approach to assess the quality of each study and to assess the role of publication bias. Eventually, these authors included 15 trials with 5540 participants. For the most part, the reviewed trials had low to moderate quality, high drop-out rates, short duration, and limited interpretability of functional improvement. Six studies evaluated tramadol alone or in combination with acetaminophen (5 compared with placebo, 1 as an active comparator against a centrally acting nonopioid); 2 studies compared buprenorphine with placebo; and 7 studies assessed strong opioids (morphine, oxymorphone, hydromorphone, oxycodone). Of the 7 trials of strong opioids, 3 were not really designed to assess opioid efficacy. Twelve of the 15 total studies were at low risk of bias. The 5 studies comparing tramadol with placebo generally had more methodologic bias and showed greater overall pain relief than placebo and greater improvement in functional outcomes than placebo. In the 2 studies of buprenorphine, the authors found very-low-quality evidence that this agent reduces pain more than placebo and that it does anything for function. The studies of strong opioids found small reductions in pain and small improvements in function.

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

IFOBTs moderately sensitive and highly specific for colon cancer

Clinical Question

Are immunochemical fecal occult blood tests sensitive and specific enough to be used for colorectal cancer screening?

Bottom Line
Immunochemical fecal occult blood tests (IFOBTs), such as OC-Micro, OC-Sensor, or OC-Light, are moderately sensitive (73% – 89%) and highly specific (92% – 95%) for identifying colorectal cancer. In comparison, Homoccult Sensa has a lower sensitivity (64% – 80%) and specificity (87% – 90%). IFOBTs also have the advantage of requiring only one sample. (LOE = 1c)

Reference

Lee JK, Liles EG, Bent S, Levin TR, Corley DA. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann Intern Med 2014;160(3):171-181.

Study Design: Meta-analysis (other) Funding: Government
Setting: Various (meta-analysis) Allocation: Unknown

Synopsis

These researchers searched 5 databases and the reference lists of included studies, finding 19 eligible studies that evaluated the diagnostic accuracy of IFOBTs. Two authors used the STARD and PRISMA protocols and independently determined study eligibility, extracted the data, and evaluated study quality. They included cohort studies and randomized studies that used colonoscopy or longitudinal follow-up as the gold standard and only included studies published in English. They excluded studies or results that evaluated only the detection of adenomas. Limiting analysis to only currently available IFOBTs found a sensitivity of 82% (95% CI, 73% – 89%) and a specificity of 94% (92% – 95%). These numbers translate into a positive likelihood ratio of 13.10 and a negative likelihood ratio of 0.19. There was no difference in performance among different commercial products, and multiple sampling was no more accurate than a single sample. Heterogeneity among the studies was acceptable when removing products that are not commercially available. There was some evidence of publication bias. There are no head-to-head studies comparing one type of test with another, and no research evaluating the effectiveness of IFOBT testing on cancer-related mortality or all-cause mortality.

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

High adenoma detection rate during colonoscopy associated with lower incidence of colorectal cancer

Clinical Question

Does a gastroenterologist’s adenoma detection rate make a difference in the subsequent incidence of colorectal cancer?
Bottom Line

There is a consistent, linear, inverse relationship between higher adenoma detection rates and a lower rate of colorectal cancer (CRC) and CRC death. I’ll be asking my gastroenterologist about his detection rate before my next colonoscopy! (LOE = 2b)

Reference

Corley DA, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med 2014;370(14):1298-1306.

Study Design: Cohort (retrospective) Funding: Foundation
Setting: Outpatient (specialty) Allocation: Unknown

Synopsis

The adenoma detection rate has been proposed as a quality measure, with professional societies recommending a rate of at least 15% for female patients and 25% for male patients. But is this a valid quality measure? These researchers at Kaiser Permanente identified all patients who received colonoscopy between 1998 and 2010 and who had at least 6 months of follow-up. Patients were followed up for 10 years, or until a diagnosis of CRC, or until they left the insurance plan. The population had a median age of 64 years, 52% were women, and 57.4% of the colonoscopies were diagnostic (ie, in a symptomatic patient). Gastroenterologists had to perform 300 or more total colonoscopies (75 or more screening colonoscopies) during the study period to be included, and colonoscopies included screening, surveillance, and diagnostic procedures. The detection rate was defined as the percentage of examinations that found at least one adenoma or adenocarcinoma. There were a total of 264,972 colonoscopies eligible for analysis of interval cancers (cancers diagnosed within 6 months of the index colonoscopy were excluded). They detected 712 interval cancers, 60% of which were proximal, and there was a median interval of 39 months from index colonoscopy to diagnosis of cancer. Adenoma detection rates varied widely among the 136 physicians, from 10% to 60% for male patients and 4% to 46% for female patients. The researchers defined quintiles of adenoma detection rates from 16.6% to 38.9%.They found that the risk of an interval CRC, an advanced stage CRC, and a fatal CRC all declined with increasing adenoma detection rates. For example, compared with the lowest quintile, patients of physicians in the highest quintile had hazard ratios of 0.52 for interval CRC (95% CI, 0.39-0.69) and 0.38 for fatal CRC (0.22 – 0.65).

