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Background context Epidural corticosteroid injections are commonly used to treat back and leg pain associated with lumbar spinal stenosis. However, little is known about which patient characteristics may predict favorable responses. Purpose The aim was to identify patient characteristics associated with benefits from epidural injections of corticosteroid with lidocaine versus epidural injections of lidocaine only for lumbar spinal stenosis symptoms. Study design/setting This was a secondary analysis of Lumbar Epidural steroid injections for Spinal Stenosis randomized controlled trial data from 16 US clinical sites. Patient sample Patients aged older than or equal to 50 years with moderate-to-severe leg pain and lumbar central spinal stenosis randomized to epidural injections of corticosteroids with lidocaine (n=200) or lidocaine only (n=200) were included. Outcome measures Primary outcomes were the Roland-Morris Disability Questionnaire (RMDQ) and 0 to 10 leg pain intensity ratings. Secondary outcomes included the Brief Pain Inventory Interference Scale and the Swiss Spinal Stenosis Questionnaire. Methods At baseline, clinicians rated severity of patient spinal stenosis, and patients completed predictor and outcome measures. Patients completed outcome measures again 3 and 6 (primary end point) weeks after randomization/initial injection. Analysis of covariance was used with treatment by covariate interactions to identify baseline predictors of greater benefit from corticosteroid+lidocaine versus lidocaine alone. We also identified nonspecific (independent of treatment) predictors of outcomes. Results Among 21 candidate predictors and six outcomes, only one baseline variable predicted greater benefit from corticosteroid+lidocaine versus lidocaine only at 3 or 6 weeks. Compared with patients who rated their health-related quality of life as high on the EQ-5D Index, patients who rated it as poor had greater improvement with corticosteroid than with lidocaine only in leg pain at 6 (but not 3) weeks (interaction coefficient=2.94; 95% confidence interval [CI]=0.11–5.76; p=.04) and in RMDQ disability scores at 3 (but not 6) weeks (interaction coefficient=4.77, 95% CI=−0.04 to 9.59; p=.05). Several baseline patient characteristics predicted outcomes regardless of treatment assignment. Conclusions Among 21 baseline patient characteristics examined, none, including clinician-rated spinal stenosis severity, were consistent predictors of benefit from epidural injections of lidocaine+corticosteroid versus lidocaine only.

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 in terval [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.)

Background Back pain represents a substantial burden globally, ranking first in a recent assessment among causes of years lived with disability. Though back pain is widely studied among working age adults, there are gaps with respect to basic descriptive epidemiology among seniors, especially in the United States. Our goal was to describe how pain, function and health-related quality of life vary by demographic and geographic factors among seniors presenting to primary care providers with new episodes of care for back pain. Methods We examined baseline data from the Back pain Outcomes using Longitudinal Data (BOLD) registry, the largest inception cohort to date of seniors presenting to a primary care provider for back pain. The sample included 5,239 patients ≥ 65 years old with a new primary care visit for back pain at three integrated health systems (Northern California Kaiser-Permanente, Henry Ford Health System [Detroit], and Harvard Vanguard Medical Associates [Boston]). We examined differences in patient characteristics across healthcare sites and associations of patient sociodemographic and clinical characteristics with baseline patient-reported measures of pain, function, and health-related quality of life. Results Patients differed across sites in demographic and other characteristics. The Detroit site had more African-American patients (50%) compared with the other sites (7-8%). The Boston site had more college graduates (68%) compared with Detroit (20%). Female sex, lower educational status, African-American race, and older age were associated with worse functional disability as measured by the Roland-Morris Disability Questionnaire. Except for age, these factors were also associated with worse pain. Conclusions Baseline pain and functional impairment varied substantially with a number of factors in the BOLD cohort. Healthcare site was an important factor. After controlling for healthcare site, lower education, female sex, African-American race, and older age were associated with worse physical disability and all of these factors except age were associated with worse pain. Trial registration Clinical Trials.gov NCT01776242; Registration date: June 13, 2012.

