Long-term effects of specific stabilizing exercises for first-episode low back pain. Analgesic efficacy and safety of tramadol/ acetaminophen combination tablets (Ultracet) in treatment of chronic low back pain: a multicenter, outpatient, randomized, double blind, placebo controlled trial. Oral opioid therapy for chronic peripheral and central neuropathic pain. Opioid substitution to improve the effectiveness of chronic noncancer pain control: a chart review. Evaluation of long-term efficacy and safety of transdermal fentanyl in the treatment of chronic noncancer pain. Evaluating the accuracy of a simple heuristic to identify serious causes of low back pain. Long-term oral opioid therapy in patients with chronic nonmalignant pain. Efficacy of transcutaneous electrical nerve stimulation (tens) for chronic low-back pain in a multiple sclerosis population: a randomized, placebo-controlled clinical trial. [Intrathecal opioids in chronic non-malignant pain: relief and life quality]. Mini-intervention for subacute low back pain: two-year follow-up and modifiers of effectiveness. Secular changes in the quality of published randomized clinical trials in rheumatology.
A randomized clinical trial with 1-year and 3-year telephone questionnaire follow-ups.
                To report a specific exercise intervention's long-term effects on recurrence rates in acute, first-episode low back pain patients.
                The pain and disability associated with an initial episode of acute low back pain (LBP) is known to resolve spontaneously in the short-term in the majority of cases. However, the recurrence rate is high, and recurrent disabling episodes remain one of the most costly problems in LBP. A deficit in the multifidus muscle has been identified in acute LBP patients, and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity. Any relation between this deficit and recurrence rate was investigated in the long-term.
                Thirty-nine patients with acute, first-episode LBP were medically managed and randomly allocated to either a control group or specific exercise group. Medical management included advice and use of medications. Intervention consisted of exercises aimed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle. One year and three years after treatment, telephone questionnaires were conducted with patients.
                Questionnaire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group. One year after treatment, specific exercise group recurrence was 30%, and control group recurrence was 84% (P < 0.001). Two to three years after treatment, specific exercise group recurrence was 35%, and control group recurrence was 75% (P < 0.01).
                Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone. To evaluate the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg (tramadol/APAP) combination tablets for treatment of chronic low back pain (LBP).
                This 91 day, multicenter, outpatient, randomized, double blind, placebo controlled study enrolled 338 patients with chronic LBP requiring daily medication for > or = 3 months. Patients with at least moderate pain [pain visual analog scale (VAS) with scores > or = 40/100 mm] after washout were randomized to tramadol/APAP or placebo. After a 10 day titration, patients received 1 or 2 tablets QID. Primary outcome measure was final pain VAS score. Secondary measures included pain relief, quality of life and physical functioning, efficacy failure, and overall medication assessments.
                In total, 336 intent-to-treat patients received tramadol/APAP (n = 167) or placebo (n = 169). Mean baseline pain VAS score was 67.8. Intent-to-treat analysis showed significantly better mean final pain VAS scores (47.4 vs 62.9; p < 0.001) and mean final pain relief scores (1.8 vs 0.7; p < 0.001) for tramadol/APAP than for placebo. Roland Disability Questionnaire scores and physical-related subcategories of the McGill Pain Questionnaire and the Medical Outcome Study Short Form-36 Health Survey were significantly better for tramadol/APAP patients. More patients rated tramadol/APAP as "very good" or "good" than placebo (63.6 vs 25.2%; p < 0.001). Kaplan-Meier estimates of cumulative discontinuation rates due to efficacy failures were 22.9% (tramadol/APAP) vs 54.7% (placebo; p < 0.001). The most common treatment related adverse events with tramadol/APAP were nausea (12.0%), dizziness (10.8%), and constipation (10.2%). Average daily dose of tramadol/APAP was 4.2 tablets (tramadol 158 mg/APAP 1369 mg).
                Tramadol 37.5 mg/APAP 325 mg combination tablets show efficacy in pain reduction, in measures of physical functioning and quality of life, and in overall medication assessments, with a tolerability profile comparable with other opioids used for the treatment of chronic LBP. Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use. Few controlled trials have been performed, and many types of neuropathic pain remain unstudied.
