Time to Align Coverage with Evidence for Treatment of Back Pain.

Despite improved knowledge about the benefits and harms of treatments for chronic back pain in the past several decades, there is a large and consequential mismatch between treatments found safe and effective and those routinely covered by health insurance. As a result, care for back pain has, if anything, deteriorated in recent decades-expenses are higher, harms are greater, and use of ineffective treatments is more common. Deficiencies in health care delivery processes and payment models are centrally involved in the failure to improve care for back pain. A key step for accelerating progress is changing insurance coverage policies to facilitate use of the safest and most helpful approaches while discouraging riskier and less effective treatments. Relatively simple changes in reimbursement policies may minimize harm and improve quality of life for many patients with chronic back and similar pain syndromes. Such changes might also reduce health care expenditures because the costs of treatments currently covered by insurance and their associated harms may well outweigh the costs of the relatively safe and effective treatments recommended by current guidelines but poorly covered by insurance. There is no justification for continuing the status quo-patients and clinicians deserve better.

A randomized trial of epidural glucocorticoid injections for spinal stenosis.

BACKGROUND: Epidural glucocorticoid injections are widely used to treat symptoms of lumbar spinal stenosis, a common cause of pain and disability in older adults. However, rigorous data are lacking regarding the effectiveness and safety of these injections. METHODS: In a double-blind, multisite trial, we randomly assigned 400 patients who had lumbar central spinal stenosis and moderate-to-severe leg pain and disability to receive epidural injections of glucocorticoids plus lidocaine or lidocaine alone. The patients received one or two injections before the primary outcome evaluation, performed 6 weeks after randomization and the first injection. The primary outcomes were the score on the Roland-Morris Disability Questionnaire (RMDQ, in which scores range from 0 to 24, with higher scores indicating greater physical disability) and the rating of the intensity of leg pain (on a scale from 0 to 10, with 0 indicating no pain and 10 indicating "pain as bad as you can imagine"). RESULTS: At 6 weeks, there were no significant between-group differences in the RMDQ score (adjusted difference in the average treatment effect between the glucocorticoid-lidocaine group and the lidocaine-alone group, -1.0 points; 95% confidence interval [CI], -2.1 to 0.1; P=0.07) or the intensity of leg pain (adjusted difference in the average treatment effect, -0.2 points; 95% CI, -0.8 to 0.4; P=0.48). A prespecified secondary subgroup analysis with stratification according to type of injection (interlaminar vs. transforaminal) likewise showed no significant differences at 6 weeks. CONCLUSIONS: In the treatment of lumbar spinal stenosis, epidural injection of glucocorticoids plus lidocaine offered minimal or no short-term benefit as compared with epidural injection of lidocaine alone. (Funded by the Agency for Healthcare Research and Quality; ClinicalTrials.gov number, NCT01238536.).

Oral steroids for acute radiculopathy due to a herniated lumbar disk: a randomized clinical trial.