Electronic data collection for monitoring pain has become increasingly popular in clinical research. However, no direct comparison has been made between electronic diaries and self-report paper diaries or phone interviews. We asked 36 patients with chronic low back pain to monitor their pain for 1 year; 20 of them used both a palmtop computer and paper diaries, and 16 used paper diaries alone. All patients were called once a week and asked to rate their pain. Regression analyses with a measurement error model were run on hourly pain scores recorded by both palmtop computer and paper diaries. Ratings of pain intensity were highly reliable between data recorded with a palmtop computer and with data from paper diaries. Patients who monitored their pain with the palmtop computer entered data on average 6.75 times a week and were 89.9% compliant with daily monitoring throughout the year. Two-way messaging available through the palmtop computer seemed to encourage continued use of the device. Internal consistency of reporting and correlations with phone reports and standardized measures were highly significant, suggesting that data from electronic diaries are both reliable and valid. Patients using electronic diaries preferred them to paper diaries and showed much higher rates of compliance and satisfaction over the 1-year trial.

Study Design. A randomized, open, long-term, repeated-dose comparison of an anti-inflammatory drug and two opioid regimens in 36 patients with back pain. Objectives. To examine the long-term safety and efficacy of chronic opioid therapy in a randomized trial of patients with back pain. Methods. All participants underwent a 4-week washout period of no opioid medication before being randomly assigned to one of three treatment regimens for 16 weeks: 1) naproxen only, 2) set-dose oxycodone, or 3) titrated-dose oxycodone and sustained-release morphine sulfate. All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks. Finallv, all participants were monitored for a 1-month posttreatment washout period. Each patient was called once a week for a report on pain, activity, mood, medication, hours awake, and adverse effects and was monitored carefully for signs of abuse and noncompliance. Results. Weekly reports during the experimental phase showed the titrated-dose group to have less pain (P < 0.001) and less emotional distress (P< 0.001) than the other two groups. Both opioid groups were significantly different from the naproxen-only group. During the titration phase, patients also reported significantly less pain and improved mood. Few differences were found in activity or hours asleep, or between average pretreatment and posttreatment phone-interview and questionnaire variables. No adverse events occurred, and only one participant showed signs of abuse behavior. Conclusions. The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep, Opioid therapy for chronic back pain was used without significant risk of abuse. However, tapered-off opioid treatment is palliative and without long-term benefit.

Patients prescribed opioids for chronic pain may suffer from inadequate postoperative pain control. Ketamine is an adjuvant demonstrating analgesic and opioid-sparing effects. We hypothesize that an intravenous ketamine infusion in addition to opioid-based patient-controlled analgesia (PCA) improves postoperative pain relief in this patient population.We evaluated 64 patients with chronic pain taking opioids undergoing nononcologic surgery. Patients were randomized to receive either postoperative hydromorphone PCA and continuous ketamine (0.2 mg/kg/hour), or hydromorphone PCA and saline. Patients provided numeric rating scale (NRS) pain scores for "worst," "average," and "least" pain following surgery. The primary outcome measure was change in patients' postoperative NRS scores compared with baseline NRS. Secondary and tertiary outcomes included postoperative day one 24-hour opioid use and the amount of opioid used 24 hours prior to hospital discharge.Fifty-nine patients were included in the analysis. Baseline patient characteristics were similar with the exception of age. Patients using ketamine had decreased "average" pain scores (percent change between postoperative and preoperative NRS) after surgery (13.5% decrease in the ketamine group vs 15.5% increase in NRS in the placebo group, P = 0.0057). There were no differences in "worst" or "least" pain scores or postoperative opioid use. Side effects between groups were similar.Our study demonstrates that a postoperative ketamine infusion at 0.2 mg/kg/hour in addition to opioids results in a statistically significant reduction of "average" pain scores in patients undergoing surgery who take opioids for chronic pain. However, "least" and "worst" pain scores and the amount of opioid used postoperatively did not differ between groups. Thus, the use of a postoperative ketamine infusion at 0.2 mg/kg/hour provides limited benefit in improving pain management for this challenging population.

Introduction In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery. Methods and analysis Based on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships. Ethics and dissemination Ethical approval of the study protocol has been obtained from Institutional Review Boards at the participating institutions. Trial results will be disseminated through scientific conference presentations and by publication in scientific journals. Trial registration number NCT02489526; pre-results.