                Adults with neuropathic pain that was refractory to treatment were randomly assigned to receive either high-strength (0.75-mg) or low-strength (0.15-mg) capsules of the potent mu-opioid agonist levorphanol for eight weeks under double-blind conditions. Intake was titrated by the patient to a maximum of 21 capsules of either strength per day. Outcome measures included the intensity of pain as recorded in a diary, the degree of pain relief, quality of life, psychological and cognitive function, the number of capsules taken daily, and blood levorphanol levels.
                Among the 81 patients exposed to the study drug, high-strength levorphanol capsules reduced pain by 36 percent, as compared with a 21 percent reduction in pain in the low-strength group (P=0.02). On average, patients in the high-strength group took 11.9 capsules per day (8.9 mg per day) and patients in the low-strength group took close to the 21 allowed (18.3 capsules per day; 2.7 mg per day). Affective distress and interference with functioning were reduced, and sleep was improved, but there were no differences between the high-strength group and the low-strength group in terms of these variables. Noncompletion of the study was primarily due to side effects of the opioid. Patients with central pain after stroke were the least likely to report benefit.
                The reduction in the intensity of neuropathic pain was significantly greater during treatment with higher doses of opioids than with lower doses. Higher doses produced more side effects without significant additional benefit in terms of other outcome measures.
                Copyright 2003 Massachusetts Medical Society We evaluated the efficacy and tolerability of opioids in the long-term management of chronic noncancer pain. This retrospective chart review included 86 outpatients who started receiving, between 1994 and 1998, long-acting opioids. For each patient, the number of different opioids used and the efficacy and tolerability of each opioid prescribed were noted. During a mean follow-up of 8.8 +/- 6.3 mo, the number of opioids used by each patient was 2.3 +/- 1.4. Patient diagnoses were: back pain (31), neuropathy (20), joint pain (13), visceral pain (7), reflex sympathetic dystrophy (7), headache (5), fibromyalgia (3). The first opioid prescribed was effective for 36% of patients, was stopped because of side effects in 30%, and was stopped for ineffectiveness in 34%. Of the remaining patients, the second opioid prescribed after the failure of the first was effective in 31%, the third in 40%, the fourth in 56%, and the fifth in 14%. There was one case of addiction and no case of tolerance. We conclude that if it is necessary to change the opioid prescription because of intolerable side effects or ineffectiveness, the cumulative percentage of efficacy increases with each new opioid tested. Failure of one opioid cannot predict the patient's response to another. Implications: This study showed that if a patient receiving chronic opioid therapy experiences an intolerable side effect or if the drug is ineffective, changing to a different opioid may result in a lessening or elimination of the side effect and/or improved analgesia. The objective of this international, multicenter, open-label trial was to assess the efficacy and safety of up to 12 months of therapy with transdermal therapeutic system (TTS) fentanyl in patients (n = 532) with chronic noncancer pain. The trial was completed by 301 (57%) of the patients. The main outcome measures were pain control assessment, global treatment satisfaction, patient preference for TTS fentanyl, and quality of life. The mean dose of transdermal fentanyl (TDF) increased from 48 to 90 microg/h during a period of 12 months. During treatment, on average 67% of patients within the efficacy analysis group (n = 524) reported very good, good, or moderate pain control. Global satisfaction (very good or good) was also stable at 42%. The majority (86%) of patients reported a preference for TDF over their previous treatment (P < .001, binomial test). Short Form 36 quality-of-life scores improved from baseline for bodily pain. The most frequent treatment-related adverse events were nausea (31%), constipation (19%), and somnolence (18%). With regard to opioid-specific adverse events (respiratory depression [< 1%], adrenal insufficiency [< 1%], drug abuse/dependence [1%], and opioid withdrawal syndrome [3%]), these were extremely rare and, with the exception of opioid withdrawal syndrome, none was considered definitively related to the treatment. Long-term treatment with TDF provided a stable degree of pain control in the majority of patients with moderate to severe chronic noncancer pain. It was preferred by the majority of patients compared with their previous opioid medication. Overall, long-term treatment with TDF was generally well tolerated, particularly in view of the low incidence of potentially serious side effects such as drug abuse/dependence and respiratory depression. However, at present, it is important that patients receiving TDF should still be subject to careful assessment and monitoring. Among patients presenting with low back pain (LBP), GPs have to identify those with serious, treatable conditions. However, excluding these conditions in every patient with LPB is time consuming and of low yield. We have suggested that identifying those patients where these serious conditions need to be considered can be made more efficient through asking patient if they feel their LBP is new or unfamiliar in some way.