IMPORTANCE: Oral steroids are commonly used to treat acute sciatica due to a herniated disk but have not been evaluated in an appropriately powered clinical trial. OBJECTIVE: To determine if oral prednisone is more effective than placebo in improving function and pain among patients with acute sciatica. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trial conducted from 2008 to 2013 in a large integrated health care delivery system in Northern California. Adults (n=269) with radicular pain for 3 months or less, an Oswestry Disability Index (ODI) score of 30 or higher (range, 0-100; higher scores indicate greater dysfunction), and a herniated disk confirmed by magnetic resonance imaging were eligible. INTERVENTIONS: Participants were randomly assigned in a 2:1 ratio to receive a tapering 15-day course of oral prednisone (5 days each of 60 mg, 40 mg, and 20 mg; total cumulative dose = 600 mg; n = 181) or matching placebo (n = 88). MAIN OUTCOMES AND MEASURES: The primary outcome was ODI change at 3 weeks; secondary outcomes were ODI change at 1 year, change in lower extremity pain (measured on a 0-10 scale; higher scores indicate more pain), spine surgery, and Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (0-100 scale; higher scores better). RESULTS: Observed baseline and 3-week mean ODI scores were 51.2 and 32.2 for the prednisone group and 51.1 and 37.5 for the placebo group, respectively. The prednisone-treated group showed an adjusted mean 6.4-point (95% CI, 1.9-10.9; P = .006) greater improvement in ODI scores at 3 weeks than the placebo group and a mean 7.4-point (95% CI, 2.2-12.5; P = .005) greater improvement at 52 weeks. Compared with the placebo group, the prednisone group showed an adjusted mean 0.3-point (95% CI, -0.4 to 1.0; P = .34) greater reduction in pain at 3 weeks and a mean 0.6-point (95% CI, -0.2 to 1.3; P = .15) greater reduction at 52 weeks. The prednisone group showed an adjusted mean 3.3-point (95% CI, 1.3-5.2; P = .001) greater improvement in the SF-36 PCS score at 3 weeks, no difference in the SF-36 PCS score at 52 weeks (mean, 2.5; 95% CI, -0.3 to 5.4; P = .08), no change in the SF-36 MCS score at 3 weeks (mean, 2.2; 95% CI, -0.4 to 4.8; P = .10), and an adjusted 3.6-point (95% CI, 0.6-6.7; P = .02) greater improvement in the SF-36 MCS score at 52 weeks. There were no differences in surgery rates at 52-week follow-up. Having 1 or more adverse events at 3-week follow-up was more common in the prednisone group than in the placebo group (49.2% vs 23.9%; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with acute radiculopathy due to a herniated lumbar disk, a short course of oral steroids, compared with placebo, resulted in modestly improved function and no improvement in pain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00668434.

Surgical versus nonsurgical therapy for lumbar spinal stenosis.

BACKGROUND: Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials. METHODS: Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care. The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and 1 and 2 years. RESULTS: A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also undergone surgery. Despite the high level of nonadherence, the intention-to-treat analysis of the randomized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain, with a mean difference in change from baseline of 7.8 (95% confidence interval, 1.5 to 14.1); however, there was no significant difference in scores on physical function or on the Oswestry Disability Index. The as-treated analysis, which combined both cohorts and was adjusted for potential confounders, showed a significant advantage for surgery by 3 months for all primary outcomes; these changes remained significant at 2 years. CONCLUSIONS: In the combined as-treated analysis, patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically. (ClinicalTrials.gov number, NCT00000411 [ClinicalTrials.gov].).

Saw palmetto for benign prostatic hyperplasia.

BACKGROUND: Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. METHODS: In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. RESULTS: There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. CONCLUSIONS: In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.).

A detailed safety assessment of a saw palmetto extract.

BACKGROUND: Saw palmetto is commonly used by men for lower-urinary tract symptoms. Despite its widespread use, very little is known about the potential toxicity of this dietary supplement. METHODS: The Saw palmetto for Treatment of Enlarged Prostates (STEP) study was a randomized clinical trial performed among 225 men with moderate-to-severe symptoms of benign prostatic hyperplasia, comparing a standardized extract of the saw palmetto berry (160 mg twice daily) with a placebo over a 1-year period. As part of this study, detailed data were collected on serious and non-serious adverse events, sexual functioning, and laboratory tests of blood and urine. Between-group differences were assessed with mixed-effects regression models. RESULTS: There were no significant differences observed between the saw palmetto and placebo-allocated participants in the risk of suffering at least one serious adverse event (5.4% vs. 9.7%, respectively; p=0.31) or non-serious symptomatic adverse event (34.8% vs. 30.1%, p=0.48). There were few significant between-group differences in sexual functioning or for most laboratory analyses, with only small differences observed in changes over time in total bilirubin (p=0.001), potassium (p=0.03), and the incidence of glycosuria (0% in the saw palmetto group vs. 3.7% in the placebo group, p=0.05). CONCLUSIONS: Despite careful assessment, no evidence for serious toxicity of saw palmetto was observed in this clinical trial. Given the sample size and length of this study, however, these data do not rule out potential rare adverse effects associated with the use of saw palmetto.