Objective. To identify predictors of persistent disability and back pain in older adults. Design. Prospective cohort study. Setting. Back pain outcomes using longitudinal data registry. Subjects. Five thousand two hundred twenty adults age 65 years and older with a new primary care visit for back pain. Methods. Baseline measurements included: demographics, health, and back pain characteristics. We abstracted imaging findings from 348 radiology reports. The primary outcomes were the Roland-Morris Disability Questionnaire (RMDQ) and back pain intensity. We defined persistent disability as RMDQ of 4/24 or higher at both six and 12 months and persistent back pain as pain 3/10 or higher at both six and 12 months. Results. There were 2,498 of 4,143 (60.3%) participants with persistent disability, and 2,099 of 4,144 (50.7%) had persistent back pain. Adjusted analyses showed the following characteristics most strongly predictive of persistent disability and persistent back pain: sex, race, worse baseline clinical characteristics of back pain, leg pain, back-related disability and duration of symptoms, smoking, anxiety symptoms, depressive symptoms, a history of falls, greater number of comorbidities, knee osteoarthritis, wide-spread pain syndromes, and an index diagnosis of lumbar spinal stenosis. Within the imaging data subset, central spinal stenosis was not associated with disability or pain. Conclusion. We found that many predictors in older adults were similar to those for younger populations.

Background Lumbar spinal stenosis is one of the most common causes of low back pain among older adults and can cause significant disability. Despite its prevalence, treatment of spinal stenosis symptoms remains controversial. Epidural steroid injections are used with increasing frequency as a less invasive, potentially safer, and more cost-effective treatment than surgery. However, there is a lack of data to judge the effectiveness and safety of epidural steroid injections for spinal stenosis. We describe our prospective, double-blind, randomized controlled trial that tests the hypothesis that epidural injections with steroids plus local anesthetic are more effective than epidural injections of local anesthetic alone in improving pain and function among older adults with lumbar spinal stenosis. Methods We will recruit up to 400 patients with lumbar central canal spinal stenosis from at least 9 clinical sites over 2 years. Patients with spinal instability who require surgical fusion, a history of prior lumbar surgery, or prior epidural steroid injection within the past 6 months are excluded. Participants are randomly assigned to receive either ESI with local anesthetic or the control intervention (epidural injections with local anesthetic alone). Subjects receive up to 2 injections prior to the primary endpoint at 6 weeks, at which time they may choose to crossover to the other intervention. Participants complete validated, standardized measures of pain, functional disability, and health-related quality of life at baseline and at 3 weeks, 6 weeks, and 3, 6, and 12 months after randomization. The primary outcomes are Roland-Morris Disability Questionnaire and a numerical rating scale measure of pain intensity at 6 weeks. In order to better understand their safety, we also measure cortisol, HbA1c, fasting blood glucose, weight, and blood pressure at baseline, and at 3 and 6 weeks post-injection. We also obtain data on resource utilization and costs to assess cost-effectiveness of epidural steroid injection. Discussion This study is the first multi-center, double-blind RCT to evaluate the effectiveness of epidural steroid injections in improving pain and function among older adults with lumbar spinal stenosis. The study will also yield data on the safety and cost-effectiveness of this procedure for older adults. Trial Registration Clinicaltrials.gov NCT01238536

Background Back pain is one of the most important causes of functional limitation, disability, and utilization of health care resources for adults of all ages, but especially among older adults. Despite the high prevalence of back pain in this population, important questions remain unanswered regarding the comparative effectiveness of commonly used diagnostic tests and treatments in the elderly. The overall goal of the Back pain Outcomes using Longitudinal Data (BOLD) project is to establish a rich, sustainable registry to describe the natural history and evaluate prospectively the effectiveness, safety, and cost-effectiveness of interventions for patients 65 and older with back pain. Methods/design BOLD is enrolling 5,000 patients ≥ 65 years old who present to a primary care physician with a new episode of back pain. We are recruiting study participants from three integrated health systems (Kaiser-Permanente Northern California, Henry Ford Health System in Detroit and Harvard Vanguard Medical Associates/ Harvard Pilgrim Health Care in Boston). Registry patients complete validated, standardized measures of pain, back pain-related disability, and health-related quality of life at enrollment and 3, 6 and 12 months later. We also have available for analysis the clinical and administrative data in the participating health systems’ electronic medical records. Using registry data, we will conduct an observational cohort study of early imaging compared to no early imaging among patients with new episodes of back pain. The aims are to: 1) identify predictors of early imaging and; 2) compare pain, functional outcomes, diagnostic testing and treatment utilization of patients who receive early imaging versus patients who do not receive early imaging. In terms of predictors, we will examine patient factors as well as physician factors. Discussion By establishing the BOLD registry, we are creating a resource that contains patient-reported outcome measures as well as electronic medical record data for elderly patients with back pain. The richness of our data will allow better matching for comparative effectiveness studies than is currently possible with existing datasets. BOLD will enrich the existing knowledge base regarding back pain in the elderly to help clinicians and patients make informed, evidence-based decisions regarding their care.