                To evaluate the diagnostic validity of a simple heuristic based on the patient's view of the familiarity of LBP.
                Cross-sectional diagnostic study with delayed-type reference standard, nested within a three-arm randomized trial of quality improvement for LBP. A total of 1378 patients presenting, with LBP, to one of 126 participating GPs were included. They were asked whether their LBP was familiar or not (index test). At 1 year, patients were interviewed with regard to relevant conditions that in hindsight might explain their LBP. Reviewers deciding on disease status (reference standard) were blinded to the results of the index test.
                Totally 1190 patients answered the index test question and were available for interview at 1 year. Only four of these had a serious cause of their LBP. Two of these were identified by the familiarity heuristic, resulting in low sensitivity.
                The number of diseased patients was too small to obtain a reliable estimate of sensitivity. Low prevalence of serious disease in primary care poses difficulties for diagnostic research. In hindsight we would question whether an RCT-setting emphasizing non-specific LBP is suitable for this kind of research. At present, the familiarity heuristic cannot be recommended for patients presenting with LBP. In contrast to the use of opioids for the treatment of acute and chronic cancer pain, the administration of chronic opioid therapy for pain not due to malignancy remains controversial. We describe 100 patients who were chronically given opioids for treatment of nonmalignant pain. Most patients experienced neuropathic pain or back pain. We used sustained-release dihydrocodeine, buprenorphine, and sustained-release morphine. Pain reduction was measured with visual analogue scales (VAS), and the Karnofsky Performance Status Scale was used to assess the patient's function. Good pain relief was obtained in 51 patients and partial pain relief was reported by 28 patients. Only 21 patients had no beneficial effect from opioid therapy. There was a close correlation between the sum and the peak VAS values (r = 0.983; p less than 0.0001) and pain reduction was associated with an increase in performance (p less than 0.0001). The most common side effects were constipation and nausea. There were no cases of respiratory depression or addiction to opioids. Our results indicate that opioids can be effective in chronic nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer pain. This study was designed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation (TENS) on chronic low-back pain (LBP) in a multiple sclerosis (MS) population.
                Ninety participants with probable or definite MS (aged 21 to 78 y) presenting with chronic LBP were recruited and randomized into 3 groups (n=30 per group): (1) low-frequency TENS group (4 Hz, 200 micros); (2) high-frequency TENS group (110 Hz, 200 micros); and (3) placebo TENS. Participants self-applied TENS for 45 minutes, a minimum of twice daily, for 6 weeks. Outcome measures were recorded at weeks 1, 6, 10, and 32. Primary outcome measures included: Visual Analog Scale for average LBP and the McGill Pain Questionnaire. Secondary outcome measures included: Visual Analog Scale for worst and weekly LBP, back and leg spasm; Roland Morris Disability Questionnaire; Barthel Index; Rivermead Mobility Index; Multiple Sclerosis Quality of Life-54 Instrument, and a daily logbook. Data were analyzed blind using parametric and nonparametric tests, as appropriate.
                Results indicated a statistically significant interactive effect between groups for average LBP (P=0.008); 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied (P>0.05). However, clinically important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods.
                Although not statistically significant, the observed effects may have implications for the clinical prescription and the use of TENS within this population. The use of opioids for treatment of non-malignant pain is controversial. The evaluation of pain relief and of the quality of life of 11 severely incapacitated chronic non-cancer pain patients treated with long term intrathecal infusion of opioids trought implantable pumps was performed. The mean duration of pain complaints was 5.3 years. The mean pain intensity was 8.6. In 7 patients, pain episodes lasted at least 6 hours daily. The mean duration of the therapy was 19.6 months. After the treatment the mean pain score became 3.9. In only 1 patient, the duration of pain episodes was still longer than 6 hours. Quality of life improved in 36.36% of the cases. The long term spinal opioids through implantable pumps for non-malignant pains results in pain relief but not necessarily improves the quality of life. Randomized controlled trial.