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

Anticoagulant plus NSAID or aspirin use associated with increased bleeding risk

Clinical Question

For patients with acute venous thromboembolism, is the use of anticoagulants plus nonsteroidal anti-inflammatory drugs or aspirin associated with an increased risk of bleeding?

Bottom Line

For patients treated with anticoagulants for acute venous thromboembolism (VTE), the use of concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin is associated with an increased risk of bleeding. This can occur in patients treated with rivaroxaban, as well as in those treated with enoxaparin plus a vitamin K antagonist (VKA). (LOE = 2b)Bottom Line

Reference

Davidson BL, Verheijen S, Lensing AW, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 2014;174(6):947-953.

Synopsis

The worldwide EINSTEIN DVT and EINSTEIN PE clinical trials compared rivaroxaban with enoxaparin plus a VKA for the treatment of acute VTE. These investigators used data from this cohort to examine the association between rivaroxaban or enoxaparin-VKA plus concomitant NSAID or aspirin use and the risk of clinically relevant and major bleeding. Clinically relevant bleeding was defined as nonmajor bleeding that resulted in either medical intervention, temporary cessation of study treatment, or patient discomfort. Major bleeding was that which resulted in death, occurred at a critical site, required transfusion of at least 2 units of red blood cells, or was associated with a 2 g/dL drop in hemoglobin. The cohort comprised 8246 patients, with half receiving rivaroxaban and half receiving enoxaparin-VKA. The NSAID analysis was adjusted for sex, as there were more women in the NSAID group. The aspirin analysis was adjusted for age and creatinine clearance, as patients in the aspirin group tended to be older with worse kidney function than the nonaspirin group. The NSAID or aspirin exposure period included 7 days after stopping the medication to reflect an ongoing risk. Clinically relevant bleeding was more likely to occur in the NSAID group as compared with the non-NSAID group (37.5 bleeding events per 100 patient-years vs 16.6 per 100 patient-years; hazard ratio [HR] = 1.77; 95% CI, 1.46-2.14). Findings were similar for both the NSAID-rivaroxaban-treated patients and NSAID-enoxaparin-VKA-treated patients. In the aspirin group, clinically relevant bleeding was also increased as compared with the nonaspirin group (36.6 bleeding events per 100 patient-years vs 16.9 per 100 patient-years; HR = 1.70; 1.38-2.11). For both the NSAID and the aspirin groups, the bleeding events were spread evenly over the duration of the use, suggesting that longer duration of use does not increase the risk of bleeding. Major bleeding increased 2.4-fold in the NSAID group and 1.5-fold in the aspirin group.

Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Northwestern University
Chicago, IL

Smoke-free legislation associated with better child and perinatal health

Clinical Question:  How much does smoke-free legislation impact the health of children?

The passage of smoke-free legislation is associated with nearly immediate and meaningful improvements in the number of preterm births and asthma exacerbations. (LOE = 1a)Bottom Line

Reference

Been JV, Nurmatov UB, Cox B, Nawrot TS, van Schayck CP, Sheikh A. Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis. Lancet 2014;383(9928):1549-1560.

Study DesignMeta-analysis (randomized controlled trials)

FundingFoundation

SettingVarious (meta-analysis)

AllocationUnknown

Synopsis

These authors searched many databases, including trials registries, to identify published and unpublished studies that evaluated the effects of smoke-free legislation on preterm birth, low birth weight, and asthma. Ultimately they included 11 studies (5 North American and 6 European) with more than 2.5 million births and nearly a quarter million asthma exacerbations! Nearly all the legislation required comprehensive and immediate changes (as opposed to the step-wise implementation used in Belgium). Four studies were deemed to have low risk of bias, 6 had moderate risk, and 1 had high risk. The higher-quality studies tended to be from Europe and the legislations invoked national-level bans on tobacco use. In 4 studies with nearly 1.4 million births, smoke-free legislation was associated with a 10% relative decrease in the frequency of preterm birth immediately after the legislation, and that result was maintained. However, the legislation had no impact on the frequency of low-birth-weight infants (6 studies with nearly 2 million participants). In 3 studies with more than 240,000 events, legislation was associated with an immediate 10% drop in the rate of hospital attendance for asthma exacerbations. There was no statistically significant subsequent decline, though. The authors provide additional data on secondary outcomes, such as small for gestational age, birth defects, and so forth, most of which were inconsistently studied and showed inconsistent results.

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