SEPTIC coronary embolism is a rare complication of endocarditis. Aortic valve (AV) vegetations have been described as a source of coronary embolism resulting in myocardial infarction. 1 The use of diagnostic coronary angiography to localize the obstruction is often considered contraindicated, since the intervention might promote further embolic events. 2 Alternatively, transesophageal echocardiography (TEE) can be used to assess proximal coronary blood flow, 3,4 however its utility in the management of a patient with suspected septic coronary embolism has not been described previously. We report a case of AV endocarditis following epidural steroid injection for treatment of lower back pain. The patient developed cardiogenic shock with electrocardiography and echocardiography indicating acute ischemia. Despite a suspected coronary embolism, angiography was not performed. The patient was taken to the operating room for emergency AV replacement (AVR) and possible coronary artery bypass grafting (CABG). However, CABG was abandoned, since precardiopulmonary-bypass TEE demonstrated laminar blood flow in the left sided coronary arteries and a resolution of regional wall motion abnormality after the AVR.

IMPLICATIONS We describe a patient with acute mental status changes, which resolved on removal of medication from the reservoir of a Synchromed intrathecal pump. This report highlights the potential adverse mental affects of chronic spinal infusions for pain therapy and discusses pitfalls in toxicology analysis using immunoassay.

Nucleoplasty is a minimally invasive procedure for treating pain caused by symptomatic disc herniation that is refractory to conservative therapy. Observational studies have reported differing outcomes for this procedure and thus its effectiveness is yet to be determined.A systematic review of the efficacy of the nucleoplasty procedure.To assess the clinical efficacy of the nucleoplasty procedure for treating back pain from symptomatic, contained disc herniation and to evaluate the methodological quality of the included studies.The relevant literature for nucleoplasty was identified through a search of the following databases: Pubmed, Ovid Medline, and the Cochrane library, and by a review of the bibliographies of the included studies. A review of the literature of the effectiveness of the nucleoplasty procedure for managing discogenic pain was performed according to the criteria for observational studies using a "Quality Index" scale to determine the methodological quality of the literature. The level of evidence was classified as Level I, II, or III based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF) for therapeutic interventions. Recommendations were based on the criteria developed by Guyatt et al.The main outcome measures evaluated were the percentage of pain relief based on visual analogue scale (VAS) or numeric rating scale (NRS), percentage of patients with more than 50% reduction in pain, percentage of patients meeting one or more success criteria after nucleoplasty, and improvement in patient function. Secondary measures noted were reports of complications and the Quality Index scores of each study that was evaluated.The quality of evidence for improvement in pain or function after a nucleoplasty procedure is Level II-3. The recommendation is 1C/strong for the nucleoplasty procedure based on the quality of evidence available. The median Quality Index score was 16 (range 12 - 19), indicating adequate methodological quality of the available literature. None of the studies reported major complications related to nucleoplasty.Observational studies suggest that nucleoplasty is a potentially effective minimally invasive treatment for patients with symptomatic disc herniations who are refractory to conservative therapy. The recommendation is a level 1C, strongly supporting the therapeutic efficacy of this procedure. However, prospective randomized controlled trials with higher quality of evidence are necessary to confirm efficacy and risks, and to determine ideal patient selection for this procedure.