Creating a culture of research.

There is widespread concern about the ability of the current model of clinical research to keep pace with the growing need for testing new approaches to disease management and prevention. In response, important innovations are emerging in critical areas of research infrastructure and practice. However, success in fulfilling the promise of clinical research will also require a fundamental shift in the relationship between the clinical-research enterprise and all segments of society. In this article, we outline proposals to help create the necessary recognition and engage participation by patients, clinicians, health-care delivery systems, and the research community to establish the long-lasting growth needed for achieving the full potential of clinical research.

Spontaneous bleeding associated with ginkgo biloba: a case report and systematic review of the literature: a case report and systematic review of the literature.

BACKGROUND: Ginkgo biloba (ginkgo) is a herbal remedy used by over 2% of the adult population in the United States. Several review articles have suggested that ginkgo may increase the risk of bleeding. OBJECTIVE: To report a case of bleeding associated with using ginkgo, to systematically review the literature for similar case reports, and to evaluate whether using ginkgo is causally related to bleeding. DATA SOURCES: We searched MEDLINE, EMBASE, IBIDS, and the Cochrane Collaboration Database from 1966 to October 2004 with no language restrictions. REVIEW METHODS: Published case reports of bleeding events in persons using ginkgo were selected. Two reviewers independently abstracted a standard set of information to assess whether ginkgo caused the bleeding event. RESULTS: Fifteen published case reports described a temporal association between using ginkgo and a bleeding event. Most cases involved serious medical conditions, including 8 episodes of intracranial bleeding. However, 13 of the case reports identified other risk factors for bleeding. Only 6 reports clearly described that ginkgo was stopped and that bleeding did not recur. Bleeding times, measured in 3 reports, were elevated when patients were taking ginkgo. CONCLUSION: A structured assessment of published case reports suggests a possible causal association between using ginkgo and bleeding events. Given the widespread use of this herb and the serious nature of the reported events, further studies are needed. Patients using ginkgo, particularly those with known bleeding risks, should be counseled about a possible increase in bleeding risk.

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration.

An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Should we reconsider the routine use of placebo controls in clinical research?

BACKGROUND: Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. METHODS: We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. RESULTS: We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. CONCLUSIONS: Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

The prognosis of acute low back pain in primary care in the United States: a 2-year prospective cohort study.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To assess the prognosis of patients presenting with acute low back pain (LBP) in a primary care setting in the United States. SUMMARY OF BACKGROUND DATA: Practice guidelines for acute LBP based on return-to-work outcomes underestimate the development of chronic pain in the primary care setting. Because of differences in inclusion criteria, chronic pain definitions, and national health systems, prognostic cohort studies have reported a wide range of results limiting interpretation and generalization. Current data from carefully designed prognostic studies of acute LBP are lacking for the US primary care system. METHODS: Members of a large health service organization were enrolled after seeking medical care for acute LBP, with or without sciatica, of up to 30 days duration, with no episode in the past 12 months and no history of spine surgery. We conducted phone interviews at baseline, 6 months, and 2 years. Based on receiver operating characteristic analyses, a combination of global perceived recovery with pain intensity was used as primary outcome for chronic pain. Recurrence and multiple secondary outcomes were assessed to allow for comparison with other studies. RESULTS: Six hundred five patients had an average pain intensity of 5.6 (numeric rating scale = 0-10) and disability of 15.8 (Roland-Morris scale = 0-24). Eight percent had declared sick leave between pain onset and baseline interview. Thirteen percent of 521 patients (86% follow-up) experienced chronic pain at 6 months and 19% of 443 patients at 2 years. At 6 months, 54% had experienced at least 1 LBP recurrence, and 47% in the subsequent 18 months. CONCLUSION: The prognosis of strictly defined acute LBP, with or without sciatica, is less favorable than commonly stated in practice guidelines based on failure to return to work. Broad initiatives to develop new means for the primary and secondary prevention of recurrent and chronic LBP are urgently needed.