                To Investigate the long-term effectiveness, costs, and effect modifiers of a mini-intervention, provided in addition to the usual care, and the incremental effect of a worksite visit for patients with subacute disabling low back pain (LBP).
                A mini-intervention was earlier proved to be an effective treatment for subacute LBP. Whether the beneficial effect is sustained is not known. Furthermore, modifiers of a treatment effect are largely unknown.
                A total of 164 patients with subacute LBP randomized into a mini-intervention (A, n = 56), a mini-intervention plus a worksite visit (B, n = 51), or the usual care (C, n = 57). Mini-intervention consisted of a detailed assessment of the patients' history, beliefs, and physical findings by a physician and a physiotherapist, followed by recommendations and advice. The usual care patients received the conventional care. Pain, disability, health-related quality of life, satisfaction with care, days on sick leave, and health care consumption and costs were measured during a 24-month follow-up. Thirteen candidate modifiers were tested for each outcome.
                There were no differences between the three treatment arms regarding the intensity of pain, the perceived disability, or the health-related quality of life. However, mini-intervention decreased occurrence of daily (A vs., C, P = 0.01) and bothersome (A vs. C, P < 0.05) pain and increased treatment satisfaction. Costs resulting from LBP were lower in the intervention groups (A 4670 Euros, B 5990 Euros) than in C (C 9510 Euros) (A vs. C, P = 0.04; and B vs. C, not significant). The average number of days on sick leave was 30 in A, 45 in B, and 62 in C (A vs. C, P = 0.03; B vs. C, not significant). The perceived risk for not recovering was the strongest modifier of treatment effect. Mental and mental-physical workers in A and B were less often on sick leave than those in C.
                Mini-intervention is an effective treatment for subacute LBP. Despite lack of a significant effect on intensity of low back pain and perceived disability, mini-intervention, including proper recommendations and advice, according to the "active approach," is able to reduce LBP-related costs. The perceived risk of not recovering was the strongest modifier of treatment effect. In alleviating pain, the intervention was most effective among the patients with a high perceived risk of not recovering. To assess the quality of published randomized clinical trials (RCTs) in rheumatology and to determine whether there has been improvement in quality between 2 time periods, 1987-1988 and 1997-1998.
                Using MEDLINE and a hand search of selected rheumatology journals, we identified RCTs of adult rheumatic diseases published in English in 1987-1988 or 1997-1998. We examined trial quality with an expanded version of the Jadad scale, which assesses the adequacy of reported random sequence generation, allocation concealment, blinding, and analysis. All trials were read by 1 reviewer, with prior standardization using a random sample read by 2 reviewers. We also evaluated "high"- versus "low"-impact journals based on citation index.
                Two hundred forty RCTs (1987-1988 119 RCTs, 1997-1998 121 RCTs) were assessed. Results showed improvement in the quality of the trials, but the rates of reported random sequence generation, allocation concealment, power, and intent-to-treat analyses were persistently low. Low rates of reports of random sequence generation, allocation concealment, and intent-to-treat analyses were present even in the high-impact journals.
                There has been improvement in the quality of reporting of RCTs in rheumatology between 1987-1988 and 1997-1998. However, methodologic problems such as lack of allocation concealment, inadequate random sequence generation, lack of reporting of power, and lack of intent-to-treat analyses remain common. Many of these problems are established sources of bias in RCTs and are easily rectifiable.
Despite concerns surrounding the use of opioids for long-term management of chronic LBP, there remain few high-quality trials assessing their efficacy. The trials in this review, although achieving high internal validity scores, were characterized by a lack of generalizability, inadequate description of study populations, poor intention-to treat analyses, and limited interpretation of functional improvement. Based on our results, the benefits of opioids in clinical practice for the long-term management of chronic LBP remain questionable. Therefore, further high-quality studies that more closely simulate clinical practice are needed to assess the usefulness, and potential risks, of opioids for individuals with chronic LBP.