Background Comorbid psychopathology is an important predictor of poor outcome for many types of treatments for back or neck pain. But it is unknown if this applies to the results of medial branch blocks (MBBs) for chronic low back or neck pain, which involves injecting the medial branch of the dorsal ramus nerves that innervate the facet joints. The objective of this study was to determine whether high levels of psychopathology are predictive of pain relief after MBB injections in the lumbar or cervical spine. Methods This was a prospective cohort study. Consecutive patients in a pain medicine practice undergoing MBBs of the lumbar or cervical facets with corticosteroids were recruited to participate. Subjects were selected for a MBB based on operationalized selection criteria and the procedure was performed in a standardized manner. Subjects completed the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) just prior to the procedure and at one-month follow up. Scores on the HADS classified the subjects into three groups based on psychiatric symptoms, which formed the primary predictor variable: Low, Moderate, or High levels of psychopathology. The primary outcome measure was the percent improvement in average daily pain rating one-month following an injection. Analysis of variance and chi-square were used to analyze the analgesia and functional rating differences between groups, and to perform a responder analysis. Results Eighty six (86) subjects completed the study. The Low psychopathology group (n = 37) reported a mean of 23% improvement in pain at one-month while the High psychopathology group (n = 29) reported a mean worsening of -5.8% in pain (p < .001). Forty five percent (45%) of the Low group had at least 30% improvement in pain versus 10% in the High group (p < .001). Using an analysis of covariance, no baseline demographic, social, or medical variables were significant predictors of pain improvement, nor did they mitigate the effect of psychopathology on the outcome. Conclusion Psychiatric comorbidity is associated with diminished pain relief after a MBB injection performed with steroid at one-month follow-up. These findings illustrate the importance of assessing comorbid psychopathology as part of a spine care evaluation.

We assessed the efficacy of dronabinol (Marinol capsules; Solvay Pharmaceuticals, Brussels, Belgium), a synthetic Δ 9 -THC (tetrahydrocannabinol), in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment. Phase I of this 2-phase study was a randomized, single-dose, double-blinded, placebo-controlled, crossover trial in which subjects were randomly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three, 8-hour visits. Baseline self-report measures, hourly ratings of pain intensity, pain relief, pain bothersomeness, treatment satisfaction, mood, side effects, and blood serum levels were obtained. Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids. Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo. No differences in benefit were found between the 20 mg and 10 mg doses. In the Phase II trial, titrated dronabinol contributed to significant relief of pain, reduced pain bothersomeness, and increased satisfaction compared with baseline. The incidence of side effects was dose-related. Overall, the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain. Perspective This study examines the effect of adding a cannabinoid to the regimen of patients with chronic pain who report significant pain despite taking stable doses of opioids. The results of our preliminary study suggest that dronabinol, a synthetic THC, may have an additive effect on pain relief.

Psychiatrische Komorbiditat geht einher mit verminderter Schmerzreduktion auf Opioide und erhohtem Opioidmissbrauch bei chronischen Kreuzschmerzpatienten. Diese Vermutung konnte nun in einer prospektiven Studie unter der Leitung von A. D. Wasan von der Klinik fur Anasthesiologie der Universitat von Pittsburgh, USA, bestatigt werden.

Im Unterschied zu jungeren wird bei alteren Patienten mit Ruckenschmerzen oft schon beim ersten Arztbesuch eine bildgebende Diagnostik empfohlen, da bei diesen die Wahrscheinlichkeit fur einen ernsten Hintergrund der Beschwerden hoher ist. Aber ergibt sich wirklich ein statistischer Vorteil durch eine fruhe Bildgebung?

Physicians can encounter problems in prescribing opioids for some patients with chronic pain such as multiple unsanctioned dose escalations, episodes of lost or stolen prescriptions, and positive urine drug screenings for illicit substances. This study explored the usefulness of questions on abuse history in predicting problems with prescribing opioids for patients at a hospital-based pain management program. One hundred forty-five (145) patients who were taking long- and short-acting opioids for their pain were classified as high or low risk on the basis of their responses to interview questions about 1) substance abuse history in their family, 2) past problems with drug or alcohol abuse, and 3) history of legal problems. The treating physicians completed a questionnaire about problems that they had encountered with their patients. Problem behaviors were verified through chart review. No differences in demographic characteristics were found between those classified as high and low risk. Patients who admitted to a family history of substance abuse, a history of legal problems, and drug or alcohol abuse were prone to more aberrant drug-related behaviors, including a higher incidence of lost or stolen prescriptions and the presence of illicit substances in their urine (P < 0.05). Patients classified as high risk also had a significantly higher frequency of reported mental health problems and motor vehicle accidents. More of these patients smoked cigarettes, tended to need a cigarette within the first hour of the day, took higher doses of opioids, and reported fewer adverse effects from the medications than did those without such a history (P < 0.05). This study demonstrates that questions about abuse history and legal problems can be useful in predicting aberrant drug-related behavior with opioid use in persons with chronic noncancer pain.