Acute low back pain and primary care: how to define recovery and chronification?

STUDY DESIGN: A prospective cohort study. OBJECTIVE: To establish outcome measures for recovery and chronic pain for studies with patients who present with recent-onset acute low back pain (LBP) in primary care. SUMMARY OF BACKGROUND DATA: Among back pain researchers, no consensus exists about outcome definitions or how to identify primary-care patients as not-recovered from an episode of LBP. Cut points for outcome scales have mostly been arbitrarily chosen. Theoretical models for establishing minimal important change values in studies of patients with LBP have been proposed and need to be applied to real data. METHODS: A sample of 521 patients who presented with acute LBP (<4 weeks) in primary care clinics were observed for 6 months and scores for pain and disability were compared with ratings on a Global Perceived Effect Scale. Using multiple potential "gold standards" as anchors (reference standards), the receiver operating characteristic method was used to determine optimal cut points for different ways of defining nonrecovery from acute LBP. RESULTS: Minimal important change values and upper limits for pain and disability scores as well as minimal important percentage changes are presented for five different definitions of recovery. A previously suggested 30% change from baseline scores does not accurately discriminate between recovered patients and nonrecovered patients in patients presenting with acute LBP in primary care. CONCLUSION: Outcome definitions that combine ratings from perceived recovery scales with pain and disability measures provide the highest accuracy in discriminating recovered patients from nonrecovered patients.

Surgical versus nonoperative treatment for lumbar spinal stenosis four-year results of the Spine Patient Outcomes Research Trial.

STUDY DESIGN: Randomized trial and concurrent observational cohort study. OBJECTIVE: To compare 4 year outcomes of surgery to nonoperative care for spinal stenosis. SUMMARY OF BACKGROUND DATA: Surgery for spinal stenosis has been shown to be more effective compared to nonoperative treatment over 2 years, but longer-term data have not been analyzed. METHODS: Surgical candidates from 13 centers in 11 US states with at least 12 weeks of symptoms and confirmatory imaging were enrolled in a randomized cohort (RC) or observational cohort (OC). Treatment was standard decompressive laminectomy or standard nonoperative care. Primary outcomes were SF-36 bodily pain (BP) and physical function scales and the modified Oswestry Disability index assessed at 6 weeks, 3 months, 6 months, and yearly up to 4 years. RESULTS: A total of 289 patients enrolled in the RC and 365 patients enrolled in the OC. An as-treated analysis combining the RC and OC and adjusting for potential confounders found that the clinically significant advantages for surgery previously reported were maintained through 4 years, with treatment effects (defined as mean change in surgery group minus mean change in nonoperative group) for bodily pain 12.6 (95% confidence interval [CI], 8.5-16.7); physical function 8.6 (95% CI, 4.6-12.6); and Oswestry Disability index -9.4 (95% CI, -12.6 to -6.2). Early advantages for surgical treatment for secondary measures such as bothersomeness, satisfaction with symptoms, and self-rated progress were also maintained. CONCLUSION: Patients with symptomatic spinal stenosis treated surgically compared to those treated nonoperatively maintain substantially greater improvement in pain and function through 4 years.

Initial experience with a group presentation of study results to research participants.

BACKGROUND: Despite ethical imperatives, informing research participants about the results of the studies in which they take part is not often performed. This is due, in part, to the costs and burdens of communicating with each participant after publication of the results. METHODS: Following the closeout and publication of a randomized clinical trial of saw palmetto for treatment of symptoms of benign prostatic hyperplasia, patients were invited back to the research center to participate in a group presentation of the study results. RESULTS: Approximately 10% of participants attended one of two presentation sessions. Reaction to the experience of the group presentation was very positive among the attendees. CONCLUSION: A group presentation to research participants is an efficient method of communicating study results to those who desire to be informed and was highly valued by those who attended. Prospectively planning for such presentations and greater scheduling flexibility may result in higher attendance rates. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov #NCT00037154.