Clinical experience supports the notion that opioids can be used successfully to treat many chronic pain conditions. Unfortunately, few controlled trials have assessed which individuals benefit from long-term opioid therapy, and there is concern about the use of long-term opioid therapy in individuals with a substance-abuse history. This article contains three sections relevant to the assessment of individuals with chronic pain and a substance-abuse history who are receiving long-term opioid therapy. The first reviews the literature on opioid therapy, with a critique of biologic and environmental susceptibility factors for addiction. The second briefly reviews uncontrolled and controlled trials of opioid therapy for pain. The third reviews areas critical in assessing treatment efficacy and substance abuse in patients with chronic pain, both in terms of documentation of past behaviors and as a measure of outcome of opioid therapy. Potential guidelines for use of opioids in patients with chronic noncancer pain are outlined. Finally, questions are posed for future investigations of the efficacy of opioid therapy for patients with chronic pain and a substance-abuse history.

Background Are trends in coronary heart disease deaths based on risk factor changes? Objective To study the relationship between trends in coronary deaths and changes in blood cholesterol in the Seven Countries Study. Material and Methods Sixteen cohorts of men aged 40–59 years from seven countries (U.S.A., Finland, the Netherlands, Italy, Croatia (former Yugoslavia), Serbia (former Yugoslavia), Greece, Japan) were units for the analyses of serum cholesterol measured at entry and after 5 and 10 years, and for mortality over 25 years. Results In the populations, the ecological relationship of mean serum cholesterol at entry to late coronary heart disease death rates during the 10- to 25-year follow-up was weak, with an R-square of 0·31. Cholesterol measurements made at year 10, and an indicator of cholesterol change during the first 10 years, increased the association (R-square, 0·49). A negative and significant interaction was shown between baseline population cholesterol levels and their 10-year change. As an indicator of acceleration in mortality, cholesterol change over 10 years was also positively correlated (partial R-square 0·44) with the ratio of 25-year to 5-year deaths. Conclusions In the Seven Countries Study, late coronary heart disease death rates are largely ‘explained’ by changes in blood cholesterol levels during the early phases of the study, mainly due to increases in lower cholesterol levels among some cohorts.

In the Seven Countries Study, carried out in Finland, Greece, Italy, Japan, The Netherlands, the United States, and Yugoslavia, among 11,325 "healthy" men aged 40-59 years in 15 years, there were 594 cancer deaths. Among 477 cancer deaths five years after cholesterol measurement, there was a significant excess of lung cancer deaths in the bottom 20% of the cholesterol distributions in the populations. Age, blood pressure, smoking habits, occupation, and relative body weight did not help explain this. A U-shaped relationship between cancer and cholesterol was not seen in any population. Trend analysis with various cutting points indicated increasing risk of lung cancer death at cholesterol levels under 170 mg/dl. The 45 men dead from cancer in the first two years had lower cholesterol levels than their compatriots who died from cancer later but they did not differ in relative weight or fatness. In contrast to relationships for individuals within populations, the highest cancer death rates were in northern Europe, where the general level of cholesterol was also highest. Other characteristics of the populations--age, relative weight, smoking habits, blood pressure, physical activity, and vitamin A and ascorbic acid in the diet--did not help in the attempt to understand the regional differences in cancer mortality. There is no evidence that any of the observed cancer-serum cholesterol relationships among or within the populations involve an effect of serum cholesterol concentration on oncogenesis or cancer mortality but the possibility of such an effect cannot be denied.

At the end of the 1950s the Seven Countries Study was designed to investigate the relations between diet and cardiovascular diseases. Sixteen cohorts were selected in Finland, Greece, Italy, Japan, The Netherlands, United States, and Yugoslavia. During the 1960s food consumption data were collected from random samples of these cohorts by use of the record method. In Finland the intake of milk, potatoes, edible fats, and sugar products was very high. A similar but lower intake pattern was observed in The Netherlands. Fruit, meat, and pastry consumption was high in the United States; cereal and alcoholic drink consumption was high in Italy; and bread consumption high in Yugoslavians except for those in Belgrade. In Greece the intake of olive oil and fruit was high and the Japanese cohorts were characterized by a high consumption of fish, rice, and soy products. These differences in food consumption patterns have lessened during the past 25 y.